Innovative hybrid pile oscillator technique in the Minerve reactor: open loop vs. closed loop

NASA Astrophysics Data System (ADS)

Geslot, Benoit; Gruel, Adrien; Bréaud, Stéphane; Leconte, Pierre; Blaise, Patrick

2018-01-01

Pile oscillator techniques are powerful methods to measure small reactivity worth of isotopes of interest for nuclear data improvement. This kind of experiments has long been implemented in the Mineve experimental reactor, operated by CEA Cadarache. A hybrid technique, mixing reactivity worth estimation and measurement of small changes around test samples is presented here. It was made possible after the development of high sensitivity miniature fission chambers introduced next to the irradiation channel. A test campaign, called MAESTRO-SL, took place in 2015. Its objective was to assess the feasibility of the hybrid method and investigate the possibility to separate mixed neutron effects, such as fission/capture or scattering/capture. Experimental results are presented and discussed in this paper, which focus on comparing two measurements setups, one using a power control system (closed loop) and another one where the power is free to drift (open loop). First, it is demonstrated that open loop is equivalent to closed loop. Uncertainty management and methods reproducibility are discussed. Second, results show that measuring the flux depression around oscillated samples provides valuable information regarding partial neutron cross sections. The technique is found to be very sensitive to the capture cross section at the expense of scattering, making it very useful to measure small capture effects of highly scattering samples.

Crimpable double tubes for segmental retraction.

PubMed

Martins, Renato Parsekian; Gandini, Luiz Gonzaga; Martins, Isabela Parsekian; Martins, Lidia Parsekian

2011-01-01

When a T-loop is used in segmental mechanics, it is generally attached posteriorly to an auxiliary tube in the first molars and anteriorly to a crimpable cross tube or a Burstone canine bracket. This article illustrates the use of a crimpable tube with a 90-degree bend on the base wire to secure a T-loop in segmental retraction. Both of these approaches allow a T-loop to be reactivated in a simple manner without undesirable changes in the system of forces, which could happen if the T-loop is skewed posteriorly.

Fundamental Physics and Practical Applications of Electromagnetic Local Flow Control in High Speed Flows (Rutgers)

DTIC Science & Technology

2010-02-16

field. Techniques utilizing this design use an open- loop control and no flow monitoring sensors are required. Conversely, reactive (or closed - loop ...and closed (dashed line) configuration. 38 closed configuration described above, the ambiguity in the critical limits of the transition...flow; a new vortex is then shed from the cavity leading edge, closing the feedback loop .[31] Open cavities with an L/D approximately greater than

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description

PubMed Central

McGonigle, John; Murphy, Anna; Paterson, Louise M; Reed, Laurence J; Nestor, Liam; Nash, Jonathan; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy SA; Newbould, Rexford; Orban, Csaba; Smith, Dana G; Taylor, Eleanor M; Waldman, Adam D; Robbins, Trevor W; Deakin, JF William; Nutt, David J; Lingford-Hughes, Anne R; Suckling, John

2016-01-01

Objectives: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction – reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. Experimental design: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. Principle observations: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task. Conclusions: In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres. PMID:27703042

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description.

PubMed

McGonigle, John; Murphy, Anna; Paterson, Louise M; Reed, Laurence J; Nestor, Liam; Nash, Jonathan; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy Sa; Newbould, Rexford; Orban, Csaba; Smith, Dana G; Taylor, Eleanor M; Waldman, Adam D; Robbins, Trevor W; Deakin, Jf William; Nutt, David J; Lingford-Hughes, Anne R; Suckling, John

2017-01-01

We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. Principle observations: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task. In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres.

Origin and control of instability in SCR/triac three-phase motor controllers

NASA Technical Reports Server (NTRS)

Dearth, J. J.

1982-01-01

The energy savings and reactive power reduction functions initiated by the power factor controller (PFC) are discussed. A three-phase PFC with soft start is examined analytically and experimentally to determine how well it controls the open loop instability and other possible modes of instability. The detailed mechanism of the open loop instability is determined and shown to impose design constraints on the closed loop system. The design is shown to meet those constraints.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Brian; Nayak, Dhananjaya; Ray, Ananya

RNA polymerase inhibitors like the CBR class that target the enzyme’s complex catalytic center are attractive leads for new antimicrobials. The catalysis by RNA polymerase involves multiple rearrangements of bridge helix, trigger loop, and active-center side chains that isomerize the triphosphate of bound NTP and two Mg 2+ ions from a preinsertion state to a reactive configuration. CBR inhibitors target a crevice between the N-terminal portion of the bridge helix and a surrounding cap region within which the bridge helix is thought to rearrange during the nucleotide addition cycle. Here, we report crystal structures of CBR inhibitor/Escherichia coli RNA polymerasemore » complexes as well as biochemical tests that establish two distinct effects of the inhibitors on the RNA polymerase catalytic site. One effect involves inhibition of trigger-loop folding via the F loop in the cap, which affects both nucleotide addition and hydrolysis of 3'-terminal dinucleotides in certain backtracked complexes. The second effect is trigger-loop independent, affects only nucleotide addition and pyrophosphorolysis, and may involve inhibition of bridge-helix movements that facilitate reactive triphosphate alignment.« less

Distinguishing West Nile virus infection using a recombinant envelope protein with mutations in the conserved fusion-loop.

PubMed

Chabierski, Stefan; Barzon, Luisa; Papa, Anna; Niedrig, Matthias; Bramson, Jonathan L; Richner, Justin M; Palù, Giorgio; Diamond, Michael S; Ulbert, Sebastian

2014-05-09

West Nile Virus (WNV) is an emerging mosquito-transmitted flavivirus that continues to spread and cause disease throughout several parts of the world, including Europe and the Americas. Specific diagnosis of WNV infections using current serological testing is complicated by the high degree of cross-reactivity between antibodies against other clinically relevant flaviviruses, including dengue, tick-borne encephalitis (TBEV), Japanese encephalitis (JEV), and yellow fever (YFV) viruses. Cross-reactivity is particularly problematic in areas where different flaviviruses co-circulate or in populations that have been immunized with vaccines against TBEV, JEV, or YFV. The majority of cross-reactive antibodies against the immunodominant flavivirus envelope (E) protein target a conserved epitope in the fusion loop at the distal end of domain II. We tested a loss-of-function bacterially expressed recombinant WNV E protein containing mutations in the fusion loop and an adjacent loop domain as a possible diagnostic reagent. By comparing the binding of sera from humans infected with WNV or other flaviviruses to the wild type and the mutant E proteins, we analyzed the potential of this technology to specifically detect WNV antibodies. Using this system, we could reliably determine WNV infections. Antibodies from WNV-infected individuals bound equally well to the wild type and the mutant protein. In contrast, sera from persons infected with other flaviviruses showed significantly decreased binding to the mutant protein. By calculating the mean differences between antibody signals detected using the wild type and the mutant proteins, a value could be assigned for each of the flaviviruses, which distinguished their pattern of reactivity. Recombinant mutant E proteins can be used to discriminate infections with WNV from those with other flaviviruses. The data have important implications for the development of improved, specific serological assays for the detection of WNV antibodies in regions where other flaviviruses co-circulate or in populations that are immunized with other flavivirus vaccines.

Analysis of function-related interactions of ATP, sodium and potassium ions with Na+- and K+-transporting ATPase studied with a thiol reagent as tool.

PubMed

Grosse, R; Eckert, K; Malur, J; Repke, K R

1978-01-01

The paper describes the interaction of ATP, Na+ and K+ with (NaK)-ATPase exploiting the inactivation by reaction with NBD-chloride as an analytical tool for the evaluation of enzyme ligandation with the various effectors. 1. The inactivation of (NaK)-ATPase by reaction with NBD-chloride showing under all conditions studied a pseudo first-order rate rests on the alkylation of thiol groups in or near catalytic centre. ATP bound to catalytic centre prevents from enzyme inactivation by NDD-chloride through protection of these thiol groups from alkylation. Na+ and K+ affect the reactivity of the thiol groups towards NBD-chloride either indirectly via influencing ATP binding or more directly via changing the conformation of catalytic centre. Proceeding from these interrelations, the interaction of the various effectors with the enzyme was analyzed. 2. The K'D-values of various nucleotides determined by our approach correspond to the values obtained by independent methods. As shown for the first time, two catalytic centres per enzyme molecule exist. They exhibit high or low affinity to both ATP and ADP apparently caused by anticooperative interaction of the half-units of the enzyme through intersubunit communication ("half-of-the-sites reactivity"). 3. In the absence of ATP, Na+ or K+ ligandation of (NaK)-ATPase produce opposite effects on the reactivity of the thiol groups of catalytic centres reflecting different changes of their conformation. This corresponds to the well-known antagonistic effect of Na+ and K+ on some partial reactions of (NaK)-ATPase. The Na+ and K+ concentrations required to change thiol reactivity are rather high, i.e. the ionophoric centres for both Na+ and K+ are not readily accessible for cation complexation in the absence of enzyme complexation with ATP. 4. Na+ being without effect on ATP binding to the enzyme also does not influence the inactivating reaction with NBD-chloride while K+ by decreasing ATP binding dramatically decreases the protective effect of ATP. The K+ affinity of the enzyme-ATP complex is by more than two orders of magnitude higher than that of free enzyme. Na+ ligandation of the K+-liganded enzyme-ATP complex reverses the effect of K+ ligandation and produces a protective effect which distinctly surpasses that of the complexation of free enzyme with ATP. Hence, the enzyme molecule carries simultaneously ionophoric centres for both Na+ and K+. 5. The findings that per enzyme molecule ionophoric centres for Na+ and K+, and two catalytic centres with anticooperative interaction coexist corroborate the corresponding basic predictions of the flip-flop concept of (NaK)-ATPase pump mechanism, and explain some peculiar kinetic features of transport and enzyme activities of (NaK)-ATPase.

Soft sensor based composition estimation and controller design for an ideal reactive distillation column.

PubMed

Vijaya Raghavan, S R; Radhakrishnan, T K; Srinivasan, K

2011-01-01

In this research work, the authors have presented the design and implementation of a recurrent neural network (RNN) based inferential state estimation scheme for an ideal reactive distillation column. Decentralized PI controllers are designed and implemented. The reactive distillation process is controlled by controlling the composition which has been estimated from the available temperature measurements using a type of RNN called Time Delayed Neural Network (TDNN). The performance of the RNN based state estimation scheme under both open loop and closed loop have been compared with a standard Extended Kalman filter (EKF) and a Feed forward Neural Network (FNN). The online training/correction has been done for both RNN and FNN schemes for every ten minutes whenever new un-trained measurements are available from a conventional composition analyzer. The performance of RNN shows better state estimation capability as compared to other state estimation schemes in terms of qualitative and quantitative performance indices. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Performance constraints and compensation for teleoperation with delay

NASA Technical Reports Server (NTRS)

Mclaughlin, J. S.; Staunton, B. D.

1989-01-01

A classical control perspective is used to characterize performance constraints and evaluate compensation techniques for teleoperation with delay. Use of control concepts such as open and closed loop performance, stability, and bandwidth yield insight to the delay problem. Teleoperator performance constraints are viewed as an open loop time delay lag and as a delay-induced closed loop bandwidth constraint. These constraints are illustrated with a simple analytical tracking example which is corroborated by a real time, 'man-in-the-loop' tracking experiment. The experiment also provides insight to those controller characteristics which are unique to a human operator. Predictive displays and feedforward commands are shown to provide open loop compensation for delay lag. Low pass filtering of telemetry or feedback signals is interpreted as closed loop compensation used to maintain a sufficiently low bandwidth for stability. A new closed loop compensation approach is proposed that uses a reactive (or force feedback) hand controller to restrict system bandwidth by impeding operator inputs.

An accurate reactive power control study in virtual flux droop control

NASA Astrophysics Data System (ADS)

Wang, Aimeng; Zhang, Jia

2017-12-01

This paper investigates the problem of reactive power sharing based on virtual flux droop method. Firstly, flux droop control method is derived, where complicated multiple feedback loops and parameter regulation are avoided. Then, the reasons for inaccurate reactive power sharing are theoretically analyzed. Further, a novel reactive power control scheme is proposed which consists of three parts: compensation control, voltage recovery control and flux droop control. Finally, the proposed reactive power control strategy is verified in a simplified microgrid model with two parallel DGs. The simulation results show that the proposed control scheme can achieve accurate reactive power sharing and zero deviation of voltage. Meanwhile, it has some advantages of simple control and excellent dynamic and static performance.

Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of domain II.

PubMed

Lai, Chih-Yun; Tsai, Wen-Yang; Lin, Su-Ru; Kao, Chuan-Liang; Hu, Hsien-Ping; King, Chwan-Chuen; Wu, Han-Chung; Chang, Gwong-Jen; Wang, Wei-Kung

2008-07-01

The antibody response to the envelope (E) glycoprotein of dengue virus (DENV) is known to play a critical role in both protection from and enhancement of disease, especially after primary infection. However, the relative amounts of homologous and heterologous anti-E antibodies and their epitopes remain unclear. In this study, we examined the antibody responses to E protein as well as to precursor membrane (PrM), capsid, and nonstructural protein 1 (NS1) of four serotypes of DENV by Western blot analysis of DENV serotype 2-infected patients with different disease severity and immune status during an outbreak in southern Taiwan in 2002. Based on the early-convalescent-phase sera tested, the rates of antibody responses to PrM and NS1 proteins were significantly higher in patients with secondary infection than in those with primary infection. A blocking experiment and neutralization assay showed that more than 90% of anti-E antibodies after primary infection were cross-reactive and nonneutralizing against heterologous serotypes and that only a minor proportion were type specific, which may account for the type-specific neutralization activity. Moreover, the E-binding activity in sera of 10 patients with primary infection was greatly reduced by amino acid replacements of three fusion loop residues, tryptophan at position 101, leucine at position 107, and phenylalanine at position 108, but not by replacements of those outside the fusion loop of domain II, suggesting that the predominantly cross-reactive anti-E antibodies recognized epitopes involving the highly conserved residues at the fusion loop of domain II. These findings have implications for our understanding of the pathogenesis of dengue and for the future design of subunit vaccine against DENV as well.

CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop.

PubMed

Wei, Zhao; Guo, Haiyang; Liu, Zhaojian; Zhang, Xiyu; Liu, Qiao; Qian, Yanyan; Gong, Yaoqin; Shao, Changshun

2015-02-01

Tumor suppressor p53 is known to regulate the level of intracellular reactive oxygen species (ROS). It can either alleviate oxidative stress under physiological and mildly stressed conditions or exacerbate oxidative stress under highly stressed conditions. We here report that a p53-ROS positive feedback loop drives a senescence program in normal human fibroblasts (NHFs) and this senescence-driving loop is negatively regulated by CUL4B. CUL4B, which can assemble various ubiquitin E3 ligases, was found to be downregulated in stress-induced senescent cells, but not in replicative senescent cells. We observed that p53-dependent ROS production was significantly augmented and stress-induced senescence was greatly enhanced when CUL4B was absent or depleted. Ectopic expression of CUL4B, on the other hand, blunted p53 activation, reduced ROS production, and attenuated cellular senescence in cells treated with H2O2. CUL4B was shown to promote p53 ubiquitination and proteosomal degradation in NHFs exposed to oxidative stress, thus dampening the p53-dependent cellular senescence. Together, our results established a critical role of CUL4B in negatively regulating the p53-ROS positive feedback loop that drives cellular senescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Quality through Networking--From Reactive Administration to Proactive Cooperation

ERIC Educational Resources Information Center

Karttu, Petri; Kiilunen, Liisa; Laulajainen, Tiina

2012-01-01

The Language Centre functions as an independent institute within the University of Helsinki. It provides services to all the faculties and units of the university by offering language services and doing its share in creating an international learning environment. Together, the Language Centre and the faculties have one goal in common, namely, a…

Experimental Verification of Application of Looped System and Centralized Voltage Control in a Distribution System with Renewable Energy Sources

NASA Astrophysics Data System (ADS)

Hanai, Yuji; Hayashi, Yasuhiro; Matsuki, Junya

The line voltage control in a distribution network is one of the most important issues for a penetration of Renewable Energy Sources (RES). A loop distribution network configuration is an effective solution to resolve voltage and distribution loss issues concerned about a penetration of RES. In this paper, for a loop distribution network, the authors propose a voltage control method based on tap change control of LRT and active/reactive power control of RES. The tap change control of LRT takes a major role of the proposed voltage control. Additionally the active/reactive power control of RES supports the voltage control when voltage deviation from the upper or lower voltage limit is unavoidable. The proposed method adopts SCADA system based on measured data from IT switches, which are sectionalizing switch with sensor installed in distribution feeder. In order to check the validity of the proposed voltage control method, experimental simulations using a distribution system analog simulator “ANSWER” are carried out. In the simulations, the voltage maintenance capability in the normal and the emergency is evaluated.

Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.

PubMed

Oscherwitz, Jon; Quinn, Conrad P; Cease, Kemp B

2015-05-11

Epitope-focused immunogens can elicit antibody against the loop neutralizing determinant (LND), a neutralizing epitope found within the 2β2-2β3 loop of protective antigen (PA), which can protect rabbits from high-dose inhalation challenge with Bacillus anthracis Ames strain. Interestingly, data suggests that this epitope is relatively immunosilent in rabbits and non-human primates immunized with full length PA. To determine whether the LND is immunosilent among humans vaccinated with PA, we screened antisera from AVA- or placebo-vaccinees from a clinical trial for antibody reactive with the LND. AVA-vaccinee sera had significant PA-specific antibody compared to placebo-vaccinee sera; however, sera from the two cohorts were indistinguishable with regard to the frequency of individuals with antibody specific for the LND. AVA-vaccinees have a low frequency of antibody reactive with the LND. As with rabbits and non-human primates, the elicitation of LND-specific antibody in humans appears to require immunization with an epitope-focused vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical-Looping Combustion and Gasification of Coals and Oxygen Carrier Development: A Brief Review

DOE PAGES

Wang, Ping; Means, Nicholas; Shekhawat, Dushyant; ...

2015-09-24

Chemical-looping technology is one of the promising CO 2 capture technologies. It generates a CO 2 enriched flue gas, which will greatly benefit CO 2 capture, utilization or sequestration. Both chemical-looping combustion (CLC) and chemical-looping gasification (CLG) have the potential to be used to generate power, chemicals, and liquid fuels. Chemical-looping is an oxygen transporting process using oxygen carriers. Recently, attention has focused on solid fuels such as coal. Coal chemical-looping reactions are more complicated than gaseous fuels due to coal properties (like mineral matter) and the complex reaction pathways involving solid fuels. The mineral matter/ash and sulfur in coalmore » may affect the activity of oxygen carriers. Oxygen carriers are the key issue in chemical-looping processes. Thermogravimetric analysis (TGA) has been widely used for the development of oxygen carriers (e.g., oxide reactivity). Two proposed processes for the CLC of solid fuels are in-situ Gasification Chemical-Looping Combustion (iG-CLC) and Chemical-Looping with Oxygen Uncoupling (CLOU). The objectives of this review are to discuss various chemical-looping processes with coal, summarize TGA applications in oxygen carrier development, and outline the major challenges associated with coal chemical-looping in iG-CLC and CLOU.« less

Understanding Which Residues of the Active Site and Loop Structure of a Tyrosine Aminomutase Define Its Mutase and Lyase Activities.

PubMed

Attanayake, Gayanthi; Walter, Tyler; Walker, Kevin D

2018-05-30

Site-directed mutations and substrate analogues were used to gain insights into the branch-point reaction of the 3,5-dihydro-5-methylidene-4 H-imidazol-4-one (MIO)-tyrosine aminomutase from Oryza sativa ( OsTAM). Exchanging the active residues of OsTAM (Y125C/N446K) for those in a phenylalanine aminomutase TcPAM altered its substrate specificity from tyrosine to phenylalanine. The aminomutase mechanism of OsTAM surprisingly changed almost exclusively to that of an ammonia lyase making cinnamic acid (>95%) over β-phenylalanine [Walter, T., et al. (2016) Biochemistry 55, 3497-3503]. We hypothesized that the missing electronics or sterics on the aryl ring of the phenylalanine substrate, compared with the sizable electron-donating hydroxyl of the natural tyrosine substrate, influenced the unexpected lyase reactivity of the OsTAM mutant. The double mutant was incubated with 16 α-phenylalanine substituent analogues of varying electronic strengths and sterics. The mutant converted each analogue principally to its acrylate with ∼50% conversion of the p-Br substrate, making only a small amount of the β-amino acid. The inner loop structure over the entrance to the active site was also mutated to assess how the lyase and mutase activities are affected. An OsTAM loop mutant, matching the loop residues of TcPAM, still chiefly made >95% of the acrylate from each substrate. A combined active site:loop mutant was most reactive but remained a lyase, making 10-fold more acrylates than other mutants did. While mutations within the active site changed the substrate specificity of OsTAM, continued exploration is needed to fully understand the interplay among the inner loop, the substrate, and the active site in defining the mutase and lyase activities.

High heating rate decomposition dynamics of copper oxide by nanocalorimetry-coupled time-of-flight mass spectrometry

NASA Astrophysics Data System (ADS)

Yi, Feng; DeLisio, Jeffery B.; Nguyen, Nam; Zachariah, Michael R.; LaVan, David A.

2017-12-01

The thermodynamics and evolved gases were measured during the rapid decomposition of copper oxide (CuO) thin film at rates exceeding 100,000 K/s. CuO decomposes to release oxygen when heated and serves as an oxidizer in reactive composites and chemical looping combustion. Other instruments have shown either one or two decomposition steps during heating. We have confirmed that CuO decomposes by two steps at both slower and higher heating rates. The decomposition path influences the reaction course in reactive Al/CuO/Al composites, and full understanding is important in designing reactive mixtures and other new reactive materials.

Efforts and Programs of the Department of Defense Relating to the Prevention, Mitigation, and Treatment of Blast Injuries

DTIC Science & Technology

2007-01-01

Combat Critical Care Engineering: Evaluation of Closed Loop Control of Ventilation and Oxygen Flow During Resuscitation in the Compensatory and...Decompensatory Phases of Hemorrhagic Shock: This effort evaluated closed loop control of ventilation and oxygen flow during resuscitation in the...Cerebral Injury Volume, Cerebral Edema, Cerebral Blood Flow and Reactivity, and Histopathology in a Rat Model of Traumatic Brain Injury and Hemorrhagic

Thermal inactivation of ileal loop-reactive Clostridium perfringens type A strains in phosphate buffer and beef gravy.

PubMed

Bradshaw, J G; Peeler, J T; Twedt, R M

1977-09-01

The thermal resistance of spore crops produced from each of two ileal loop-reactive strains of Clostridium perfringens type A was determined in two suspending vehicles consisting of 0.067 M (pH 7.0) phosphate buffer and a commercial beef gravy. D115.6 values obtained in buffer and enumerated after pretreatment with sodium ethylenediaminetetraacetate and recovery in plating medium containing lysozyme were two- to threefold greater than those obtained without this treatment. D115.6 values obtained with beef gravy were less than those obtained in buffer with or without lysozyme; however, the D98.9 and D104.4 values were 1.3 to 2 times greater than those obtained in buffer with lysozyme. The z values were within the ranges reported by previous investigators.

Thermal inactivation of ileal loop-reactive Clostridium perfringens type A strains in phosphate buffer and beef gravy.

PubMed Central

Bradshaw, J G; Peeler, J T; Twedt, R M

1977-01-01

The thermal resistance of spore crops produced from each of two ileal loop-reactive strains of Clostridium perfringens type A was determined in two suspending vehicles consisting of 0.067 M (pH 7.0) phosphate buffer and a commercial beef gravy. D115.6 values obtained in buffer and enumerated after pretreatment with sodium ethylenediaminetetraacetate and recovery in plating medium containing lysozyme were two- to threefold greater than those obtained without this treatment. D115.6 values obtained with beef gravy were less than those obtained in buffer with or without lysozyme; however, the D98.9 and D104.4 values were 1.3 to 2 times greater than those obtained in buffer with lysozyme. The z values were within the ranges reported by previous investigators. PMID:199113

Hardware-in-the-loop grid simulator system and method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fox, John Curtiss; Collins, Edward Randolph; Rigas, Nikolaos

A hardware-in-the-loop (HIL) electrical grid simulation system and method that combines a reactive divider with a variable frequency converter to better mimic and control expected and unexpected parameters in an electrical grid. The invention provides grid simulation in a manner to allow improved testing of variable power generators, such as wind turbines, and their operation once interconnected with an electrical grid in multiple countries. The system further comprises an improved variable fault reactance (reactive divider) capable of providing a variable fault reactance power output to control a voltage profile, therein creating an arbitrary recovery voltage. The system further comprises anmore » improved isolation transformer designed to isolate zero-sequence current from either a primary or secondary winding in a transformer or pass the zero-sequence current from a primary to a secondary winding.« less

Closed-Loop Targeted Memory Reactivation during Sleep Improves Spatial Navigation.

PubMed

Shimizu, Renee E; Connolly, Patrick M; Cellini, Nicola; Armstrong, Diana M; Hernandez, Lexus T; Estrada, Rolando; Aguilar, Mario; Weisend, Michael P; Mednick, Sara C; Simons, Stephen B

2018-01-01

Sounds associated with newly learned information that are replayed during non-rapid eye movement (NREM) sleep can improve recall in simple tasks. The mechanism for this improvement is presumed to be reactivation of the newly learned memory during sleep when consolidation takes place. We have developed an EEG-based closed-loop system to precisely deliver sensory stimulation at the time of down-state to up-state transitions during NREM sleep. Here, we demonstrate that applying this technology to participants performing a realistic navigation task in virtual reality results in a significant improvement in navigation efficiency after sleep that is accompanied by increases in the spectral power especially in the fast (12-15 Hz) sleep spindle band. Our results show promise for the application of sleep-based interventions to drive improvement in real-world tasks.

Wavelet Transform Analysis of the Power Spectrum of Centre of Pressure Signals to Detect the Critical Point Interval of Postural Control

NASA Astrophysics Data System (ADS)

Singh, Neeraj Kumar; Snoussi, Hichem; Hewson, David; Duchêne, Jacques

The aim of this study was to develop a method to detecting the critical point interval (CPI) when sensory feedback is used as part of a closed-loop postural control strategy. Postural balance was evaluated using centre of pressure (COP) displacements from a force plate for 17 control and 10 elderly subjects under eyes open, eyes closed, and vibration conditions. A modified local-maximum-modulus wavelet transform analysis using the power spectrum of COP signals was used to calculate CPI. Lower CPI values indicate increased closed-loop postural control with a quicker response to sensory input. Such a strategy requires greater energy expenditure due to the repeated muscular interventions to remain stable. The CPI for elderly occurred significantly quicker than for controls, indicating tighter control of posture. Similar results were observed for eyes closed and vibration conditions. The CPI parameter can be used to detect differences in postural control due to ageing.

Asymmetric photoredox transition-metal catalysis activated by visible light.

PubMed

Huo, Haohua; Shen, Xiaodong; Wang, Chuanyong; Zhang, Lilu; Röse, Philipp; Chen, Liang-An; Harms, Klaus; Marsch, Michael; Hilt, Gerhard; Meggers, Eric

2014-11-06

Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical industries. And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical processes. For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest. Photoredox catalysis provides the opportunity to generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions. In such systems, photoactivated sensitizers initiate a single electron transfer from (or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion. Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the photoredox centre, offers new opportunities for the 'green' synthesis of non-racemic chiral molecules.

Asymmetric photoredox transition-metal catalysis activated by visible light

NASA Astrophysics Data System (ADS)

Huo, Haohua; Shen, Xiaodong; Wang, Chuanyong; Zhang, Lilu; Röse, Philipp; Chen, Liang-An; Harms, Klaus; Marsch, Michael; Hilt, Gerhard; Meggers, Eric

2014-11-01

Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical industries. And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical processes. For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest. Photoredox catalysis provides the opportunity to generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions. In such systems, photoactivated sensitizers initiate a single electron transfer from (or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion. Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the photoredox centre, offers new opportunities for the `green' synthesis of non-racemic chiral molecules.

Insulin delivery and nocturnal glucose control in children and adolescents with type 1 diabetes.

PubMed

Tauschmann, Martin; Hovorka, Roman

2017-12-01

Nocturnal glucose control remains challenging in children and adolescents with type 1 diabetes due to highly variable overnight insulin requirements. The issue may be addressed by glucose responsive insulin delivery based on real-time continuous glucose measurements. Areas covered: This review outlines recent developments of glucose responsive insulin delivery systems from a paediatric perspective. We cover threshold-based suspend application, predictive low glucose suspend, and more advanced single hormone and dual-hormone closed-loop systems. Approaches are evaluated in relation to nocturnal glucose control particularly during outpatient randomised controlled trials. Expert opinion: Significant progress translating research from controlled clinical centre settings to free-living unsupervised home studies have been achieved over the past decade. Nocturnal glycaemic control can be improved whilst reducing the risk of hypoglycaemia with closed-loop systems. Following the US regulatory approval of the first hybrid closed-loop system in non-paediatric population, large multinational closed-loop clinical trials and pivotal studies including paediatric populations are underway or in preparation to facilitate the use of closed-loop systems in clinical practice.

Feedback between p21 and reactive oxygen production is necessary for cell senescence

PubMed Central

Passos, João F; Nelson, Glyn; Wang, Chunfang; Richter, Torsten; Simillion, Cedric; Proctor, Carole J; Miwa, Satomi; Olijslagers, Sharon; Hallinan, Jennifer; Wipat, Anil; Saretzki, Gabriele; Rudolph, Karl Lenhard; Kirkwood, Tom B L; von Zglinicki, Thomas

2010-01-01

Cellular senescence—the permanent arrest of cycling in normally proliferating cells such as fibroblasts—contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of ‘deep' cellular senescence. The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFβ. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype. PMID:20160708

Regenerable mixed copper-iron-inert support oxygen carriers for solid fuel chemical looping combustion process

DOEpatents

Siriwardane, Ranjani V.; Tian, Hanjing

2016-12-20

The disclosure provides an oxygen carrier for a chemical looping cycle, such as the chemical looping combustion of solid carbonaceous fuels, such as coal, coke, coal and biomass char, and the like. The oxygen carrier is comprised of at least 24 weight % (wt %) CuO, at least 10 wt % Fe2O3, and an inert support, and is typically a calcine. The oxygen carrier exhibits a CuO crystalline structure and an absence of iron oxide crystalline structures under XRD crystallography, and provides an improved and sustained combustion reactivity in the temperature range of 600.degree. C.-1000.degree. C. particularly for solid fuels such as carbon and coal.

Application of a hybrid MPI/OpenMP approach for parallel groundwater model calibration using multi-core computers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Guoping; D'Azevedo, Ed F; Zhang, Fan

2010-01-01

Calibration of groundwater models involves hundreds to thousands of forward solutions, each of which may solve many transient coupled nonlinear partial differential equations, resulting in a computationally intensive problem. We describe a hybrid MPI/OpenMP approach to exploit two levels of parallelisms in software and hardware to reduce calibration time on multi-core computers. HydroGeoChem 5.0 (HGC5) is parallelized using OpenMP for direct solutions for a reactive transport model application, and a field-scale coupled flow and transport model application. In the reactive transport model, a single parallelizable loop is identified to account for over 97% of the total computational time using GPROF.more » Addition of a few lines of OpenMP compiler directives to the loop yields a speedup of about 10 on a 16-core compute node. For the field-scale model, parallelizable loops in 14 of 174 HGC5 subroutines that require 99% of the execution time are identified. As these loops are parallelized incrementally, the scalability is found to be limited by a loop where Cray PAT detects over 90% cache missing rates. With this loop rewritten, similar speedup as the first application is achieved. The OpenMP-parallelized code can be run efficiently on multiple workstations in a network or multiple compute nodes on a cluster as slaves using parallel PEST to speedup model calibration. To run calibration on clusters as a single task, the Levenberg Marquardt algorithm is added to HGC5 with the Jacobian calculation and lambda search parallelized using MPI. With this hybrid approach, 100 200 compute cores are used to reduce the calibration time from weeks to a few hours for these two applications. This approach is applicable to most of the existing groundwater model codes for many applications.« less

Structural mechanism for the carriage and release of thyroxine in the blood.

PubMed

Zhou, Aiwu; Wei, Zhenquan; Read, Randy J; Carrell, Robin W

2006-09-05

The hormones that most directly control tissue activities in health and disease are delivered by two noninhibitory members of the serpin family of protease inhibitors, thyroxine-binding globulin (TBG) and corticosteroid-binding globulin. The structure of TBG bound to tetra-iodo thyroxine, solved here at 2.8 A, shows how the thyroxine is carried in a surface pocket on the molecule. This unexpected binding site is confirmed by mutations associated with a loss of hormone binding in both TBG and also homologously in corticosteroid-binding globulin. TBG strikingly differs from other serpins in having the upper half of its main beta-sheet fully opened, so its reactive center peptide loop can readily move in and out of the sheet to give an equilibrated binding and release of thyroxine. The entry of the loop triggers a conformational change, with a linked contraction of the binding pocket and release of the bound thyroxine. The ready reversibility of this change is due to the unique presence in the reactive loop of TBG of a proline that impedes the full and irreversible entry of the loop that occurs in other serpins. Thus, TBG has adapted the serpin inhibitory mechanism to give a reversible flip-flop transition, from a high-affinity to a low-affinity form. The complexity and ready triggering of this conformational mechanism strongly indicates that TBG has evolved to allow a modulated and targeted delivery of thyroxine to the tissues.

A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein

PubMed Central

Jiang, Tao; Wang, Hua-Jing; Yang, Hai-ou; Tan, Weng-Long; Liu, Ran; Yu, Man; Ge, Bao-Xue; Zhu, Qing-Yu; Qin, E-De; Guo, Ya-Jun; Qin, Cheng-Feng

2011-01-01

Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1–4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1–4, YFV, and WNV and confers protection from lethal challenge with DENV 1–4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans. PMID:21264311

Crystal structure of a looped-chain CoII coordination polymer: catena-poly[[bis-(nitrato-κO)cobalt(II)]bis-[μ-bis-(pyridin-3-ylmeth-yl)sulfane-κ2N:N'

PubMed

Moon, Suk-Hee; Seo, Joobeom; Park, Ki-Min

2017-11-01

The asymmetric unit of the title compound, [Co(NO 3 ) 2 (C 12 H 12 N 2 S) 2 ] n , contains a bis-(pyridin-3-ylmeth-yl)sulfane ( L ) ligand, an NO 3 - anion and half a Co II cation, which lies on an inversion centre. The Co II cation is six-coordinated, being bound to four pyridine N atoms from four symmetry-related L ligands. The remaining coordination sites are occupied by two O atoms from two symmetry-related nitrate anions in a monodentate manner. Thus, the Co II centre adopts a distorted octa-hedral geometry. Two symmetry-related L ligands are connected by two symmetry-related Co II cations, forming a 20-membered cyclic dimer, in which the Co II atoms are separated by 10.2922 (7) Å. The cyclic dimers are connected to each other by sharing Co II atoms, giving rise to the formation of an infinite looped chain propagating along the [101] direction. Inter-molecular C-H⋯π (H⋯ring centroid = 2.89 Å) inter-actions between one pair of corresponding L ligands and C-H⋯O hydrogen bonds between the L ligands and the nitrate anions occur in the looped chain. In the crystal, adjacent looped chains are connected by inter-molecular π-π stacking inter-actions [centroid-to-centroid distance = 3.8859 (14) Å] and C-H⋯π hydrogen bonds (H⋯ring centroid = 2.65 Å), leading to the formation of layers parallel to (101). These layers are further connected through C-H⋯O hydrogen bonds between the layers, resulting in the formation of a three-dimensional supra-molecular architecture.

Driving student-centred calculus: results of a comprehensive case study for Kaizen learning in the Sultanate of Oman

NASA Astrophysics Data System (ADS)

Heim, Bernhard; Rupp, Florian; Viet, Nils; Stockhausen, Paul v.; Gallenkämper, Jonas; Kreuzer, Judith

2015-04-01

The art of teaching freshmen students is undergoing a rapid paradigm change. Classical forms of teaching are not applicable any more and an unmanageable offer of new multimedia tools and concepts is glutting the market. Moreover, compared to previous courses, the class size triples. In view of these challenges, we implemented a new teaching concept best described as Kaizen learning. By Kaizen learning, we define a teaching philosophy that is based on a concise mix of short learning units (with feedback loops and tests) and of carefully chosen repetitions (also with feedback loops and tests) to calibrate a course for the students. Here, this intensive blended, student-centred learning paradigm is analysed together with its direct impact on the students' performance. This case study leads to easy-to-implement key drivers for successfully teaching science in Oman, such as (1) human-human interaction, (2) clearly communicated expectations, (3) avoidance of a short-term learning attitude, (4) a no-calculator policy, (5) continuous Kaizen learning, and (6) balanced combination of traditional teaching and e-learning.

Nickel-centred proton reduction catalysis in a model of [NiFe] hydrogenase

NASA Astrophysics Data System (ADS)

Brazzolotto, Deborah; Gennari, Marcello; Queyriaux, Nicolas; Simmons, Trevor R.; Pécaut, Jacques; Demeshko, Serhiy; Meyer, Franc; Orio, Maylis; Artero, Vincent; Duboc, Carole

2016-11-01

Hydrogen production through water splitting is one of the most promising solutions for the storage of renewable energy. [NiFe] hydrogenases are organometallic enzymes containing nickel and iron centres that catalyse hydrogen evolution with performances that rival those of platinum. These enzymes provide inspiration for the design of new molecular catalysts that do not require precious metals. However, all heterodinuclear NiFe models reported so far do not reproduce the Ni-centred reactivity found at the active site of [NiFe] hydrogenases. Here, we report a structural and functional NiFe mimic that displays reactivity at the Ni site. This is shown by the detection of two catalytic intermediates that reproduce structural and electronic features of the Ni-L and Ni-R states of the enzyme during catalytic turnover. Under electrocatalytic conditions, this mimic displays high rates for H2 evolution (second-order rate constant of 2.5 × 104 M-1 s-1 turnover frequency of 250 s-1 at 10 mM H+ concentration) from mildly acidic solutions.

Implementation of reflex loops in a biomechanical finite element model.

PubMed

Salin, Dorian; Arnoux, Pierre-Jean; Kayvantash, Kambiz; Behr, Michel

2016-11-01

In the field of biomechanics, the offer of models which are more and more realistic requires to integrate a physiological response, in particular, the controlled muscle bracing and the reflexes. The following work aims to suggest a unique methodology which couples together a sensory and motor loop with a finite element model. Our method is applied to the study of the oscillation of the elbow in the case of a biceps brachial stretch reflex. The results obtained are promising in the purpose of the development of reactive human body models.

Flare particle acceleration in the interaction of twisted coronal flux ropes

NASA Astrophysics Data System (ADS)

Threlfall, J.; Hood, A. W.; Browning, P. K.

2018-03-01

Aim. The aim of this work is to investigate and characterise non-thermal particle behaviour in a three-dimensional (3D) magnetohydrodynamical (MHD) model of unstable multi-threaded flaring coronal loops. Methods: We have used a numerical scheme which solves the relativistic guiding centre approximation to study the motion of electrons and protons. The scheme uses snapshots from high resolution numerical MHD simulations of coronal loops containing two threads, where a single thread becomes unstable and (in one case) destabilises and merges with an additional thread. Results: The particle responses to the reconnection and fragmentation in MHD simulations of two loop threads are examined in detail. We illustrate the role played by uniform background resistivity and distinguish this from the role of anomalous resistivity using orbits in an MHD simulation where only one thread becomes unstable without destabilising further loop threads. We examine the (scalable) orbit energy gains and final positions recovered at different stages of a second MHD simulation wherein a secondary loop thread is destabilised by (and merges with) the first thread. We compare these results with other theoretical particle acceleration models in the context of observed energetic particle populations during solar flares.

Arg354 in the catalytic centre of bovine liver catalase is protected from methylglyoxal-mediated glycation.

PubMed

Scheckhuber, Christian Q

2015-12-30

In addition to controlled post-translational modifications proteins can be modified with highly reactive compounds. Usually this leads to a compromised functionality of the protein. Methylglyoxal is one of the most common agents that attack arginine residues. Methylglyoxal is also regarded as a pro-oxidant that affects cellular redox homeostasis by contributing to the formation of reactive oxygen species. Antioxidant enzymes like catalase are required to protect the cell from oxidative damage. These enzymes are also targets for methylglyoxal-mediated modification which could severely affect their catalytic activity in breaking down reactive oxygen species to less reactive or inert compounds. Here, bovine liver catalase was incubated with high levels of methylglyoxal to induce its glycation. This treatment did not lead to a pronounced reduction of enzymatic activity. Subsequently methylglyoxal-mediated arginine modifications (hydroimidazolone and dihydroxyimidazolidine) were quantitatively analysed by sensitive nano high performance liquid chromatography/electron spray ionisation/tandem mass spectrometry. Whereas several arginine residues displayed low to moderate levels of glycation (e.g., Arg93, Arg365, Arg444) Arg354 in the active centre of catalase was never found to be modified. Bovine liver catalase is able to tolerate very high levels of the modifying α-oxoaldehyde methylglyoxal so that its essential enzymatic function is not impaired.

Cyclic strain rate effects in fatigued face-centred and body-centred cubic metals

NASA Astrophysics Data System (ADS)

Mughrabi, Haël

2013-09-01

The present work deals mainly with the effect and the use of strain rate and temperature changes during cyclic deformation as a means to obtain valuable information on the thermally activated dislocation glide processes, based on the assessment of reversible changes of the thermal effective stress and of transient changes of the athermal stress. The importance of closed-loop testing in true plastic strain control with constant cyclic plastic strain rate throughout the cycle is explained and emphasized, especially with respect to the case of strain rate sensitive materials. Stress responses of face-centred cubic and body-centred cubic (bcc) metals to cyclic strain rate changes are presented to illustrate that the deformation modes of these two classes of materials differ characteristically at temperatures below that the so-called knee temperature of bcc metals. When such tests are performed in cyclic saturation, the temperature and strain rate dependence of bcc metals can be measured very accurately on one and the same specimen, permitting a thorough analysis of thermal activation.

Increasing the hydrolysis constant of the reactive site upon introduction of an engineered Cys¹⁴-Cys³⁹ bond into the ovomucoid third domain from silver pheasant.

PubMed

Hemmi, Hikaru; Kumazaki, Takashi; Kojima, Shuichi; Yoshida, Takuya; Ohkubo, Tadayasu; Yokosawa, Hideyoshi; Miura, Kin-Ichiro; Kobayashi, Yuji

2011-08-01

P14C/N39C is the disulfide variant of the ovomucoid third domain from silver pheasant (OMSVP3) introducing an engineered Cys¹⁴-Cys³⁹ bond near the reactive site on the basis of the sequence homology between OMSVP3 and ascidian trypsin inhibitor. This variant exhibits a narrower inhibitory specificity. We have examined the effects of introducing a Cys¹⁴-Cys³⁹ bond into the flexible N-terminal loop of OMSVP3 on the thermodynamics of the reactive site peptide bond hydrolysis, as well as the thermal stability of reactive site intact inhibitors. P14C/N39C can be selectively cleaved by Streptomyces griseus protease B at the reactive site of OMSVP3 to form a reactive site modified inhibitor. The conversion rate of intact to modified P14C/N39C is much faster than that for wild type under any pH condition. The pH-independent hydrolysis constant (K(hyd) °) is estimated to be approximately 5.5 for P14C/N39C, which is higher than the value of 1.6 for natural OMSVP3. The reactive site modified form of P14C/N39C is thermodynamically more stable than the intact one. Thermal denaturation experiments using intact inhibitors show that the temperature at the midpoint of unfolding at pH 2.0 is 59 °C for P14C/N39C and 58 °C for wild type. There have been no examples, except P14C/N39C, where introducing an engineered disulfide causes a significant increase in K(hyd) °, but has no effect on the thermal stability. The site-specific disulfide introduction into the flexible N-terminal loop of natural Kazal-type inhibitors would be useful to further characterize the thermodynamics of the reactive site peptide bond hydrolysis. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

Application of a Virtual Reactivity Feedback Control Loop in Non-Nuclear Testing of a Fast Spectrum Reactor

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Forsbacka, Matthew

2004-01-01

For a compact, fast-spectrum reactor, reactivity feedback is dominated by core deformation at elevated temperature. Given the use of accurate deformation measurement techniques, it is possible to simulate nuclear feedback in non-nuclear electrically heated reactor tests. Implementation of simulated reactivity feedback in response to measured deflection is being tested at the NASA Marshall Space Flight Center Early Flight Fission Test Facility (EFF-TF). During tests of the SAFE-100 reactor prototype, core deflection was monitored using a high resolution camera. "virtual" reactivity feedback was accomplished by applying the results of Monte Carlo calculations (MCNPX) to core deflection measurements; the computational analysis was used to establish the reactivity worth of van'ous core deformations. The power delivered to the SAFE-100 prototype was then dusted accordingly via kinetics calculations, The work presented in this paper will demonstrate virtual reactivity feedback as core power was increased from 1 kilowatt(sub t), to 10 kilowatts(sub t), held approximately constant at 10 kilowatts (sub t), and then allowed to decrease based on the negative thermal reactivity coefficient.

Foreign body giant cells selectively covering haptics of intraocular lens implants: indicators of poor toleration?

PubMed

Wolter, J R

1983-10-01

A Sputnik lens implant removed after five years because of bullous keratopathy exhibits a dense covering of its Supramid anterior staves with large foreign body giant cells, while its Prolene loops and Polymethylmethacrylate optics have attracted only few of these cell units. The glass-membrane-like component of the reactive membrane also shows significant differences on the different parts of this implant. The use of observation of the components of reactive membranes on lens implants as indicators of toleration in the eye is suggested.

Do quiet standing centre of pressure measures within specific frequencies differ based on ability to recover balance in individuals with stroke?

PubMed Central

Schinkel-Ivy, Alison; Singer, Jonathan C.; Inness, Elizabeth L.; Mansfield, Avril

2016-01-01

Objective To determine whether quiet standing measures at specific frequency levels (representative of reactive control) differed between individuals with stroke based on their ability to recover balance (failed or successful responses to external perturbations). Methods Individuals with stroke completed a clinical assessment, including 30 s of quiet standing and lean-and-release postural perturbations, at admission to in-patient rehabilitation. Quiet standing centre of pressure (COP) signals were calculated and discrete wavelet decomposition was performed. Net COP amplitude, between-limb synchronization, and ratios of individual-limb COP were determined for each frequency level of interest, and for the non-decomposed signal (all frequency levels). Outcome measures were compared between individuals who exhibited failed and successful responses during a) unconstrained and b) encouraged-use lean-and-release trials. Results Individuals with failed responses during the unconstrained lean-and-release trials displayed greater net COP amplitude than those with successful responses, specifically within a frequency range of 0.40–3.20 Hz. Conclusions Reduced ability to recover balance among individuals with stroke may be reflected in impaired reactive control of quiet standing. Significance These results provide insight into the mechanism by which reactive control of quiet standing is impaired in individuals with stroke, and may inform assessment and rehabilitation strategies for post-stroke reactive balance control. PMID:27178866

Endo-β-D-1,4-mannanase from Chrysonilia sitophila displays a novel loop arrangement for substrate selectivity.

PubMed

Gonçalves, Ana Maria D; Silva, Catarina S; Madeira, Tânia I; Coelho, Ricardo; de Sanctis, Daniele; San Romão, Maria Vitória; Bento, Isabel

2012-11-01

The crystal structure of wild-type endo-β-D-1,4-mannanase (EC 3.2.1.78) from the ascomycete Chrysonilia sitophila (CsMan5) has been solved at 1.40 Å resolution. The enzyme isolated directly from the source shows mixed activity as both an endo-glucanase and an endo-mannanase. CsMan5 adopts the (β/α)(8)-barrel fold that is well conserved within the GH5 family and has highest sequence and structural homology to the GH5 endo-mannanases. Superimposition with proteins of this family shows a unique structural arrangement of three surface loops of CsMan5 that stretch over the active centre, promoting an altered topography of the binding cleft. The most relevant feature results from the repositioning of a long loop at the extremity of the binding cleft, resulting in a shortened glycone-binding region with two subsites. The other two extended loops flanking the binding groove produce a narrower cleft compared with the wide architecture observed in GH5 homologues. Two aglycone subsites (+1 and +2) are identified and a nonconserved tryptophan (Trp271) at the +1 subsite may offer steric hindrance. Taken together, these findings suggest that the discrimination of mannan substrates is achieved through modified loop length and structure.

Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin.

PubMed

Scott, Benjamin M; Matochko, Wadim L; Gierczak, Richard F; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2-P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352-356 (P7-P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7-P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of "designer serpins" with novel reactivity and/or specificity.

Phage Display of the Serpin Alpha-1 Proteinase Inhibitor Randomized at Consecutive Residues in the Reactive Centre Loop and Biopanned with or without Thrombin

PubMed Central

Scott, Benjamin M.; Matochko, Wadim L.; Gierczak, Richard F.; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P.

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2–P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352–356 (P7–P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7–P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of “designer serpins” with novel reactivity and/or specificity. PMID:24427287

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pin, F.G.; Bender, S.R.

Most fuzzy logic-based reasoning schemes developed for robot control are fully reactive, i.e., the reasoning modules consist of fuzzy rule bases that represent direct mappings from the stimuli provided by the perception systems to the responses implemented by the motion controllers. Due to their totally reactive nature, such reasoning systems can encounter problems such as infinite loops and limit cycles. In this paper, we proposed an approach to remedy these problems by adding a memory and memory-related behaviors to basic reactive systems. Three major types of memory behaviors are addressed: memory creation, memory management, and memory utilization. These are firstmore » presented, and examples of their implementation for the recognition of limit cycles during the navigation of an autonomous robot in a priori unknown environments are then discussed.« less

Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals

NASA Astrophysics Data System (ADS)

Murphy, John J.; Bastida, David; Paria, Suva; Fagnoni, Maurizio; Melchiorre, Paolo

2016-04-01

An important goal of modern organic chemistry is to develop new catalytic strategies for enantioselective carbon-carbon bond formation that can be used to generate quaternary stereogenic centres. Whereas considerable advances have been achieved by exploiting polar reactivity, radical transformations have been far less successful. This is despite the fact that open-shell intermediates are intrinsically primed for connecting structurally congested carbons, as their reactivity is only marginally affected by steric factors. Here we show how the combination of photoredox and asymmetric organic catalysis enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to obtain quaternary carbon stereocentres with high fidelity. Critical to our success was the design of a chiral organic catalyst, containing a redox-active carbazole moiety, that drives the formation of iminium ions and the stereoselective trapping of photochemically generated carbon-centred radicals by means of an electron-relay mechanism. We demonstrate the generality of this organocatalytic radical-trapping strategy with two sets of open-shell intermediates, formed through unrelated light-triggered pathways from readily available substrates and photoredox catalysts—this method represents the application of iminium ion activation (a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.

Does a hypnosis session reduce the required propofol dose during closed-loop anaesthesia induction?: A randomised controlled trial.

PubMed

Bataille, Aurélien; Guirimand, Avit; Szekely, Barbara; Michel-Cherqui, Mireille; Dumans, Virginie; Liu, Ngai; Chazot, Thierry; Fischler, Marc; Le Guen, Morgan

2017-11-27

Hypnosis has a positive effect on peri-operative anxiety and pain. The objective of this study was to assess the impact of a formal deep hypnosis session on the consumption of propofol for anaesthetic induction using automated administration of propofol guided by the bispectral index (BIS) in a closed loop. A 1 : 1 randomised, usual-care-controlled, single-centre trial. Tertiary care centre in France from April 2014 to December 2015. Female adult patients scheduled for outpatient gynaecological surgery under general anaesthesia. Before surgery, patients were randomised to receive either a deep hypnosis session or routine care. Anaesthetic induction was performed automatically by propofol without opioids and was assisted by the BIS in a closed loop. The primary endpoint was the propofol dose required for anaesthesia induction, defined as a BIS less than 60 for at least 30 s. Data for 31 patients in the hypnosis group and 35 in the control group were analysed. There was no evidence of a difference in the mean required propofol dose for anaesthetic induction between the hypnosis and the control groups (2.06 mg kg (95% confidence interval [1.68 to 2.43]) versus 1.79 mg kg (95% CI [1.54 to 2.03]), P = 0.25, respectively). The current study, which was designed to determine the effect of a deep hypnosis session on anaesthesia induction using an automated tool for propofol administration, failed to detect a difference in the required dose of propofol. ClinicalTrials.gov, NCT02249364.

A DFIG Islanding Detection Scheme Based on Reactive Power Infusion

NASA Astrophysics Data System (ADS)

Wang, M.; Liu, C.; He, G. Q.; Li, G. H.; Feng, K. H.; Sun, W. W.

2017-07-01

A lot of research has been done on photovoltaic (the “PV”) power system islanding detection in recent years. As a comparison, much less attention has been paid to islanding in wind turbines. Meanwhile, wind turbines can work in islanding conditions for quite a long period, which can be harmful to equipments and cause safety hazards. This paper presents and examines a double fed introduction generation (the “DFIG”) islanding detection scheme based on feedback of reactive power and frequency and uses a trigger signal of reactive power infusion which can be obtained by dividing the voltage total harmonic distortion (the "THD") by the voltage THD of last cycle to avoid the deterioration of power quality. This DFIG islanding detection scheme uses feedback of reactive power current loop to amplify the frequency differences in islanding and normal conditions. Simulation results show that the DFIG islanding detection scheme is effective.

Neutron Stars in Supernova Remnants and Beyond

NASA Astrophysics Data System (ADS)

Gvaramadze, V. V.

We discuss a concept of off-centred cavity supernova explosion as applied to neutron star/supernova remnant associations and show how this concept could be used to preclude the anti-humane decapitating the Duck (G5.4-1.2 + G5.27-0.9) and dismembering the Swan (Cygnus Loop), as well as to search for a stellar remnant associated with the supernova remnant RCW86.

Discriminative Features Mining for Offline Handwritten Signature Verification

NASA Astrophysics Data System (ADS)

Neamah, Karrar; Mohamad, Dzulkifli; Saba, Tanzila; Rehman, Amjad

2014-03-01

Signature verification is an active research area in the field of pattern recognition. It is employed to identify the particular person with the help of his/her signature's characteristics such as pen pressure, loops shape, speed of writing and up down motion of pen, writing speed, pen pressure, shape of loops, etc. in order to identify that person. However, in the entire process, features extraction and selection stage is of prime importance. Since several signatures have similar strokes, characteristics and sizes. Accordingly, this paper presents combination of orientation of the skeleton and gravity centre point to extract accurate pattern features of signature data in offline signature verification system. Promising results have proved the success of the integration of the two methods.

Analysis of boron dilution in a four-loop PWR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, J.G.; Sha, W.T.

1995-12-31

Thermal mixing and boron dilution in a pressurized water reactor were analyzed with COMMIX codes. The reactor system was the four loop Zion reactor. Two boron dilution scenarios were analyzed. In the first scenario, the plant is in cold shutdown and the reactor coolant system has just been filled after maintenance on the steam generators. To flush the air out of the steam generator tubes, a reactor coolant pump (RCP) is started, with the water in the pump suction line devoid of boron and at the same temperature as the coolant in the system. In the second scenario, the plantmore » is at hot standby and the reactor coolant system has been heated up to operating temperature after a long outage. It is assumed that an RCP is started, with the pump suction line filled with cold unborated water, forcing a slug of diluted coolant down the downcomer and subsequently through the reactor core. The subsequent transient thermal mixing and boron dilution that would occur in the reactor system is simulated for these two scenarios. The reactivity insertion rate and the total reactivity are evaluated.« less

Identification of Human Papillomavirus Type 16 L1 Surface Loops Required for Neutralization by Human Sera†

PubMed Central

Carter, Joseph J.; Wipf, Greg C.; Madeleine, Margaret M.; Schwartz, Stephen M.; Koutsky, Laura A.; Galloway, Denise A.

2006-01-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface. PMID:16641259

Identification of human papillomavirus type 16 L1 surface loops required for neutralization by human sera.

PubMed

Carter, Joseph J; Wipf, Greg C; Madeleine, Margaret M; Schwartz, Stephen M; Koutsky, Laura A; Galloway, Denise A

2006-05-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface.

Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure.

PubMed Central

Neudecker, Philipp; Lehmann, Katrin; Nerkamp, Jörg; Haase, Tanja; Wangorsch, Andrea; Fötisch, Kay; Hoffmann, Silke; Rösch, Paul; Vieths, Stefan; Scheurer, Stephan

2003-01-01

Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy. PMID:12943529

Structure of the Ni(II) complex of Escherichia coli peptide deformylase and suggestions on deformylase activities depending on different metal(II) centres.

PubMed

Yen, Ngo Thi Hai; Bogdanović, Xenia; Palm, Gottfried J; Kühl, Olaf; Hinrichs, Winfried

2010-02-01

Crystal structures of polypeptide deformylase (PDF) of Escherichia coli with nickel(II) replacing the native iron(II) have been solved with chloride and formate as metal ligands. The chloro complex is a model for the correct protonation state of the hydrolytic hydroxo ligand and the protonated status of the Glu133 side chain as part of the hydrolytic mechanism. The ambiguity that recently some PDFs have been identified with Zn(2+) ion as the active-site centre whereas others are only active with Fe(2+) (or Co(2+), Ni(2+) is discussed with respect to Lewis acid criteria of the metal ion and substrate activation by the CD loop.

String loops in the field of braneworld spherically symmetric black holes and naked singularities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stuchlík, Z.; Kološ, M., E-mail: zdenek.stuchlik@fpf.slu.cz, E-mail: martin.kolos@fpf.slu.cz

We study motion of current-carrying string loops in the field of braneworld spherically symmetric black holes and naked singularities. The spacetime is described by the Reissner-Nordström geometry with tidal charge b reflecting the non-local tidal effects coming from the external dimension; both positive and negative values of the spacetime parameter b are considered. We restrict attention to the axisymmetric motion of string loops when the motion can be fully governed by an appropriately defined effective potential related to the energy and angular momentum of the string loops. In dependence on these two constants of the motion, the string loops canmore » be captured, trapped, or can escape to infinity. In close vicinity of stable equilibrium points at the centre of trapped states the motion is regular. We describe how it is transformed to chaotic motion with growing energy of the string loop. In the field of naked singularities the trapped states located off the equatorial plane of the system exist and trajectories unable to cross the equatorial plane occur, contrary to the trajectories in the field of black holes where crossing the equatorial plane is always admitted. We concentrate our attention to the so called transmutation effect when the string loops are accelerated in the deep gravitational field near the black hole or naked singularity by transforming the oscillatory energy to the energy of the transitional motion. We demonstrate that the influence of the tidal charge can be substantial especially in the naked singularity spacetimes with b > 1 where the acceleration to ultrarelativistic velocities with Lorentz factor γ ∼ 100 can be reached, being more than one order higher in comparison with those obtained in the black hole spacetimes.« less

The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency

PubMed Central

Mousseau, Guillaume; Kessing, Cari F.; Fromentin, Rémi; Trautmann, Lydie; Chomont, Nicolas

2015-01-01

ABSTRACT Antiretroviral therapy (ART) inhibits HIV-1 replication, but the virus persists in latently infected resting memory CD4+ T cells susceptible to viral reactivation. The virus-encoded early gene product Tat activates transcription of the viral genome and promotes exponential viral production. Here we show that the Tat inhibitor didehydro-cortistatin A (dCA), unlike other antiretrovirals, reduces residual levels of viral transcription in several models of HIV latency, breaks the Tat-mediated transcriptional feedback loop, and establishes a nearly permanent state of latency, which greatly diminishes the capacity for virus reactivation. Importantly, treatment with dCA induces inactivation of viral transcription even after its removal, suggesting that the HIV promoter is epigenetically repressed. Critically, dCA inhibits viral reactivation upon CD3/CD28 or prostratin stimulation of latently infected CD4+ T cells from HIV-infected subjects receiving suppressive ART. Our results suggest that inclusion of a Tat inhibitor in current ART regimens may contribute to a functional HIV-1 cure by reducing low-level viremia and preventing viral reactivation from latent reservoirs. PMID:26152583

Volitional control of anticipatory ocular pursuit responses under stabilised image conditions in humans.

PubMed

Barnes, G; Goodbody, S; Collins, S

1995-01-01

Ocular pursuit responses have been examined in humans in three experiments in which the pursuit target image has been fully or partially stabilised on the fovea by feeding a recorded eye movement signal back to drive the target motion. The objective was to establish whether subjects could volitionally control smooth eye movement to reproduce trajectories of target motion in the absence of a concurrent target motion stimulus. In experiment 1 subjects were presented with a target moving with a triangular waveform in the horizontal axis with a frequency of 0.325 Hz and velocities of +/- 10-50 degrees/s. The target was illuminated twice per cycle for pulse durations (PD) of 160-640 ms as it passed through the centre position; otherwise subjects were in darkness. Subjects initially tracked the target motion in a conventional closed-loop mode for four cycles. Prior to the next target presentation the target image was stabilised on the fovea, so that any target motion generated resulted solely from volitional eye movement. Subjects continued to make anticipatory smooth eye movements both to the left and the right with a velocity trajectory similar to that observed in the closed-loop phase. Peak velocity in the stabilised-image mode was highly correlated with that in the prior closed-loop phase, but was slightly less (84% on average). In experiment 2 subjects were presented with a continuously illuminated target that was oscillated sinusoidally at frequencies of 0.2-1.34 Hz and amplitudes of +/- 5-20 degrees. After four cycles of closed-loop stimulation the image was stabilised on the fovea at the time of peak target displacement. Subjects continued to generate an oscillatory smooth eye velocity pattern that mimicked the sinusoidal motion of the previous closed-loop phase for at least three further cycles. The peak eye velocity generated ranged from 57-95% of that in the closed-loop phase at frequencies up to 0.8 Hz but decreased significantly at 1.34 Hz. In experiment 3 subjects were presented with a stabilised display throughout and generated smooth eye movements with peak velocity up to 84 degrees/s in the complete absence of any prior external target motion stimulus, by transferring their attention alternately to left and right of the centre of the display. Eye velocity was found to be dependent on the eccentricity of the centre of attention and the frequency of alternation. When the target was partially stabilised on the retina by feeding back only a proportion (Kf = 0.6-0.9) of the eye movement signal to drive the target, subjects were still able to generate smooth movements at will, even though the display did not move as far or as fast as the eye. Peak eye velocity decreased as Kf decreased, suggesting that there was a continuous competitive interaction between the volitional drive and the visual feedback provided by the relative motion of the display with respect to the retina. These results support the evidence for two separate mechanisms of smooth eye movement control in ocular pursuit: reflex control from retinal velocity error feedback and volitional control from an internal source. Arguments are presented to indicate how smooth pursuit may be controlled by matching a voluntarily initiated estimate of the required smooth movement, normally derived from storage of past re-afferent information, against current visual feedback information. Such a mechanism allows preemptive smooth eye movements to be made that can overcome the inherent delays in the visual feedback pathway.

Compatibility of Space Nuclear Power Plant Materials in an Inert He/Xe Working Gas Containing Reactive Impurities

DOE Office of Scientific and Technical Information (OSTI.GOV)

MM Hall

2006-01-31

A major materials selection and qualification issue identified in the Space Materials Plan is the potential for creating materials compatibility problems by combining dissimilar reactor core, Brayton Unit and other power conversion plant materials in a recirculating, inert He/Xe gas loop containing reactive impurity gases. Reported here are results of equilibrium thermochemical analyses that address the compatibility of space nuclear power plant (SNPP) materials in high temperature impure He gas environments. These studies provide early information regarding the constraints that exist for SNPP materials selection and provide guidance for establishing test objectives and environments for SNPP materials qualification testing.

Design and implementation of a simple nuclear power plant simulator

NASA Astrophysics Data System (ADS)

Miller, William H.

1983-02-01

A simple PWR nuclear power plant simulator has been designed and implemented on a minicomputer system. The system is intended for students use in understanding the power operation of a nuclear power plant. A PDP-11 minicomputer calculates reactor parameters in real time, uses a graphics terminal to display the results and a keyboard and joystick for control functions. Plant parameters calculated by the model include the core reactivity (based upon control rod positions, soluble boron concentration and reactivity feedback effects), the total core power, the axial core power distribution, the temperature and pressure in the primary and secondary coolant loops, etc.

An almost head-on collision as the origin of two off-centre rings in the Andromeda galaxy.

PubMed

Block, D L; Bournaud, F; Combes, F; Groess, R; Barmby, P; Ashby, M L N; Fazio, G G; Pahre, M A; Willner, S P

2006-10-19

The unusual morphology of the Andromeda galaxy (Messier 31, the closest spiral galaxy to the Milky Way) has long been an enigma. Although regarded for decades as showing little evidence of a violent history, M31 has a well-known outer ring of star formation at a radius of ten kiloparsecs whose centre is offset from the galaxy nucleus. In addition, the outer galaxy disk is warped, as seen at both optical and radio wavelengths. The halo contains numerous loops and ripples. Here we report the presence of a second, inner dust ring with projected dimensions of 1.5 x 1 kiloparsecs and offset by about half a kiloparsec from the centre of the galaxy (based upon an analysis of previously-obtained data). The two rings appear to be density waves propagating in the disk. Numerical simulations indicate that both rings result from a companion galaxy plunging through the centre of the disk of M31. The most likely interloper is M32. Head-on collisions between galaxies are rare, but it appears nonetheless that one took place 210 million years ago in our Local Group of galaxies.

Neuro-estimator based GMC control of a batch reactive distillation.

PubMed

Prakash, K J Jithin; Patle, Dipesh S; Jana, Amiya K

2011-07-01

In this paper, an artificial neural network (ANN)-based nonlinear control algorithm is proposed for a simulated batch reactive distillation (RD) column. In the homogeneously catalyzed reactive process, an esterification reaction takes place for the production of ethyl acetate. The fundamental model has been derived incorporating the reaction term in the model structure of the nonreactive distillation process. The process operation is simulated at the startup phase under total reflux conditions. The open-loop process dynamics is also addressed running the batch process at the production phase under partial reflux conditions. In this study, a neuro-estimator based generic model controller (GMC), which consists of an ANN-based state predictor and the GMC law, has been synthesized. Finally, this proposed control law has been tested on the representative batch reactive distillation comparing with a gain-scheduled proportional integral (GSPI) controller and with its ideal performance (ideal GMC). Copyright © 2011 ISA. Published by Elsevier Ltd. All rights reserved.

Multivariable model predictive control design of reactive distillation column for Dimethyl Ether production

NASA Astrophysics Data System (ADS)

Wahid, A.; Putra, I. G. E. P.

2018-03-01

Dimethyl ether (DME) as an alternative clean energy has attracted a growing attention in the recent years. DME production via reactive distillation has potential for capital cost and energy requirement savings. However, combination of reaction and distillation on a single column makes reactive distillation process a very complex multivariable system with high non-linearity of process and strong interaction between process variables. This study investigates a multivariable model predictive control (MPC) based on two-point temperature control strategy for the DME reactive distillation column to maintain the purities of both product streams. The process model is estimated by a first order plus dead time model. The DME and water purity is maintained by controlling a stage temperature in rectifying and stripping section, respectively. The result shows that the model predictive controller performed faster responses compared to conventional PI controller that are showed by the smaller ISE values. In addition, the MPC controller is able to handle the loop interactions well.

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production.

PubMed

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis . Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis . More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress.

Chemical looping coal gasification with calcium ferrite and barium ferrite via solid--solid reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siriwardane, Ranjani; Riley, Jarrett; Tian, Hanjing

Coal gasification to produce synthesis gas by chemical looping was investigated with two oxygen carriers, barium ferrite (BaFe2O4) and calcium ferrite (CaFe2O4). Thermo-gravimetric analysis (TGA) and fixed-bed flow reactor data indicated that a solid–solid interaction occurred between oxygen carriers and coal to produce synthesis gas. Both thermodynamic analysis and experimental data indicated that BaFe2O4 and CaFe2O4 have high reactivity with coal but have a low reactivity with synthesis gas, which makes them very attractive for the coal gasification process. Adding steam increased the production of hydrogen (H2) and carbon monoxide (CO), but carbon dioxide (CO2) remained low because these oxygenmore » carriers have minimal reactivity with H2 and CO. Therefore, the combined steam–oxygen carrier produced the highest quantity of synthesis gas. It appeared that neither the water–gas shift reaction nor the water splitting reaction promoted additional H2 formation with the oxygen carriers when steam was present. Wyodak coal, which is a sub-bituminous coal, had the best gasification yield with oxygen carrier–steam while Illinois #6 coal had the lowest. The rate of gasification and selectivity for synthesis gas production was significantly higher when these oxygen carriers were present during steam gasification of coal. The rates and synthesis gas yields during the temperature ramps of coal–steam with oxygen carriers were better than with gaseous oxygen.« less

Magnetic activity in the Galactic Centre region - fast downflows along rising magnetic loops

NASA Astrophysics Data System (ADS)

Kakiuchi, Kensuke; Suzuki, Takeru K.; Fukui, Yasuo; Torii, Kazufumi; Enokiya, Rei; Machida, Mami; Matsumoto, Ryoji

2018-06-01

We studied roles of the magnetic field on the gas dynamics in the Galactic bulge by a three-dimensional global magnetohydrodynamical simulation data, particularly focusing on vertical flows that are ubiquitously excited by magnetic activity. In local regions where the magnetic field is stronger, it is frequently seen that fast downflows slide along inclined magnetic field lines that are associated with buoyantly rising magnetic loops. The vertical velocity of these downflows reaches ˜100 km s-1 near the footpoint of the loops by the gravitational acceleration towards the Galactic plane. The two footpoints of rising magnetic loops are generally located at different radial locations and the field lines are deformed by the differential rotation. The angular momentum is transported along the field lines, and the radial force balance breaks down. As a result, a fast downflow is often observed only at the one footpoint located at the inner radial position. The fast downflow compresses the gas to form a dense region near the footpoint, which will be important in star formation afterwards. Furthermore, the horizontal components of the velocity are also fast near the footpoint because the downflow is accelerated along the magnetic sliding slope. As a result, the high-velocity flow creates various characteristic features in a simulated position-velocity diagram, depending on the viewing angle.

Voluntary sway and rapid orthogonal transitions of voluntary sway in young adults, and low and high fall-risk older adults.

PubMed

Tucker, Murray G; Kavanagh, Justin J; Morrison, Steven; Barrett, Rod S

2009-10-01

Falls amongst older people have been linked to reduced postural stability and slowed movement responses. The objective of this study was to examine differences in postural stability and the speed of response between young adults, low fall-risk older adults, and high fall-risk older adults during voluntary postural sway movements. Twenty-five young adults (25+/-4 years), and 32 low fall-risk (74+/-5 years), and 16 high fall-risk (79+/-7 years) older adults performed voluntary sway and rapid orthogonal transitions of voluntary sway between the anterior-posterior and medial-lateral directions. Measures included reaction and movement time and the amplitudes of the centre of pressure, centre of mass, and the separation distance between the centre of pressure and centre of mass. Both fall-risk groups compared to the young had slower reaction and movement time, greater centre of pressure and/or centre of mass amplitude in the orthogonal (non-target) direction during voluntary sway, and reduced anterior-posterior and medial-lateral separation between the centre of pressure and centre of mass during voluntary sway and orthogonal transitions. High compared to low fall-risk individuals had slower reaction and movement time, increased non-target centre of mass amplitude during voluntary sway, and reduced medial-lateral centre of pressure and centre of mass separation during voluntary sway and orthogonal transitions. Age-related deterioration of postural control resulted in slower reactive responses and reduced control of the direction of body movement during voluntary sway and orthogonal transitions. Slower postural reaction and movement time and reduced medial-lateral control of the centre of mass during voluntary sway movements are associated with increased fall-risk in community-living older people.

Instantaneous power control of a high speed permanent magnet synchronous generator based on a sliding mode observer and a phase locked loop

NASA Astrophysics Data System (ADS)

Duan, Jiandong; Fan, Shaogui; Wu, Fengjiang; Sun, Li; Wang, Guanglin

2018-06-01

This paper proposes an instantaneous power control method for high speed permanent magnet synchronous generators (PMSG), to realize the decoupled control of active power and reactive power, through vector control based on a sliding mode observer (SMO), and a phase locked loop (PLL). Consequently, the high speed PMSG has a high internal power factor, to ensure efficient operation. Vector control and accurate estimation of the instantaneous power require an accurate estimate of the rotor position. The SMO is able to estimate the back electromotive force (EMF). The rotor position and speed can be obtained using a combination of the PLL technique and the phase compensation method. This method has the advantages of robust operation, and being resistant to noise when estimating the position of the rotor. Using instantaneous power theory, the relationship between the output active power, reactive power, and stator current of the PMSG is deduced, and the power constraint condition is analysed for operation at the unit internal power factor. Finally, the accuracy of the rotor position detection, the instantaneous power detection, and the control methods are verified using simulations and experiments.

In-loop flow [11 C]CO2 fixation and radiosynthesis of N,N'-[11 C]dibenzylurea.

PubMed

Downey, Joseph; Bongarzone, Salvatore; Hader, Stefan; Gee, Antony D

2018-03-01

Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([ 11 C]CO 2 ), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [ 11 C]CO 2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [ 11 C]CO 2 , and the advantages afforded by the use of a loop-based system used in 11 C-methylation and 11 C-carboxylation reactions inspired us to apply the [ 11 C]CO 2 fixation "in-loop." In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [ 11 C]CO 2 fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [ 11 C]CO 2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N'-[ 11 C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3 minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [ 11 C]CO 2 fixation can be achieved in a low-volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11-labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [ 11 C]CO 2 trapping/fixation reactions for the production of PET radiotracers. © 2017 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals Published by John Wiley & Sons, Ltd.

Attentional and non-attentional systems in the maintenance of verbal information in working memory: the executive and phonological loops

PubMed Central

Camos, Valérie; Barrouillet, Pierre

2014-01-01

Working memory is the structure devoted to the maintenance of information at short term during concurrent processing activities. In this respect, the question regarding the nature of the mechanisms and systems fulfilling this maintenance function is of particular importance and has received various responses in the recent past. In the time-based resource-sharing (TBRS) model, we suggest that only two systems sustain the maintenance of information at the short term, counteracting the deleterious effect of temporal decay and interference. A non-attentional mechanism of verbal rehearsal, similar to the one described by Baddeley in the phonological loop model, uses language processes to reactivate phonological memory traces. Besides this domain-specific mechanism, an executive loop allows the reconstruction of memory traces through an attention-based mechanism of refreshing. The present paper reviews evidence of the involvement of these two independent systems in the maintenance of verbal memory items. PMID:25426049

Sensitivity of coronal loop sausage mode frequencies and decay rates to radial and longitudinal density inhomogeneities: a spectral approach

NASA Astrophysics Data System (ADS)

Cally, Paul S.; Xiong, Ming

2018-01-01

Fast sausage modes in solar magnetic coronal loops are only fully contained in unrealistically short dense loops. Otherwise they are leaky, losing energy to their surrounds as outgoing waves. This causes any oscillation to decay exponentially in time. Simultaneous observations of both period and decay rate therefore reveal the eigenfrequency of the observed mode, and potentially insight into the tubes’ nonuniform internal structure. In this article, a global spectral description of the oscillations is presented that results in an implicit matrix eigenvalue equation where the eigenvalues are associated predominantly with the diagonal terms of the matrix. The off-diagonal terms vanish identically if the tube is uniform. A linearized perturbation approach, applied with respect to a uniform reference model, is developed that makes the eigenvalues explicit. The implicit eigenvalue problem is easily solved numerically though, and it is shown that knowledge of the real and imaginary parts of the eigenfrequency is sufficient to determine the width and density contrast of a boundary layer over which the tubes’ enhanced internal densities drop to ambient values. Linearized density kernels are developed that show sensitivity only to the extreme outside of the loops for radial fundamental modes, especially for small density enhancements, with no sensitivity to the core. Higher radial harmonics do show some internal sensitivity, but these will be more difficult to observe. Only kink modes are sensitive to the tube centres. Variation in internal and external Alfvén speed along the loop is shown to have little effect on the fundamental dimensionless eigenfrequency, though the associated eigenfunction becomes more compact at the loop apex as stratification increases, or may even displace from the apex.

The Nosé–Hoover looped chain thermostat for low temperature thawed Gaussian wave-packet dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coughtrie, David J.; Tew, David P.

2014-05-21

We have used a generalised coherent state resolution of the identity to map the quantum canonical statistical average for a general system onto a phase-space average over the centre and width parameters of a thawed Gaussian wave packet. We also propose an artificial phase-space density that has the same behaviour as the canonical phase-space density in the low-temperature limit, and have constructed a novel Nosé–Hoover looped chain thermostat that generates this density in conjunction with variational thawed Gaussian wave-packet dynamics. This forms a new platform for evaluating statistical properties of quantum condensed-phase systems that has an explicit connection to themore » time-dependent Schrödinger equation, whilst retaining many of the appealing features of path-integral molecular dynamics.« less

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production

PubMed Central

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis. Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis. More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress. PMID:27899933

Differences in Glycoprotein Complex Receptor Binding Site Accessibility Prompt Poor Cross-Reactivity of Neutralizing Antibodies between Closely Related Arenaviruses

PubMed Central

Brouillette, Rachel B.; Phillips, Elisabeth K.; Ayithan, Natarajan

2017-01-01

ABSTRACT The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide, GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have nearly identical overall GPC architecture and share a host receptor, transferrin receptor 1 (TfR1). Given structural and functional similarities of the GP1 receptor binding site (RBS) of these viruses and the recent demonstration that the RBS is an important target for neutralizing antibodies, it is not clear how these viruses avoid cross-neutralization. To address this, MACV/JUNV chimeric GPCs were assessed for interaction with a group of α-JUNV GPC monoclonal antibodies (MAbs) and mouse antisera against JUNV or MACV GPC. All six MAbs targeted GP1, with those that neutralized JUNV GPC-pseudovirions competing with each other for RBS binding. However, these MAbs were unable to bind to a chimeric GPC composed of JUNV GP1 containing a small disulfide bonded loop (loop 10) unique to MACV GPC, suggesting that this loop may block MAbs interaction with the GP1 RBS. Consistent with this loop causing interference, mouse anti-JUNV GPC antisera that solely neutralized pseudovirions bearing autologous GP1 provided enhanced neutralization of MACV GPC when this loop was removed. Our studies provide evidence that loop 10, which is unique to MACV GP1, is an important impediment to binding of neutralizing antibodies and contributes to the poor cross-neutralization of α-JUNV antisera against MACV. IMPORTANCE Multiple New World arenaviruses can cause severe disease in humans, and some geographic overlap exists among these viruses. A vaccine that protects against a broad range of New World arenaviruses is desirable for purposes of simplicity, cost, and broad protection against multiple National Institute of Allergy and Infectious Disease-assigned category A priority pathogens. In this study, we sought to better understand how closely related arenaviruses elude cross-species neutralization by investigating the structural bases of antibody binding and avoidance. In our studies, we found that neutralizing antibodies against two New World arenaviruses, Machupo virus (MACV) and Junín virus (JUNV), bound to the envelope glycoprotein 1 (GP1) with JUNV monoclonal antibodies targeting the receptor binding site (RBS). We further show that altered structures surrounding the RBS pocket in MACV GP1 impede access of JUNV-elicited antibodies. PMID:28100617

Differences in Glycoprotein Complex Receptor Binding Site Accessibility Prompt Poor Cross-Reactivity of Neutralizing Antibodies between Closely Related Arenaviruses.

PubMed

Brouillette, Rachel B; Phillips, Elisabeth K; Ayithan, Natarajan; Maury, Wendy

2017-04-01

The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide, GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have nearly identical overall GPC architecture and share a host receptor, transferrin receptor 1 (TfR1). Given structural and functional similarities of the GP1 receptor binding site (RBS) of these viruses and the recent demonstration that the RBS is an important target for neutralizing antibodies, it is not clear how these viruses avoid cross-neutralization. To address this, MACV/JUNV chimeric GPCs were assessed for interaction with a group of α-JUNV GPC monoclonal antibodies (MAbs) and mouse antisera against JUNV or MACV GPC. All six MAbs targeted GP1, with those that neutralized JUNV GPC-pseudovirions competing with each other for RBS binding. However, these MAbs were unable to bind to a chimeric GPC composed of JUNV GP1 containing a small disulfide bonded loop (loop 10) unique to MACV GPC, suggesting that this loop may block MAbs interaction with the GP1 RBS. Consistent with this loop causing interference, mouse anti-JUNV GPC antisera that solely neutralized pseudovirions bearing autologous GP1 provided enhanced neutralization of MACV GPC when this loop was removed. Our studies provide evidence that loop 10, which is unique to MACV GP1, is an important impediment to binding of neutralizing antibodies and contributes to the poor cross-neutralization of α-JUNV antisera against MACV. IMPORTANCE Multiple New World arenaviruses can cause severe disease in humans, and some geographic overlap exists among these viruses. A vaccine that protects against a broad range of New World arenaviruses is desirable for purposes of simplicity, cost, and broad protection against multiple National Institute of Allergy and Infectious Disease-assigned category A priority pathogens. In this study, we sought to better understand how closely related arenaviruses elude cross-species neutralization by investigating the structural bases of antibody binding and avoidance. In our studies, we found that neutralizing antibodies against two New World arenaviruses, Machupo virus (MACV) and Junín virus (JUNV), bound to the envelope glycoprotein 1 (GP1) with JUNV monoclonal antibodies targeting the receptor binding site (RBS). We further show that altered structures surrounding the RBS pocket in MACV GP1 impede access of JUNV-elicited antibodies. Copyright © 2017 American Society for Microbiology.

α1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: Application as an antipathogenic agent

PubMed Central

Jean, François; Stella, Kori; Thomas, Laurel; Liu, Gseping; Xiang, Yang; Reason, Andrew J.; Thomas, Gary

1998-01-01

The important role of furin in the proteolytic activation of many pathogenic molecules has made this endoprotease a target for the development of potent and selective antiproteolytic agents. Here, we demonstrate the utility of the protein-based inhibitor α1-antitrypsin Portland (α1-PDX) as an antipathogenic agent that can be used prophylactically to block furin-dependent cell killing by Pseudomonas exotoxin A. Biochemical analysis of the specificity of a bacterially expressed His- and FLAG-tagged α1-PDX (α1-PDX/hf) revealed the selectivity of the α1-PDX/hf reactive site loop for furin (Ki, 600 pM) but not for other proprotein convertase family members or other unrelated endoproteases. Kinetic studies show that α1-PDX/hf inhibits furin by a slow tight-binding mechanism characteristic of serpin molecules and functions as a suicide substrate inhibitor. Once bound to furin’s active site, α1-PDX/hf partitions with equal probability to undergo proteolysis by furin at the C-terminal side of the reactive center -Arg355-Ile-Pro-Arg358-↓ or to form a kinetically trapped SDS-stable complex with the enzyme. This partitioning between the complex-forming and proteolytic pathways contributes to the ability of α1-PDX/hf to differentially inhibit members of the proprotein convertase family. Finally, we propose a structural model of the α1-PDX-reactive site loop that explains the high degree of enzyme selectivity of this serpin and which can be used to generate small molecule furin inhibitors. PMID:9636142

Cross-reactivity and epitope analysis of Pru a 1, the major cherry allergen.

PubMed

Scheurer, S; Son, D Y; Boehm, M; Karamloo, F; Franke, S; Hoffmann, A; Haustein, D; Vieths, S

1999-02-01

A high percentage of birch pollen allergic patients experiences food hypersensivity after ingestion of fresh fruits and vegetables. The cross-reactivity of the major allergens of sweet cherry (Pru a 1), apple (Mal d 1), pear (Pyr c 1), celery tuber (Api g 1) and carrot (Dau c 1) is due to structural similarities which are reflected by high amino acid sequence identities with Bet v 1a, the major birch pollen allergen. Apart from a strong cross-reactivity to Bet v 1a, IgE inhibition experiments with Mal d 1, Pru a 1 and Api g 1 demonstrated the presence of common and different epitopes among the tested food allergens. Secondary structure prediction of all investigated allergens indicated the presence of almost identical structural elements. In particular, the 'P-loop' region is a common domain of the pollen related food allergens and of pathogenesis related proteins. To identify the IgE binding epitopes, five overlapping recombinant Pru a 1 fragments representing the entire amino acid sequence with lengths of approximately 60-120 residues were investigated. Weak IgE binding capacity was measured exclusively with Pru a IF4 (1-120) by immunoblotting, whereas none of the fragments showed allergenicity in the rat basophil leukaemia cell mediator release assay. Site-directed mutagenesis experiments with Pru a 1 revealed that amino acid S112 is critical for IgE binding of almost all patients sera tested. This reduced IgE binding was also observed with a single point mutant of Bet v 1a (S112P) and thus indicated serine 112 as an essential residue for preserving the structure of a cross-reactive IgE epitope. Moreover, two Pru a 1 mutants with an altered 'P-loop' region, showed a lowered IgE binding capacity for IgE from a subgroup of allergic patients. The investigation of essential features for preserving cross-reactive IgE-epitopes provides the structural basis for understanding the clinically observed cross-allergenicity between pollen and fruits. Moreover, non-anaphylactic allergen fragments or variants derived from the IgE-inducing pollen allergens may serve as useful tools for a new strategy of specific immunotherapy.

Exposure of Epitope Residues on the Outer Face of the Chikungunya Virus Envelope Trimer Determines Antibody Neutralizing Efficacy

PubMed Central

Fong, Rachel H.; Banik, Soma S. R.; Mattia, Kimberly; Barnes, Trevor; Tucker, David; Liss, Nathan; Lu, Kai; Selvarajah, Suganya; Srinivasan, Surabhi; Mabila, Manu; Miller, Adam; Muench, Marcus O.; Michault, Alain; Rucker, Joseph B.; Paes, Cheryl; Simmons, Graham; Kahle, Kristen M.

2014-01-01

ABSTRACT Chikungunya virus (CHIKV) is a reemerging alphavirus that causes a debilitating arthritic disease and infects millions of people and for which no specific treatment is available. Like many alphaviruses, the structural targets on CHIKV that elicit a protective humoral immune response in humans are poorly defined. Here we used phage display against virus-like particles (VLPs) to isolate seven human monoclonal antibodies (MAbs) against the CHIKV envelope glycoproteins E2 and E1. One MAb, IM-CKV063, was highly neutralizing (50% inhibitory concentration, 7.4 ng/ml), demonstrated high-affinity binding (320 pM), and was capable of therapeutic and prophylactic protection in multiple animal models up to 24 h postexposure. Epitope mapping using a comprehensive shotgun mutagenesis library of 910 mutants with E2/E1 alanine mutations demonstrated that IM-CKV063 binds to an intersubunit conformational epitope on domain A, a functionally important region of E2. MAbs against the highly conserved fusion loop have not previously been reported but were also isolated in our studies. Fusion loop MAbs were broadly cross-reactive against diverse alphaviruses but were nonneutralizing. Fusion loop MAb reactivity was affected by temperature and reactivity conditions, suggesting that the fusion loop is hidden in infectious virions. Visualization of the binding sites of 15 different MAbs on the structure of E2/E1 revealed that all epitopes are located at the membrane-distal region of the E2/E1 spike. Interestingly, epitopes on the exposed topmost and outer surfaces of the E2/E1 trimer structure were neutralizing, whereas epitopes facing the interior of the trimer were not, providing a rationale for vaccine design and therapeutic MAb development using the intact CHIKV E2/E1 trimer. IMPORTANCE CHIKV is the most important alphavirus affecting humans, resulting in a chronic arthritic condition that can persist for months or years. In recent years, millions of people have been infected globally, and the spread of CHIKV to the Americas is now beginning, with over 100,000 cases occurring in the Caribbean within 6 months of its arrival. Our study reports on seven human MAbs against the CHIKV envelope, including a highly protective MAb and rarely isolated fusion loop MAbs. Epitope mapping of these MAbs demonstrates how some E2/E1 epitopes are exposed or hidden from the human immune system and suggests a structural mechanism by which these MAbs protect (or fail to protect) against CHIKV infection. Our results suggest that the membrane-distal end of CHIKV E2/E1 is the primary target for the humoral immune response to CHIKV, and antibodies targeting the exposed topmost and outer surfaces of the E2/E1 trimer determine the neutralizing efficacy of this response. PMID:25275138

A prospective randomized controlled trial comparing early postoperative complications in patients undergoing loop colostomy with and without a stoma rod.

PubMed

Franklyn, J; Varghese, G; Mittal, R; Rebekah, G; Jesudason, M R; Perakath, B

2017-07-01

A stoma rod or bridge has been traditionally placed under the bowel loop while constructing a loop colostomy. This is believed to prevent stomal retraction and provide better faecal diversion. However, the rod can cause complications such as mucosal congestion, oedema and necrosis. This single-centre prospective randomized controlled trial compared outcomes after creation of loop colostomy with and without a supporting stoma rod. The primary outcome studied was stoma retraction rate; other stoma-related complications were studied as secondary outcomes. One hundred and fifty-one patients were randomly allotted to one of two arms, colostomy with or without a supporting rod. Postoperative complications such as retraction, mucocutaneous separation, congestion and re-exploration for stoma-related complications were recorded. There was no difference in the stoma retraction rate between the two arms (8.1% in the rod arm and 6.6% in the no-rod arm; P = 0.719). Stomal necrosis (10.7% vs 1.3%; P = 0.018), oedema (23% vs 3.9%; P = 0.001), congestion (20.3% vs 2.6%; P = 0.001) and re-admission rates (8.5% vs 0%; P = 0.027) were significantly increased in the arm randomized to the rod. The stoma rod does not prevent stomal retraction. However, complication rates are significantly higher when a stoma rod is used. Routine use of a stoma rod for construction of loop colostomy can be avoided. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

EUDOR-A multi-centre research program: A naturalistic, European Multi-centre Clinical study of EDOR Test in adult patients with primary depression.

PubMed

Sarchiapone, Marco; Iosue, Miriam; Carli, Vladimir; Amore, Mario; Baca-Garcia, Enrique; Batra, Anil; Cosman, Doina; Courtet, Philippe; Di Sciascio, Guido; Gusmao, Ricardo; Parnowski, Tadeusz; Pestality, Peter; Saiz, Pilar; Thome, Johannes; Tingström, Anders; Wojnar, Marcin; Zeppegno, Patrizia; Thorell, Lars-Håkan

2017-03-23

Electrodermal reactivity has been successfully used as indicator of interest, curiosity as well as depressive states. The measured reactivity depends on the quantity of sweat secreted by those eccrine sweat glands that are located in the hypodermis of palmar and plantar regions. Electrodermal hyporeactive individuals are those who show an unusual rapid habituation to identical non-significant stimuli. Previous findings suggested that electrodermal hyporeactivity has a high sensitivity and a high specificity for suicide. The aims of the present study are to test the effectiveness and the usefulness of the EDOR (ElectroDermal Orienting Reactivity) Test as a support in the suicide risk assessment of depressed patients and to assess the predictive value of electrodermal hyporeactivity, measured through the EDOR Test, for suicide and suicide attempt in adult patients with a primary diagnosis of depression. 1573 patients with a primary diagnosis of depression, whether currently depressed or in remission, have been recruited at 15 centres in 9 different European countries. Depressive symptomatology was evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts were registered and the suicide intent of the worst attempt was rated according to the first eight items of the Beck Suicide Intent Scale. The suicide risk was also assessed according to rules and traditions at the centre. The EDOR Test was finally performed. During the EDOR Test, two fingers are put on gold electrodes and direct current of 0.5 V is passed through the epidermis of the fingers according to standards. A moderately strong tone is presented through headphones now and then during the test. The electrodermal responses to the stimuli represent an increase in the conductance due to the increased number of filled sweat ducts that act as conductors through the electrically highly resistant epidermis. Each patient is followed up for one year in order to assess the occurrence of intentional self-harm. Based on previous studies, expected results would be that patients realizing a suicide attempt with a strong intent or committing suicide should be electrodermally hyporeactive in most cases and non-hyporeactive patients should show only few indications of death intent or suicides. The German Clinical Trials Register, DRKS00010082 . Registered May 31 st , 2016. Retrospectively registered.

Point of care platelet activity measurement in primary PCI [PINPOINT-PPCI]: a protocol paper.

PubMed

Johnson, Thomas W; Marsden, Debbie; Mumford, Andrew; Pike, Katie; Mundell, Stuart; Butler, Mark; Strange, Julian W; Bowles, Ruth; Rogers, Chris; Baumbach, Andreas; Reeves, Barnaby C

2014-04-04

Optimal treatment of acute ST-elevation myocardial infarction (STEMI) involves rapid diagnosis, and transfer to a cardiac centre capable of percutaneous coronary intervention (PCI) for immediate mechanical revascularisation. Successful treatment requires rapid return of perfusion to the myocardium achieved by thromboaspiration, passivation of the culprit lesion with stent scaffolding and systemic inhibition of thrombosis and platelet activation. A delicate balance exists between thrombosis and bleeding and consequently anti-thrombotic and antiplatelet treatment regimens continue to evolve. The desire to achieve reperfusion as soon as possible, in the setting of high platelet reactivity, requires potent and fast-acting anti-thrombotic/anti-platelet therapies. The associated bleeding risk may be minimised by use of short-acting anti-thrombotic intravenous agents. However, effective oral platelet inhibition is required to prevent recurrent thrombosis. The interaction between baseline platelet reactivity, timing of revascularisation and effective inhibition of thrombosis is yet to be formally investigated. We present a protocol for a prospective observational study in patients presenting with acute STEMI treated with primary PCI (PPCI) and receiving bolus/infusion bivalirudin and prasugrel therapy. The objective of this study is to describe variation in platelet reactivity, as measured by the multiplate platelet function analyser, at presentation, the end of the PPCI procedure and 1, 2, & 24 hours post-procedure. We intend to assess the prevalence of high residual platelet reactivity within 24 hours of PPCI in acute STEMI patients receiving prasugrel and bivalirudin. Additionally, we will investigate the association between high platelet reactivity before and after PPCI and the door-to-procedure completion time.This is a single centre study with a target sample size of 108 participants. The baseline platelet reactivity on presentation with a STEMI may impact on the effect of acute anti-thrombotic and anti-platelet therapy and expose patients to a heightened risk of bleeding or ongoing thrombosis. This study will define the baseline variation in platelet reactivity in a population of patients experiencing acute STEMI and assess the pharmacodynamic response to combined treatment with bivalirudin and prasugrel. The data obtained from this trial will be hypothesis generating for future trials testing alternative pharmacotherapies in the acute phase of treatment for STEMI. This study has approval from Wiltshire research ethics committee (10/H0106/87) and is registered with current controlled trials (http://www.controlled-trials.com/ISRCTN82257414).

A quantum protective mechanism in photosynthesis

NASA Astrophysics Data System (ADS)

Marais, Adriana; Sinayskiy, Ilya; Petruccione, Francesco; van Grondelle, Rienk

2015-03-01

Since the emergence of oxygenic photosynthesis, living systems have developed protective mechanisms against reactive oxygen species. During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product yield in bacteria is observed to be reduced by weak magnetic fields. Reaction centres from plants' photosystem II share many features with bacterial reaction centres, including a high-spin iron whose function has remained obscure. To explain observations that the magnetic field effect is reduced by the iron, we propose that its fast-relaxing spin plays a protective role in photosynthesis by generating an effective magnetic field. We consider a simple model of the system, derive an analytical expression for the effective magnetic field and analyse the resulting triplet yield reduction. The protective mechanism is robust for realistic parameter ranges, constituting a clear example of a quantum effect playing a macroscopic role vital for life.

A quantum protective mechanism in photosynthesis.

PubMed

Marais, Adriana; Sinayskiy, Ilya; Petruccione, Francesco; van Grondelle, Rienk

2015-03-03

Since the emergence of oxygenic photosynthesis, living systems have developed protective mechanisms against reactive oxygen species. During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product yield in bacteria is observed to be reduced by weak magnetic fields. Reaction centres from plants' photosystem II share many features with bacterial reaction centres, including a high-spin iron whose function has remained obscure. To explain observations that the magnetic field effect is reduced by the iron, we propose that its fast-relaxing spin plays a protective role in photosynthesis by generating an effective magnetic field. We consider a simple model of the system, derive an analytical expression for the effective magnetic field and analyse the resulting triplet yield reduction. The protective mechanism is robust for realistic parameter ranges, constituting a clear example of a quantum effect playing a macroscopic role vital for life.

The molecular basis of herpes simplex virus latency

PubMed Central

Nicoll, Michael P; Proença, João T; Efstathiou, Stacey

2012-01-01

Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. Although incompletely understood, this review will focus on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation. This review considers current knowledge and hypotheses relating to the mechanisms involved in the establishment, maintenance and reactivation herpes simplex virus latency. PMID:22150699

A role for catalase-peroxidase large loop 2 revealed by deletion mutagenesis: control of active site water and ferric enzyme reactivity.

PubMed

Kudalkar, Shalley N; Njuma, Olive J; Li, Yongjiang; Muldowney, Michelle; Fuanta, N Rene; Goodwin, Douglas C

2015-03-03

Catalase-peroxidases (KatGs), the only catalase-active members of their superfamily, all possess a 35-residue interhelical loop called large loop 2 (LL2). It is essential for catalase activity, but little is known about its contribution to KatG function. LL2 shows weak sequence conservation; however, its length is nearly identical across KatGs, and its apex invariably makes contact with the KatG-unique C-terminal domain. We used site-directed and deletion mutagenesis to interrogate the role of LL2 and its interaction with the C-terminal domain in KatG structure and catalysis. Single and double substitutions of the LL2 apex had little impact on the active site heme [by magnetic circular dichroism or electron paramagnetic resonance (EPR)] and activity (catalase or peroxidase). Conversely, deletion of a single amino acid from the LL2 apex reduced catalase activity by 80%. Deletion of two or more apex amino acids or all of LL2 diminished catalase activity by 300-fold. Peroxide-dependent but not electron donor-dependent kcat/KM values for deletion variant peroxidase activity were reduced 20-200-fold, and kon for cyanide binding diminished by 3 orders of magnitude. EPR spectra for deletion variants were all consistent with an increase in the level of pentacoordinate high-spin heme at the expense of hexacoordinate high-spin states. Together, these data suggest a shift in the distribution of active site waters, altering the reactivity of the ferric state, toward, among other things, compound I formation. These results identify the importance of LL2 length conservation for maintaining an intersubunit interaction that is essential for an active site water distribution that facilitates KatG catalytic activity.

Impact of mixing chemically heterogeneous groundwaters on the sustainability of an open-loop groundwater heat pump

NASA Astrophysics Data System (ADS)

Burté, L.; Farasin, J.; Cravotta, C., III; Gerard, M. F.; Cotiche Baranger, C.; Aquilina, L.; Le Borgne, T.

2017-12-01

Geothermal systems using shallow aquifers are commonly used for heating and cooling. The sustainability of these systems can be severely impacted by the occurrence of clogging process. The geothermal loop operation (including pumping of groundwater, filtering and heat extraction through exchangers and cooled water injection) can lead to an unexpected biogeochemical reactivity and scaling formation that can ultimately lead to the shutdown of the geothermal doublet. Here, we report the results of investigations carried out on a shallow geothermal doublet (< 40 m depth) affected by rapid clogging processes linked to iron and manganese oxidation. Using a reactive transport model, we determine the parameters controlling clogging. To characterize the biogeochemical processes induced by the operation of the production well, we combined hydrodynamic measurements by flowmeter and in-situ chemical depth profiles. We thus investigated the chemical heterogeneity into the pumping well as a function of the operating conditions (static or dynamic). Hydrochemical data collected at the pumping well showed that groundwater was chemically heterogeneous long the 11 meters well screen. While the aquifer was dominantly oxic, a localized inflow of anoxic water was detected and evaluated to produce about 40% of the total flow . The mixture of chemically heterogeneous water induced by pumping lead to the oxidation of reductive species and thus to the formation of biogenic precipitates responsible for clogging. The impact of pumping waters of different redox potential and chemical characteristics was quantified by numerical modeling using PHREEQC. These results shows that natural chemical heterogeneity can occur at a small scale in heterogeneous aquifers and highlight the importance of their characterization during the production well testing and the geothermal loop operation in order to take preventive measures to avoid clogging.

Sulfur evolution in chemical looping combustion of coal with MnFe2O4 oxygen carrier.

PubMed

Wang, Baowen; Gao, Chuchang; Wang, Weishu; Zhao, Haibo; Zheng, Chuguang

2014-05-01

Chemical looping combustion (CLC) of coal has gained increasing attention as a novel combustion technology for its advantages in CO2 capture. Sulfur evolution from coal causes great harm from either the CLC operational or environmental perspective. In this research, a combined MnFe2O4 oxygen carrier (OC) was synthesized and its reaction with a typical Chinese high sulfur coal, Liuzhi (LZ) bituminous coal, was performed in a thermogravimetric analyzer (TGA)-Fourier transform infrared (FT-IR) spectrometer. Evolution of sulfur species during reaction of LZ coal with MnFe2O4 OC was systematically investigated through experimental means combined with thermodynamic simulation. TGA-FTIR analysis of the LZ reaction with MnFe2O4 indicated MnFe2O4 exhibited the desired superior reactivity compared to the single reference oxides Mn3O4 or Fe2O3, and SO2 produced was mainly related to oxidization of H2S by MnFe2O4. Experimental analysis of the LZ coal reaction with MnFe2O4, including X-ray diffraction and X-ray photoelectron spectroscopy analysis, verified that the main reduced counterparts of MnFe2O4 were Fe3O4 and MnO, in good agreement with the related thermodynamic simulation. The obtained MnO was beneficial to stabilize the reduced MnFe2O4 and avoid serious sintering, although the oxygen in MnO was not fully utilized. Meanwhile, most sulfur present in LZ coal was converted to solid MnS during LZ reaction with MnFe2O4, which was further oxidized to MnSO4. Finally, the formation of both MnS and such manganese silicates as Mn2SiO4 and MnSiO3 should be addressed to ensure the full regeneration of the reduced MnFe2O4. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Fusion loop peptide of the West Nile virus envelope protein is essential for pathogenesis and is recognized by a therapeutic cross-reactive human monoclonal antibody.

PubMed

Sultana, Hameeda; Foellmer, Harald G; Neelakanta, Girish; Oliphant, Theodore; Engle, Michael; Ledizet, Michel; Krishnan, Manoj N; Bonafé, Nathalie; Anthony, Karen G; Marasco, Wayne A; Kaplan, Paul; Montgomery, Ruth R; Diamond, Michael S; Koski, Raymond A; Fikrig, Erol

2009-07-01

West Nile virus is an emerging pathogen that can cause fatal neurological disease. A recombinant human mAb, mAb11, has been described as a candidate for the prevention and treatment of West Nile disease. Using a yeast surface display epitope mapping assay and neutralization escape mutant, we show that mAb11 recognizes the fusion loop, at the distal end of domain II of the West Nile virus envelope protein. Ab mAb11 cross-reacts with all four dengue viruses and provides protection against dengue (serotypes 2 and 4) viruses. In contrast to the parental West Nile virus, a neutralization escape variant failed to cause lethal encephalitis (at higher infectious doses) or induce the inflammatory responses associated with blood-brain barrier permeability in mice, suggesting an important role for the fusion loop in viral pathogenesis. Our data demonstrate that an intact West Nile virus fusion loop is critical for virulence, and that human mAb11 targeting this region is efficacious against West Nile virus infection. These experiments define the molecular determinant on the envelope protein recognized by mAb11 and demonstrate the importance of this region in causing West Nile encephalitis.

Sphingolipid-Mediated Apoptosis and Tumor Suppression in Breast Carcinoma.

DTIC Science & Technology

1996-10-01

diacylglycerol and ceramide. The radioactive spots corresponding to phosphatidic acid and ceramide-phosphate, the phosphorylated products of diacylglycerol (DAG...threonine protein phosphatase (7). This phosphatase is inhibited by okadaic acid , and okadaic acid appears to inhibit the effects of ceramide on...Arg to Thr at amino acid 291 in the reactive site loop. In MCF-7 cells expressing this mutant, there was no significant inhibition of ceramide

Analysis of boron dilution in a four-loop PWR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, J.G.; Sha, W.T.

1995-03-01

Thermal mixing and boron dilution in a pressurized water reactor were analyzed with COMMIX codes. The reactor system was the four-loop Zion reactor. Two boron dilution scenarios were analyzed. In the first scenario, the plant is in cold shutdown and the reactor coolant system has just been filled after maintenance on the steam generators. To flush the air out of the steam generator tubes, a reactor coolant pump (RCP) is started, with the water in the pump suction line devoid of boron and at the same temperature as the coolant in the system. In the second scenario, the plant ismore » at hot standby and the reactor coolant system has been heated to operating temperature after a long outage. It is assumed that an RCP is started, with the pump suction line filled with cold unborated water, forcing a slug of diluted coolant down the downcomer and subsequently through the reactor core. The subsequent transient thermal mixing and boron dilution that would occur in the reactor system is simulated for these two scenarios. The reactivity insertion rate and the total reactivity are evaluated and a sensitivity study is performed to assess the accuracy of the numerical modeling of the geometry of the reactor coolant system.« less

Apparatus and method for closed-loop control of reactor power in minimum time

DOEpatents

Bernard, Jr., John A.

1988-11-01

Closed-loop control law for altering the power level of nuclear reactors in a safe manner and without overshoot and in minimum time. Apparatus is provided for moving a fast-acting control element such as a control rod or a control drum for altering the nuclear reactor power level. A computer computes at short time intervals either the function: .rho.=(.beta.-.rho.).omega.-.lambda..sub.e '.rho.-.SIGMA..beta..sub.i (.lambda..sub.i -.lambda..sub.e ')+l* .omega.+l* [.omega..sup.2 +.lambda..sub.e '.omega.] or the function: .rho.=(.beta.-.rho.).omega.-.lambda..sub.e .rho.-(.lambda..sub.e /.lambda..sub.e)(.beta.-.rho.)+l* .omega.+l* [.omega..sup.2 +.lambda..sub.e .omega.-(.lambda..sub.e /.lambda..sub.e).omega.] These functions each specify the rate of change of reactivity that is necessary to achieve a specified rate of change of reactor power. The direction and speed of motion of the control element is altered so as to provide the rate of reactivity change calculated using either or both of these functions thereby resulting in the attainment of a new power level without overshoot and in minimum time. These functions are computed at intervals of approximately 0.01-1.0 seconds depending on the specific application.

ESEEM of industrial quartz powders: insights into crystal chemistry of Al defects

NASA Astrophysics Data System (ADS)

Romanelli, Maurizio; Di Benedetto, Francesco; Bartali, Laura; Innocenti, Massimo; Fornaciai, Gabriele; Montegrossi, Giordano; Pardi, Luca A.; Zoleo, Alfonso; Capacci, Fabio

2012-06-01

A set of raw industrial materials, that is, pure quartz and quartz-rich mixtures, were investigated through electron paramagnetic resonance and electron spin echo-envelope modulation spectroscopies, with the aim of evaluating the effective role played by defect centres and of assessing whether they can be used to monitor changes in the physical properties of quartz powders with reference to their health effects. The obtained results point to two interactions of the Al defect centres with H+, hosted in sites within the channels parallel and perpendicular to the c axis of quartz, respectively. These two Al/H+ (hAl) centres exhibit a weak chemical bond, and their relative amounts appear to be modified/controlled by the thermo-mechanical processes underwent by powders. Indeed, a mechanically promoted inter-conversion between the two kinds of site is suggested. As a consequence, the hAl centres are effective in monitoring even modest activations of powders, through thermal or mechanical processes, and they are also supposed to play a specific, relevant role in quartz reactivity during the considered industrial processes.

Liver Resections Combined with Closure of Loop Ileostomies: A Retrospective Analysis

PubMed Central

Lordan, Jeffrey T.; Riga, Angela T.; Karanjia, Nariman D.

2008-01-01

Background. The management of patients with colorectal liver metastases and loop ileostomies remains controversial. This study was performed to assess the outcome of combined liver resection and loop ileostomy closure. Methods. Analysis of prospectively collected perioperative data, including morbidity and mortality, of 283 consecutive hepatectomies for colorectal liver metastases was undertaken. Consecutive liver resections were performed from 1996 to 2006 in one centre by a single surgeon (NDK). Fourteen of these patients had combined liver resection and ileostomy closure. Case-matched analysis was undertaken. Results. Six (2.2%) patients died in the hepatectomy only group and none died in the combined group. There was no difference in operative blood loss between the two groups (0.09). Perioperative morbidity was 36% in the combined group and 23% in the hepatectomy alone group (P = 0.33). Mean hospital stay was 14 days in the combined group and 11 days in the hepatectomy only group (P = 0.046). Case-matched analysis showed a significant increase in hospital stay (P = 0.03) and complications (P = 0.049) in the combined group. Conclusion. In patients with CRLM, combined liver resection and closure of ileostomy may be associated with a higher operative morbidity and a prolonged hospital stay. PMID:19096524

Study of a control strategy for grid side converter in doubly- fed wind power system

NASA Astrophysics Data System (ADS)

Zhu, D. J.; Tan, Z. L.; Yuan, F.; Wang, Q. Y.; Ding, M.

2016-08-01

The grid side converter is an important part of the excitation system of doubly-fed asynchronous generator used in wind power system. As a three-phase voltage source PWM converter, it can not only transfer slip power in the form of active power, but also adjust the reactive power of the grid. This paper proposed a control approach for improving its performance. In this control approach, the dc voltage is regulated by a sliding mode variable structure control scheme and current by a variable structure controller based on the input output linearization. The theoretical bases of the sliding mode variable structure control were introduced, and the stability proof was presented. Switching function of the system has been deduced, sliding mode voltage controller model has been established, and the output of the outer voltage loop is the instruction of the inner current loop. Affine nonlinear model of two input two output equations on d-q axis for current has been established its meeting conditions of exact linearization were proved. In order to improve the anti-jamming capability of the system, a variable structure control was added in the current controller, the control law was deduced. The dual-loop control with sliding mode control in outer voltage loop and linearization variable structure control in inner current loop was proposed. Simulation results demonstrate the effectiveness of the proposed control strategy even during the dc reference voltage and system load variation.

Generating carbyne equivalents with photoredox catalysis

NASA Astrophysics Data System (ADS)

Wang, Zhaofeng; Herraiz, Ana G.; Del Hoyo, Ana M.; Suero, Marcos G.

2018-02-01

Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species—carbocations, carbanions, radicals and carbenes—that is fundamental to our understanding of chemical reactivity. In contrast, the carbyne—a monovalent carbon with three non-bonded electrons—is a relatively unexplored reactive intermediate; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an ‘assembly point’ disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon-hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon-hydrogen bonds, while complementing current translational late-stage functionalization processes. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.

Preparation and investigation of sputtered vanadium dioxide films with large phase-transition hysteresis loops

NASA Astrophysics Data System (ADS)

Zhang, Huafu; Wu, Zhiming; He, Qiong; Jiang, Yadong

2013-07-01

Vanadium dioxide (VO2) films with large phase-transition hysteresis loops were fabricated on glass substrates by reactive direct current (DC) magnetron sputtering in Ar/O2 atmosphere and subsequent in situ annealing process in pure oxygen. The crystal structure, chemical composition, morphology and metal-insulator transition (MIT) properties of the deposited films were investigated. The results reveal that the films show a polycrystalline nature with a (0 1 1) preferred orientation and consist of small spheroidal nanoparticles. All the deposited VO2 films show large hysteresis loops due to the small density of nucleating defects and the large interfacial energies, which are determined by the characteristics of the particles in the films, namely the small transversal grain size and the spheroidal shape. The film comprising the smallest spheroidal nanoparticles not only shows a large hysteresis width of 36.3 °C but also shows a low transition temperature of 32.2 °C upon cooling. This experiment facilitates the civilian applications of the VO2 films on glass substrates in optical storage-type devices.

Chemical Looping Combustion Reactions and Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarofim, Adel; Lighty, JoAnn; Smith, Philip

2014-03-01

Chemical Looping Combustion (CLC) is one promising fuel-combustion technology, which can facilitate economic CO{sub 2} capture in coal-fired power plants. It employs the oxidation/reduction characteristics of a metal, or oxygen carrier, and its oxide, the oxidizing gas (typically air) and the fuel source may be kept separate. This topical report discusses the results of four complementary efforts: (5.1) the development of process and economic models to optimize important design considerations, such as oxygen carrier circulation rate, temperature, residence time; (5.2) the development of high-performance simulation capabilities for fluidized beds and the collection, parameter identification, and preliminary verification/uncertainty quantification; (5.3) themore » exploration of operating characteristics in the laboratoryscale bubbling bed reactor, with a focus on the oxygen carrier performance, including reactivity, oxygen carrying capacity, attrition resistance, resistance to deactivation, cost and availability; and (5.4) the identification of kinetic data for copper-based oxygen carriers as well as the development and analysis of supported copper oxygen carrier material. Subtask 5.1 focused on the development of kinetic expressions for the Chemical Looping with Oxygen Uncoupling (CLOU) process and validating them with reported literature data. The kinetic expressions were incorporated into a process model for determination of reactor size and oxygen carrier circulation for the CLOU process using ASPEN PLUS. An ASPEN PLUS process model was also developed using literature data for the CLC process employing an iron-based oxygen carrier, and the results of the process model have been utilized to perform a relative economic comparison. In Subtask 5.2, the investigators studied the trade-off between modeling approaches and available simulations tools. They quantified uncertainty in the high-performance computing (HPC) simulation tools for CLC bed applications. Furthermore, they performed a sensitivity analysis for velocity, height and polydispersity and compared results against literature data for experimental studies of CLC beds with no reaction. Finally, they present an optimization space using simple non-reactive configurations. In Subtask 5.3, through a series of experimental studies, behavior of a variety of oxygen carriers with different loadings and manufacturing techniques was evaluated under both oxidizing and reducing conditions. The influences of temperature, degree of carrier conversion and thermodynamic driving force resulting from the difference between equilibrium and system O{sub 2} partial pressures were evaluated through several experimental campaigns, and generalized models accounting for these influences were developed to describe oxidation and oxygen release. Conversion of three solid fuels with widely ranging reactivities was studied in a small fluidized bed system, and all but the least reactive fuel (petcoke) were rapidly converted by oxygen liberated from the CLOU carrier. Attrition propensity of a variety of carriers was also studied, and the carriers produced by freeze granulation or impregnation of preformed substrates displayed the lowest rates of attrition. Subtask 5.4 focused on gathering kinetic data for a copper-based oxygen carrier to assist with modeling of a functioning chemical looping reactor. The kinetics team was also responsible for the development and analysis of supported copper oxygen carrier material.« less

Recovery Act: Novel Oxygen Carriers for Coal-fueled Chemical Looping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Wei-Ping; Cao, Yan

2012-11-30

Chemical Looping Combustion (CLC) could totally negate the necessity of pure oxygen by using oxygen carriers for purification of CO{sub 2} stream during combustion. It splits the single fuel combustion reaction into two linked reactions using oxygen carriers. The two linked reactions are the oxidation of oxygen carriers in the air reactor using air, and the reduction of oxygen carriers in the fuel reactor using fuels (i.e. coal). Generally metal/metal oxides are used as oxygen carriers and operated in a cyclic mode. Chemical looping combustion significantly improves the energy conversion efficiency, in terms of the electricity generation, because it improvesmore » the reversibility of the fuel combustion process through two linked parallel processes, compared to the conventional combustion process, which is operated far away from its thermo-equilibrium. Under the current carbon-constraint environment, it has been a promising carbon capture technology in terms of fuel combustion for power generation. Its disadvantage is that it is less mature in terms of technological commercialization. In this DOE-funded project, accomplishment is made by developing a series of advanced copper-based oxygen carriers, with properties of the higher oxygen-transfer capability, a favorable thermodynamics to generate high purity of CO{sub 2}, the higher reactivity, the attrition-resistance, the thermal stability in red-ox cycles and the achievement of the auto-thermal heat balance. This will be achieved into three phases in three consecutive years. The selected oxygen carriers with final-determined formula were tested in a scaled-up 10kW coal-fueled chemical looping combustion facility. This scaled-up evaluation tests (2-day, 8-hour per day) indicated that, there was no tendency of agglomeration of copper-based oxygen carriers. Only trace-amount of coke or carbon deposits on the copper-based oxygen carriers in the fuel reactor. There was also no evidence to show the sulphidization of oxygen carriers in the system by using the high-sulfur-laden asphalt fuels. In all, the scaled-up test in 10 kW CLC facility demonstrated that the preparation method of copper-based oxygen carrier not only help to maintain its good reactivity, also largely minimize its agglomeration tendency.« less

Initial diagnosis of small lymphocytic lymphoma in parotidectomy for Warthin tumour, a rare collision tumour

PubMed Central

Saxena, A; Memauri, B; Hasegawa, W

2005-01-01

Warthin tumours (WT) and malignant lymphomas are only rarely associated, and most are examples of involvement of the lymphoid stroma of WT by a disseminated lymphoma. This report describes a case where excision of a parotid mass led to the initial diagnosis of WT and small lymphocytic lymphoma (SLL). The diagnosis of SLL was confirmed by immunohistochemistry and molecular studies. The patient had stage IV A disease and is currently in chemotherapy induced complete remission. This case highlights the extremely rare association of SLL with WT and the importance of evaluation of the WT stroma, where the pale proliferation centres of SLL may mimic germinal centres of reactive lymphoid nodules. PMID:15735173

Why social attachment and oxytocin protect against addiction and stress: Insights from the dynamics between ventral and dorsal corticostriatal systems.

PubMed

Tops, Mattie; Koole, Sander L; IJzerman, Hans; Buisman-Pijlman, Femke T A

2014-04-01

The present article advances a neurobiological model of the reciprocal associations between social attachment and drug abuse, and social attachment and chronic stress, as overlapping systems are involved in stress coping and social attachment. In terms of coping, responding to a novel stressor or challenge involves initial novelty processing and activation of learning mechanisms that allow habituation to the stressor through familiarization. Similarly, social attachments are initially formed by being attracted by rewarding properties of an as-yet novel individual, and subsequently developing feelings of attachment towards the familiarized individual. Attachment and familiarization increase the availability of "internal working models" for the control of behavior and emotion, which may explain why secure attachments are associated with increased resilience in the face of stress, accompanied by less reactive reward responding (i.e., increased resilience against drug addiction). The present article seeks to illuminate the role of the neuropeptide oxytocin, which may be involved in the overlapping mechanisms of stable attachment formation and stress coping by shifting processing from novelty and reward seeking to appreciation of familiarity. Oxytocin may accomplish this by facilitating a ventral-to-dorsal shift in activation in corticostriatal loops, which produces a shift from a reactive reward drive (wanting) to stable appreciation of familiar social aspects ("liking" or "loving"). The authors suggest that through dopaminergic, serotonergic and endogenous opioid mechanisms, oxytocin is involved in shifting the balance between wanting and liking in corticostriatal loops by facilitating consolidation of social information from ventral reactive reward systems to dorsal internal working models that aid in prospectively selecting optimal actions in the future, increasing resilience in the face of stress and addiction. © 2013.

Structure, aromaticity and reactivity of corannulene and its analogues: a conceptual density functional theory and density functional reactivity theory study

NASA Astrophysics Data System (ADS)

Deng, Youer; Yu, Donghai; Cao, Xiaofang; Liu, Lianghong; Rong, Chunying; Lu, Tian; Liu, Shubin

2018-04-01

Corannulene is an interesting yet special molecule, which has witnessed widespread applications. It is aromatic, but not planar and the total number of 20 π electrons is in conflict with Hückel's 4n + 2 rule. In this work, we design a series of analogous model systems based on this molecule with the central ring size extended from five members to three to eight members. A number of theoretical and analytical tools available in the literature are employed to systematically examine their structure, aromaticity and reactivity properties. We found that structurally speaking, they change from bowl-like to planar and then to saddle shapes as the central ring size increases from three to eight. From the reactivity perspective, species with five and six-membered-rings in the centre are chemically more stable and less reactive, which are confirmed by the numerical results from aromaticity indexes and quantities from the information-theoretic approach. Overall, our results show that only corannulene and its six-membered-ring, coronene, analogue are aromatic. Even though these two systems are aromatic in nature, they are markedly different in a number of ways in structure, reactivity and other properties. These results should provide with us insights and understanding about the phenomenon of three-dimensional and non-planarity aromaticity.

FK506 binding protein 51 integrates pathways of adaptation: FKBP51 shapes the reactivity to environmental change.

PubMed

Rein, Theo

2016-09-01

This review portraits FK506 binding protein (FKBP) 51 as "reactivity protein" and collates recent publications to develop the concept of FKBP51 as contributor to different levels of adaptation. Adaptation is a fundamental process that enables unicellular and multicellular organisms to adjust their molecular circuits and structural conditions in reaction to environmental changes threatening their homeostasis. FKBP51 is known as chaperone and co-chaperone of heat shock protein (HSP) 90, thus involved in processes ensuring correct protein folding in response to proteotoxic stress. In mammals, FKBP51 both shapes the stress response and is calibrated by the stress levels through an ultrashort molecular feedback loop. More recently, it has been linked to several intracellular pathways related to the reactivity to drug exposure and stress. Through its role in autophagy and DNA methylation in particular it influences adaptive pathways, possibly also in a transgenerational fashion. Also see the video abstract here. © 2016 WILEY Periodicals, Inc.

Research on Robust Control Strategies for VSC-HVDC

NASA Astrophysics Data System (ADS)

Zhu, Kaicheng; Bao, Hai

2018-01-01

In the control system of VSC-HVDC, the phase locked loop provides phase signals to voltage vector control and trigger pulses to generate the required reference phase. The PLL is a typical second-order system. When the system is in unstable state, it will oscillate, make the trigger angle shift, produce harmonic, and make active power and reactive power coupled. Thus, considering the external disturbances introduced by the PLL in VSC-HVDC control system, the parameter perturbations of the controller and the model uncertainties, a H∞ robust controller of mixed sensitivity optimization problem is designed by using the Hinf function provided by the robust control toolbox. Then, compare it with the proportional integral controller through the MATLAB simulation experiment. By contrast, when the H∞ robust controller is added, active and reactive power of the converter station can track the change of reference values more accurately and quickly, and reduce overshoot. When the step change of active and reactive power occurs, mutual influence is reduced and better independent regulation is achieved.

In‐loop flow [11C]CO2 fixation and radiosynthesis of N,N′‐[11C]dibenzylurea

PubMed Central

Downey, Joseph; Bongarzone, Salvatore; Hader, Stefan

2017-01-01

Cyclotron‐produced carbon‐11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon‐11 carbon dioxide ([11C]CO2), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [11C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop‐based system used in 11C‐methylation and 11C‐carboxylation reactions inspired us to apply the [11C]CO2 fixation “in‐loop.” In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop‐based [11C]CO2 fixation method, enabling the fast and efficient, direct‐from‐cyclotron, in‐loop trapping of [11C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof‐of‐concept in‐loop flow radiosynthesis of N,N′‐[11C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio‐HPLC), giving an overall nonisolated radiochemical yield of 72% (decay‐corrected) within just 3 minutes from end of bombardment. This proof‐of‐concept reaction has demonstrated that efficient [11C]CO2 fixation can be achieved in a low‐volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in‐loop flow radiosynthesis of carbon‐11–labelled products. This new in‐loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers. PMID:28977686

OpenGeoSys-GEMS: Hybrid parallelization of a reactive transport code with MPI and threads

NASA Astrophysics Data System (ADS)

Kosakowski, G.; Kulik, D. A.; Shao, H.

2012-04-01

OpenGeoSys-GEMS is a generic purpose reactive transport code based on the operator splitting approach. The code couples the Finite-Element groundwater flow and multi-species transport modules of the OpenGeoSys (OGS) project (http://www.ufz.de/index.php?en=18345) with the GEM-Selektor research package to model thermodynamic equilibrium of aquatic (geo)chemical systems utilizing the Gibbs Energy Minimization approach (http://gems.web.psi.ch/). The combination of OGS and the GEM-Selektor kernel (GEMS3K) is highly flexible due to the object-oriented modular code structures and the well defined (memory based) data exchange modules. Like other reactive transport codes, the practical applicability of OGS-GEMS is often hampered by the long calculation time and large memory requirements. • For realistic geochemical systems which might include dozens of mineral phases and several (non-ideal) solid solutions the time needed to solve the chemical system with GEMS3K may increase exceptionally. • The codes are coupled in a sequential non-iterative loop. In order to keep the accuracy, the time step size is restricted. In combination with a fine spatial discretization the time step size may become very small which increases calculation times drastically even for small 1D problems. • The current version of OGS is not optimized for memory use and the MPI version of OGS does not distribute data between nodes. Even for moderately small 2D problems the number of MPI processes that fit into memory of up-to-date workstations or HPC hardware is limited. One strategy to overcome the above mentioned restrictions of OGS-GEMS is to parallelize the coupled code. For OGS a parallelized version already exists. It is based on a domain decomposition method implemented with MPI and provides a parallel solver for fluid and mass transport processes. In the coupled code, after solving fluid flow and solute transport, geochemical calculations are done in form of a central loop over all finite element nodes with calls to GEMS3K and consecutive calculations of changed material parameters. In a first step the existing MPI implementation was utilized to parallelize this loop. Calculations were split between the MPI processes and afterwards data was synchronized by using MPI communication routines. Furthermore, multi-threaded calculation of the loop was implemented with help of the boost thread library (http://www.boost.org). This implementation provides a flexible environment to distribute calculations between several threads. For each MPI process at least one and up to several dozens of worker threads are spawned. These threads do not replicate the complete OGS-GEM data structure and use only a limited amount of memory. Calculation of the central geochemical loop is shared between all threads. Synchronization between the threads is done by barrier commands. The overall number of local threads times MPI processes should match the number of available computing nodes. The combination of multi-threading and MPI provides an effective and flexible environment to speed up OGS-GEMS calculations while limiting the required memory use. Test calculations on different hardware show that for certain types of applications tremendous speedups are possible.

Comparison of Conventional PCR, Multiplex PCR, and Loop-Mediated Isothermal Amplification Assays for Rapid Detection of Arcobacter Species

PubMed Central

Wang, Xiaoyu; Seo, Dong Joo; Lee, Min Hwa

2014-01-01

This study aimed to develop a loop-mediated isothermal amplification (LAMP) method for the rapid detection of Arcobacter species. Specific primers targeting the 23S ribosomal RNA gene were used to detect Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii. The specificity of the LAMP primer set was assessed using DNA samples from a panel of Arcobacter and Campylobacter species, and the sensitivity was determined using serial dilutions of Arcobacter species cultures. LAMP showed a 10- to 1,000-fold-higher sensitivity than multiplex PCR, with a detection limit of 2 to 20 CFU per reaction in vitro. Whereas multiplex PCR showed cross-reactivity with Campylobacter species, the LAMP method developed in this study was more sensitive and reliable than conventional PCR or multiplex PCR for the detection of Arcobacter species. PMID:24478488

Optimal tracking and second order sliding power control of the DFIG wind turbine

NASA Astrophysics Data System (ADS)

Abdeddaim, S.; Betka, A.; Charrouf, O.

2017-02-01

In the present paper, an optimal operation of a grid-connected variable speed wind turbine equipped with a Doubly Fed Induction Generator (DFIG) is presented. The proposed cascaded nonlinear controller is designed to perform two main objectives. In the outer loop, a maximum power point tracking (MPPT) algorithm based on fuzzy logic theory is designed to permanently extract the optimal aerodynamic energy, whereas in the inner loop, a second order sliding mode control (2-SM) is applied to achieve smooth regulation of both stator active and reactive powers quantities. The obtained simulation results show a permanent track of the MPP point regardless of the turbine power-speed slope moreover the proposed sliding mode control strategy presents attractive features such as chattering-free, compared to the conventional first order sliding technique (1-SM).

A Model-based Approach to Reactive Self-Configuring Systems

NASA Technical Reports Server (NTRS)

Williams, Brian C.; Nayak, P. Pandurang

1996-01-01

This paper describes Livingstone, an implemented kernel for a self-reconfiguring autonomous system, that is reactive and uses component-based declarative models. The paper presents a formal characterization of the representation formalism used in Livingstone, and reports on our experience with the implementation in a variety of domains. Livingstone's representation formalism achieves broad coverage of hybrid software/hardware systems by coupling the concurrent transition system models underlying concurrent reactive languages with the discrete qualitative representations developed in model-based reasoning. We achieve a reactive system that performs significant deductions in the sense/response loop by drawing on our past experience at building fast prepositional conflict-based algorithms for model-based diagnosis, and by framing a model-based configuration manager as a prepositional, conflict-based feedback controller that generates focused, optimal responses. Livingstone automates all these tasks using a single model and a single core deductive engine, thus making significant progress towards achieving a central goal of model-based reasoning. Livingstone, together with the HSTS planning and scheduling engine and the RAPS executive, has been selected as the core autonomy architecture for Deep Space One, the first spacecraft for NASA's New Millennium program.

Comparing Reactivation Behavior of TIG and Laser Beam Welded Alloy 690

NASA Astrophysics Data System (ADS)

Abraham, Geogy J.; Bhambroo, Rajan; Kain, V.; Dey, G. K.; Raja, V. S.

2013-02-01

The nickel base Alloy 690 was subjected to simulated autogenous welding treatment employing two different techniques, laser beam welding (LBW) and tungsten inert gas (TIG) welding. The resultant weld fusion zone (WFZ) and heat-affected zone (HAZ) were compared by studying the reactivation behavior. The chromium depletion effect was assessed by measuring the degree of sensitization (DOS) from the electrochemical potentiodynamic reactivation (EPR) test. A double-loop EPR test for Alloy 690 was employed to measure the DOS at different regions of weldments by masking the remaining regions. The results clearly demonstrated that Alloy 690 showed no sensitization in the parent material and the WFZ region of both TIG and laser weldments. However, it exhibited reactivation in the HAZ region of both the weldments. The DOS values measured for Alloy 690 were very low for all the regions of the LBW weldment as compared to that in the TIG weldment. The HAZ region of the LBW weldment showed the highest DOS value in any region of the weldment but even this value was quite low indicating absence of sensitization in LBW weldment. The attack along the grain boundaries for the weldments after EPR experiments were studied using optical and scanning electron microscopy.

Genealogical correspondence of a forebrain centre implies an executive brain in the protostome–deuterostome bilaterian ancestor

PubMed Central

2016-01-01

Orthologous genes involved in the formation of proteins associated with memory acquisition are similarly expressed in forebrain centres that exhibit similar cognitive properties. These proteins include cAMP-dependent protein kinase A catalytic subunit (PKA-Cα) and phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKII), both required for long-term memory formation which is enriched in rodent hippocampus and insect mushroom bodies, both implicated in allocentric memory and both possessing corresponding neuronal architectures. Antibodies against these proteins resolve forebrain centres, or their equivalents, having the same ground pattern of neuronal organization in species across five phyla. The ground pattern is defined by olfactory or chemosensory afferents supplying systems of parallel fibres of intrinsic neurons intersected by orthogonal domains of afferent and efferent arborizations with local interneurons providing feedback loops. The totality of shared characters implies a deep origin in the protostome–deuterostome bilaterian ancestor of elements of a learning and memory circuit. Proxies for such an ancestral taxon are simple extant bilaterians, particularly acoels that express PKA-Cα and pCaMKII in discrete anterior domains that can be properly referred to as brains. PMID:26598732

Electrochemical insights into the mechanism of NiFe membrane-bound hydrogenases

PubMed Central

Flanagan, Lindsey A.; Parkin, Alison

2016-01-01

Hydrogenases are enzymes of great biotechnological relevance because they catalyse the interconversion of H2, water (protons) and electricity using non-precious metal catalytic active sites. Electrochemical studies into the reactivity of NiFe membrane-bound hydrogenases (MBH) have provided a particularly detailed insight into the reactivity and mechanism of this group of enzymes. Significantly, the control centre for enabling O2 tolerance has been revealed as the electron-transfer relay of FeS clusters, rather than the NiFe bimetallic active site. The present review paper will discuss how electrochemistry results have complemented those obtained from structural and spectroscopic studies, to present a complete picture of our current understanding of NiFe MBH. PMID:26862221

Advancing the Food-Energy-Water Nexus: Closing Nutrient Loops in Arid River Corridors.

PubMed

Mortensen, Jacob G; González-Pinzón, Ricardo; Dahm, Clifford N; Wang, Jingjing; Zeglin, Lydia H; Van Horn, David J

2016-08-16

Closing nutrient loops in terrestrial and aquatic ecosystems is integral to achieve resource security in the food-energy-water (FEW) nexus. We performed multiyear (2005-2008), monthly sampling of instream dissolved inorganic nutrient concentrations (NH4-N, NO3-N, soluble reactive phosphorus-SRP) along a ∼ 300-km arid-land river (Rio Grande, NM) and generated nutrient budgets to investigate how the net source/sink behavior of wastewater and irrigated agriculture can be holistically managed to improve water quality and close nutrient loops. Treated wastewater on average contributed over 90% of the instream dissolved inorganic nutrients (101 kg/day NH4-N, 1097 kg/day NO3-N, 656 kg/day SRP). During growing seasons, the irrigation network downstream of wastewater outfalls retained on average 37% of NO3-N and 45% of SRP inputs, with maximum retention exceeding 60% and 80% of NO3-N and SRP inputs, respectively. Accurate quantification of NH4-N retention was hindered by low loading and high variability. Nutrient retention in the irrigation network and instream processes together limited downstream export during growing seasons, with total retention of 33-99% of NO3-N inputs and 45-99% of SRP inputs. From our synoptic analysis, we identify trade-offs associated with wastewater reuse for agriculture within the scope of the FEW nexus and propose strategies for closing nutrient loops in arid-land rivers.

Epidermal Growth Factor Receptor mediated cellular and subcellular targeted delivery of Iron oxide core-Titanium dioxide shell nanoparticles

NASA Astrophysics Data System (ADS)

Yuan, Ye

TiO2 nanomaterials can carry a multitude of therapeutic and diagnostic agents and the semiconductor properties of TiO2 allow for the production of cytotoxic reactive oxygen species following photoactivation. However, the delivery of these nanomaterials to specific cancer cells and specific subcellular organelles within these cells can have a substantial impact on the efficacy and safety of TiO2 nanoparticle therapeutics. Targeting cell surface receptors that are overexpressed by cancer cells is one strategy to improve the specificity of nanoparticle delivery. Therefore we decided to target the Epidermal Growth Factor Receptor (EGFR) because ligand- binding induces rapid receptor endocytosis and ligand-bound EGFR can translocate to the nucleus of cancer cells. To create NPs that can bind EGFR, we identified a peptide derived from the B-loop of Epidermal Growth Factor (EGF) that has been shown to bind and activate EGFR and conjugated it to the surface of Fe3O4 core-TiO2 shell NPs to produce B-loop NCs. We then devised a pulldown assay to show that B-loop NCs, but not bare NPs or NCs carrying a scrambled B-loop peptide, can bind and extract EGFR from HeLa cell protein extracts. Interestingly, B-loop NCs can also pulldown importin-beta, a protein that can transport EGFR to the nucleus. Furthermore, we used flow cytometry and fluorescently labeled NPs to show that B-loop peptides can significantly improve the internalization of NPs by EGFR-expressing HeLa cells. We determined that B-loop NCs can bind EGFR on the membrane of HeLa cells and that these NCs can be transported to the nucleus, by using a combination of confocal microscopy and X-ray Fluorescence Microscopy (XFM) to indirectly and directly track the subcellular distribution of NCs. Finally, we demonstrate how the Bionanoprobe, a novel high-resolution XFM apparatus that can scan whole-mounted, frozen-hydrated cells at multiple angles can be used to verify the subcellular distribution of B-loop NCs.

Point of care platelet activity measurement in primary PCI [PINPOINT-PPCI]: a protocol paper

PubMed Central

2014-01-01

Background Optimal treatment of acute ST-elevation myocardial infarction (STEMI) involves rapid diagnosis, and transfer to a cardiac centre capable of percutaneous coronary intervention (PCI) for immediate mechanical revascularisation. Successful treatment requires rapid return of perfusion to the myocardium achieved by thromboaspiration, passivation of the culprit lesion with stent scaffolding and systemic inhibition of thrombosis and platelet activation. A delicate balance exists between thrombosis and bleeding and consequently anti-thrombotic and antiplatelet treatment regimens continue to evolve. The desire to achieve reperfusion as soon as possible, in the setting of high platelet reactivity, requires potent and fast-acting anti-thrombotic/anti-platelet therapies. The associated bleeding risk may be minimised by use of short-acting anti-thrombotic intravenous agents. However, effective oral platelet inhibition is required to prevent recurrent thrombosis. The interaction between baseline platelet reactivity, timing of revascularisation and effective inhibition of thrombosis is yet to be formally investigated. Methods/Design We present a protocol for a prospective observational study in patients presenting with acute STEMI treated with primary PCI (PPCI) and receiving bolus/infusion bivalirudin and prasugrel therapy. The objective of this study is to describe variation in platelet reactivity, as measured by the multiplate platelet function analyser, at presentation, the end of the PPCI procedure and 1, 2, & 24 hours post-procedure. We intend to assess the prevalence of high residual platelet reactivity within 24 hours of PPCI in acute STEMI patients receiving prasugrel and bivalirudin. Additionally, we will investigate the association between high platelet reactivity before and after PPCI and the door-to-procedure completion time. This is a single centre study with a target sample size of 108 participants. Discussion The baseline platelet reactivity on presentation with a STEMI may impact on the effect of acute anti-thrombotic and anti-platelet therapy and expose patients to a heightened risk of bleeding or ongoing thrombosis. This study will define the baseline variation in platelet reactivity in a population of patients experiencing acute STEMI and assess the pharmacodynamic response to combined treatment with bivalirudin and prasugrel. The data obtained from this trial will be hypothesis generating for future trials testing alternative pharmacotherapies in the acute phase of treatment for STEMI. Trial registration This study has approval from Wiltshire research ethics committee (10/H0106/87) and is registered with current controlled trials (http://www.controlled-trials.com/ISRCTN82257414). PMID:24708700

Zinc and cadmium complexes of a plant metallothionein under radical stress: desulfurisation reactions associated with the formation of trans-lipids in model membranes.

PubMed

Torreggiani, Armida; Domènech, Jordi; Orihuela, Ruben; Ferreri, Carla; Atrian, Sílvia; Capdevila, Mercè; Chatgilialoglu, Chryssostomos

2009-06-08

Metallothioneins (MTs) are sulfur-rich proteins capable of binding metal ions to give metal clusters. The metal-MT aggregates used in this work were Zn- and Cd-QsMT, where QsMT is an MT from the plant Quercus suber. Reactions of reductive reactive species (H(*) atoms and e(aq)(-)), produced by gamma irradiation of water, with Zn- and Cd-QsMT were carried out in both aqueous solutions and vesicle suspensions, and were characterized by different approaches. By using a biomimetic model based on unsaturated lipid vesicle suspensions, the occurrence of tandem protein/lipid damage was shown. The reactions of reductive reactive species with methionine residues and/or sulfur-containing ligands afford diffusible sulfur-centred radicals, which migrate from the aqueous phase to the lipid bilayer and transform the cis double bond of the oleate moiety into the trans isomer. Tailored experiments allowed the reaction mechanism to be elucidated in some detail. The formation of sulfur-centred radicals is accompanied by the modification of the metal-QsMT complexes, which were monitored by various spectroscopic and spectrometric techniques (Raman, CD, and ESI-MS). Attack of the H(*) atom and e(aq)(-) on the metal-QsMT aggregates can induce significant structural changes such as partial deconstruction and/or rearrangement of the metal clusters and breaking of the protein backbone. Substantial differences were observed in the behaviour of the Zn- and Cd-QsMT aggregates towards the reactive species, depending on the different folding of the polypeptide in these two cases.

Tertiary network in mammalian mitochondrial tRNAAsp revealed by solution probing and phylogeny

PubMed Central

Messmer, Marie; Pütz, Joern; Suzuki, Takeo; Suzuki, Tsutomu; Sauter, Claude; Sissler, Marie; Catherine, Florentz

2009-01-01

Primary and secondary structures of mammalian mitochondrial (mt) tRNAs are divergent from canonical tRNA structures due to highly skewed nucleotide content and large size variability of D- and T-loops. The nonconservation of nucleotides involved in the expected network of tertiary interactions calls into question the rules governing a functional L-shaped three-dimensional (3D) structure. Here, we report the solution structure of human mt-tRNAAsp in its native post-transcriptionally modified form and as an in vitro transcript. Probing performed with nuclease S1, ribonuclease V1, dimethylsulfate, diethylpyrocarbonate and lead, revealed several secondary structures for the in vitro transcribed mt-tRNAAsp including predominantly the cloverleaf. On the contrary, the native tRNAAsp folds into a single cloverleaf structure, highlighting the contribution of the four newly identified post-transcriptional modifications to correct folding. Reactivities of nucleotides and phosphodiester bonds in the native tRNA favor existence of a full set of six classical tertiary interactions between the D-domain and the variable region, forming the core of the 3D structure. Reactivities of D- and T-loop nucleotides support an absence of interactions between these domains. According to multiple sequence alignments and search for conservation of Leontis–Westhof interactions, the tertiary network core building rules apply to all tRNAAsp from mammalian mitochondria. PMID:19767615

Drosophila serpin 4 functions as a neuroserpin-like inhibitor of subtilisin-like proprotein convertases.

PubMed

Osterwalder, Thomas; Kuhnen, Angela; Leiserson, William M; Kim, You-Seung; Keshishian, Haig

2004-06-16

The proteolytic processing of neuropeptide precursors is believed to be regulated by serine proteinase inhibitors, or serpins. Here we describe the molecular cloning and functional expression of a novel member of the serpin family, Serine protease inhibitor 4 (Spn4), that we propose is involved in the regulation of peptide maturation in Drosophila. The Spn4 gene encodes at least two different serpin proteins, generated by alternate splicing of the last coding exon. The closest vertebrate homolog to Spn4 is neuroserpin. Like neuroserpin, one of the Spn4 proteins (Spn4.1) features a unique C-terminal extension, reminiscent of an endoplasmic reticulum (ER) retention signal; however, Spn4.1 and neuroserpin have divergent reactive site loops, with Spn4.1 showing a generic recognition site for furin/SPC1, the founding member of the intracellularly active family of subtilisin-like proprotein convertases (SPCs). In vitro, Spn4.1 forms SDS-stable complexes with the SPC furin and directly inhibits it. When Spn4.1 is overexpressed in specific peptidergic cells of Drosophila larvae, the animals exhibit a phenotype consistent with disrupted neuropeptide processing. This observation, together with the unique combination of an ER-retention signal, a target sequence for SPCs in the reactive site loop, and the in vitro inhibitory activity against furin, strongly suggests that Spn4.1 is an intracellular regulator of SPCs.

Acute liver failure.

PubMed

Slack, Andy; Wendon, Julia

2011-06-01

ALF is a multisystem disorder necessitating both predictive and reactive management strategies to support and protect organs from the initial and subsequent insults encountered. Early referral to a specialist liver centre with the option of liver transplantation is recommended. Furthermore, a good understanding of the poor prognostic variables is necessary to determine those most at risk of developing ALF in order to facilitate timely, safe transfer and listing for liver transplantation.

Principle of Magnetodynamics for Composite Magnetic Pole

NASA Astrophysics Data System (ADS)

Animalu, Alexander

2014-03-01

It is shown in this paper that geometry provides the key to the new magnetodynamics principle of operation of the machine (invented by Dr. Ezekiel Izuogu) which has an unexpected feature of driving a motor with static magnetic field. Essentially, because an array of like magnetic poles of the machine is arranged in a half circular array of a cylindrical geometry, the array creates a non-pointlike magnet pole that may be represented by a ``magnetic current loop'' at the position of the pivot of the movable arm. As a result, in three-dimensional space, it is possible to characterize the symmetry of the stator magnetic field B and the magnetic current loop J as a cube-hexagon system by a 6-vector (J,B) (with J.B ≠0) comprising a 4x4 antisymmetric tensor analogous to the conventional electric and magnetic 6-vector (E,B) (with E.B ≠0) comprising the 4x4 antisymmetric tensor of classical electrodynamics The implications are discussed. Supported by International Centre for Basic Research, Abuja, Nigeria.

Structural basis of ligand recognition in 5-HT3 receptors

PubMed Central

Kesters, Divya; Thompson, Andrew J; Brams, Marijke; van Elk, René; Spurny, Radovan; Geitmann, Matthis; Villalgordo, Jose M; Guskov, Albert; Helena Danielson, U; Lummis, Sarah C R; Smit, August B; Ulens, Chris

2013-01-01

The 5-HT3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation–π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT3 receptor. PMID:23196367

Reactivation of mutant p53: Constraints on mechanism highlighted by principal component analysis of the DNA binding domain.

PubMed

Ouaray, Zahra; ElSawy, Karim M; Lane, David P; Essex, Jonathan W; Verma, Chandra

2016-10-01

Most p53 mutations associated with cancer are located in its DNA binding domain (DBD). Many structures (X-ray and NMR) of this domain are available in the protein data bank (PDB) and a vast conformational heterogeneity characterizes the various free and complexed states. The major difference between the apo and the holo-complexed states appears to lie in the L1 loop. In particular, the conformations of this loop appear to depend intimately on the sequence of DNA to which it binds. This conclusion builds upon recent observations that implicate the tetramerization and the C-terminal domains (respectively TD and Cter) in DNA binding specificity. Detailed PCA analysis of the most recent collection of DBD structures from the PDB have been carried out. In contrast to recommendations that small molecules/drugs stabilize the flexible L1 loop to rescue mutant p53, our study highlights a need to retain the flexibility of the p53 DNA binding surface (DBS). It is the adaptability of this region that enables p53 to engage in the diverse interactions responsible for its functionality. Proteins 2016; 84:1443-1461. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

PREFACE: Loops 11: Non-Perturbative / Background Independent Quantum Gravity

NASA Astrophysics Data System (ADS)

Mena Marugán, Guillermo A.; Barbero G, J. Fernando; Garay, Luis J.; Villaseñor, Eduardo J. S.; Olmedo, Javier

2012-05-01

Loops 11 The international conference LOOPS'11 took place in Madrid from the 23-28 May 2011. It was hosted by the Instituto de Estructura de la Materia (IEM), which belongs to the Consejo Superior de Investigaciones Cientĺficas (CSIC). Like previous editions of the LOOPS meetings, it dealt with a wealth of state-of-the-art topics on Quantum Gravity, with special emphasis on non-perturbative background-independent approaches to spacetime quantization. The main topics addressed at the conference ranged from the foundations of Quantum Gravity to its phenomenological aspects. They encompassed different approaches to Loop Quantum Gravity and Cosmology, Polymer Quantization, Quantum Field Theory, Black Holes, and discrete approaches such as Dynamical Triangulations, amongst others. In addition, this edition celebrated the 25th anniversary of the introduction of the now well-known Ashtekar variables and the Wednesday morning session was devoted to this silver jubilee. The structure of the conference was designed to reflect the current state and future prospects of research on the different topics mentioned above. Plenary lectures that provided general background and the 'big picture' took place during the mornings, and the more specialised talks were distributed in parallel sessions during the evenings. To be more specific, Monday evening was devoted to Shape Dynamics and Phenomenology Derived from Quantum Gravity in Parallel Session A, and to Covariant Loop Quantum Gravity and Spin foams in Parallel Session B. Tuesday's three Parallel Sessions dealt with Black Hole Physics and Dynamical Triangulations (Session A), the continuation of Monday's session on Covariant Loop Quantum Gravity and Spin foams (Session B) and Foundations of Quantum Gravity (Session C). Finally, Thursday and Friday evenings were devoted to Loop Quantum Cosmology (Session A) and to Hamiltonian Loop Quantum Gravity (Session B). The result of the conference was very satisfactory and enlightening. Not only was it a showroom for the research currently being carried out by many groups throughout the world, but there was also a permanent look towards the future. During these days, the CSIC Campus witnessed many scientific conversations triggered by the interaction amongst the people and groups that participated in LOOPS'11 Madrid and which, in many cases, will crystallise into new results and advances in the field. The conference would not have been possible without the generous help of a number of national and international institutions. The organizers would like to acknowledge the financial support provided by the Spanish Ministry of Science and Innovation (Ministerio de Ciencia e Innovación), the Spanish Research Council, CSIC (Consejo Superior de Investigaciones Cientĺficas), The BBVA Foundation (Fundación BBVA), The CONSOLIDER-CPAN project, the Spanish Society for Gravitation and Relativity (SEGRE), The Universidad Carlos III of Madrid (UC3M), and the European Science Foundation (ESF). The ESF, through the Quantum Gravity and Quantum Geometry network, provided full support for a number of young participants that have contributed to these proceedings: Dario Benedetti (Albert Einstein Institute, Potsdam, Germany), Norbert Bodendorfer (Institute for Theoretical Physics III, FAU Erlangen Nürnberg, Germany), Mariam Bouhmadi López (CENTRA, Centro Multidisciplinar de Astrofĺsica, Lisbon), Timothy Budd (Institute for Theoretical Physics, Utrecht University, The Netherlands), Miguel Campiglia (Institute for Gravitation and the Cosmos, Penn State University, USA), Gianluca Delfino (School of Mathematical Sciences, University of Nottingham, UK), Maite Dupuis (Institute for Theoretical Physics III, FAU Erlangen Nürnberg, Germany), Michał Dziendzikowski (Institute of Theoretical Physics, Warsaw University, Poland), Muxin Han (Centre de Physique Théorique de Luminy, Marseille, France), Philipp Höhn (Institute for Theoretical Physics, Utrecht University, The Netherlands), Jacek Puchta (Centre de Physique Théorique de Luminy, Marseille, France), James Ryan (Albert Einstein Institute, Potsdam, Germany), Lorenzo Sindoni (Albert Einstein Institute, Golm, Germany), David Sloan (Institute for Theoretical Physics, Utrecht University, The Netherlands), Johannes Tambornino (Laboratoire de Physique, ENS Lyon, France), Andreas Thurn (Institute for Theoretical Physics III, FAU Erlangen Nürnberg, Germany), Francesca Vidotto (Laboratoire de Physique Subatomique et de Cosmologie, Grenoble, France), and Matteo Smerlak (Albert Einstein Institute, Golm, Germany). We would like to conclude this preamble by thanking all the attendants of the conference for their high and enthusiastic participation. The presence of a large number of past and present Loop Quantum Gravity practitioners, as well as a significant number of top researchers in other approaches to quantum gravity, provided ample opportunities for fruitful scientific exchanges and a very lively atmosphere. It is encouraging to see that, 25 years after the inception of Loop Quantum Gravity, there is a vibrant young community of researchers entering the field. Let us hope that, with their help, the quantization of general relativity can be successfully accomplished in the near future. The Editors Conference photograph

A DFT study of the mechanism and the regioselectivity of [3 + 2] cycloaddition reactions of nitrile oxides with α,β-acetylenic aldehyde

NASA Astrophysics Data System (ADS)

Sobhi, Chafia; Nacereddine, Abdelmalek Khorief; Nasri, Lilia; Lechtar, Zohra; Djerourou, Abdelhafid

2016-11-01

A DFT study of the (32CA) reaction of a series of some nitrile oxides with electron-deficient alkyne (3-phenylpropionlaldehyde) in gas phase and in toluene has been carried out using B3LYP functional with 6-31G(d) basis set. Two reactive channels 4- and 5-associated with the two regioisomeric modes have been located and characterised. These 32CA reactions are characterised by a low asynchronous one-step mechanism with a low-polar character. Analysis of the DFT reactivity indices indicates that the nucleophilic centre of the different nitrile oxides accounts for the 4-regioselectivity. Our calculations are in a good agreement with the experimental findings.

Development of a Small Molecule P2X7R Antagonist as a Treatment for Acute SCI

DTIC Science & Technology

2013-10-01

microglia in response to SCI, and of the role of P2X7 receptor activation in that process . Indeed, in parallel work using uninjured human brain tissue...distinct glial fates are instructed, and how that process may be manipulated for therapeutic purposes. Thus, on the basis of the injury-associated...autocrine loop for the self -maintenance of glial progenitors, the perturbation of which might dictate progenitor recruitment as either reactive glia or

Exchange coupled CoPd/TbCo magneto-optic storage films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gambino, R.J.; Ruf, R.R.; Rishi, R.

1989-09-01

Films of CoPd with weak perpendicular anisotropy are shown to exchange couple to square loop TbCo films on both the Tb and Co sides of compensation. The exchange is sensitive to reactive impurities at the interface and is broken under conditions that produce as little as one monolayer of paramagnetic compound. Even when the coupling at the interface is strong, the authors show that only a limited thickness of the CoPd layer is spin oriented perpendicular.

Prostate Specific Expression of Maspin in a Transgenic Mouse Model: Implications in Prostate Carcinogenesis

DTIC Science & Technology

2004-05-01

should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. 20050603 257 r...such material. Where material from documents designated for limited distribution is quoted, permission has been obtained to use the material...amino acid peptide located in the reactive site loop of maspin, a region designated as AbS4A. The antibody was purified using an AbS4A sulfo-linked

Simplest bifurcation diagrams for monotone families of vector fields on a torus

NASA Astrophysics Data System (ADS)

Baesens, C.; MacKay, R. S.

2018-06-01

In part 1, we prove that the bifurcation diagram for a monotone two-parameter family of vector fields on a torus has to be at least as complicated as the conjectured simplest one proposed in Baesens et al (1991 Physica D 49 387–475). To achieve this, we define ‘simplest’ by sequentially minimising the numbers of equilibria, Bogdanov–Takens points, closed curves of centre and of neutral saddle, intersections of curves of centre and neutral saddle, Reeb components, other invariant annuli, arcs of rotational homoclinic bifurcation of horizontal homotopy type, necklace points, contractible periodic orbits, points of neutral horizontal homoclinic bifurcation and half-plane fan points. We obtain two types of simplest case, including that initially proposed. In part 2, we analyse the bifurcation diagram for an explicit monotone family of vector fields on a torus and prove that it has at most two equilibria, precisely four Bogdanov–Takens points, no closed curves of centre nor closed curves of neutral saddle, at most two Reeb components, precisely four arcs of rotational homoclinic connection of ‘horizontal’ homotopy type, eight horizontal saddle-node loop points, two necklace points, four points of neutral horizontal homoclinic connection, and two half-plane fan points, and there is no simultaneous existence of centre and neutral saddle, nor contractible homoclinic connection to a neutral saddle. Furthermore, we prove that all saddle-nodes, Bogdanov–Takens points, non-neutral and neutral horizontal homoclinic bifurcations are non-degenerate and the Hopf condition is satisfied for all centres. We also find it has four points of degenerate Hopf bifurcation. It thus provides an example of a family satisfying all the assumptions of part 1 except the one of at most one contractible periodic orbit.

Real-Time In Vivo Monitoring of Reactive Oxygen Species in Guard Cells.

PubMed

Park, Ky Young; Roubelakis-Angelakis, Kalliopi A

2018-01-01

The intra-/intercellular homeostasis of reactive oxygen species (ROS), and especially of superoxides (O 2 .- ) and hydrogen peroxide (O 2 .- ) participate in signalling cascades which dictate developmental processes and reactions to biotic/abiotic stresses. Polyamine oxidases terminally oxidize/back convert polyamines generating H 2 O 2 . Recently, an NADPH-oxidase/Polyamine oxidase feedback loop was identified to control oxidative burst under salinity. Thus, the real-time localization/monitoring of ROS in specific cells, such as the guard cells, can be of great interest. Here we present a detailed description of the real-time in vivo monitoring of ROS in the guard cells using H 2 O 2 - and O 2 .- specific fluorescing probes, which can be used for studying ROS accumulation generated from any source, including the amine oxidases-dependent pathway, during development and stress.

Automated startup of the MIT research reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwok, K.S.

1992-01-01

This summary describes the development, implementation, and testing of a generic method for performing automated startups of nuclear reactors described by space-independent kinetics under conditions of closed-loop digital control. The technique entails first obtaining a reliable estimate of the reactor's initial degree of subcriticality and then substituting that estimate into a model-based control law so as to permit a power increase from subcritical on a demanded trajectory. The estimation of subcriticality is accomplished by application of the perturbed reactivity method. The shutdown reactor is perturbed by the insertion of reactivity at a known rate. Observation of the resulting period permitsmore » determination of the initial degree of subcriticality. A major advantage to this method is that repeated estimates are obtained of the same quantity. Hence, statistical methods can be applied to improve the quality of the calculation.« less

Testing of an Integrated Reactor Core Simulator and Power Conversion System with Simulated Reactivity Feedback

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Hervol, David S.; Godfroy, Thomas J.

2009-01-01

A Direct Drive Gas-Cooled (DDG) reactor core simulator has been coupled to a Brayton Power Conversion Unit (BPCU) for integrated system testing at NASA Glenn Research Center (GRC) in Cleveland, OH. This is a closed-cycle system that incorporates an electrically heated reactor core module, turbo alternator, recuperator, and gas cooler. Nuclear fuel elements in the gas-cooled reactor design are replaced with electric resistance heaters to simulate the heat from nuclear fuel in the corresponding fast spectrum nuclear reactor. The thermodynamic transient behavior of the integrated system was the focus of this test series. In order to better mimic the integrated response of the nuclear-fueled system, a simulated reactivity feedback control loop was implemented. Core power was controlled by a point kinetics model in which the reactivity feedback was based on core temperature measurements; the neutron generation time and the temperature feedback coefficient are provided as model inputs. These dynamic system response tests demonstrate the overall capability of a non-nuclear test facility in assessing system integration issues and characterizing integrated system response times and response characteristics.

Testing of an Integrated Reactor Core Simulator and Power Conversion System with Simulated Reactivity Feedback

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Hervol, David S.; Godfroy, Thomas J.

2010-01-01

A Direct Drive Gas-Cooled (DDG) reactor core simulator has been coupled to a Brayton Power Conversion Unit (BPCU) for integrated system testing at NASA Glenn Research Center (GRC) in Cleveland, Ohio. This is a closed-cycle system that incorporates an electrically heated reactor core module, turboalternator, recuperator, and gas cooler. Nuclear fuel elements in the gas-cooled reactor design are replaced with electric resistance heaters to simulate the heat from nuclear fuel in the corresponding fast spectrum nuclear reactor. The thermodynamic transient behavior of the integrated system was the focus of this test series. In order to better mimic the integrated response of the nuclear-fueled system, a simulated reactivity feedback control loop was implemented. Core power was controlled by a point kinetics model in which the reactivity feedback was based on core temperature measurements; the neutron generation time and the temperature feedback coefficient are provided as model inputs. These dynamic system response tests demonstrate the overall capability of a non-nuclear test facility in assessing system integration issues and characterizing integrated system response times and response characteristics.

Safer one-pot synthesis of the ‘SHAPE’ reagent 1-methyl-7-nitroisatoic anhydride (1m7)

PubMed Central

Turner, Rushia; Shefer, Kinneret; Ares, Manuel

2013-01-01

Estimating the reactivity of 2′-hydroxyl groups along an RNA chain of interest aids in the modeling of the folded RNA structure; flexible loops tend to be reactive, whereas duplex regions are generally not. Among the most useful reagents for probing 2′-hydroxyl reactivity is 1-methyl-7-nitroisatoic anhydride (1m7), but the absence of a reliable, inexpensive source has prevented widespread adoption. An existing protocol for the conversion of an inexpensive precursor 4-nitroisatoic anhydride (4NIA) recommends the use of NaH in dimethylformamide (DMF), a reagent combination that most molecular biology labs are not equipped to handle, and that does not scale safely in any case. Here we describe a safer, one-pot method for bulk conversion of 4NIA to 1m7 that reduces costs and bypasses the use of NaH. We show that 1m7 produced by this method is free of side products and can be used to probe RNA structure in vitro. PMID:24141619

Proximity vs. strain in intramolecular ring-closing reactions

NASA Astrophysics Data System (ADS)

Karaman, Rafik

2010-07-01

The DFT and ab initio calculation results for ring-closing reactions of eight different ω-bromoalkanecarboxylate anions (1-8) reveal that the activation energy (ΔG ‡) for the intramolecular cyclization process is strongly correlated with both (i) the experimental intramolecular cyclization rate (log k intra) and (ii) the distance between the two reactive centres, whereas the slope values of the change in enthalpy (ΔH) vs. the attack angle (α) and the distance between the two reacting centres (r) were found to correlate strongly with the experimental strain energy of the cycle being formed (E s Exp). These results assist in designing pro-prodrug systems that can be utilized to improve the overall biopharmaceutical profile of current medications in order to enhance their effectiveness and ease their utility.

The Dynamics of the Human Leukocyte Antigen Head Domain Modulates Its Recognition by the T-Cell Receptor.

PubMed

García-Guerrero, Estefanía; Pérez-Simón, José Antonio; Sánchez-Abarca, Luis Ignacio; Díaz-Moreno, Irene; De la Rosa, Miguel A; Díaz-Quintana, Antonio

2016-01-01

Generating the immune response requires the discrimination of peptides presented by the human leukocyte antigen complex (HLA) through the T-cell receptor (TCR). However, how a single amino acid substitution in the antigen bonded to HLA affects the response of T cells remains uncertain. Hence, we used molecular dynamics computations to analyze the molecular interactions between peptides, HLA and TCR. We compared immunologically reactive complexes with non-reactive and weakly reactive complexes. MD trajectories were produced to simulate the behavior of isolated components of the various p-HLA-TCR complexes. Analysis of the fluctuations showed that p-HLA binding barely restrains TCR motions, and mainly affects the CDR3 loops. Conversely, inactive p-HLA complexes displayed significant drop in their dynamics when compared with its free versus ternary forms (p-HLA-TCR). In agreement, the free non-reactive p-HLA complexes showed a lower amount of salt bridges than the responsive ones. This resulted in differences between the electrostatic potentials of reactive and inactive p-HLA species and larger vibrational entropies in non-elicitor complexes. Analysis of the ternary p-HLA-TCR complexes also revealed a larger number of salt bridges in the responsive complexes. To summarize, our computations indicate that the affinity of each p-HLA complex towards TCR is intimately linked to both, the dynamics of its free species and its ability to form specific intermolecular salt-bridges in the ternary complexes. Of outstanding interest is the emerging concept of antigen reactivity involving its interplay with the HLA head sidechain dynamics by rearranging its salt-bridges.

Influence of high-temperature steam on the reactivity of CaO sorbent for CO₂ capture.

PubMed

Donat, Felix; Florin, Nicholas H; Anthony, Edward J; Fennell, Paul S

2012-01-17

Calcium looping is a high-temperature CO(2) capture technology applicable to the postcombustion capture of CO(2) from power station flue gas, or integrated with fuel conversion in precombustion CO(2) capture schemes. The capture technology uses solid CaO sorbent derived from natural limestone and takes advantage of the reversible reaction between CaO and CO(2) to form CaCO(3); that is, to achieve the separation of CO(2) from flue or fuel gas, and produce a pure stream of CO(2) suitable for geological storage. An important characteristic of the sorbent, affecting the cost-efficiency of this technology, is the decay in reactivity of the sorbent over multiple CO(2) capture-and-release cycles. This work reports on the influence of high-temperature steam, which will be present in flue (about 5-10%) and fuel (∼20%) gases, on the reactivity of CaO sorbent derived from four natural limestones. A significant increase in the reactivity of these sorbents was found for 30 cycles in the presence of steam (from 1-20%). Steam influences the sorbent reactivity in two ways. Steam present during calcination promotes sintering that produces a sorbent morphology with most of the pore volume associated with larger pores of ∼50 nm in diameter, and which appears to be relatively more stable than the pore structure that evolves when no steam is present. The presence of steam during carbonation reduces the diffusion resistance during carbonation. We observed a synergistic effect, i.e., the highest reactivity was observed when steam was present for both calcination and carbonation.

Atypical profiles and modulations of heme-enzymes catalyzed outcomes by low amounts of diverse additives suggest diffusible radicals' obligatory involvement in such redox reactions.

PubMed

Manoj, Kelath Murali; Parashar, Abhinav; Venkatachalam, Avanthika; Goyal, Sahil; Satyalipsu; Singh, Preeti Gunjan; Gade, Sudeep K; Periyasami, Kalaiselvi; Jacob, Reeba Susan; Sardar, Debosmita; Singh, Shanikant; Kumar, Rajan; Gideon, Daniel A

2016-06-01

Peroxidations mediated by heme-enzymes have been traditionally studied under a single-site (heme distal pocket), non-sequential (ping-pong), two-substrates binding scheme of Michaelis-Menten paradigm. We had reported unusual modulations of peroxidase and P450 reaction outcomes and explained it invoking diffusible reactive species [Manoj, 2006; Manoj et al., 2010; Andrew et al., 2011, Parashar et al., 2014 & Venkatachalam et al., 2016]. A systematic investigation of specific product formation rates was undertaken to probe the hypothesis that involvement of diffusible reactive species could explain undefined substrate specificities and maverick modulations (sponsored by additives) of heme-enzymes. When the rate of specific product formation was studied as a function of reactants' concentration or environmental conditions, we noted marked deviations from normal profiles. We report that heme-enzyme mediated peroxidations of various substrates are inhibited (or activated) by sub-equivalent concentrations of diverse redox-active additives and this is owing to multiple redox equilibriums in the milieu. At low enzyme and peroxide concentrations, the enzyme is seen to recycle via a one-electron (oxidase) cycle, which does not require the substrate to access the heme centre. Schemes are provided that explain the complex mechanistic cycle, kinetics & stoichiometry. It is not obligatory for an inhibitor or substrate to interact with the heme centre for influencing overall catalysis. Roles of diffusible reactive species explain catalytic outcomes at low enzyme and reactant concentrations. The current work highlights the scope/importance of redox enzyme reactions that could occur "out of the active site" in biological or in situ systems. Copyright © 2016 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

Nucleic acid testing: Is it the only answer for safe Blood in India?

PubMed Central

Naidu, N. K.; Bharucha, Z. S.; Sonawane, Vandana; Ahmed, Imran

2016-01-01

Background: With the implementation of NAT in countries around the world, there is a growing pressure on the transfusion services in India to adopt NAT testing. India has about 2545 licensed Blood Centres. The Transfusion Services in India are fragmented, poorly regulated and the quality standards are poorly implemented. Blood Centres are still dependent on replacement/family donors and in most places laboratory testing for Transfusion transmitted infections is not quality assured, laboratory equipment are not calibrated and maintained, and validation of results is not carried out. Against the current scenario introducing NAT for screening of blood donors in India would pose a challenge. Aim: To study the prudence of universal NAT testing in India. Materials and Methods: A retrospective study of 5 years from 2008-2012 was undertaken to study the true reactivity of donors using WHO strategy II and III and therefore the true seroprevalence of TTI infections in the donor populations. Results: The true reactivity of the donors was much less as compared to the initially reactive donors due to the use of a well designed testing algorithm. In addition having a total voluntary blood collection along with good pre-donation counseling program also reduces the transmission of infections. Conclusions: What India essentially needs to do is religiously implement the strategies outlined in the WHO Aide-memoire. The blood should be collected only from voluntary non remunerative and repeat donors, there should be stringent donor selection with pre-donation counseling instituted. Strict implementation of quality management system, development of well defined testing startegies and strong haemovigilance system could take us a step in the right direction. PMID:27011677

Virtual solar field - An opportunity to optimize transient processes in line-focus CSP power plants

NASA Astrophysics Data System (ADS)

Noureldin, Kareem; Hirsch, Tobias; Pitz-Paal, Robert

2017-06-01

Optimizing solar field operation and control is a key factor to improve the competitiveness of line-focus solar thermal power plants. However, the risks of assessing new and innovative control strategies on operational power plants hinder such optimizations and result in applying more conservative control schemes. In this paper, we describe some applications for a whole solar field transient in-house simulation tool developed at the German Aerospace Centre (DLR), the Virtual Solar Field (VSF). The tool offers a virtual platform to simulate real solar fields while coupling the thermal and hydraulic conditions of the field with high computational efficiency. Using the tool, developers and operator can probe their control strategies and assess the potential benefits while avoiding the high risks and costs. In this paper, we study the benefits gained from controlling the loop valves and of using direct normal irradiance maps and forecasts for the field control. Loop valve control is interesting for many solar field operators since it provides a high degree of flexibility to the control of the solar field through regulating the flow rate in each loop. This improves the reaction to transient condition, such as passing clouds and field start-up in the morning. Nevertheless, due to the large number of loops and the sensitivity of the field control to the valve settings, this process needs to be automated and the effect of changing the setting of each valve on the whole field control needs to be taken into account. We used VSF to implement simple control algorithms to control the loop valves and to study the benefits that could be gained from using active loop valve control during transient conditions. Secondly, we study how using short-term highly spatially-resolved DNI forecasts provided by cloud cameras could improve the plant energy yield. Both cases show an improvement in the plant efficiency and outlet temperature stability. This paves the road for further investigations of new control strategies or for optimizations of the currently implemented ones.

Pre-T Cell Receptors (Pre-TCRs) Leverage Vβ Complementarity Determining Regions (CDRs) and Hydrophobic Patch in Mechanosensing Thymic Self-ligands.

PubMed

Das, Dibyendu Kumar; Mallis, Robert J; Duke-Cohan, Jonathan S; Hussey, Rebecca E; Tetteh, Paul W; Hilton, Mark; Wagner, Gerhard; Lang, Matthew J; Reinherz, Ellis L

2016-12-02

The pre-T cell receptor (pre-TCR) is a pTα-β heterodimer functioning in early αβ T cell development. Although once thought to be ligand-autonomous, recent studies show that pre-TCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe pre-TCR bonding with pMHC at the single molecule level. Like the αβTCR, the pre-TCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes and exploiting allosteric control regulated via the Cβ FG loop region. The pre-TCR structural transitions exhibit greater reversibility than TCRαβ and ordered force-bond lifetime curves. Higher piconewton force requires binding through both complementarity determining region loops and hydrophobic Vβ patch apposition. This patch functions in the pre-TCR as a surrogate Vα domain, fostering ligand promiscuity to favor development of β chains with self-reactivity but is occluded by α subunit replacement of pTα upon αβTCR formation. At the double negative 3 thymocyte stage where the pre-TCR is first expressed, pre-TCR interaction with self-pMHC ligands imparts growth and survival advantages as revealed in thymic stromal cultures, imprinting fundamental self-reactivity in the T cell repertoire. Collectively, our data imply the existence of sequential mechanosensor αβTCR repertoire tuning via the pre-TCR. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Antagonistic Basic Helix-Loop-Helix/bZIP Transcription Factors Form Transcriptional Modules That Integrate Light and Reactive Oxygen Species Signaling in Arabidopsis[W

PubMed Central

Chen, Dongqin; Xu, Gang; Tang, Weijiang; Jing, Yanjun; Ji, Qiang; Fei, Zhangjun; Lin, Rongcheng

2013-01-01

The critical developmental switch from heterotrophic to autotrophic growth of plants involves light signaling transduction and the production of reactive oxygen species (ROS). ROS function as signaling molecules that regulate multiple developmental processes, including cell death. However, the relationship between light and ROS signaling remains unclear. Here, we identify transcriptional modules composed of the basic helix-loop-helix and bZIP transcription factors PHYTOCHROME-INTERACTING FACTOR1 (PIF1), PIF3, ELONGATED HYPOCOTYL5 (HY5), and HY5 HOMOLOGY (HYH) that bridge light and ROS signaling to regulate cell death and photooxidative response. We show that pif mutants release more singlet oxygen and exhibit more extensive cell death than the wild type during Arabidopsis thaliana deetiolation. Genome-wide expression profiling indicates that PIF1 represses numerous ROS and stress-related genes. Molecular and biochemical analyses reveal that PIF1/PIF3 and HY5/HYH physically interact and coordinately regulate the expression of five ROS-responsive genes by directly binding to their promoters. Furthermore, PIF1/PIF3 and HY5/HYH function antagonistically during the seedling greening process. In addition, phytochromes, cryptochromes, and CONSTITUTIVE PHOTOMORPHOGENIC1 act upstream to regulate ROS signaling. Together, this study reveals that the PIF1/PIF3-HY5/HYH transcriptional modules mediate crosstalk between light and ROS signaling and sheds light on a new mechanism by which plants adapt to the light environments. PMID:23645630

Pre-T Cell Receptors (Pre-TCRs) Leverage Vβ Complementarity Determining Regions (CDRs) and Hydrophobic Patch in Mechanosensing Thymic Self-ligands*♦

PubMed Central

Das, Dibyendu Kumar; Mallis, Robert J.; Duke-Cohan, Jonathan S.; Hussey, Rebecca E.; Tetteh, Paul W.; Hilton, Mark; Wagner, Gerhard; Lang, Matthew J.; Reinherz, Ellis L.

2016-01-01

The pre-T cell receptor (pre-TCR) is a pTα-β heterodimer functioning in early αβ T cell development. Although once thought to be ligand-autonomous, recent studies show that pre-TCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe pre-TCR bonding with pMHC at the single molecule level. Like the αβTCR, the pre-TCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes and exploiting allosteric control regulated via the Cβ FG loop region. The pre-TCR structural transitions exhibit greater reversibility than TCRαβ and ordered force-bond lifetime curves. Higher piconewton force requires binding through both complementarity determining region loops and hydrophobic Vβ patch apposition. This patch functions in the pre-TCR as a surrogate Vα domain, fostering ligand promiscuity to favor development of β chains with self-reactivity but is occluded by α subunit replacement of pTα upon αβTCR formation. At the double negative 3 thymocyte stage where the pre-TCR is first expressed, pre-TCR interaction with self-pMHC ligands imparts growth and survival advantages as revealed in thymic stromal cultures, imprinting fundamental self-reactivity in the T cell repertoire. Collectively, our data imply the existence of sequential mechanosensor αβTCR repertoire tuning via the pre-TCR. PMID:27707880

Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families

PubMed Central

Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A.; Turjanski, Adrián G.

2015-01-01

Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes. However, cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species, leading to a loss of their catalytic function. Therefore, cysteine oxidation is emerging as a relevant physiological regulatory mechanism. Formation of a cyclic sulfenyl amide residue at the active site of redox-regulated proteins has been proposed as a protection mechanism against irreversible oxidation as the sulfenyl amide intermediate has been identified in several proteins. However, how and why only some specific cysteine residues in particular proteins react to form this intermediate is still unknown. In the present work using in-silico based tools, we have identified a constrained conformation that accelerates sulfenyl amide formation. By means of combined MD and QM/MM calculation we show that this conformation positions the NH backbone towards the sulfenic acid and promotes the reaction to yield the sulfenyl amide intermediate, in one step with the concomitant release of a water molecule. Moreover, in a large subset of the proteins we found a conserved beta sheet-loop-helix motif, which is present across different protein folds, that is key for sulfenyl amide production as it promotes the previous formation of sulfenic acid. For catalytic activity, in several cases, proteins need the Cysteine to be in the cysteinate form, i.e. a low pKa Cys. We found that the conserved motif stabilizes the cysteinate by hydrogen bonding to several NH backbone moieties. As cysteinate is also more reactive toward ROS we propose that the sheet-loop-helix motif and the constraint conformation have been selected by evolution for proteins that need a reactive Cys protected from irreversible oxidation. Our results also highlight how fold conservation can be correlated to redox chemistry regulation of protein function. PMID:25741692

Aerosol Liquid Water Driven by Anthropogenic inorganic salts: Playing a key role in the winter haze formation over North China Plain

NASA Astrophysics Data System (ADS)

Wu, Z.; Liu, Y.; Tan, T.; Wang, Y.; Shang, D.; Xiao, Y.; Li, M.; Zeng, L.; Hu, M.

2017-12-01

Aerosol liquid water influences ambient particulate matter mass concentrations and aerosol optical properties, and can serve as a reactor for multiphase reactions that perturb local photochemistry1. Our observations revealed that ambient relative humidity, inorganic fraction (sulfate, ammonium, nitrate), and PM2.5 mass concentration generally simultaneously elevated during haze episodes, resulting in the abundant anthropogenic aerosol water in the atmosphere of Beijing. The enrichment of aerosol liquid water may significantly affect the particle phase, which plays a key role in determining the reactive uptake, gas-particle partitioning, and heterogeneous chemical reactivity2. A newly-built three-arm impactor was used to detect the particle rebound fraction. The observations showed the increased RH and inorganic-rich particulate matter led to an increased aerosol liquid water content, and thus a liquid phase state during haze episode during wintertime. Here, we proposed that the transition to a liquid phase state marked the beginning of the haze episode and kicked off a positive feedback loop, wherein the liquid particles readily uptake pollutants that could react to form inorganics which could then uptake more water. The strict controlling strategy of sulfur emissions in China might lead to a decreased sulfate fraction and increased nitrate fraction in PM1. As a result, due to the lower deliquescence RH of nitrate, the feedback loop proposed could start at an even lower RH in the future. Reference1 Herrmann, H., T. Schaefer, A. Tilgner, S. A. Styler, C. Weller, M. Teich, and T. Otto (2015), Tropospheric Aqueous-Phase Chemistry: Kinetics, Mechanisms, and Its Coupling to a Changing Gas Phase, Chemical Reviews, 115(10), 4259-4334.2 M. Kuwata, S. T. Martin (2012), Phase of atmospheric secondary organic material affects its reactivity, Proceedings of the National Academy of Sciences of the United States of America, 109(43):17354-17359

Trauma teams and time to early management during in situ trauma team training

PubMed Central

Härgestam, Maria; Lindkvist, Marie; Jacobsson, Maritha; Brulin, Christine

2016-01-01

Objectives To investigate the association between the time taken to make a decision to go to surgery and gender, ethnicity, years in profession, experience of trauma team training, experience of structured trauma courses and trauma in the trauma team, as well as use of closed-loop communication and leadership styles during trauma team training. Design In situ trauma team training. The patient simulator was preprogrammed to represent a severely injured patient (injury severity score: 25) suffering from hypovolemia due to external trauma. Setting An emergency room in an urban Scandinavian level one trauma centre. Participants A total of 96 participants were divided into 16 trauma teams. Each team consisted of six team members: one surgeon/emergency physician (designated team leader), one anaesthesiologist, one registered nurse anaesthetist, one registered nurse from the emergency department, one enrolled nurse from the emergency department and one enrolled nurse from the operating theatre. Primary outcome HRs with CIs (95% CI) for the time taken to make a decision to go to surgery was computed from a Cox proportional hazards model. Results Three variables remained significant in the final model. Closed-loop communication initiated by the team leader increased the chance of a decision to go to surgery (HR: 3.88; CI 1.02 to 14.69). Only 8 of the 16 teams made the decision to go to surgery within the timeframe of the trauma team training. Conversely, call-outs and closed-loop communication initiated by the team members significantly decreased the chance of a decision to go to surgery, (HR: 0.82; CI 0.71 to 0.96, and HR: 0.23; CI 0.08 to 0.71, respectively). Conclusions Closed-loop communication initiated by the leader appears to be beneficial for teamwork. In contrast, a high number of call-outs and closed-loop communication initiated by team members might lead to a communication overload. PMID:26826152

Differential Targeting of Unpaired Bases within Duplex DNA by the Natural Compound Clerocidin: A Valuable Tool to Dissect DNA Secondary Structure

PubMed Central

Nadai, Matteo; Palù, Giorgio; Palumbo, Manlio; Richter, Sara N.

2012-01-01

Non-canonical DNA structures have been postulated to mediate protein-nucleic acid interactions and to function as intermediates in the generation of frame-shift mutations when errors in DNA replication occur, which result in a variety of diseases and cancers. Compounds capable of binding to non-canonical DNA conformations may thus have significant diagnostic and therapeutic potential. Clerocidin is a natural diterpenoid which has been shown to selectively react with single-stranded bases without targeting the double helix. Here we performed a comprehensive analysis on several non-canonical DNA secondary structures, namely mismatches, nicks, bulges, hairpins, with sequence variations in both the single-stranded region and the double-stranded flanking segment. By analysis of clerocidin reactivity, we were able to identify the exposed reactive residues which provided information on both the secondary structure and the accessibility of the non-paired sites. Mismatches longer than 1 base were necessary to be reached by clerocidin reactive groups, while 1-base nicks were promptly targeted by clerocidin; in hairpins, clerocidin reactivity increased with the length of the hairpin loop, while, interestingly, reactivity towards bulges reached a maximum in 3-base-long bulges and declined in longer bulges. Electrophoretic mobility shift analysis demonstrated that bulges longer than 3 bases (i.e. 5- and 7-bases) folded or stacked on the duplex region therefore being less accessible by the compound. Clerocidin thus represents a new valuable diagnostic tool to dissect DNA secondary structures. PMID:23285245

Differential targeting of unpaired bases within duplex DNA by the natural compound clerocidin: a valuable tool to dissect DNA secondary structure.

PubMed

Nadai, Matteo; Palù, Giorgio; Palumbo, Manlio; Richter, Sara N

2012-01-01

Non-canonical DNA structures have been postulated to mediate protein-nucleic acid interactions and to function as intermediates in the generation of frame-shift mutations when errors in DNA replication occur, which result in a variety of diseases and cancers. Compounds capable of binding to non-canonical DNA conformations may thus have significant diagnostic and therapeutic potential. Clerocidin is a natural diterpenoid which has been shown to selectively react with single-stranded bases without targeting the double helix. Here we performed a comprehensive analysis on several non-canonical DNA secondary structures, namely mismatches, nicks, bulges, hairpins, with sequence variations in both the single-stranded region and the double-stranded flanking segment. By analysis of clerocidin reactivity, we were able to identify the exposed reactive residues which provided information on both the secondary structure and the accessibility of the non-paired sites. Mismatches longer than 1 base were necessary to be reached by clerocidin reactive groups, while 1-base nicks were promptly targeted by clerocidin; in hairpins, clerocidin reactivity increased with the length of the hairpin loop, while, interestingly, reactivity towards bulges reached a maximum in 3-base-long bulges and declined in longer bulges. Electrophoretic mobility shift analysis demonstrated that bulges longer than 3 bases (i.e. 5- and 7-bases) folded or stacked on the duplex region therefore being less accessible by the compound. Clerocidin thus represents a new valuable diagnostic tool to dissect DNA secondary structures.

Trans-oceanic Remote Power Hardware-in-the-Loop: Multi-site Hardware, Integrated Controller, and Electric Network Co-simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundstrom, Blake R.; Palmintier, Bryan S.; Rowe, Daniel

Electric system operators are increasingly concerned with the potential system-wide impacts of the large-scale integration of distributed energy resources (DERs) including voltage control, protection coordination, and equipment wear. This prompts a need for new simulation techniques that can simultaneously capture all the components of these large integrated smart grid systems. This paper describes a novel platform that combines three emerging research areas: power systems co-simulation, power hardware in the loop (PHIL) simulation, and lab-lab links. The platform is distributed, real-time capable, allows for easy internet-based connection from geographically-dispersed participants, and is software platform agnostic. We demonstrate its utility by studyingmore » real-time PHIL co-simulation of coordinated solar PV firming control of two inverters connected in multiple electric distribution network models, prototypical of U.S. and Australian systems. Here, the novel trans-pacific closed-loop system simulation was conducted in real-time using a power network simulator and physical PV/battery inverter at power at the National Renewable Energy Laboratory in Golden, CO, USA and a physical PV inverter at power at the Commonwealth Scientific and Industrial Research Organisation's Energy Centre in Newcastle, NSW, Australia. This capability enables smart grid researchers throughout the world to leverage their unique simulation capabilities for multi-site collaborations that can effectively simulate and validate emerging smart grid technology solutions.« less

Trans-oceanic Remote Power Hardware-in-the-Loop: Multi-site Hardware, Integrated Controller, and Electric Network Co-simulation

DOE PAGES

Lundstrom, Blake R.; Palmintier, Bryan S.; Rowe, Daniel; ...

2017-07-24

Electric system operators are increasingly concerned with the potential system-wide impacts of the large-scale integration of distributed energy resources (DERs) including voltage control, protection coordination, and equipment wear. This prompts a need for new simulation techniques that can simultaneously capture all the components of these large integrated smart grid systems. This paper describes a novel platform that combines three emerging research areas: power systems co-simulation, power hardware in the loop (PHIL) simulation, and lab-lab links. The platform is distributed, real-time capable, allows for easy internet-based connection from geographically-dispersed participants, and is software platform agnostic. We demonstrate its utility by studyingmore » real-time PHIL co-simulation of coordinated solar PV firming control of two inverters connected in multiple electric distribution network models, prototypical of U.S. and Australian systems. Here, the novel trans-pacific closed-loop system simulation was conducted in real-time using a power network simulator and physical PV/battery inverter at power at the National Renewable Energy Laboratory in Golden, CO, USA and a physical PV inverter at power at the Commonwealth Scientific and Industrial Research Organisation's Energy Centre in Newcastle, NSW, Australia. This capability enables smart grid researchers throughout the world to leverage their unique simulation capabilities for multi-site collaborations that can effectively simulate and validate emerging smart grid technology solutions.« less

Evolution of a designed retro-aldolase leads to complete active site remodeling

PubMed Central

Giger, Lars; Caner, Sami; Obexer, Richard; Kast, Peter; Baker, David; Ban, Nenad; Hilvert, Donald

2013-01-01

Evolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that dramatic molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400 fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate, and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. PMID:23748672

Comparison of two serpins of Clonorchis sinensis by bioinformatics, expression, and localization in metacercaria

PubMed Central

Yang, Yabo; Hu, Dong; Wang, Lexun; Liang, Chi; Hu, Xuchu; Xu, Jin; Huang, Yan; Yu, Xinbing

2014-01-01

Clonorchiasis, which has been an important public health problem in China, is caused by ingestion of raw or undercooked fish contaminated by live metacercaria. Therefore, preventing fish from infecting is of great significance for controlling the disease. SERPINs (serine protease inhibitors) are well known as negative regulators of hemostasis, thrombolysis, and innate immune responses. In the present study, two full-length sequences encoding SERPIN were identified from metacercaria cDNA library of Clonorchis sinensis (C. sinensis) and were denominated as CsSERPIN and CsSERPIN3, respectively. Bioinformatics analysis showed that the two sequences shares 35.9% identity to each other. Both of the sequences have SERPIN domain and the greatest difference between the two domains is the reactive centre loop. Transmembrane region was found in CsSERPIN3 while not in CsSERPIN. The expression of the two CsSERPINs was significantly higher at the life stage of metacercaria than that of adult. The transcription levels of CsSERPIN and CsSERPIN3 at metacercaria stage were 3.249- and 11.314-fold of that at adult stage, respectively. Furthermore, the expression of CsSERPIN was 4.32-fold of that of CsSERPIN3 at metacercaria stage. Immunobiochemistry revealed that CsERPIN was dispersed at subtegument and oral sucker of metacercaria, while CsSERPIN3 localized intensely in the tegument of metacercaria of C. sinensis inside of the cyst wall. All these indicated that the CsSERPINs play important roles at metacercaria stage of the parasite. CsSERPIN may take part in regulation of endogenous serine proteinase and CsSERPIN3 may be involved in immune evasion and be a potential candidate for vaccine and drug target for clonorchiasis. PMID:24831344

Comparison of two serpins of Clonorchis sinensis by bioinformatics, expression, and localization in metacercaria.

PubMed

Yang, Yabo; Hu, Dong; Wang, Lexun; Liang, Chi; Hu, Xuchu; Xu, Jin; Huang, Yan; Yu, Xinbing

2014-06-01

Clonorchiasis, which has been an important public health problem in China, is caused by ingestion of raw or undercooked fish contaminated by live metacercaria. Therefore, preventing fish from infecting is of great significance for controlling the disease. SERPINs (serine protease inhibitors) are well known as negative regulators of hemostasis, thrombolysis, and innate immune responses. In the present study, two full-length sequences encoding SERPIN were identified from metacercaria cDNA library of Clonorchis sinensis (C. sinensis) and were denominated as CsSERPIN and CsSERPIN3, respectively. Bioinformatics analysis showed that the two sequences shares 35.9% identity to each other. Both of the sequences have SERPIN domain and the greatest difference between the two domains is the reactive centre loop. Transmembrane region was found in CsSERPIN3 while not in CsSERPIN. The expression of the two CsSERPINs was significantly higher at the life stage of metacercaria than that of adult. The transcription levels of CsSERPIN and CsSERPIN3 at metacercaria stage were 3.249- and 11.314-fold of that at adult stage, respectively. Furthermore, the expression of CsSERPIN was 4.32-fold of that of CsSERPIN3 at metacercaria stage. Immunobiochemistry revealed that CsERPIN was dispersed at subtegument and oral sucker of metacercaria, while CsSERPIN3 localized intensely in the tegument of metacercaria of C. sinensis inside of the cyst wall. All these indicated that the CsSERPINs play important roles at metacercaria stage of the parasite. CsSERPIN may take part in regulation of endogenous serine proteinase and CsSERPIN3 may be involved in immune evasion and be a potential candidate for vaccine and drug target for clonorchiasis.

Natural circulation in a liquid metal one-dimensional loop

NASA Astrophysics Data System (ADS)

Tarantino, M.; De Grandis, S.; Benamati, G.; Oriolo, F.

2008-06-01

A wide use of pure lead, as well as its alloys (such as lead-bismuth, lead-lithium), is foreseen in several nuclear-related fields: it is studied as coolant in critical and sub-critical nuclear reactors, as spallation target for neutron generation in several applications and for tritium generation in fusion systems. In this framework, a new facility named NAtural CIrculation Experiment (NACIE), has been designed at ENEA-Brasimone Research Centre. NACIE is a rectangular loop, made by stainless steel pipes. It consists mainly of a cold and hot leg and an expansion tank installed on the top of the loop. A fuel bundle simulator, made by three electrical heaters placed in a triangular lattice, is located in the lower part of the cold leg, while a tube in tube heat exchanger is installed in the upper part of the hot leg. The adopted secondary fluid is THT oil, while the foreseen primary fluid for the tests is lead-bismuth in eutectic composition (LBE). The aim of the facility is to carry out experimental tests of natural circulation and collect data on the heat transfer coefficient (HTC) for heavy liquid metal flowing through rod bundles. The paper is focused on the preliminary estimation of the LBE flow rate along the loop. An analytical methodology has been applied, solving the continuity, momentum and energy transport equations under appropriate hypothesis. Moreover numerical simulations have been performed. The FLUENT 6.2 CFD code has been utilized for the numerical simulations. The main results carried out from the pre-tests simulations are illustrated in the paper, and a comparison with the theoretical estimations is done.

Towards a geology training and outreach centre in western Ireland

NASA Astrophysics Data System (ADS)

Lacchia, Anthea; Haughton, Peter; Shannon, Patrick

2017-04-01

An outreach and education centre is in the initial phases of development for the coastal area of County Clare, western Ireland. The high Carboniferous sea cliffs of the Loop Head area provide a rich training ground for geoscientists from industry and academia. The cliffs offer a unique, margin-scale perspective of a sedimentary basin fill succession that developed during the height of the Late Palaeozoic glaciation. The rocks, about which there is a long legacy of research, record several glacial cycles, associated with significant eustatic changes in sea level. For geoscientists working with or in industry, the value of the area lies in its analogy with hydrocarbon-bearing, deltaic to deep-water sedimentary successions on several continental margins, such as Miocene and Pliocene successions in the Gulf of Mexico. A programme of behind-outcrop drilling involving UCD and Statoil has acquired over 1350 m of core from 12 boreholes behind the sea cliffs. This core is already being used in training and research both in UCD and at Statoil. The coastal cliffs are also visited by tourists and special interest groups, such as birdwatchers. It is envisioned that the centre will involve the local community and wider public, facilitating links between geoscience, energy and environment. Transport of cores and training materials to the centre, where they will be made available to visiting field parties, is planned for this year. Progress to date, including public engagement activities with schools and at conferences as well as audience research and public consultation, and future plans will be outlined.

Modeling of the EAST ICRF antenna with ICANT Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin Chengming; Zhao Yanping; Colas, L.

2007-09-28

A Resonant Double Loop (RDL) antenna for ion-cyclotron range of frequencies (ICRF) on Experimental Advanced Superconducting Tokamak (EAST) is under construction. The new antenna is analyzed using the antenna coupling code ICANT which self-consistently determines the surface currents on all antenna parts. In this work, the modeling of the new ICRF antenna using this code is to assess the near-fields in front of the antenna and analysis its coupling capabilities. Moreover, the antenna reactive radiated power computed by ICANT and shows a good agreement with deduced from Transmission Line (TL) theory.

Modeling of the EAST ICRF antenna with ICANT Code

NASA Astrophysics Data System (ADS)

Qin, Chengming; Zhao, Yanping; Colas, L.; Heuraux, S.

2007-09-01

A Resonant Double Loop (RDL) antenna for ion-cyclotron range of frequencies (ICRF) on Experimental Advanced Superconducting Tokamak (EAST) is under construction. The new antenna is analyzed using the antenna coupling code ICANT which self-consistently determines the surface currents on all antenna parts. In this work, the modeling of the new ICRF antenna using this code is to assess the near-fields in front of the antenna and analysis its coupling capabilities. Moreover, the antenna reactive radiated power computed by ICANT and shows a good agreement with deduced from Transmission Line (TL) theory.

Differential Resonant Ring YIG Tuned Oscillator

NASA Technical Reports Server (NTRS)

Parrott, Ronald A.

2010-01-01

A differential SiGe oscillator circuit uses a resonant ring-oscillator topology in order to electronically tune the oscillator over multi-octave bandwidths. The oscillator s tuning is extremely linear, because the oscillator s frequency depends on the magnetic tuning of a YIG sphere, whose resonant frequency is equal to a fundamental constant times the DC magnetic field. This extremely simple circuit topology uses two coupling loops connecting a differential pair of SiGe bipolar transistors into a feedback configuration using a YIG tuned filter creating a closed-loop ring oscillator. SiGe device technology is used for this oscillator in order to keep the transistor s 1/f noise to an absolute minimum in order to achieve minimum RF phase noise. The single-end resonant ring oscillator currently has an advantage in fewer parts, but when the oscillation frequency is greater than 16 GHz, the package s parasitic behavior couples energy to the sphere and causes holes and poor phase noise performance. This is because the coupling to the YIG is extremely low, so that the oscillator operates at near the unloaded Q. With the differential resonant ring oscillator, the oscillation currents are just in the YIG coupling mechanisms. The phase noise is even better, and the physical size can be reduced to permit monolithic microwave integrated circuit oscillators. This invention is a YIG tuned oscillator circuit making use of a differential topology to simultaneously achieve an extremely broadband electronic tuning range and ultra-low phase noise. As a natural result of its differential circuit topology, all reactive elements, such as tuning stubs, which limit tuning bandwidth by contributing excessive open loop phase shift, have been eliminated. The differential oscillator s open-loop phase shift is associated with completely non-dispersive circuit elements such as the physical angle of the coupling loops, a differential loop crossover, and the high-frequency phase shift of the n-p-n transistors. At the input of the oscillator s feedback loop is a pair of differentially connected n-p-n SiGe transistors that provides extremely high gain, and because they are bulk-effect devices, extremely low 1/f noise (leading to ultralow RF phase noise). The 1/f corner frequency for n-p-n SiGe transistors is approximately 500 Hz. The RF energy from the transistor s collector output is connected directly to the top-coupling loop (the excitation loop) of a single-sphere YIG tuned filter. A uniform magnetic field to bias the YIG must be at a right angle to any vector associated with an RF current in a coupling loop in order for the precession to interact with the RF currents.

A new crystal form of a hyperthermophilic endocellulase

PubMed Central

Kataoka, Misumi; Ishikawa, Kazuhiko

2014-01-01

The hyperthermophilic glycoside hydrolase family endocellulase 12 from the archaeon Pyrococcus furiosus (EGPf; Gene ID PF0854; EC 3.2.1.4) catalyzes the hydrolytic cleavage of the β-1,4-glucosidic linkage in β-glucan in lignocellulose biomass. A crystal of EGPf was previously prepared at pH 9.0 and its structure was determined at an atomic resolution of 1.07 Å. This article reports the crystallization of EGPf at the more physiologically relevant pH of 5.5. Structure determination showed that this new crystal form has the symmetry of space group C2. Two molecules of the enzyme are observed in the asymmetric unit. Crystal packing is weak at pH 5.5 owing to two flexible interfaces between symmetry-related molecules. Comparison of the EGPf structures obtained at pH 9.0 and pH 5.5 reveals a significant conformational difference at the active centre and in the surface loops. The interfaces in the vicinity of the flexible surface loops impact the quality of the EGPf crystal. PMID:25005081

An investigation of reactivity effect due to inadvertent filling of the irradiation channels with water in NIRR-1 Nigeria Research Reactor-1.

PubMed

Iliyasu, U; Ibrahim, Y V; Umar, Sadiq; Agbo, S A; Jibrin, Y

2017-05-01

Investigation of reactivity variation due to flooding of the irradiation channels of Nigeria Research Reactor (NIRR-1) a low power miniature neutron source reactor (MNSR) located at the Centre for Energy Research and Training, Ahmadu Bello University, Zaria Nigeria using the MCNP code for High Enrich Uranium (HEU) and Low Enrich Uranium (LEU) core has been simulated in this present study. In this work, the excess reactivity worth of flooding HEU core for 1 inner, 2 inner, 3 inner, 4 inner and all inner are 0.318mk, 0.577mk, 0.318mk, 1.204mk and 1.503mk respectively, and outer irradiation channels are 0.119mk, 0.169mk, 0.348mk, 0.438mk and 0.418mk respectively, the highest excess reactivity result from flooding both inner and outer irradiation channels is 2.04mk (±1.72×10 -7 ), the excess reactivity for LEU core was 0.299mk, 0.568mk, 0.896mk, 1.195mk and 1.524mk in the inner irradiation channels, and the outer irradiation channels are 0.129mk, 0.189mk, 0.219mk, 0.269mk and 0.548mk where the highest excess reactivity was 1.942mk (±1.64×10 -7 ) resulting from flooding inner and outer irradiation channels. The reactivity induced by flooding of the irradiation channels of NIRR-1 with water is within design safety limit enshrined in Safety Analysis Report of NIRR-1. The results also compare well with literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

VERifyNow in DIabetes high-on-treatment platelet reactivity: a pharmacodynamic study on switching from clopidogrel to prasugrel.

PubMed

Cubero Gómez, José M; Acosta Martínez, Juan; Mendias Benítez, Crsitina; Díaz De La Llera, Luis S; Fernández-Quero, Mónica; Guisado Rasco, Agustí; Villa Gil-Ortega, Manuel; Sánchez González, Ángel

2015-12-01

Diabetic patients with an acute coronary syndrome undergoing percutaneous coronary intervention frequently exhibit high platelet reactivity while on clopidogrel. We hypothesized that in diabetic patients undergoing percutaneous coronary intervention, who exhibit high-platelet-reactivity after standard treatment with clopidogrel, a 60-mg prasugrel loading dose is superior to standard treatment with clopidogrel for optimal P2Y12 inhibition within the first 24-36 h post-angioplasty. VERDI was a prospective, randomized, single-centre, single-blind, parallel-design study (NCT01684813). Consecutive diabetic patients with an non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention and loaded with clopidogrel were considered for platelet reactivity assessment immediately before angioplasty with the VerifyNow assay measured in P2Y12 reaction units (PRU). Fifty of 63 screened patients (79.4%) had high platelet reactivity (PRU ≥ 208) and were randomized to receive a 60-mg prasugrel loading dose (n = 25) versus clopidogrel standard dose (n = 25). Platelet function was assessed again 24 hours post-angioplasty. Prasugrel achieved greater platelet inhibition than clopidogrel 24 hours post-angioplasty (median [interquartile range], 38 [9-72] vs 285 [240-337], respectively; P < 0.001). The non-high-platelet-reactivity rate (PRU < 208) at 24 h post-angioplasty (primary end point) was higher with prasugrel; 25 patients (100%) in the prasugrel group achieved optimal antiaggregation vs 4 patients (16%) in the clopidogrel group (P < 0.001). No significant acute bleeding was documented in either group. Among type 2 diabetic patients suffering an acute coronary syndrome with high-platelet-reactivity undergoing percutaneous coronary intervention, switching from clopidogrel to prasugrel was superior to standard treatment with clopidogrel for the achievement of optimal antiaggregation within the first 24 hours post-angioplasty.

Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death

PubMed Central

Graham, Nicholas A; Tahmasian, Martik; Kohli, Bitika; Komisopoulou, Evangelia; Zhu, Maggie; Vivanco, Igor; Teitell, Michael A; Wu, Hong; Ribas, Antoni; Lo, Roger S; Mellinghoff, Ingo K; Mischel, Paul S; Graeber, Thomas G

2012-01-01

The altered metabolism of cancer can render cells dependent on the availability of metabolic substrates for viability. Investigating the signaling mechanisms underlying cell death in cells dependent upon glucose for survival, we demonstrate that glucose withdrawal rapidly induces supra-physiological levels of phospho-tyrosine signaling, even in cells expressing constitutively active tyrosine kinases. Using unbiased mass spectrometry-based phospho-proteomics, we show that glucose withdrawal initiates a unique signature of phospho-tyrosine activation that is associated with focal adhesions. Building upon this observation, we demonstrate that glucose withdrawal activates a positive feedback loop involving generation of reactive oxygen species (ROS) by NADPH oxidase and mitochondria, inhibition of protein tyrosine phosphatases by oxidation, and increased tyrosine kinase signaling. In cells dependent on glucose for survival, glucose withdrawal-induced ROS generation and tyrosine kinase signaling synergize to amplify ROS levels, ultimately resulting in ROS-mediated cell death. Taken together, these findings illustrate the systems-level cross-talk between metabolism and signaling in the maintenance of cancer cell homeostasis. PMID:22735335

CK1/Doubletime activity delays transcription activation in the circadian clock

PubMed Central

O'Neil, Jenna L; Merz, Gregory E; Dusad, Kritika; Crane, Brian R; Young, Michael W

2018-01-01

In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock. PMID:29611807

Development of a loop-mediated isothermal amplification assay for detection of Trichomonas vaginalis.

PubMed

Reyes, John Carlo B; Solon, Juan Antonio A; Rivera, Windell L

2014-07-01

A loop-mediated isothermal amplification (LAMP) assay targeting the 2-kbp repeated DNA species-specific sequence was developed for detection of Trichomonas vaginalis, the causative agent of trichomoniasis. The analytical sensitivity and specificity of the LAMP assay were evaluated using pooled genital swab and urine specimens, respectively, spiked with T. vaginalis trophozoites. Genital secretion and urine did not inhibit the detection of the parasite. The sensitivity of the LAMP was 10-1000 times higher than the PCR performed. The detection limit of LAMP was 1 trichomonad for both spiked genital swab and urine specimens. Also, LAMP did not exhibit cross-reactivity with closely-related trichomonads, Trichomonas tenax and Pentatrichomonas hominis, and other enteric and urogenital microorganisms, Entamoeba histolytica, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. This is the first report of a LAMP assay for the detection of T. vaginalis and has prospective application for rapid diagnosis and control of trichomoniasis. Copyright © 2014 Elsevier Inc. All rights reserved.

Rapid and sensitive detection of human astrovirus in water samples by loop-mediated isothermal amplification with hydroxynaphthol blue dye.

PubMed

Yang, Bo-Yun; Liu, Xiao-Lu; Wei, Yu-Mei; Wang, Jing-Qi; He, Xiao-Qing; Jin, Yi; Wang, Zi-Jian

2014-02-14

The aim of this paper was to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, sensitive and inexpensive detection of astrovirus. The detection limit of LAMP using in vitro RNA transcripts was 3.6 × 10 copies·μL⁻¹, which is as sensitive as the presently used PCR assays. However, the LAMP products could be identified as different colors with the naked eye following staining with hydroxynaphthol blue dye (HNB). No cross-reactivity with other gastroenteric viruses (rotavirus and norovirus) was observed, indicating the relatively high specificity of LAMP. The RT-LAMP method with HNB was used to effectively detect astrovirus in reclaimed water samples. The LAMP technique described in this study is a cheap, sensitive, specific and rapid method for the detection of astrovirus. The RT-LAMP method can be simply applied for the specific detection of astrovirus and has the potential to be utilized in the field as a screening test.

Observation of longitudinal spin-Seebeck effect in cobalt-ferrite epitaxial thin films

NASA Astrophysics Data System (ADS)

Niizeki, Tomohiko; Kikkawa, Takashi; Uchida, Ken-ichi; Oka, Mineto; Suzuki, Kazuya Z.; Yanagihara, Hideto; Kita, Eiji; Saitoh, Eiji

2015-05-01

The longitudinal spin-Seebeck effect (LSSE) has been investigated in cobalt ferrite (CFO), an exceptionally hard magnetic spinel ferrite. A bilayer of a polycrystalline Pt and an epitaxially-strained CFO(110) exhibiting an in-plane uniaxial anisotropy was prepared by reactive rf sputtering technique. Thermally generated spin voltage in the CFO layer was measured via the inverse spin-Hall effect in the Pt layer. External-magnetic-field (H) dependence of the LSSE voltage (VLSSE) in the Pt/CFO(110) sample with H ∥ [001] was found to exhibit a hysteresis loop with a high squareness ratio and high coercivity, while that with H ∥ [ 1 1 ¯ 0 ] shows a nearly closed loop, reflecting the different anisotropies induced by the epitaxial strain. The magnitude of VLSSE has a linear relationship with the temperature difference (ΔT), giving the relatively large VLSSE /ΔT of about 3 μV/K for CFO(110) which was kept even at zero external field.

Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8+ T cell response.

PubMed

Culshaw, Abigail; Ladell, Kristin; Gras, Stephanie; McLaren, James E; Miners, Kelly L; Farenc, Carine; van den Heuvel, Heleen; Gostick, Emma; Dejnirattisai, Wanwisa; Wangteeraprasert, Apirath; Duangchinda, Thaneeya; Chotiyarnwong, Pojchong; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida; Dong, Tao; Rossjohn, Jamie; Mongkolsapaya, Juthathip; Price, David A; Screaton, Gavin R

2017-11-01

Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8 + T cell populations specific for variants of the nonstructural protein epitope NS3 133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3 133 -DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2 + TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second β-chain complementarity-determining region (CDR2β). Extensive mutagenesis studies of three distinct TRBV11-2 + TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2β loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs.

Crystal structure of four-stranded Oxytricha telomeric DNA

NASA Technical Reports Server (NTRS)

Kang, C.; Zhang, X.; Ratliff, R.; Moyzis, R.; Rich, A.

1992-01-01

The sequence d(GGGGTTTTGGGG) from the 3' overhang of the Oxytricha telomere has been crystallized and its three-dimensional structure solved to 2.5 A resolution. The oligonucleotide forms hairpins, two of which join to make a four-stranded helical structure with the loops containing four thymine residues at either end. The guanine residues are held together by cyclic hydrogen bonding and an ion is located in the centre. The four guanine residues in each segment have a glycosyl conformation that alternates between anti and syn. There are two four-stranded molecules in the asymmetric unit showing that the structure has some intrinsic flexibility.

Efficient sampling of reversible cross-linking polymers: Self-assembly of single-chain polymeric nanoparticles

NASA Astrophysics Data System (ADS)

Oyarzún, Bernardo; Mognetti, Bortolo Matteo

2018-03-01

We present a new simulation technique to study systems of polymers functionalized by reactive sites that bind/unbind forming reversible linkages. Functionalized polymers feature self-assembly and responsive properties that are unmatched by the systems lacking selective interactions. The scales at which the functional properties of these materials emerge are difficult to model, especially in the reversible regime where such properties result from many binding/unbinding events. This difficulty is related to large entropic barriers associated with the formation of intra-molecular loops. In this work, we present a simulation scheme that sidesteps configurational costs by dedicated Monte Carlo moves capable of binding/unbinding reactive sites in a single step. Cross-linking reactions are implemented by trial moves that reconstruct chain sections attempting, at the same time, a dimerization reaction between pairs of reactive sites. The model is parametrized by the reaction equilibrium constant of the reactive species free in solution. This quantity can be obtained by means of experiments or atomistic/quantum simulations. We use the proposed methodology to study the self-assembly of single-chain polymeric nanoparticles, starting from flexible precursors carrying regularly or randomly distributed reactive sites. We focus on understanding differences in the morphology of chain nanoparticles when linkages are reversible as compared to the well-studied case of irreversible reactions. Intriguingly, we find that the size of regularly functionalized chains, in good solvent conditions, is non-monotonous as a function of the degree of functionalization. We clarify how this result follows from excluded volume interactions and is peculiar of reversible linkages and regular functionalizations.

Study of microdefects and their distribution in dislocation-free Si-doped HB GaAs by X-ray diffuse scattering on triple-crystal diffractometer

NASA Astrophysics Data System (ADS)

Charniy, L. A.; Morozov, A. N.; Bublik, V. T.; Scherbachev, K. D.; Stepantsova, I. V.; Kaganer, V. M.

1992-03-01

Microdefects in dislocation-free Si-doped (n = (1-3) × 10 18cm-3) HB GaAs crystals were studied by X-ray diffuse scattering measured with the help of a triple-crystal diffractometer. The intensity of the diffuse scattering as well as the isointensity contours around different reciprocal lattice points were analysed. A comparison of the measured isointensity contours with the theoretically calculated ones showed that the microdefects detected are interstitial dislocation loops with the Burgers vectors b = {1}/{2}<110 #3862;; lying in the planes #38;{110} and {111}. The mean radius of the dislocation loops R0 was determined using the wave vector q0 alpha; R-10 corresponding to the transmition point where the Huang diffuse scattering I( q) alpha q-2 ( q < q0) changed to the asymptotic scattering I( q) alpha q-4 ( q #62 q0). The analysis of a D-shaped cross-sectional (111) wafer cut from the end part of the HB ingot showed that R0 changed smoothly along the [ overline211] symmetry axis of the wafer. The highly inhomogeneous "new-moon"-like distribution of the non-dislocational etch-pits was also obtained. The maximal loop radius obtained at the edges of the wafer, R 0 = 1 μm, corresponds to the wafer area enriched with etch-pits and the minimal one, R 0 = 0.3 μm, corresponds to the bound of the new-moon-like area denuded from etch-pits. Microdefects of a new type were detected in the denuded area. These microdefects consist of nuclei, 0.1 μm in radius, and an extended atmosphere of interstitials. The minimal microdefect radius in the centre of the wafer corresponds to the maximum local value of the lattice parameter a = 5.655380 Å, and the minimum local value a = 5.65372 Å was obtained at the wafer edges enriched with microdefect-related etch-pits. Absolute X-ray diffuse intensity measurements were used for microdefect concentration determination. Normalization of I( q) was based on the comparison of the Huang intensity with the thermal diffuse scattering intensity which is predominant for the wave vector q å R-10. The microdefect concentration determined in this way appeared to be 4 × 10 9 cm -3 at the edges of the wafer and 4 × 10 11 cm -3 at the centre of the new-moon-like etch-pit denuded zone. The number of interstitial atoms forming dislocation loops is shown to be the same across the area of the wafer and equal to 10 16 cm -3.

Passive Safety Features Evaluation of KIPT Neutron Source Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong, Zhaopeng; Gohar, Yousry

2016-06-01

Argonne National Laboratory (ANL) of the United States and Kharkov Institute of Physics and Technology (KIPT) of Ukraine have cooperated on the development, design, and construction of a neutron source facility. The facility was constructed at Kharkov, Ukraine and its commissioning process is underway. It will be used to conduct basic and applied nuclear research, produce medical isotopes, and train young nuclear specialists. The facility has an electron accelerator-driven subcritical assembly. The electron beam power is 100 kW using 100 MeV electrons. Tungsten or natural uranium is the target material for generating neutrons driving the subcritical assembly. The subcritical assemblymore » is composed of WWR-M2 - Russian fuel assemblies with U-235 enrichment of 19.7 wt%, surrounded by beryllium reflector assembles and graphite blocks. The subcritical assembly is seated in a water tank, which is a part of the primary cooling loop. During normal operation, the water coolant operates at room temperature and the total facility power is ~300 KW. The passive safety features of the facility are discussed in in this study. Monte Carlo computer code MCNPX was utilized in the analyses with ENDF/B-VII.0 nuclear data libraries. Negative reactivity temperature feedback was consistently observed, which is important for the facility safety performance. Due to the design of WWR-M2 fuel assemblies, slight water temperature increase and the corresponding water density decrease produce large reactivity drop, which offset the reactivity gain by mistakenly loading an additional fuel assembly. The increase of fuel temperature also causes sufficiently large reactivity decrease. This enhances the facility safety performance because fuel temperature increase provides prompt negative reactivity feedback. The reactivity variation due to an empty fuel position filled by water during the fuel loading process is examined. Also, the loading mistakes of removing beryllium reflector assemblies and replacing them with dummy assemblies were analyzed. In all these circumstances, the reactivity change results do not cause any safety concerns.« less

Signature of dislocations and stacking faults of face-centred cubic nanocrystals in coherent X-ray diffraction patterns: a numerical study.

PubMed

Dupraz, Maxime; Beutier, Guillaume; Rodney, David; Mordehai, Dan; Verdier, Marc

2015-06-01

Crystal defects induce strong distortions in diffraction patterns. A single defect alone can yield strong and fine features that are observed in high-resolution diffraction experiments such as coherent X-ray diffraction. The case of face-centred cubic nanocrystals is studied numerically and the signatures of typical defects close to Bragg positions are identified. Crystals of a few tens of nanometres are modelled with realistic atomic potentials and 'relaxed' after introduction of well defined defects such as pure screw or edge dislocations, or Frank or prismatic loops. Diffraction patterns calculated in the kinematic approximation reveal various signatures of the defects depending on the Miller indices. They are strongly modified by the dissociation of the dislocations. Selection rules on the Miller indices are provided, to observe the maximum effect of given crystal defects in the initial and relaxed configurations. The effect of several physical and geometrical parameters such as stacking fault energy, crystal shape and defect position are discussed. The method is illustrated on a complex structure resulting from the simulated nanoindentation of a gold nanocrystal.

Signature of dislocations and stacking faults of face-centred cubic nanocrystals in coherent X-ray diffraction patterns: a numerical study1

PubMed Central

Dupraz, Maxime; Beutier, Guillaume; Rodney, David; Mordehai, Dan; Verdier, Marc

2015-01-01

Crystal defects induce strong distortions in diffraction patterns. A single defect alone can yield strong and fine features that are observed in high-resolution diffraction experiments such as coherent X-ray diffraction. The case of face-centred cubic nanocrystals is studied numerically and the signatures of typical defects close to Bragg positions are identified. Crystals of a few tens of nanometres are modelled with realistic atomic potentials and ‘relaxed’ after introduction of well defined defects such as pure screw or edge dislocations, or Frank or prismatic loops. Diffraction patterns calculated in the kinematic approximation reveal various signatures of the defects depending on the Miller indices. They are strongly modified by the dissociation of the dislocations. Selection rules on the Miller indices are provided, to observe the maximum effect of given crystal defects in the initial and relaxed configurations. The effect of several physical and geometrical parameters such as stacking fault energy, crystal shape and defect position are discussed. The method is illustrated on a complex structure resulting from the simulated nanoindentation of a gold nanocrystal. PMID:26089755

Using the centre of percussion to design a steering controller for an autonomous race car

NASA Astrophysics Data System (ADS)

Kritayakirana, Krisada; Gerdes, J. Christian

2012-01-01

Understanding how a race car driver controls a vehicle at its friction limits can provide insights into the development of vehicle safety systems. In this paper, a race car driver's behaviour inspires the design of an autonomous racing controller. The resulting controller uses the vehicle's centre of percussion (COP) to design feedforward and feedback steering. At the COP, the effects of rotation and translation from the rear tire force cancel each other out; consequently, the feedforward steering command is robust to the disturbances from the rear tire force. Using the COP also simplifies the equations of motion, as the vehicle's lateral motion is decoupled from the vehicle's yaw motion and highlights the challenge of controlling a vehicle when the rear tires are highly saturated. The resulting dynamics can be controlled with a linear state feedback based on a lane-keeping system with additional yaw damping. Utilising Lyapunov theory, the closed-loop system is shown to remain stable even when the rear tires are highly saturated. The experimental results demonstrate that an autonomous vehicle can operate at its limits while maintaining a minimal lateral error.

An Autoregulatory Loop Controlling CYP1A1 Gene Expression: Role of H2O2 and NFI

PubMed Central

Morel, Yannick; Mermod, Nicolas; Barouki, Robert

1999-01-01

Cytochrome P450 1A1 (CYP1A1), like many monooxygenases, can produce reactive oxygen species during its catalytic cycle. Apart from the well-characterized xenobiotic-elicited induction, the regulatory mechanisms involved in the control of the steady-state activity of CYP1A1 have not been elucidated. We show here that reactive oxygen species generated from the activity of CYP1A1 limit the levels of induced CYP1A1 mRNAs. The mechanism involves the repression of the CYP1A1 gene promoter activity in a negative-feedback autoregulatory loop. Indeed, increasing the CYP1A1 activity by transfecting CYP1A1 expression vectors into hepatoma cells elicited an oxidative stress and led to the repression of a reporter gene driven by the CYP1A1 gene promoter. This negative autoregulation is abolished by ellipticine (an inhibitor of CYP1A1) and by catalase (which catalyzes H2O2 catabolism), thus implying that H2O2 is an intermediate. Down-regulation is also abolished by the mutation of the proximal nuclear factor I (NFI) site in the promoter. The transactivating domain of NFI/CTF was found to act in synergy with the arylhydrocarbon receptor pathway during the induction of CYP1A1 by 2,3,7,8-tetrachloro-p-dibenzodioxin. Using an NFI/CTF-Gal4 fusion, we show that NFI/CTF transactivating function is decreased by a high activity of CYP1A1. This regulation is also abolished by catalase or ellipticine. Consistently, the transactivating function of NFI/CTF is repressed in cells treated with H2O2, a novel finding indicating that the transactivating domain of a transcription factor can be targeted by oxidative stress. In conclusion, an autoregulatory loop leads to the fine tuning of the CYP1A1 gene expression through the down-regulation of NFI activity by CYP1A1-based H2O2 production. This mechanism allows a limitation of the potentially toxic CYP1A1 activity within the cell. PMID:10490621

Positive and negative feedback loops in nutrient phytoplankton interactions related to climate dynamics factors in a shallow temperate estuary (Vistula Lagoon, southern Baltic)

NASA Astrophysics Data System (ADS)

Kruk, Marek; Kobos, Justyna; Nawrocka, Lidia; Parszuto, Katarzyna

2018-04-01

This study aims to demonstrate that factors associated with climate dynamics, such as temperature and wind, affect the ecosystem of the shallow Vistula Lagoon in the southern Baltic and cause nutrient forms phytoplankton interactions: the growth of biomass and constraints of it. This occurs through a network of direct and indirect relationships between environmental and phytoplankton factors, including interactions of positive and negative feedback loops. Path analysis supported by structural equation modeling (SEM) was used to test hypotheses regarding the impact of climate factors on algal assemblages. Increased phytoplankton biomass was affected directly by water temperature and salinity, while the wind speed effect was indirect as it resulted in increased concentrations of suspended solids (SS) in the water column. Simultaneously, the concentration of SS in the water was positively correlated with particulate organic carbon (POC), particulate nitrogen (PN), and particulate phosphorus (PP), and was negatively correlated with the total nitrogen to phosphorus (N:P) ratio. Particulate forms of C, N, and phosphorus (P), concentrations of soluble reactive phosphorus (SRP) and nitrate and nitrite nitrogen (NO3-N + NO2-N), and ratios of the total N:P and DIN:SRP, all indirectly effected Cyanobacteria C concentrations. These processes influence other phytoplankton groups (Chlorophyta, Bacillariophyceae and the picophytoplankton fraction). Increased levels of SRP associated with organic matter (POC), which stemmed from reduced DIN:SRP ratios, contributed to increased Cyanoprokaryota and picophytoplankton C concentrations, which created a positive feedback loop. However, a simultaneous reduction in the total N:P ratio could have inhibited increases in the biomass of these assemblages by limiting N, which likely formed a negative feedback loop. The study indicates that the nutrients-phytoplankton feedback loop phenomenon can intensify eutrophication in a temperate lagoon, including increases of the biomass of Cyanobacteria and picophytoplankton. However, it can also constrain this increase.

Patient outcome of emergency laparotomy improved with increasing "number of surgeons on-call" in a university hospital: Audit loop.

PubMed

Hussain, Anwar; Mahmood, Fahad; Teng, Chui; Jafferbhoy, Sadaf; Luke, David; Tsiamis, Achilleas

2017-11-01

Emergency laparotomy is a commonly performed high-mortality surgical procedure. The National Emergency Laparotomy Network (NELA) published an average mortality rate of 11.1% and a median length of stay equivalent to 16.3 days in patients undergoing emergency laparotomy. This study presents a completed audit loop after implementing the change of increasing the number of on-call surgeons in the general surgery rota of a university hospital. The aim of this study was to evaluate the outcomes of emergency laparotomy in a single UK tertiary centre after addition of one more consultant in the daily on-call rota. This is a retrospective study involving patients who underwent emergency laparotomy between March to May 2013 (first audit) and June to August 2015 (second audit). The study parameters stayed the same. The adult patients undergoing emergency laparotomy under the general surgical take were included. Appendicectomy, cholecystectomy and simple inguinal hernia repair patients were excluded. Data was collected on patient demographics, ASA, morbidity, 30-day mortality and length of hospital stay. Statistical analysis including logistic regression was performed using SPSS. During the second 3-month period, 123 patients underwent laparotomy compared to 84 in the first audit. Median age was 65(23-93) years. 56.01% cases were ASA III or above in the re-audit compared to 41.9% in the initial audit. 38% patients had bowel anastomosis compared to 35.7% in the re-audit with 4.2% leak rate in the re-audit compared to 16.6% in the first audit. 30-day mortality was 10.50% in the re-audit compared to 21% and median length of hospital stay 11 days in the re-audit compared to 16 days. The lower ASA grade was significantly associated with increased likelihood of being alive, as was being female, younger age and not requiring ITU admission post-operatively. However, having a second on-call consultant was 2.231 times more likely to increase the chances of patients not dying (p = 0.031). Our audit-loop suggests that adding a second consultant to the daily on-call rota significantly reduces postoperative mortality and morbidity. Age, ASA and ITU admission are other independent factors affecting patient outcomes. We suggest this change be applied to other high volume centres across the country to improve the outcomes after emergency laparotomy.

Carbon–hydrogen (C–H) bond activation at PdIV: a Frontier in C–H functionalization catalysis

PubMed Central

Topczewski, Joseph J.

2015-01-01

The direct functionalization of carbon–hydrogen (C–H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C–H bond activation, catalytic processes that utilize a PdII/PdIV redox cycle are increasingly common. The C–H activation step in most of these catalytic cycles is thought to occur at a PdII centre. However, a number of recent reports have suggested the feasibility of C–H cleavage occurring at PdIV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at PdII. This mini review highlights proposed examples of C–H activation at PdIV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed. PMID:25544882

Carbon-Hydrogen (C-H) Bond Activation at PdIV: A Frontier in C-H Functionalization Catalysis.

PubMed

Topczewski, Joseph J; Sanford, Melanie S

2015-01-01

The direct functionalization of carbon-hydrogen (C-H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C-H bond activation, catalytic processes that utilize a Pd II /Pd IV redox cycle are increasingly common. The C-H activation step in most of these catalytic cycles is thought to occur at a Pd II centre. However, a number of recent reports have suggested the feasibility of C-H cleavage occurring at Pd IV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at Pd II . This Mini Review highlights proposed examples of C-H activation at Pd IV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed.

Human cataract: the mechanisms responsible; light and butterfly eyes.

PubMed

Truscott, R J W

2003-11-01

Age-related cataract is the leading cause of world blindness. Until recently, the biochemical mechanisms that result in human cataract formation have remained a mystery. In the case of nuclear cataract, it is becoming apparent that changes that take place within the lens at middle age may be ultimately responsible. The centre of the lens contains proteins that were synthesised prior to birth and while these crystallins are remarkably stable, it appears that an antioxidant environment may be necessary in order for them to remain soluble and for lens transparency. Once an internal barrier to the movement of small molecules, such as antioxidants, develops in the normal lens at middle age, the long-lived proteins in the lens centre become susceptible both to covalent attachment of reactive molecules, such as UV filters, and to oxidation. These processes of protein modification may, over time, lead inevitably to lens opacification and cataract.

Prevalence of HIV in pregnant women identified with a risk factor at a tertiary care hospital.

PubMed

Mahmud, Ghazala; Abbas, Shazra

2009-01-01

HIV is an epidemic quite unlike any other, combining the problems of a lifelong medical disease with immense social, psychological, economic and public health consequences. Since we are living in a global village where human interactions has become fast and frequent, diseases like HIV are no more alien to us. HIV/AIDS in Pakistan is slowly gaining recognition as a public health issue of great importance. Objectives of this study were to determine the prevalence of HIV in pregnant women identified with a high risk factor/behaviour at a tertiary care hospital. It is a Descriptive study. All pregnant women attending antenatal booking clinic were assessed via a pre-designed 'Risk assessment questionnaire'. Women identified with a risk factor were offered HIV Rapid screening test (Capillus HIV1/2). Positive (reactive) results on screening test were confirmed with ELISA. During the study period (March 2007-May 2008), out of 5263 antenatal bookings 785 (14%) women were identified with a risk factor. HIV screening test was done in 779 (99%), and 6 women refused testing. Three women (0.3%) were found positive (reactive) on screening. Two out of 3 women were confirmed positive (0.2%) on ELISA. Husbands of both women were tested and one found positive (migrant from Dubai). Second women had history of blood transfusion. Her husband was HIV negative. During the study period, in addition to 2 pregnant women diagnosed as HIV positive through ANC risk screening, 6 confirmed HIV positive women, found pregnant were referred from 'HIV Treatment Centre', Pakistan Institute of Medical Sciences (PIMS) to Prevention of Parent to Child Transmission (PPTCT) centre for obstetric care. Spouses of 5 out of 6 had history of working abroad and extramarital sexual relationships. All positive (8) women were referred to PPTCT centre for further management. A simple 'Risk Assessment Questionnaire' can help us in identifying women who need HIV screening. Sexual transmission still remains the commonest cause of HIV transmission.

Interface Matters: The Stiffness Route to Stability of a Thermophilic Tetrameric Malate Dehydrogenase

PubMed Central

Kalimeri, Maria; Girard, Eric; Madern, Dominique; Sterpone, Fabio

2014-01-01

In this work we investigate by computational means the behavior of two orthologous bacterial proteins, a mesophilic and a thermophilic tetrameric malate dehydrogenase (MalDH), at different temperatures. Namely, we quantify how protein mechanical rigidity at different length- and time-scales correlates to protein thermophilicity as commonly believed. In particular by using a clustering analysis strategy to explore the conformational space of the folded proteins, we show that at ambient conditions and at the molecular length-scale the thermophilic variant is indeed more rigid that the mesophilic one. This rigidification is the result of more efficient inter-domain interactions, the strength of which is further quantified via ad hoc free energy calculations. When considered isolated, the thermophilic domain is indeed more flexible than the respective mesophilic one. Upon oligomerization, the induced stiffening of the thermophilic protein propagates from the interface to the active site where the loop, controlling the access to the catalytic pocket, anchors down via an extended network of ion-pairs. On the contrary in the mesophilic tetramer the loop is highly mobile. Simulations at high temperature, could not re-activate the mobility of the loop in the thermophile. This finding opens questions on the similarities of the binding processes for these two homologues at their optimal working temperature and suggests for the thermophilic variant a possible cooperative role of cofactor/substrate. PMID:25437494

Interface matters: the stiffness route to stability of a thermophilic tetrameric malate dehydrogenase.

PubMed

Kalimeri, Maria; Girard, Eric; Madern, Dominique; Sterpone, Fabio

2014-01-01

In this work we investigate by computational means the behavior of two orthologous bacterial proteins, a mesophilic and a thermophilic tetrameric malate dehydrogenase (MalDH), at different temperatures. Namely, we quantify how protein mechanical rigidity at different length- and time-scales correlates to protein thermophilicity as commonly believed. In particular by using a clustering analysis strategy to explore the conformational space of the folded proteins, we show that at ambient conditions and at the molecular length-scale the thermophilic variant is indeed more rigid that the mesophilic one. This rigidification is the result of more efficient inter-domain interactions, the strength of which is further quantified via ad hoc free energy calculations. When considered isolated, the thermophilic domain is indeed more flexible than the respective mesophilic one. Upon oligomerization, the induced stiffening of the thermophilic protein propagates from the interface to the active site where the loop, controlling the access to the catalytic pocket, anchors down via an extended network of ion-pairs. On the contrary in the mesophilic tetramer the loop is highly mobile. Simulations at high temperature, could not re-activate the mobility of the loop in the thermophile. This finding opens questions on the similarities of the binding processes for these two homologues at their optimal working temperature and suggests for the thermophilic variant a possible cooperative role of cofactor/substrate.

Customization of home closed-loop insulin delivery in adult patients with type 1 diabetes, assisted with structured remote monitoring: the pilot WP7 Diabeloop study.

PubMed

Benhamou, Pierre Yves; Huneker, Erik; Franc, Sylvia; Doron, Maeva; Charpentier, Guillaume

2018-06-01

Improvement in closed-loop insulin delivery systems could result from customization of settings to individual needs and remote monitoring. This pilot home study evaluated the efficacy and relevance of this approach. A bicentric clinical trial was conducted for 3 weeks, using an MPC-based algorithm (Diabeloop Artificial Pancreas system) featuring five settings designed to modulate the reactivity of regulation. Remote monitoring was ensured by expert nurses with a web platform generating automatic Secured Information Messages (SIMs) and with a structured procedure. Endpoints were glucose metrics and description of impact of monitoring on regulation parameters. Eight patients with type 1 diabetes (six men, age 41.8 ± 11.4 years, HbA1c 7.7 ± 1.0%) were included. Time spent in the 70-180 mg/dl range was 70.2% [67.5; 76.9]. Time in hypoglycemia < 70 mg/dl was 2.9% [2.1; 3.4]. Eleven SIMs led to phone intervention. Original default settings were modified in all patients by the intervention of the nurses. This pilot trial suggests that the Diabeloop closed-loop system could be efficient regarding metabolic outcomes, whereas its telemedical monitoring feature could contribute to enhanced efficacy and safety. This study is registered at ClinicalTrials.gov with trial registration number NCT02987556.

Development and evaluation of a loop-mediated isothermal amplification assay for rapid detection of lymphocystis disease virus.

PubMed

Li, Qiong; Yue, Zhiqin; Liu, Hong; Liang, Chengzhu; Zheng, Xiaolong; Zhao, Yuran; Chen, Xiao; Xiao, Xizhi; Chen, Changfu

2010-02-01

A loop-mediated isothermal amplification (LAMP) assay was developed for the detection of lymphocystis disease virus (LCDV). A set of five specific primers, two inner and two outer primers and a loop primer, were designed on the basis of the major capsid protein gene of LCDV. The reaction time and temperatures were optimized for 60 min at 63 degrees C, respectively. LAMP amplification products were detected by a ladder-like appearance on agarose gel electrophoresis or a naked-eye inspection of a color change in the reaction tube by addition of SYBR Green I. The assay was specific for LCDV, and there was no cross-reactivity with white spot syndrome virus (WSSV) or six other Iridoviridae viruses (epizootic hematopoietic necrosis virus, EHNV; tiger frog virus, TFV; Bohle iridovirus, BIV; soft-shelled turtle iridovirus, STIV; infectious spleen and kidney necrosis virus, ISKNV; red sea bream iridovirus, RSIV). The detection limit of the LAMP assay was 15 fg, which was similar to that of real-time quantitative polymerase chain reaction (PCR) and 10-fold higher than the conventional PCR. The LAMP assay was evaluated using 109 clinical samples, and the results indicated the suitability and simplicity of the test as a rapid, field diagnostic tool for detection of LCDV. The LCDV LAMP assay has potential for early diagnosis of LCDV infection. 2009 Elsevier B.V. All rights reserved.

Buoyancy Driven Coolant Mixing Studies of Natural Circulation Flows at the ROCOM Test Facility Using ANSYS CFX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hohne, Thomas; Kliem, Soren; Rohde, Ulrich

2006-07-01

Coolant mixing in the cold leg, downcomer and the lower plenum of pressurized water reactors is an important phenomenon mitigating the reactivity insertion into the core. Therefore, mixing of the de-borated slugs with the ambient coolant in the reactor pressure vessel was investigated at the four loop 1:5 scaled ROCOM mixing test facility. Thermal hydraulics analyses showed, that weakly borated condensate can accumulate in particular in the pump loop seal of those loops, which do not receive safety injection. After refilling of the primary circuit, natural circulation in the stagnant loops can re-establish simultaneously and the de-borated slugs are shiftedmore » towards the reactor pressure vessel (RPV). In the ROCOM experiments, the length of the flow ramp and the initial density difference between the slugs and the ambient coolant was varied. From the test matrix experiments with 0 resp. 2% density difference between the de-borated slugs and the ambient coolant were used to validate the CFD software ANSYS CFX. To model the effects of turbulence on the mean flow a higher order Reynolds stress turbulence model was employed and a mesh consisting of 6.4 million hybrid elements was utilized. Only the experiments and CFD calculations with modeled density differences show a stratification in the downcomer. Depending on the degree of density differences the less dense slugs flow around the core barrel at the top of the downcomer. At the opposite side the lower borated coolant is entrained by the colder safety injection water and transported to the core. The validation proves that ANSYS CFX is able to simulate appropriately the flow field and mixing effects of coolant with different densities. (authors)« less

Effects of V2O3 buffer layers on sputtered VO2 smart windows: Improved thermochromic properties, tunable width of hysteresis loops and enhanced durability

NASA Astrophysics Data System (ADS)

Long, Shiwei; Cao, Xun; Sun, Guangyao; Li, Ning; Chang, Tianci; Shao, Zewei; Jin, Ping

2018-05-01

Vanadium dioxide (VO2) is one of the most well-known thermochromic materials, which exhibits a notable optical change from transparent to reflecting in the infrared region upon a metal-insulator phase transition. For practical applications, VO2 thin films should be in high crystalline quality to obtain a strong solar modulation ability (ΔTsol). Meanwhile, narrow hysteresis loops and robust ambient durability are also indispensable for sensitivity and long-lived utilization, respectively. In this work, a series of high-quality V2O3/VO2 bilayer structures were grown on quartz glass substrates by reactive magnetron sputtering. Basically, the bottom V2O3 acts as the buffer layer to improve the crystallinity of the top VO2, while the VO2 serves as the thermochromic layer to guarantee the solar modulation ability for energy-saving. We observed an obvious increase in ΔTsol of 76% (from 7.5% to 13.2%) for VO2 films after introducing V2O3 buffer layers. Simultaneously, a remarkable reduction by 79% (from 21.9 °C to 4.7 °C) in width of hysteresis loop was obtained when embedding 60 nm V2O3 buffer for 60 nm VO2. In addition, VO2 with non-stoichiometry of V2O3±x buffer demonstrates a broadening hysteresis loops width, which is derived from the lattice distortion caused by lattice imperfection. Finally, durability of VO2 has been significantly improved due to positive effects of V2O3 buffer layer. Our results lead to a comprehensive enhancement in crystallinity of VO2 and shed new light on the promotion of thermochromic property by homologous oxides for VO2.

Trauma teams and time to early management during in situ trauma team training.

PubMed

Härgestam, Maria; Lindkvist, Marie; Jacobsson, Maritha; Brulin, Christine; Hultin, Magnus

2016-01-29

To investigate the association between the time taken to make a decision to go to surgery and gender, ethnicity, years in profession, experience of trauma team training, experience of structured trauma courses and trauma in the trauma team, as well as use of closed-loop communication and leadership styles during trauma team training. In situ trauma team training. The patient simulator was preprogrammed to represent a severely injured patient (injury severity score: 25) suffering from hypovolemia due to external trauma. An emergency room in an urban Scandinavian level one trauma centre. A total of 96 participants were divided into 16 trauma teams. Each team consisted of six team members: one surgeon/emergency physician (designated team leader), one anaesthesiologist, one registered nurse anaesthetist, one registered nurse from the emergency department, one enrolled nurse from the emergency department and one enrolled nurse from the operating theatre. HRs with CIs (95% CI) for the time taken to make a decision to go to surgery was computed from a Cox proportional hazards model. Three variables remained significant in the final model. Closed-loop communication initiated by the team leader increased the chance of a decision to go to surgery (HR: 3.88; CI 1.02 to 14.69). Only 8 of the 16 teams made the decision to go to surgery within the timeframe of the trauma team training. Conversely, call-outs and closed-loop communication initiated by the team members significantly decreased the chance of a decision to go to surgery, (HR: 0.82; CI 0.71 to 0.96, and HR: 0.23; CI 0.08 to 0.71, respectively). Closed-loop communication initiated by the leader appears to be beneficial for teamwork. In contrast, a high number of call-outs and closed-loop communication initiated by team members might lead to a communication overload. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Synthesis, structure and reaction chemistry of a nucleophilic aluminyl anion.

PubMed

Hicks, Jamie; Vasko, Petra; Goicoechea, Jose M; Aldridge, Simon

2018-05-01

The reactivity of aluminium compounds is dominated by their electron deficiency and consequent electrophilicity; these compounds are archetypal Lewis acids (electron-pair acceptors). The main industrial roles of aluminium, and classical methods of synthesizing aluminium-element bonds (for example, hydroalumination and metathesis), draw on the electron deficiency of species of the type AlR 3 and AlCl 3 1,2 . Whereas aluminates, [AlR 4 ] - , are well known, the idea of reversing polarity and using an aluminium reagent as the nucleophilic partner in bond-forming substitution reactions is unprecedented, owing to the fact that low-valent aluminium anions analogous to nitrogen-, carbon- and boron-centred reagents of the types [NX 2 ] - , [CX 3 ] - and [BX 2 ] - are unknown 3-5 . Aluminium compounds in the +1 oxidation state are known, but are thermodynamically unstable with respect to disproportionation. Compounds of this type are typically oligomeric 6-8 , although monomeric systems that possess a metal-centred lone pair, such as Al(Nacnac) Dipp (where (Nacnac) Dipp  = (NDippCR) 2 CH and R =  t Bu, Me; Dipp = 2,6- i Pr 2 C 6 H 3 ), have also been reported 9,10 . Coordination of these species, and also of (η 5 -C 5 Me 5 )Al, to a range of Lewis acids has been observed 11-13 , but their primary mode of reactivity involves facile oxidative addition to generate Al(III) species 6-8,14-16 . Here we report the synthesis, structure and reaction chemistry of an anionic aluminium(I) nucleophile, the dimethylxanthene-stabilized potassium aluminyl [K{Al(NON)}] 2 (NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene). This species displays unprecedented reactivity in the formation of aluminium-element covalent bonds and in the C-H oxidative addition of benzene, suggesting that it could find further use in both metal-carbon and metal-metal bond-forming reactions.

Structure and reactivity of a mononuclear non-haem iron(III)–peroxo complex

PubMed Central

Cho, Jaeheung; Jeon, Sujin; Wilson, Samuel A.; Liu, Lei V.; Kang, Eun A; Braymer, Joseph J.; Lim, Mi Hee; Hedman, Britt; Hodgson, Keith O.; Valentine, Joan Selverstone; Solomon, Edward I.; Nam, Wonwoo

2012-01-01

Oxygen-containing mononuclear iron species—iron(III)–peroxo, iron(III)–hydroperoxo and iron(IV)–oxo—are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes1–7. It has been difficult to generate synthetic analogues of these three active iron–oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron centre during catalysis and the factors that control their chemical reactivities with substrates. Here we report the high-resolution crystal structure of a mononuclear non-haem side-on iron(III)–peroxo complex, [Fe(III)(TMC)(OO)]+. We also report a series of chemical reactions in which this iron(III)–peroxo complex is cleanly converted to the iron(III)–hydroperoxo complex, [Fe(III)(TMC)(OOH)]2+, via a short-lived intermediate on protonation. This iron(III)–hydroperoxo complex then cleanly converts to the ferryl complex, [Fe(IV)(TMC)(O)]2+, via homolytic O–O bond cleavage of the iron(III)–hydroperoxo species. All three of these iron species—the three most biologically relevant iron–oxygen intermediates—have been spectroscopically characterized; we note that they have been obtained using a simple macrocyclic ligand. We have performed relative reactivity studies on these three iron species which reveal that the iron(III)–hydroperoxo complex is the most reactive of the three in the deformylation of aldehydes and that it has a similar reactivity to the iron(IV)–oxo complex in C–H bond activation of alkylaromatics. These reactivity results demonstrate that iron(III)–hydroperoxo species are viable oxidants in both nucleophilic and electrophilic reactions by iron-containing enzymes. PMID:22031443

TREAT Neutronics Analysis of Water-Loop Concept Accommodating LWR 9-rod Bundle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, Connie M.; Woolstenhulme, Nicolas E.; Parry, James R.

Abstract. Simulation of a variety of transient conditions has been successfully achieved in the Transient Reactor Test (TREAT) facility during operation between 1959 and 1994 to support characterization and safety analysis of nuclear fuels and materials. A majority of previously conducted tests were focused on supporting sodium-cooled fast reactor (SFR) designs. Experiments evolved in complexity. Simulation of thermal-hydraulic conditions expected to be encountered by fuels and materials in a reactor environment was realized in the development of TREAT sodium loop experiment vehicles. These loops accommodated up to 7-pin fuel bundles and served to simulate more closely the reactor environment whilemore » safely delivering large quantities of energy into the test specimen. Some of the immediate TREAT restart operations will be focused on testing light water reactor (LWR) accident tolerant fuels (ATF). Similar to the sodium loop objectives, a water loop concept, developed and analyzed in the 1990’s, aimed at achieving thermal-hydraulic conditions encountered in commercial power reactors. The historic water loop concept has been analyzed in the context of a reactivity insertion accident (RIA) simulation for high burnup LWR 2-pin and 3-pin fuel bundles. Findings showed sufficient energy could be deposited into the specimens for evaluation. Similar results of experimental feasibility for the water loop concept (past and present) have recently been obtained using MCNP6.1 with ENDF/B-VII.1 nuclear data libraries. The old water loop concept required only two central TREAT core grid spaces. Preparation for future experiments has resulted in a modified water loop conceptual design designated the TREAT water environment recirculating loop (TWERL). The current TWERL design requires nine TREAT core grid spaces in order to place the water recirculating pump under the TREAT core. Due to the effectiveness of water moderation, neutronics analysis shows that removal of seven additional TREAT fuel elements to facilitate the experiment will not inhibit the ability to successfully simulate a RIA for the 2-pin or 3-pin bundle. This new water loop design leaves room for accommodating a larger fuel pin bundle than previously analyzed. The 7-pin fuel bundle in a hexagonal array with similar spacing of fuel pins in a SFR fuel assembly was considered the minimum needed for one central fuel pin to encounter the most correct thermal conditions. The 9-rod fuel bundle in a square array similar in spacing to pins in a LWR fuel assembly would be considered the LWR equivalent. MCNP analysis conducted on a preliminary LWR 9-rod bundle design shows that sufficient energy deposition into the central pin can be achieved well within range to investigate fuel and cladding performance in a simulated RIA. This is achieved by surrounding the flow channel with an additional annulus of water. Findings also show that a highly significant increase in TREAT to specimen power coupling factor (PCF) within the central pin can be achieved by surrounding the experiment with one to two rings of TREAT upgrade fuel assemblies. The experiment design holds promise for the performance evaluation of PWR fuel at extremely high burnup under similar reactor environment conditions.« less

Integrative systems control approach for reactivating Kaposi's sarcoma-associated herpesvirus (KSHV) with combinatory drugs

PubMed Central

Sun, Chien-Pin; Usui, Takane; Yu, Fuqu; Al-Shyoukh, Ibrahim; Shamma, Jeff; Sun, Ren; Ho, Chih-Ming

2009-01-01

Cells serve as basic units of life and represent intricate biological molecular systems. The vast number of cellular molecules with their signaling and regulatory circuitries forms an intertwined network. In this network, each pathway interacts non-linearly with others through different intermediates. Thus, the challenge of manipulating cellular functions for desired outcomes, such as cancer eradication and controlling viral infection lies within the integrative system of regulatory circuitries. By using a closed-loop system control scheme, we can efficiently analyze biological signaling networks and manipulate their behavior through multiple stimulations on a collection of pathways. Specifically, we aimed to maximize the reactivation of Kaposi's Sarcoma-associated Herpesvirus (KSHV) in a Primary Effusion Lymphoma cell line. The advantage of this approach is that it is well-suited to study complex integrated systems; it circumvents the need for detailed information of individual signaling components; and it investigates the network as a whole by utilizing key systemic outputs as indicators. PMID:19851479

Integrative systems control approach for reactivating Kaposi's sarcoma-associated herpesvirus (KSHV) with combinatory drugs.

PubMed

Sun, Chien-Pin; Usui, Takane; Yu, Fuqu; Al-Shyoukh, Ibrahim; Shamma, Jeff; Sun, Ren; Ho, Chih-Ming

2009-01-01

Cells serve as basic units of life and represent intricate biological molecular systems. The vast number of cellular molecules with their signaling and regulatory circuitries forms an intertwined network. In this network, each pathway interacts non-linearly with others through different intermediates. Thus, the challenge of manipulating cellular functions for desired outcomes, such as cancer eradication and controlling viral infection lies within the integrative system of regulatory circuitries. By using a closed-loop system control scheme, we can efficiently analyze biological signaling networks and manipulate their behavior through multiple stimulations on a collection of pathways. Specifically, we aimed to maximize the reactivation of Kaposi's Sarcoma-associated Herpesvirus (KSHV) in a Primary Effusion Lymphoma cell line. The advantage of this approach is that it is well-suited to study complex integrated systems; it circumvents the need for detailed information of individual signaling components; and it investigates the network as a whole by utilizing key systemic outputs as indicators.

Atmospheric-pressure plasma decontamination/sterilization chamber

DOEpatents

Herrmann, Hans W.; Selwyn, Gary S.

2001-01-01

An atmospheric-pressure plasma decontamination/sterilization chamber is described. The apparatus is useful for decontaminating sensitive equipment and materials, such as electronics, optics and national treasures, which have been contaminated with chemical and/or biological warfare agents, such as anthrax, mustard blistering agent, VX nerve gas, and the like. There is currently no acceptable procedure for decontaminating such equipment. The apparatus may also be used for sterilization in the medical and food industries. Items to be decontaminated or sterilized are supported inside the chamber. Reactive gases containing atomic and metastable oxygen species are generated by an atmospheric-pressure plasma discharge in a He/O.sub.2 mixture and directed into the region of these items resulting in chemical reaction between the reactive species and organic substances. This reaction typically kills and/or neutralizes the contamination without damaging most equipment and materials. The plasma gases are recirculated through a closed-loop system to minimize the loss of helium and the possibility of escape of aerosolized harmful substances.

Effects of sputtering mode on the microstructure and ionic conductivity of yttria-stabilized zirconia films

NASA Astrophysics Data System (ADS)

Yeh, Tsung-Her; Lin, Ruei-De; Cherng, Bo-Ruei; Cherng, Jyh-Shiarn

2018-05-01

The microstructure and ionic conductivity of reactively sputtered yttria-stabilized zirconia (YSZ) films are systematically studied. Those films were reactively sputtered in various sputtering modes using a closed-loop controlled system with plasma emission monitoring. A transition-mode sputtering corresponding to 45% of target poisoning produces a microstructure with ultrafine crystallites embedded in an amorphous matrix, which undergoes an abnormal grain growth upon annealing at 800 °C. At 500 °C, the measured ionic conductivity of this annealed film is higher, by about a half order of magnitude, than those of its poisoned-mode counterparts, which are in turn significantly higher than that of the YSZ bulk by about two orders of magnitude. The abnormally-grown ultra-large grain size of the film deposited in the transition mode and then annealed is believed to be responsible for the former comparison due to the suppression of the grain boundary blocking effect, while the latter comparison can be attributed to the interface effect.

The geometric phase controls ultracold chemistry

DOE PAGES

Kendrick, B. K.; Hazra, Jisha; Balakrishnan, N.

2015-07-30

In this study, the geometric phase is shown to control the outcome of an ultracold chemical reaction. The control is a direct consequence of the sign change on the interference term between two scattering pathways (direct and looping), which contribute to the reactive collision process in the presence of a conical intersection (point of degeneracy between two Born–Oppenheimer electronic potential energy surfaces). The unique properties of the ultracold energy regime lead to an effective quantization of the scattering phase shift enabling maximum constructive or destructive interference between the two pathways. By taking the O + OH → H + Omore » 2 reaction as an illustrative example, it is shown that inclusion of the geometric phase modifies ultracold reaction rates by nearly two orders of magnitude. Interesting experimental control possibilities include the application of external electric and magnetic fields that might be used to exploit the geometric phase effect reported here and experimentally switch on or off the reactivity.« less

Phosphorylation of basic helix-loop-helix transcription factor Twist in development and disease.

PubMed

Xue, Gongda; Hemmings, Brian A

2012-02-01

The transcription factor Twist plays vital roles during embryonic development through regulating/controlling cell migration. However, postnatally, in normal physiological settings, Twist is either not expressed or inactivated. Increasing evidence shows a strong correlation between Twist reactivation and both cancer progression and malignancy, where the transcriptional activities of Twist support cancer cells to disseminate from primary tumours and subsequently establish a secondary tumour growth in distant organs. However, it is largely unclear how this signalling programme is reactivated or what signalling pathways regulate its activity. The present review discusses recent advances in Twist regulation and activity, with a focus on phosphorylation-dependent Twist activity, potential upstream kinases and the contribution of these factors in transducing biological signals from upstream signalling complexes. The recent advances in these areas have shed new light on how phosphorylation-dependent regulation of the Twist proteins promotes or suppresses Twist activity, leading to differential regulation of Twist transcriptional targets and thereby influencing cell fate.

Evaluation by the Double Loop Electrochemical Potentiokinetic Reactivation Test of Aged Ferritic Stainless Steel Intergranular Corrosion Susceptibility

NASA Astrophysics Data System (ADS)

Sidhom, H.; Amadou, T.; Braham, C.

2010-12-01

An experimental design method was used to determine the effect of factors that significantly affect the response of the double loop-electrochemical potentiokinetic reactivation (DL-EPR) test in controlling the susceptibility to intergranular corrosion (IGC) of UNS S43000 (AISI 430) ferritic stainless steel. The test response is expressed in terms of the reactivation/activation current ratio ( I r / I a pct). Test results analysed by the analysis of variance (ANOVA) method show that the molarity of the H2SO4 electrolyte and the potential scanning rate have a more significant effect on the DL-EPR test response than the temperature and the depassivator agent concentration. On the basis of these results, a study was conducted in order to determine the optimal operating conditions of the test as a nondestructive technique for evaluating IGC resistance of ferritic stainless steel components. Three different heat treatments are considered in this study: solution annealing (nonsensitized), aging during 3 hours at 773 K (500 °C) (slightly sensitized), and aging during 2 hours at 873 K (600 °C) (highly sensitized). The aim is to find the operating conditions that simultaneously ensure the selectivity of the attack (intergranular and chromium depleted zone) and are able to detect the effect of low dechromization. It is found that a potential scanning rate of 2.5 mV/s in an electrolyte composed of H2SO4 3 M solution without depassivator, at a temperature around 293 K (20 °C), is the optimal operating condition for the DL-EPR test. Using this condition, it is possible to assess the degree of sensitization (DOS) to the IGC of products manufactured in ferritic stainless steels rapidly, reliably, and quantitatively. A time-temperature-start of sensitization (TTS) diagram for the UNS S43000 (France Inox, Villepinte, France) stainless steel was obtained with acceptable accuracy by this method when the IGC sensitization criterion was set to I r / I a > 1 pct. This diagram is in good agreement with the time-temperature-start of precipitation (TTP) diagram that delineates the domain of low dechromization consecutive to chromium carbide precipitation.

Multiple-object tracking as a tool for parametrically modulating memory reactivation

PubMed Central

Poppenk, J.; Norman, K.A.

2017-01-01

Converging evidence supports the “non-monotonic plasticity” hypothesis that although complete retrieval may strengthen memories, partial retrieval weakens them. Yet, the classic experimental paradigms used to study effects of partial retrieval are not ideally suited to doing so, because they lack the parametric control needed to ensure that the memory is activated to the appropriate degree (i.e., that there is some retrieval, but not enough to cause memory strengthening). Here we present a novel procedure designed to accommodate this need. After participants learned a list of word-scene associates, they completed a cued mental visualization task that was combined with a multiple-object tracking (MOT) procedure, which we selected for its ability to interfere with mental visualization in a parametrically adjustable way (by varying the number of MOT targets). We also used fMRI data to successfully train an “associative recall” classifier for use in this task: this classifier revealed greater memory reactivation during trials in which associative memories were cued while participants tracked one, rather than five MOT targets. However, the classifier was insensitive to task difficulty when recall was not taking place, suggesting it had indeed tracked memory reactivation rather than task difficulty per se. Consistent with the classifier findings, participants’ introspective ratings of visualization vividness were modulated by MOT task difficulty. In addition, we observed reduced classifier output and slowing of responses in a post-reactivation memory test, consistent with the hypothesis that partial reactivation, induced by MOT, weakened memory. These results serve as a “proof of concept” that MOT can be used to parametrically modulate memory retrieval – a property that may prove useful in future investigation of partial retrieval effects, e.g., in closed-loop experiments. PMID:28387587

Crystal structure of a c-kit promoter quadruplex reveals the structural role of metal ions and water molecules in maintaining loop conformation.

PubMed

Wei, Dengguo; Parkinson, Gary N; Reszka, Anthony P; Neidle, Stephen

2012-05-01

We report here the 1.62 Å crystal structure of an intramolecular quadruplex DNA formed from a sequence in the promoter region of the c-kit gene. This is the first reported crystal structure of a promoter quadruplex and the first observation of localized magnesium ions in a quadruplex structure. The structure reveals that potassium and magnesium ions have an unexpected yet significant structural role in stabilizing particular quadruplex loops and grooves that is distinct from but in addition to the role of potassium ions in the ion channel at the centre of all quadruplex structures. The analysis also shows how ions cluster together with structured water molecules to stabilize the quadruplex arrangement. This particular quadruplex has been previously studied by NMR methods, and the present X-ray structure is in accord with the earlier topology assignment. However, as well as the observations of potassium and magnesium ions, the crystal structure has revealed a highly significant difference in the dimensions of the large cleft in the structure, which is a plausible target for small molecules. This difference can be understood by the stabilizing role of structured water networks.

Intracellular Serine Protease Inhibitor SERPINB4 Inhibits Granzyme M-Induced Cell Death

PubMed Central

de Koning, Pieter J. A.; Kummer, J. Alain; de Poot, Stefanie A. H.; Quadir, Razi; Broekhuizen, Roel; McGettrick, Anne F.; Higgins, Wayne J.; Devreese, Bart; Worrall, D. Margaret; Bovenschen, Niels

2011-01-01

Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e. GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of intracellular serine protease inhibitors (serpins) is one of the mechanisms by which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular expression of SERPINB9 by tumor cells renders them resistant to GrB-induced apoptosis. In contrast to GrB, however, no physiological intracellular inhibitors are known for the other four human granzymes. In the present study, we show that SERPINB4 formed a typical serpin-protease SDS-stable complex with both recombinant and native human GrM. Mutation of the P2-P1-P1′ triplet in the SERPINB4 reactive center loop completely abolished complex formation with GrM and N-terminal sequencing revealed that GrM cleaves SERPINB4 after P1-Leu. SERPINB4 inhibited GrM activity with a stoichiometry of inhibition of 1.6 and an apparent second order rate constant of 1.3×104 M−1s−1. SERPINB4 abolished cleavage of the macromolecular GrM substrates α-tubulin and nucleophosmin. Overexpression of SERPINB4 in tumor cells inhibited recombinant GrM-induced as well as NK cell-mediated cell death and this inhibition depended on the reactive center loop of the serpin. As SERPINB4 is highly expressed by squamous cell carcinomas, our results may represent a novel mechanism by which these tumor cells evade cytotoxic lymphocyte-induced GrM-mediated cell death. PMID:21857942

Pyrite footprinting of RNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlatterer, Joerg C., E-mail: joerg.schlatterer@einstein.yu.edu; Wieder, Matthew S.; Jones, Christopher D.

2012-08-24

Highlights: Black-Right-Pointing-Pointer RNA structure is mapped by pyrite mediated {sup {center_dot}}OH footprinting. Black-Right-Pointing-Pointer Repetitive experiments can be done in a powdered pyrite filled cartridge. Black-Right-Pointing-Pointer High {sup {center_dot}}OH reactivity of nucleotides imply dynamic role in Diels-Alderase catalysis. -- Abstract: In RNA, function follows form. Mapping the surface of RNA molecules with chemical and enzymatic probes has revealed invaluable information about structure and folding. Hydroxyl radicals ({sup {center_dot}}OH) map the surface of nucleic acids by cutting the backbone where it is accessible to solvent. Recent studies showed that a microfluidic chip containing pyrite (FeS{sub 2}) can produce sufficient {sup {center_dot}}OH tomore » footprint DNA. The 49-nt Diels-Alder RNA enzyme catalyzes the C-C bond formation between a diene and a dienophile. A crystal structure, molecular dynamics simulation and atomic mutagenesis studies suggest that nucleotides of an asymmetric bulge participate in the dynamic architecture of the ribozyme's active center. Of note is that residue U42 directly interacts with the product in the crystallized RNA/product complex. Here, we use powdered pyrite held in a commercially available cartridge to footprint the Diels-Alderase ribozyme with single nucleotide resolution. Residues C39 to U42 are more reactive to {sup {center_dot}}OH than predicted by the solvent accessibility calculated from the crystal structure suggesting that this loop is dynamic in solution. The loop's flexibility may contribute to substrate recruitment and product release. Our implementation of pyrite-mediated {sup {center_dot}}OH footprinting is a readily accessible approach to gleaning information about the architecture of small RNA molecules.« less

Loop-mediated isothermal amplification (LAMP): early detection of Toxoplasma gondii infection in mice.

PubMed

Kong, Qing-Ming; Lu, Shao-Hong; Tong, Qun-Bo; Lou, Di; Chen, Rui; Zheng, Bin; Kumagai, Takashi; Wen, Li-Yong; Ohta, Nobuo; Zhou, Xiao-Nong

2012-01-03

Toxoplasmosis is a widespread zoonotic parasitic disease that occurs in both animals and humans. Traditional molecular assays are often difficult to perform, especially for the early diagnosis of Toxoplasma gondii infections. Here, we established a novel loop-mediated isothermal amplification targeting the 529 bp repeat element (529 bp-LAMP) to detect T. gondii DNA in blood samples of experimental mice infected with tachyzoites of the RH strain. The assay was performed with Bst DNA polymerase at 65°C for 1 h. The detection limit of the 529 bp-LAMP assay was as low as 0.6 fg of T. gondii DNA. The sensitivity of this assay was 100 and 1000 fold higher than that of the LAMP targeting B1 gene (B1-LAMP) and nested PCR targeting 529 bp repeat element (529 bp-nested PCR), respectively. The specificity of the 529 bp-LAMP assay was determined using the DNA samples of Trypanosoma evansi, Plasmodium falciparum, Paragonimus westermani, Schistosoma japonicum, Fasciola hepatica and Angiostrongylus cantonensis. No cross-reactivity with the DNA of any parasites was found. The assay was able to detect T. gondii DNA in all mouse blood samples at one day post infection (dpi). We report the following findings: (i) The detection limit of the 529 bp-LAMP assay is 0.6 fg of T. gondii DNA; (ii) The assay does not involve any cross-reactivity with the DNA of other parasites; (iii) This is the first report on the application of the LAMP assay for early diagnosis of toxoplasmosis in blood samples from experimentally infected mice. Due to its simplicity, sensitivity and cost-effectiveness for common use, we suggest that this assay should be used as an early diagnostic tool for health control of toxoplasmosis.

Optimization of protease-inhibitor interactions by randomizing adventitious contacts

PubMed Central

Komiyama, Tomoko; VanderLugt, Bryan; Fugère, Martin; Day, Robert; Kaufman, Randal J.; Fuller, Robert S.

2003-01-01

Polypeptide protease inhibitors are often found to inhibit targets with which they did not coevolve, as in the case of high-affinity inhibition of bacterial subtilisin by the leech inhibitor eglin c. Two kinds of contacts exist in such complexes: (i) reactive site loop-active site contacts and (ii) interactions outside of these that form the broader enzyme-inhibitor interface. We hypothesized that the second class of “adventitious” contacts could be optimized to generate significant increases in affinity for a target enzyme or discrimination of an inhibitor for closely related target proteases. We began with a modified eglin c, Arg-42–Arg-45–eglin, in which the reactive site loop had been optimized for subtilisin-related processing proteases of the Kex2/furin family. We randomized 10 potential adventitious contact residues and screened for inhibition of soluble human furin. Substitutions at one of these sites, Y49, were also screened against yeast Kex2 and human PC7. These screens identified not only variants that exhibited increased affinity (up to 20-fold), but also species that exhibited enhanced selectivity, that is, increased discrimination between the target enzymes (up to 41-fold for furin versus PC7 and 20-fold for PC7 versus furin). One variant, Asp-49–Arg-42–Arg-45–eglin, exhibited a Ki of 310 pM for furin and blocked furin-dependent processing of von Willebrand factor in COS-1 cells when added to the culture medium of the cells. The exploitation of adventitious contact sites may provide a versatile technique for developing potent, selective inhibitors for newly discovered proteases and could in principle be applied to optimize numerous protein–protein interactions. PMID:12832612

Rapid and sensitive detection of human astrovirus in water samples by loop-mediated isothermal amplification with hydroxynaphthol blue dye

PubMed Central

2014-01-01

Background The aim of this paper was to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, sensitive and inexpensive detection of astrovirus. Results The detection limit of LAMP using in vitro RNA transcripts was 3.6×10 copies·μL-1, which is as sensitive as the presently used PCR assays. However, the LAMP products could be identified as different colors with the naked eye following staining with hydroxynaphthol blue dye (HNB). No cross-reactivity with other gastroenteric viruses (rotavirus and norovirus) was observed, indicating the relatively high specificity of LAMP. The RT-LAMP method with HNB was used to effectively detect astrovirus in reclaimed water samples. Conclusions The LAMP technique described in this study is a cheap, sensitive, specific and rapid method for the detection of astrovirus. The RT-LAMP method can be simply applied for the specific detection of astrovirus and has the potential to be utilized in the field as a screening test. PMID:24524254

Revisiting the electrochemical impedance spectroscopy of magnesium with online inductively coupled plasma atomic emission spectroscopy.

PubMed

Shkirskiy, Viacheslav; King, Andrew D; Gharbi, Oumaïma; Volovitch, Polina; Scully, John R; Ogle, Kevin; Birbilis, Nick

2015-02-23

The electrochemical impedance of reactive metals such as magnesium is often complicated by an obvious inductive loop with decreasing frequency of the AC polarising signal. The characterisation and ensuing explanation of this phenomenon has been lacking in the literature to date, being either ignored or speculated. Herein, we couple electrochemical impedance spectroscopy (EIS) with online atomic emission spectroelectrochemistry (AESEC) to simultaneously measure Mg-ion concentration and electrochemical impedance spectra during Mg corrosion, in real time. It is revealed that Mg dissolution occurs via Mg(2+) , and that corrosion is activated, as measured by AC frequencies less than approximately 1 Hz approaching DC conditions. The result of this is a higher rate of Mg(2+) dissolution, as the voltage excitation becomes slow enough to enable all Mg(2+) -enabling processes to adjust in real time. The manifestation of this in EIS data is an inductive loop. The rationalisation of such EIS behaviour, as it relates to Mg, is revealed for the first time by using concurrent AESEC. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Management and Outcome of Reduced Fetal Movements-is Ultrasound Necessary?

PubMed

Awad, Nasser Abu; Jordan, Thomas; Mundle, Robert; Farine, Dan

2018-04-01

To review the management and outcome of pregnancies of women presenting to obstetrical triage with decreased fetal movements (DFM). A retrospective review of women presenting with DFMs to two large Canadian obstetrical centres with a combined 9490 deliveries per year. The charts were reviewed for compliance with the Canadian guidelines for demographics (age, parity, GA, comorbidities, etc.), pregnancy management (admission vs. discharge, need to deliver), and pregnancy outcomes (mortality, morbidity, GA at delivery, Apgar scores, etc.). Patients who did not comply with the Canadian guidelines (requiring the patient to count six movements within two hours) were not excluded. The charts of 579 patients who self-reported DFMs between January 2012 and December 2012 were reviewed. The distribution of ages was between 18 and 47 year old. The majority of these patients had no comorbidities (454/579). A significant minority of patients had FM in the triage area (231/579). The Canadian guidelines were interpreted differently in the two centres. In one (level 3), the protocol was to have a biophysical profile (BPP) on all patients prior to discharge, whereas in the other (level 2), only patients with a non-reactive non-stress test (NST) and/or oligohydramnios or intrauterine growth restriction (IUGR) underwent a BPP. All patients had an evaluation by an RN and MD and had a NST on arrival. A combination of NST and BPP was performed on 235/579. The frequency of DFM was 6.1% (level 3 centre: 5.6%, level 2 centre: 7.8%). There were 8 stillbirths on arrival. The 187 patients who had a reactive NST and a normal BPP and were sent home did not have a single stillbirth within 2 weeks. In the level 3 centre, 19 patients were sent home without a BPP and one had a stillbirth within 2 days (5%); in the level 2 hospital, there was only one stillbirth among the NST-only group (0.35%). There were 65 admissions; 46 of them (71%) were delivered, and 50% of them had a Caesarean delivery (baseline around 30%). This is the first study looking at the performance of the Canadian guidelines of 2007. We found that the DFM rate was compatible with the literature (6.1% vs. 5%). The frequency of stillbirth on arrival was 1.4% (8/579). Patients discharged after normal NST and BPP did extremely well (no stillbirths), whereas those admitted following DFM had a relatively high Caesarean delivery rate (50%). This study was not designed to address changes in stillbirth rate, but it outlines the patients who experience DFM and their eventual outcomes. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study

PubMed Central

Turgeon, Alexis F.; Lauzier, François; Simard, Jean-François; Scales, Damon C.; Burns, Karen E.A.; Moore, Lynne; Zygun, David A.; Bernard, Francis; Meade, Maureen O.; Dung, Tran Cong; Ratnapalan, Mohana; Todd, Stephanie; Harlock, John; Fergusson, Dean A.

2011-01-01

Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine. Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale). Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%–35.2%) and ranged from 10.8% to 44.2% across centres (χ2 test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%–75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ2 test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care. Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury. PMID:21876014

Severe multiple sclerosis reactivation during prolonged lymphopenia after dimethyl fumarate discontinuation.

PubMed

Zecca, C; Antozzi, C G; Torri Clerici, V; Ferrazzini, M; Mantegazza, R E; Rossi, S; Gobbi, C

2018-06-01

Delayed-release dimethyl fumarate (DMF) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation. We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36-year-old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta-1a. DMF was suspended after 4 months because of persistent lymphopenia for 3 months. Six months later, the patient had a severe relapse with multiple enhancing brain lesions at MRI although lymphopenia was still persistent. Haematological assessment excluded other causes of lymphopenia, which was evaluated as a probable iatrogenic complication of DMF. The patient was treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical recovery. Prolonged lymphopenia after DMT discontinuation does not protect against disease reactivation. Starting a new immune therapy should be balanced against the option of a "wait and see." A different immunotherapeutic strategy such as an anti-B therapeutic approach could be considered. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Predicting outcome in severe traumatic brain injury using a simple prognostic model.

PubMed

Sobuwa, Simpiwe; Hartzenberg, Henry Benjamin; Geduld, Heike; Uys, Corrie

2014-06-17

Several studies have made it possible to predict outcome in severe traumatic brain injury (TBI) making it beneficial as an aid for clinical decision-making in the emergency setting. However, reliable predictive models are lacking for resource-limited prehospital settings such as those in developing countries like South Africa. To develop a simple predictive model for severe TBI using clinical variables in a South African prehospital setting. All consecutive patients admitted at two level-one centres in Cape Town, South Africa, for severe TBI were included. A binary logistic regression model was used, which included three predictor variables: oxygen saturation (SpO₂), Glasgow Coma Scale (GCS) and pupil reactivity. The Glasgow Outcome Scale was used to assess outcome on hospital discharge. A total of 74.4% of the outcomes were correctly predicted by the logistic regression model. The model demonstrated SpO₂ (p=0.019), GCS (p=0.001) and pupil reactivity (p=0.002) as independently significant predictors of outcome in severe TBI. Odds ratios of a good outcome were 3.148 (SpO₂ ≥ 90%), 5.108 (GCS 6 - 8) and 4.405 (pupils bilaterally reactive). This model is potentially useful for effective predictions of outcome in severe TBI.

Microplasma array patterning of reactive oxygen and nitrogen species onto polystyrene

NASA Astrophysics Data System (ADS)

Szili, Endre J.; Dedrick, James; Oh, Jun-Seok; Bradley, James W.; Boswell, Roderick W.; Charles, Christine; Short, Robert D.; Al-Bataineh, Sameer A.

2017-02-01

We investigate an approach for the patterning of reactive oxygen and nitrogen species (RONS) onto polystyrene using atmospheric-pressure microplasma arrays. The spectrally integrated and time-resolved optical emission from the array is characterised with respect to the applied voltage, applied-voltage frequency and pressure; and the array is used to achieve spatially resolved modification of polystyrene at three pressures: 500 Torr, 760 Torr and 1000 Torr. As determined by time-of-flight secondary ion mass spectrometry (ToF-SIMS), regions over which surface modification occurs are clearly restricted to areas that are exposed to individual microplasma cavities. Analysis of the negative-ion ToF-SIMS mass spectra from the centre of the modified microspots shows that the level of oxidation is dependent on the operating pressure, and closely correlated with the spatial distribution of the optical emission. The functional groups that are generated by the microplasma array on the polystyrene surface are shown to readily participate in an oxidative reaction in phosphate buffered saline solution (pH 7.4). Patterns of oxidised and chemically reactive functionalities could potentially be applied to the future development of biomaterial surfaces, where spatial control over biomolecule or cell function is needed.

Improving secondary prevention in coronary bypass patients: closing the audit loop

PubMed Central

Martin, T N; Irving, R J; Sutherland, M; Sutherland, K; Bloomfield, P

2005-01-01

Objectives: To complete the audit loop assessing secondary preventative care of patients who had had coronary artery bypass graft (CABG) surgery. Design: Two separate surveys of 1000 patients who had had CABG at the regional centre between 1988 and 1997, selected in 1998 and 2001. A single page questionnaire was sent to the patient’s general practitioner. Interventions: A list was sent to each general practice in Lothian, Scotland, of their patients on the CABG database and the results of the original survey. Lothian Health organised a project to contact and recall patients with cardiac disease in each practice. Sixty five (of 128) practices participated. Main outcome measures: Blood pressure, smoking status, serum cholesterol concentrations, and prescription of lipid lowering drugs and aspirin. Results: 918 questionnaires (92%) in the second survey were returned describing 875 patients: 151 (17%) patients smoked and 752 patients (86%) took aspirin. Mean (SD) systolic blood pressure was lower in the second survey (142.5 (19.2) mm Hg in the first survey v 139.4 (19.1) mm Hg, p < 0.005). In our first survey 34% of patients had cholesterol concentrations less than target (5.2 mmol/l). This increased from 12% of patients operated on in 1988 to 50% of patients operated on in 1997 (Spearman rank correlation 0.77, p < 0.01). In the second survey this proportion had risen to 65% and the correlation with year of operation was abolished. Conclusions: By closing the audit loop, substantial improvements were shown in the management of risk factors in patients who have had coronary artery surgery in Lothian. PMID:15772197

Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study.

PubMed

Bally, Lia; Thabit, Hood; Kojzar, Harald; Mader, Julia K; Qerimi-Hyseni, Jehona; Hartnell, Sara; Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Pieber, Thomas R; Evans, Mark L; Hovorka, Roman

2017-04-01

Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA 1c below 7·5% (58 mmol/mol). In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA 1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed. Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% [SD 8·1] when participants used usual pump therapy vs 76·2% [6·4] when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53-74, p<0·0001) and below 2·8 mmol/L by 76% (59-86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred. Use of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA 1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted. Swiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z). Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joseph, J.S.; Saikatendu, K.S.; Subramanian, V.

Mature nonstructural protein-15 (nsp15) from the severe acute respiratory syndrome coronavirus (SARS-CoV) contains a novel uridylate-specific Mn{sup 2+}-dependent endoribonuclease (NendoU). Structure studies of the full-length form of the obligate hexameric enzyme from two CoVs, SARS-CoV and murine hepatitis virus, and its monomeric homologue, XendoU from Xenopus laevis, combined with mutagenesis studies have implicated several residues in enzymatic activity and the N-terminal domain as the major determinant of hexamerization. However, the tight link between hexamerization and enzyme activity in NendoUs has remained an enigma. Here, we report the structure of a trimmed, monomeric form of SARS-CoV nsp15 (residues 28 to 335)more » determined to a resolution of 2.9 Angstroms. The catalytic loop (residues 234 to 249) with its two reactive histidines (His 234 and His 249) is dramatically flipped by {approx}120 degrees into the active site cleft. Furthermore, the catalytic nucleophile Lys 289 points in a diametrically opposite direction, a consequence of an outward displacement of the supporting loop (residues 276 to 295). In the full-length hexameric forms, these two loops are packed against each other and are stabilized by intimate intersubunit interactions. Our results support the hypothesis that absence of an adjacent monomer due to deletion of the hexamerization domain is the most likely cause for disruption of the active site, offering a structural basis for why only the hexameric form of this enzyme is active.« less

CRITICAL TESTS FOR PRT REACTOR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Triplett, J.R.; Anderson, J.K.; Dunn, R.E.

1960-07-01

Critical teste to be performed on the Plutonium Recycle Te st Heactor are described. Exponential, approach-tocritical, critical, and substitution experiments will be carried out. These experiments include: calibration of moderator level; determination of the wori of various fuel loadings; calibration of the shim system including determination of maximum control strength of the entire system; substitution experiments to determine reflector savings, void effects, effects of H/sub 2/O and degraded D/sub 2/O coolants, and effects of loop and other material intsllations; determination of fuel-plus-coolant and moderator temperature coefficients; and kinetic experiments to determine response of the reactor to reactivity changes. (M.C.G.)

Pregnancy Specific Glycoprotein 17 Binds to the Extracellular Loop 2 of Its Receptor, CD9, and Induces the Secretion of IL-10, IL-6, PGE2, and TGFBeta1 in Murine Macrophages

DTIC Science & Technology

2004-01-01

deficiency of placental IL-10 in preeclampsia . J Immunol, 1999. 163(6): p. 3491-5. 53. Raghupathy, R., et al., Maternal Th1- and Th2-type reactivity to...10 in preeclampsia . J Immunol, 1999. 163(6): p. 3491-5. 149. Chaouat, G., et al., IL-10 prevents naturally occurring fetal loss in the CBA x DBA/2...release of trophoblast cells in vitro. Cytokine, 2003. 23(4-5): p. 119- 25. 189. Orange, S., J. Horvath, and A. Hennessy, Preeclampsia is associated

Mitochondria as integrators of information in an early-evolving animal: insights from a triterpenoid metabolite

PubMed Central

Blackstone, Neil W; Kelly, Molly M; Haridas, Valsala; Gutterman, Jordan U

2005-01-01

Mitochondria have the capacity to integrate environmental signals and, in animals with active stem cell populations, trigger responses in terms of growth and growth form. Colonial hydroids, which consist of feeding polyps connected by tube-like stolons, were treated with avicins, triterpenoid electrophiles whose anti-cancer properties in human cells are mediated in part by mitochondria. In treated hydroids, both oxygen uptake and mitochondrial reactive oxygen species were diminished relative to controls, similar to that observed in human cells exposed to avicins. While untreated colonies exhibit more stolon branches and connections in the centre of the colony than at the periphery, treated colonies exhibit the opposite: fewer stolon branches in the centre of the colony than at the periphery. The resulting growth form suggests an inversion of the normal pattern of colony development mediated by mitochondrial and redox-related perturbations. An as-yet-uncharacterized gradient within the colony may determine the ultimate phenotypic effect of avicin perturbation. PMID:15799949

Identification of two small RNAs within the first 1.5-kb of the herpes simplex virus type 1-encoded latency-associated transcript.

PubMed

Peng, Weiping; Vitvitskaia, Olga; Carpenter, Dale; Wechsler, Steven L; Jones, Clinton

2008-01-01

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected neurons. In the rabbit or mouse ocular models of infection, expression of the first 1.5 kb of LAT coding sequences is sufficient for and necessary for wild-type levels of spontaneous reactivation from latency. The antiapoptosis functions of LAT, which maps to the same 1.5 kb of LAT, are important for the latency-reactivation cycle because replacement of LAT with other antiapoptosis genes (the baculovirus IAP gene or the bovine herpesvirus type 1 latency-related gene) restores wild-type levels of reactivation to a LAT null mutant. A recent study identified a micro-RNA within LAT that can inhibit apoptosis (Gupta et al, Nature 442: 82-85). In this study, the authors analyzed the first 1.5 kb of LAT for additional small RNAs that may have regulatory functions. Two LAT-specific small RNAs were detected in productively infected human neuroblastoma cells within the first 1.5 kb of LAT, in a region that is important for inhibiting apoptosis. Although these small RNAs possess extensive secondary structure and a stem-loop structure, bands migrating near 23 bases were not detected suggesting these small RNAs are not true micro-RNAs. Both of the small LAT-specific RNAs have the potential to base pair with the ICP4 mRNA. These two small LAT RNAs may play a role in the latency-reactivation cycle by reducing apoptosis and/or by reducing ICP4 RNA expression.

Gallic acid grafting modulates the oxidative potential of ferrimagnetic bioactive glass-ceramic SC-45.

PubMed

Corazzari, Ingrid; Tomatis, Maura; Turci, Francesco; Ferraris, Sara; Bertone, Elisa; Prenesti, Enrico; Vernè, Enrica

2016-12-01

Magnetite-containing glass-ceramics are promising bio-materials for replacing bone tissue after tumour resection. Thanks to their ferrimagnetic properties, they generate heat when subjected to an alternated magnetic field. In virtue of this they can be employed for the hyperthermic treatment of cancer. Moreover, grafting anti-cancer drugs onto their surface produces specific anti-neoplastic activity in these biomaterials. Gallic acid (GA) exhibits antiproliferative activity which renders it a promising candidate for anticancer applications. In the present paper, the reactivity of ferrimagnetic glass-ceramic SC-45 grafted with GA (SC-45+GA) was studied in terms of ROS release, rupture of the C-H bond of the formate molecule and Fenton reactivity by EPR/spin trapping in acellular systems. The ability of these materials to cause lipid peroxidation was assessed by UV-vis/TBA assay employing linoleic acid as a model of membrane lipid. The results, compared to those obtained with SC-45, showed that GA grafting (i) significantly enhanced the Fenton reactivity and (ii) restored the former reactivity of SC-45 towards both the C-H bond and linoleic acid which had been completely suppressed by prolonged contact with water. Fe 2+ centres at the surface are probably implicated. GA, acting as a pro-oxidant, reduces Fe 3+ to Fe 2+ by maintaining a supply of Fe 2+ at the surface of SC-45+GA. Copyright © 2016 Elsevier B.V. All rights reserved.

'Pharmacists have been left out of the loop': exploring the role of pharmacists in the management of HIV/AIDS in South Africa.

PubMed

Gilbert, Leah

2016-02-01

The aim of this paper is to portray and critically analyse the role played by pharmacists in the management of the HIV/AIDS epidemic in South Africa. The data used for this article originate in secondary and primary sources. They were collected by means of a documentary analysis of all relevant documents of significance as well as exploratory telephone interviews conducted with a systematic random sample of community pharmacies in Greater Johannesburg in 2004 and 2010. It is clear from the original strategic framework that the government envisaged pharmacists playing a significant role in the various facets of the epidemic. Following these intentions, the South African Pharmacy Council and the Pharmaceutical Society of South Africa embarked on a process of establishing AIDS Resource Centres in pharmacies. However, although in some areas pharmacists are contributing to the management of HIV/AIDS, the overall scenario revealed is that of lack of willingness to go for additional training and/or to invest in restructuring the pharmacy to 'accommodate' the activities of an 'AIDS Resource Centre' without the prospects of adequate financial gains. In a parallel process, the original, more meaningful role for pharmacists in the management of HIV/AIDS has not been featured in recent professional and governmental documentation. The reality on the ground is that of a missed opportunity as the pharmacists have not risen to the challenge and they remain on the margins, and not at the centre, of those professionals managing HIV/AIDS in South Africa. © 2015 Royal Pharmaceutical Society.

Two polymeric nickel(II) complexes with aromatic benzene-1,2,4,5-tetracarboxylate and pyridine-2,5-dicarboxylate linkers.

PubMed

Atria, Ana María; Corsini, Gino; González, Lissette; Garland, Maria Teresa; Baggio, Ricardo

2009-07-01

(Mu-benzene-1,2,4,5-tetracarboxylato-kappa(2)O(1):O(4))bis[aquabis(2,2-methylpropane-1,3-diamine-kappa(2)N,N')nickel(II)] methanol disolvate tetrahydrate, [Ni(2)(C(10)H(2)O(8))(C(5)H(14)N(2))(4)(H(2)O)(2)].2CH(4)O.4H(2)O, (I), is dinuclear, with elemental units built up around an inversion centre halving the benzene-1,2,4,5-tetracarboxylate (btc) anion, which bridges two symmetry-related Ni(II) cations. The octahedral Ni polyhedron is completed by two chelating 2,2-methylpropane-1,3-diamine (dmpda) groups and a terminal aqua ligand. Two methanol and four water solvent molecules are involved in a number of N-H...O and O-H...O hydrogen bonds which define a strongly bound two-dimensional supramolecular structure. The structure of catena-poly[[[bis(2,2-methylpropane-1,3-diamine-kappa(2)N,N')nickel(II)]-mu-pyridine-2,5-dicarboxylato-kappa(3)O(5):N,O(2)-[(2,2-methylpropane-1,3-diamine-kappa(2)N,N')nickel(II)]-mu-pyridine-2,5-dicarboxylato-kappa(3)N,O(2):O(5)] octahydrate], {[Ni(2)(C(7)H(3)NO(4))(2)(C(5)H(14)N(2))(3)].8H(2)O}(n), (II), is polymeric, forming twisted chains around three independent Ni centres, two of which lie on inversion centres and the third in a general position. There are three chelating dmpda ligands (one disordered over two equally populated positions), which are each attached to a different cation, and two pyridine-2,5-dicarboxylate (pdc) anions, both chelating the Ni centre in general positions through an -O-C-C-N- loop, while acting as bridges to the remaining two centrosymmetric Ni atoms. There are, in addition, eight noncoordinated water molecules in the structure, some of which are disordered.

Planner-Based Control of Advanced Life Support Systems

NASA Technical Reports Server (NTRS)

Muscettola, Nicola; Kortenkamp, David; Fry, Chuck; Bell, Scott

2005-01-01

The paper describes an approach to the integration of qualitative and quantitative modeling techniques for advanced life support (ALS) systems. Developing reliable control strategies that scale up to fully integrated life support systems requires augmenting quantitative models and control algorithms with the abstractions provided by qualitative, symbolic models and their associated high-level control strategies. This will allow for effective management of the combinatorics due to the integration of a large number of ALS subsystems. By focusing control actions at different levels of detail and reactivity we can use faster: simpler responses at the lowest level and predictive but complex responses at the higher levels of abstraction. In particular, methods from model-based planning and scheduling can provide effective resource management over long time periods. We describe reference implementation of an advanced control system using the IDEA control architecture developed at NASA Ames Research Center. IDEA uses planning/scheduling as the sole reasoning method for predictive and reactive closed loop control. We describe preliminary experiments in planner-based control of ALS carried out on an integrated ALS simulation developed at NASA Johnson Space Center.

Effect of Doping on Surface Reactivity and Conduction Mechanism in Sm-doped CeO2 Thin Films

DOE PAGES

Yang, Nan; Belianinov, Alex; Strelcov, Evgheni; ...

2014-11-21

Scanning probe microscopy measurements show irreversible surface electrochemistry in Sm-doped CeO2 thin films, which depends on humidity, temperature and doping concentration. A systematic study by electrochemical strain microscopy (ESM) in samples with two different Sm content and in several working conditions allows disclosing the microscopic mechanism underlying the difference in water adsorption and splitting with subsequent proton liberation. We measure the behavior of the hysteresis loops by changing temperature and humidity, both in standard ESM configuration and using the first order reversal curve (FORC) method. Complementing our study with spectroscopic measurements by hard x-ray photoemission spectroscopy we find that watermore » incorporation is favored until the doping with Sm is too high to allow the presence of Ce3+. The influence of doping on the surface reactivity and conduction mechanism clearly emerges from all of our experimental results. We find that at lower Sm concentration proton conduction is prevalent, featured by lower activation energy and higher mobility. Defect concentrations determine the type of the prevalent charge carrier in a doping dependent manner.« less

Harnessing redox activity for the formation of uranium tris(imido) compounds

NASA Astrophysics Data System (ADS)

Anderson, Nickolas H.; Odoh, Samuel O.; Yao, Yiyi; Williams, Ursula J.; Schaefer, Brian A.; Kiernicki, John J.; Lewis, Andrew J.; Goshert, Mitchell D.; Fanwick, Phillip E.; Schelter, Eric J.; Walensky, Justin R.; Gagliardi, Laura; Bart, Suzanne C.

2014-10-01

Classically, late transition-metal organometallic compounds promote multielectron processes solely through the change in oxidation state of the metal centre. In contrast, uranium typically undergoes single-electron chemistry. However, using redox-active ligands can engage multielectron reactivity at this metal in analogy to transition metals. Here we show that a redox-flexible pyridine(diimine) ligand can stabilize a series of highly reduced uranium coordination complexes by storing one, two or three electrons in the ligand. These species reduce organoazides easily to form uranium-nitrogen multiple bonds with the release of dinitrogen. The extent of ligand reduction dictates the formation of uranium mono-, bis- and tris(imido) products. Spectroscopic and structural characterization of these compounds supports the idea that electrons are stored in the ligand framework and used in subsequent reactivity. Computational analyses of the uranium imido products probed their molecular and electronic structures, which facilitated a comparison between the bonding in the tris(imido) structure and its tris(oxo) analogue.

Screening for antibody to HTLV-III in blood donors of Liguria. Ligurian Committee for the Study of Infections Transmitted through Blood and Blood Products.

PubMed

1985-01-01

Anti-HTLV III had been detected in 12,689 serum samples collected within August 1985 from 12 Transfusion Centres of Liguria. In the course of the first test, carried out by ELISA using disrupted virions as antigen, 12,666 samples (99.81%) resulted non reactive; 14 (0.1%) belonged to the grey-zone and 9 (0.08%) were clearly reactive. The samples of the last two classes were tested again in the same way and, whenever the cases were suspect as positive, by Western-blot technique. All positive cases, but three, were linked with risk factors such as intravenous drug use or drug addicts partners. Even if the prevalence of blood donors anti-HTLV III positive resulted, on the whole, very low (0.063%), the investigations carried out prove the importance of regular screening of blood units for the prevention of HTLV III infection.

Photocatalytic degradation of C. I. Reactive Red 24 solution with K₆SiW₁₁O₃₉Sn(II.).

PubMed

Guo, Guixiang; Zhu, Xiuhua; Shi, Fuyou; Wang, Anning; Wang, Wei; Mu, Jun; Wan, Quanli; Zhang, Rong

2013-12-01

Environmental friendly materials, K6SiW11O39Sn (SiWSn), was synthesized. SiWSn photocatalytic decomposition of C. I. Reactive Red 24 (RR24) with the UV-lamp (253.7 nm, 20 W), Xenon lamp filtered less than 390 nm light (500 W) and sun light was investigated. The results showed that RR24 solution could be effectively decolorized with the SiWSn photocatalyst. The photocatalytic degradation efficiency of RR24 with SiWSn was affected by the initial concentration of RR2 solution, the amount of SiWSn and the photolysis time. It is demonstrated that the process of photodegradation of RR24 with SiWSn is a pesudo first-order reaction, which can be described by Langmuir-Hinshelwood equation. Hydroxyl radicals and holes are both the main oxidants in the photocatalytic reaction of RR24 with SiWSn. Copyright © 2013 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Nickel centred H+ reduction catalysis in a model of [NiFe] Hydrogenase

PubMed Central

Brazzolotto, Deborah; Gennari, Marcello; Queyriaux, Nicolas; Simmons, Trevor R.; Pécaut, Jacques; Demeshko, Serhiy; Meyer, Franc; Orio, Maylis; Artero, Vincent; Duboc, Carole

2017-01-01

Hydrogen production through water splitting is one of the most promising solutions for the storage of renewable energy. [NiFe] hydrogenases are organometallic enzymes containing nickel and iron centers that catalyze hydrogen evolution with performances that rival those of platinum. These enzymes provide inspiration for the design of new molecular catalysts that do not require precious metals. However, all heterodinuclear NiFe models reported so far do not reproduce the Ni-centered reactivity found at the active site of [NiFe] hydrogenases. Here we report a structural and functional NiFe mimic that displays reactivity at the Ni site. This is shown by the detection of two catalytic intermediates that reproduce structural and electronic features of the Ni-L and Ni-R states of the enzyme during catalytic turnover. Under electrocatalytic conditions, this mimic displays high rates for H2 evolution (second order rate constant of 2.5 104 M-1s-1; turnover frequency of 225 s-1 at 10 mM H+ concentration) from mildly acidic solutions. PMID:27768098

Synthesis, crystal structure analysis, molecular docking studies and density functional theory predictions of the local reactive properties and degradation properties of a novel halochalcone

NASA Astrophysics Data System (ADS)

Arshad, Suhana; Pillai, Renjith Raveendran; Zainuri, Dian Alwani; Khalib, Nuridayanti Che; Razak, Ibrahim Abdul; Armaković, Stevan; Armaković, Sanja J.

2017-09-01

In the present study, single crystals of E)-3-(3,5-dichlorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one, were prepared and structurally characterized by single crystal X-ray diffraction analysis. The molecular structure crystallized in monoclinic crystal system with P21/c space group. Sensitivity of the title molecule towards electrophilic attacks has been examined by calculations of average localized ionization energies (ALIE) and their mapping to electron density surface. Further determination of atoms that could be important reactive centres has been performed by calculations of Fukui functions. Sensitivity of title molecule towards autoxidation and hydrolysis mechanisms has been assessed by calculations of bond dissociation energies and radial distribution functions (RDF), respectively. Also, in order to explore possible binding mode of the title compound towards Dihydrofolate reductase enzyme, we have utilized in silico molecular docking to explore possible binding modes of the title compound with the DHFR enzyme.

[Juvenile criminality: general strain theory and the reactive-proactive aggression trait].

PubMed

Greco, Romy; Curci, Antonietta; Grattagliano, Ignazio

2009-01-01

The aims of the present study are to test General Strain Theory's (GST) assumptions, and to integrate the model including the proactive-reactive aggression trait. GST hypothesizes crime to be enacted in response to extra-personal stimuli (strain) and their subsequent negative emotions, especially anger. However, there exist also internally-driven manifestations of crime (instrumental or proactive), motivated by stimuli that are of an intrapersonal origin. Further, individuals differ to each other in the tendency to commit reactive or proactive or both manifestations of crime. With the goal to gain a more comprehensive model, GST variables and the reactive-proactive aggression trait are together tested as to their ability to predict criminal behaviour. Participants in the present research are 68 adolescent males with age ranging from 14 to 19 (M = 16.94, SD = 0.95). Half of the participants were jailed adolescents at the Fornelli Juvenile Detention Centre in Bari, while the remaining were adolescents with no criminal record, matched for age and level of education with the former group. An interview was administered to assess the experienced strain events, anger, and crime committed by the participants in the three months preceding the interview and also before. The reactive-proactive aggression trait was additionally measured. Results of the present study supported GST's assumptions, and confirmed the utility of integrating the model to include the proactive-reactive aggression trait. Strain events experienced in three-month time were found to influence property and violent offences committed by participants in the same time-interval as well as over this time. Furthermore,jailed participants were more likely to react with anger, and violence to strain events than non-jailed individuals, although the number of events experienced by both groups in the preceding months is similar. Finally, the results of the present study showed that proactive aggression is a strong predictor of criminal behaviour.

Analysis of mitochondrial DNA in Bolivian llama, alpaca and vicuna populations: a contribution to the phylogeny of the South American camelids.

PubMed

Barreta, J; Gutiérrez-Gil, B; Iñiguez, V; Saavedra, V; Chiri, R; Latorre, E; Arranz, J J

2013-04-01

The objectives of this work were to assess the mtDNA diversity of Bolivian South American camelid (SAC) populations and to shed light on the evolutionary relationships between the Bolivian camelids and other populations of SACs. We have analysed two different mtDNA regions: the complete coding region of the MT-CYB gene and 513 bp of the D-loop region. The populations sampled included Bolivian llamas, alpacas and vicunas, and Chilean guanacos. High levels of genetic diversity were observed in the studied populations. In general, MT-CYB was more variable than D-loop. On a species level, the vicunas showed the lowest genetic variability, followed by the guanacos, alpacas and llamas. Phylogenetic analyses performed by including additional available mtDNA sequences from the studied species confirmed the existence of the two monophyletic clades previously described by other authors for guanacos (G) and vicunas (V). Significant levels of mtDNA hybridization were found in the domestic species. Our sequence analyses revealed significant sequence divergence within clade G, and some of the Bolivian llamas grouped with the majority of the southern guanacos. This finding supports the existence of more than the one llama domestication centre in South America previously suggested on the basis of archaeozoological evidence. Additionally, analysis of D-loop sequences revealed two new matrilineal lineages that are distinct from the previously reported G and V clades. The results presented here represent the first report on the population structure and genetic variability of Bolivian camelids and may help to elucidate the complex and dynamic domestication process of SAC populations. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Coherent feedback control of a single qubit in diamond

NASA Astrophysics Data System (ADS)

Hirose, Masashi; Cappellaro, Paola

2016-04-01

Engineering desired operations on qubits subjected to the deleterious effects of their environment is a critical task in quantum information processing, quantum simulation and sensing. The most common approach relies on open-loop quantum control techniques, including optimal-control algorithms based on analytical or numerical solutions, Lyapunov design and Hamiltonian engineering. An alternative strategy, inspired by the success of classical control, is feedback control. Because of the complications introduced by quantum measurement, closed-loop control is less pervasive in the quantum setting and, with exceptions, its experimental implementations have been mainly limited to quantum optics experiments. Here we implement a feedback-control algorithm using a solid-state spin qubit system associated with the nitrogen vacancy centre in diamond, using coherent feedback to overcome the limitations of measurement-based feedback, and show that it can protect the qubit against intrinsic dephasing noise for milliseconds. In coherent feedback, the quantum system is connected to an auxiliary quantum controller (ancilla) that acquires information about the output state of the system (by an entangling operation) and performs an appropriate feedback action (by a conditional gate). In contrast to open-loop dynamical decoupling techniques, feedback control can protect the qubit even against Markovian noise and for an arbitrary period of time (limited only by the coherence time of the ancilla), while allowing gate operations. It is thus more closely related to quantum error-correction schemes, although these require larger and increasing qubit overheads. Increasing the number of fresh ancillas enables protection beyond their coherence time. We further evaluate the robustness of the feedback protocol, which could be applied to quantum computation and sensing, by exploring a trade-off between information gain and decoherence protection, as measurement of the ancilla-qubit correlation after the feedback algorithm voids the protection, even if the rest of the dynamics is unchanged.

Driver-centred vehicle automation: using network analysis for agent-based modelling of the driver in highly automated driving systems.

PubMed

Banks, Victoria A; Stanton, Neville A

2016-11-01

To the average driver, the concept of automation in driving infers that they can become completely 'hands and feet free'. This is a common misconception, however, one that has been shown through the application of Network Analysis to new Cruise Assist technologies that may feature on our roads by 2020. Through the adoption of a Systems Theoretic approach, this paper introduces the concept of driver-initiated automation which reflects the role of the driver in highly automated driving systems. Using a combination of traditional task analysis and the application of quantitative network metrics, this agent-based modelling paper shows how the role of the driver remains an integral part of the driving system implicating the need for designers to ensure they are provided with the tools necessary to remain actively in-the-loop despite giving increasing opportunities to delegate their control to the automated subsystems. Practitioner Summary: This paper describes and analyses a driver-initiated command and control system of automation using representations afforded by task and social networks to understand how drivers remain actively involved in the task. A network analysis of different driver commands suggests that such a strategy does maintain the driver in the control loop.

Stress and transcriptional regulation of tick ferritin HC.

PubMed

Mulenga, A; Simser, J A; Macaluso, K R; Azad, A F

2004-08-01

We previously identified a partial Dermacentor variabilis cDNA encoding ferritin HC (HC) subunit homolog (DVFER) that was differentially upregulated in Rickettsia montanensis infected ticks (Mulenga et al., 2003a). We have used rapid amplification of cDNA ends to clone full-length DVFER cDNA and its apparent ortholog from the wood tick, D. andersoni (DAFER), both of which show high sequence similarity to vertebrate than insect ferritin. Both DVFER and DAFER contain the stem-loop structure of a putative iron responsive element in the 5' untranslated region (nucleotide positions, 16-42) and the feroxidase centre loop typical for vertebrate ferritin HC subunits. Quantitative Western and Northern blotting analyses of protein and RNA from unfed and partially fed whole tick as well as dissected tick tissues demonstrated that DVFER is constitutively and ubiquitously expressed. Based on densitometric analysis of detected protein and mRNA bands, DVFER is predominantly expressed in the midgut, and to a lesser extent in the salivary glands, ovary and fatbody. Sham treatment (mechanical injury) and Escherichia coli challenge of D. variabilis ticks stimulated statistically significant (approximately 1.5- and approximately 3.0-fold, respectively) increases in DVFER mRNA abundance over time point matched naive control ticks. These data suggest that DVFER mRNA is nonspecifically up regulated in response to mechanical injury or bacterial infection induced stress.

Surface transport and stable trapping of particles and cells by an optical waveguide loop.

PubMed

Hellesø, Olav Gaute; Løvhaugen, Pål; Subramanian, Ananth Z; Wilkinson, James S; Ahluwalia, Balpreet Singh

2012-09-21

Waveguide trapping has emerged as a useful technique for parallel and planar transport of particles and biological cells and can be integrated with lab-on-a-chip applications. However, particles trapped on waveguides are continuously propelled forward along the surface of the waveguide. This limits the practical usability of the waveguide trapping technique with other functions (e.g. analysis, imaging) that require particles to be stationary during diagnosis. In this paper, an optical waveguide loop with an intentional gap at the centre is proposed to hold propelled particles and cells. The waveguide acts as a conveyor belt to transport and deliver the particles/cells towards the gap. At the gap, the diverging light fields hold the particles at a fixed position. The proposed waveguide design is numerically studied and experimentally implemented. The optical forces on the particle at the gap are calculated using the finite element method. Experimentally, the method is used to transport and trap micro-particles and red blood cells at the gap with varying separations. The waveguides are only 180 nm thick and thus could be integrated with other functions on the chip, e.g. microfluidics or optical detection, to make an on-chip system for single cell analysis and to study the interaction between cells.

A distal mutation perturbs dynamic amino acid networks in dihydrofolate reductase

PubMed Central

Bae, Sung-Hun; Duggan, Brendan M.; Benkovic, Stephen J.; Dyson, H. Jane; Wright, Peter E

2013-01-01

Correlated networks of amino acids have been proposed to play a fundamental role in allostery and enzyme catalysis. These networks of amino acids can be traced from surface-exposed residues all the way into the active site, and disruption of these networks can decrease enzyme activity. Substitution of the distal Gly121 residue in E.coli dihydrofolate reductase results in up to a 200-fold decrease in the hydride transfer rate despite the fact that the residue is located 15 Å from the active-site center. In the present study, NMR relaxation experiments are used to demonstrate that dynamics on the ps-ns and μs-ms timescales are changed significantly in the G121V mutant of dihydrofolate reductase. In particular, ps-ns timescale dynamics are decreased in the FG loop (containing the mutated residue 121) and the neighboring active-site loop (the Met20 loop) in the mutant compared to wild-type enzyme, suggesting that these loops are dynamically coupled. Changes in methyl order parameters reveal a pathway by which dynamic perturbations can be propagated more than 25 Å across the protein from the site of mutation. All of the enzyme complexes, including the model Michaelis complex with folate and NADP+ bound, assume an occluded ground state conformation, and we do not observe sampling of a higher energy closed conformation by 15N R2 relaxation dispersion. This is highly significant, since it is only in the closed conformation that the cofactor and substrate reactive centers are positioned for reaction. The mutation also impairs μs - ms timescale fluctuations that have been implicated in product release from the wild type enzyme. Our results are consistent with an important role for Gly121 in controlling protein dynamics critical for enzyme function and further validate the dynamic energy landscape hypothesis of enzyme catalysis. PMID:23758161

Fabrication and processing of next-generation oxygen carrier materials for chemical looping combustion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nadarajah, Arunan

Among numerous methods of controlling the global warming effect, Chemical Looping Combustion is known to be the most viable option currently. A key factor to a successful chemical looping process is the presence of highly effective oxygen carriers that enable fuel combustion by going through oxidation and reduction in the presence of air and fuel respectively. In this study, CaMnO 3-δ was used as the base material and doped on the A-site (Sr or La) and B-site (Fe, Ti, Zn and Al) by 10 mol % of dopants. Solid state reaction followed by mechanical extrusion (optimized paste formula) was usedmore » as the preparation method A series of novel doped perovskite-type oxygen carrier particles (Ca xLa (Or Sa) 1-x Mn 1-yByO 3-δ (B-site = Fe, Ti, Al, or Zr)) were synthesized by the proposed extrusion formula. The produced samples were characterized with XRD, SEM, BET and TGA techniques. According to the results obtained from TGA analysis, the oxygen capacity of the samples ranged between 1.2 for CLMZ and 1.75 for CSMF. Reactivity and oxygen uncoupling behaviors of the prepared samples were also evaluated using a fluidized bed chemical looping reactor using methane as the fuel at four different temperatures (800, 850, 900, 950 °C). All of the oxygen carriers showed oxygen uncoupling behavior and they were able to capture and release oxygen. Mass-based conversion of the perovskites was calculated and temperature increase proved to increase the mass-based conversion rate in all of the samples under study. Gas yield was calculated at 950 °C as well, and results showed that CLMZ, CM and CSMF showed 100% gas yields and CLMF and CSMZ showed approximately 85% yield in fluidized bed reactor, which is a high and acceptable quantity. Based on extended reactor tests the modified calcium manganese perovskite structures (CSMF) can be a good candidate for future pilot tests.« less

Unique phase identification of trimetallic copper iron manganese oxygen carrier using simultaneous differential scanning calorimetry/thermogravimetric analysis during chemical looping combustion reactions with methane

DOE PAGES

Benincosa, William; Siriwardane, Ranjani; Tian, Hanjing; ...

2017-07-05

Chemical looping combustion (CLC) is a promising combustion technology that generates heat and sequestration-ready carbon dioxide that is undiluted by nitrogen from the combustion of carbonaceous fuels with an oxygen carrier, or metal oxide. This process is highly dependent on the reactivity and stability of the oxygen carrier. The development of oxygen carriers remains one of the major barriers for commercialization of CLC. Synthetic oxygen carriers, consisting of multiple metal components, have demonstrated enhanced performance and improved CLC operation compared to single metal oxides. However, identification of the complex mixed metal oxide phases that form after calcination or during CLCmore » reactions has been challenging. Without an understanding of the dominant metal oxide phase, it is difficult to determine reaction parameters and the oxygen carrier reduction pathway, which are necessary for CLC reactor design. This is particularly challenging for complex multi-component oxygen carriers such as copper iron manganese oxide (CuFeMnO 4). This study aims to differentiate the unique phase formation of a highly reactive, complex trimetallic oxygen carrier, CuFeMnO 4, from its single and bimetallic counterparts using thermochemical and reaction data obtained from simultaneous differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) during temperature programmed reductions (TPR) with methane. DSC/TGA experiments during TPR with methane provides heat flow data and corresponding reaction rate data that can be used to determine reaction routes and mechanisms during methane reduction. Furthermore, non-isothermal TPR data provides the advantage of distinguishing reactions that may not be observable in isothermal analysis. The detailed thermochemical and reaction data, obtained during TPR with methane, distinguished a unique reduction pathway for CuFeMnO 4 that differed from its single and bimetallic counterparts. This is remarkable since X-ray diffraction (XRD) data alone could not be used to distinguish the reactive trimetallic oxide phase due to overlapping peaks from various single and mixed metal oxides. The unique reduction pathway of CuFeMnO 4 was further characterized in this study using in-situ XRD TPR with methane to determine changes in the dominant trimetallic phase that influenced the thermochemical and reaction rate data.« less

Unique phase identification of trimetallic copper iron manganese oxygen carrier using simultaneous differential scanning calorimetry/thermogravimetric analysis during chemical looping combustion reactions with methane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benincosa, William; Siriwardane, Ranjani; Tian, Hanjing

Chemical looping combustion (CLC) is a promising combustion technology that generates heat and sequestration-ready carbon dioxide that is undiluted by nitrogen from the combustion of carbonaceous fuels with an oxygen carrier, or metal oxide. This process is highly dependent on the reactivity and stability of the oxygen carrier. The development of oxygen carriers remains one of the major barriers for commercialization of CLC. Synthetic oxygen carriers, consisting of multiple metal components, have demonstrated enhanced performance and improved CLC operation compared to single metal oxides. However, identification of the complex mixed metal oxide phases that form after calcination or during CLCmore » reactions has been challenging. Without an understanding of the dominant metal oxide phase, it is difficult to determine reaction parameters and the oxygen carrier reduction pathway, which are necessary for CLC reactor design. This is particularly challenging for complex multi-component oxygen carriers such as copper iron manganese oxide (CuFeMnO 4). This study aims to differentiate the unique phase formation of a highly reactive, complex trimetallic oxygen carrier, CuFeMnO 4, from its single and bimetallic counterparts using thermochemical and reaction data obtained from simultaneous differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) during temperature programmed reductions (TPR) with methane. DSC/TGA experiments during TPR with methane provides heat flow data and corresponding reaction rate data that can be used to determine reaction routes and mechanisms during methane reduction. Furthermore, non-isothermal TPR data provides the advantage of distinguishing reactions that may not be observable in isothermal analysis. The detailed thermochemical and reaction data, obtained during TPR with methane, distinguished a unique reduction pathway for CuFeMnO 4 that differed from its single and bimetallic counterparts. This is remarkable since X-ray diffraction (XRD) data alone could not be used to distinguish the reactive trimetallic oxide phase due to overlapping peaks from various single and mixed metal oxides. The unique reduction pathway of CuFeMnO 4 was further characterized in this study using in-situ XRD TPR with methane to determine changes in the dominant trimetallic phase that influenced the thermochemical and reaction rate data.« less

Rapid detection of contagious ecthyma by loop-mediated isothermal amplification and epidemiology in Jilin Province China.

PubMed

Wang, Kai; Shao, Hongze; Pei, Zhihua; Hu, Guixue

2016-01-01

The aim of this experiment was to develop a loop-mediated isothermal amplification (LAMP) assay and to research the recent epidemiology of contagious ecthyma in Jilin Province, China, using the assay. A LAMP assay targeting a highly conserved region of the F1L gene was developed to detect contagious ecthyma virus (CEV). Three hundred and sixty-five cases from 64 flocks in 9 different areas of Jilin Province, China, from 2011 to 2014 were tested using the LAMP assay. The results showed that the sensitivity of the LAMP assay was 100 copies of the standard plasmid, which is 100-fold higher than the sensitivity of PCR. No cross-reactivity was observed with capripoxvirus, fowlpox virus, foot-and-mouth disease virus serotype O, foot-and-mouth disease virus serotype Asia I and bluetongue virus. The average positive rate was 19.73% (72/365), and the positive rate was highest in lambs aged 1-6 months. Our results demonstrated that CEV infection was very widespread in the flocks of Jilin Province and that the LAMP assay allows for easy, rapid, accurate and sensitive detection of CEV infection.

Real-Life Use of Neurohormonal Antagonists and Loop Diuretics in Chronic Heart Failure: Analysis of Serial Biomarker Measurements and Clinical Outcome.

PubMed

Brankovic, Milos; Akkerhuis, K Martijn; van Boven, Nick; Manintveld, Olivier; Germans, Tjeerd; Brugts, Jasper; Caliskan, Kadir; Umans, Victor; Constantinescu, Alina; Kardys, Isabella

2017-11-06

We determined the temporal effects of neurohormonal antagonists and loop diuretics on serially assessed (3-monthly) cardiorenal biomarkers, functional status, and clinical outcomes in 250 patients with chronic heart failure (CHF) with reduced ejection fraction. In blood, we measured NT-proBNP, troponin T, C-reactive protein, creatinine, cystatin C; in urine, N-acetyl-beta-d-glucosaminidase and kidney-injury-molecule-1. Angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) were inversely associated with cardiac impairment, inflammation, and renal tubular damage, but not with glomerular dysfunction. Diuretics were associated with worse biomarker profiles and with a hazard ratio for adverse clinical outcome of 1.12 (95% confidence interval: 1.03-1.22) per 40 mg higher doses. ACE-inhibitors/ARBs were more frequently downtitrated and diuretics more frequently uptitrated in patients who experienced endpoints than in those who did not. In conclusion, a decrease or withholding of ACE-inhibitors/ARBs solely based on glomerular function is not justified because of the beneficial effects on the heart, inflammation, and renal tubules. Higher and increased diuretic doses mark progression towards endstage CHF. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Detection of Brucellosis in Sika Deer ( Cervus nippon ) through Loop-mediated Isothermal Amplification (LAMP).

PubMed

Liu, Qianhong; Wei, Jie; Sun, Qingsong; Wang, Ben; Wang, Yuting; Hu, Ying; Wu, Wenrong

2017-07-01

Brucellosis (Brucella bovis) in sika deer ( Cervus nippon ) can cause enormous losses to stag breeding, especially in areas in which stag breeding has become an important industry. It also poses a threat to humans because it is a zoonotic disease. Use of the loop-mediated isothermal amplification (LAMP) assay has been poorly described in the diagnosis of brucellosis in deer. We developed a LAMP assay targeting the omp25 gene sequence to detect brucellosis in sika deer. The reaction can be completed in 60 min at 63 C and, with a detection limit of 17 pg, it was more sensitive than conventional PCR, with its detection limit of 1.7 ng. No cross-reactivity was observed with four bacteria: Escherichia coli , Salmonella enterica subsp. enterica, Clostridium pasteurianum , and Pseudomonas aeruginosa . We used 263 samples of blood to evaluate the reaction. The percentage of agreement between LAMP and PCR reached 91%; relative specificity reached 87%, and relative sensitivity reached 100%. The results indicate LAMP can be a simple and rapid diagnostic tool for detecting brucellosis in sika deer, particularly in the field, where it is essential to control brucellosis in deer with a rapid and accurate diagnosis for removal of positive animals.

Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

PubMed

Wang, Qian; Huang, Lihong; Yue, Jianbo

2017-06-01

High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative detection of pork in commercial meat products by TaqMan® real-time PCR assay targeting the mitochondrial D-loop region.

PubMed

Kim, Miju; Yoo, Insuk; Lee, Shin-Young; Hong, Yeun; Kim, Hae-Yeong

2016-11-01

The TaqMan® real-time PCR assay using the mitochondrial D-loop region was developed for the quantitative detection of pork in processed meat products. The newly designed primers and probe specifically amplified pork without any cross-reactivity with non-target animal species. The limit of detection of the real-time PCR assay was 0.1pg of heat-treated pork meat and 0.1% (w/w) pork meat in beef and chicken meat mixtures. The quantitative real-time PCR assay was applied to analyze the pork meat content in 22 commercial processed meat products including jerkies, press hams, sausages, hamburger patties and steaks, grilled short rib patties, and nuggets. The developed real-time PCR method was able to detect pork meat in various types of processed meat products that declared the use of pork meat on their label. All processed meat products that declared no use of pork meat showed a negative result in the assay. The method developed in this study showed sensitivity and specificity in the quantification of pork meat in commercial processed meat products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Activation and reactivation of the RNA polymerase II trigger loop for intrinsic RNA cleavage and catalysis

PubMed Central

Čabart, Pavel; Jin, Huiyan; Li, Liangtao; Kaplan, Craig D

2014-01-01

In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process. Here we show that a single amino-acid substitution in the trigger loop (TL) of Saccharomyces RNAP II, Rpb1 H1085Y, engenders a gain of intrinsic cleavage activity where the substituted tyrosine appears to participate in acid-base chemistry at alkaline pH for both intrinsic cleavage and nucleotidyl transfer. We extensively characterize this TL substitution for each of these reactions by examining the responses RNAP II enzymes to catalytic metals, altered pH, and factor inputs. We demonstrate that TFIIF stimulation of the first phosphodiester bond formation by RNAP II requires wild type TL function and that H1085Y substitution within the TL compromises or alters RNAP II responsiveness to both TFIIB and TFIIF. Finally, Mn2+ stimulation of H1085Y RNAP II reveals possible allosteric effects of TFIIB on the active center and cooperation between TFIIB and TFIIF. PMID:25764335

Structure-Guided Combinatorial Engineering Facilitates Affinity and Specificity Optimization of Anti-CD81 Antibodies.

PubMed

Nelson, Bryce; Adams, Jarrett; Kuglstatter, Andreas; Li, Zhijian; Harris, Seth F; Liu, Yang; Bohini, Sandya; Ma, Han; Klumpp, Klaus; Gao, Junjun; Sidhu, Sachdev S

2018-07-06

Hepatitis C viral infection is the major cause of chronic hepatitis that affects as many as 71 million people worldwide. Rather than target the rapidly shifting viruses and their numerous serotypes, four independent antibodies were made to target the host antigen CD81 and were shown to block hepatitis C viral entry. The single-chain variable fragment of each antibody was crystallized in complex with the CD81 large extracellular loop in order to guide affinity maturation of two distinct antibodies by phage display. Affinity maturation of antibodies using phage display has proven to be critical to therapeutic antibody development and typically involves modification of the paratope for increased affinity, improved specificity, enhanced stability or a combination of these traits. One antibody was engineered for increased affinity for human CD81 large extracellular loop that equated to increased efficacy, while the second antibody was engineered for cross-reactivity with cynomolgus CD81 to facilitate animal model testing. The use of structures to guide affinity maturation library design demonstrates the utility of combining structural analysis with phage display technologies. Copyright © 2018 Elsevier Ltd. All rights reserved.

The role of niobium carbide in radiation induced segregation behaviour of type 347 austenitic stainless steel

NASA Astrophysics Data System (ADS)

Ahmedabadi, Parag; Kain, Vivekanand; Gupta, Manu; Samajdar, I.; Sharma, S. C.; Bhagwat, P.; Chowdhury, R.

2011-08-01

The effect of niobium carbide precipitates on radiation induced segregation (RIS) behaviour in type 347 stainless steel was investigated. The material in the as-received condition was irradiated using double-loop 4.8 MeV protons at 300 °C for 0.43 dpa (displacement per atom). The RIS in the proton irradiated specimen was characterized using double-loop electrochemical potentiokinetic reactivation (DL-EPR) test followed by atomic force microscopic examination. The nature of variation of DL-EPR values with the depth matched with the variation of the calculated irradiation damage (dpa) with the depth. The attack on grain boundaries during EPR tests was negligible indicating absence of chromium depletion zones. The interface between niobium carbide and the matrix acts as a sink for point defects generated during irradiation and this had reduced point defect flux toward grain boundaries. The attack was noticed at a few large cluster of niobium carbide after the DL-EPR test at the depth of maximum attack for the irradiated specimen. Pit-like features were not observed within the matrix indicating the absence of chromium depletion regions within the matrix.

Multifrequency electron paramagnetic resonance and electron-nuclear double-resonance studies of photo-hole processes in AgBr and AgCl emulsion grains

NASA Astrophysics Data System (ADS)

Eachus, R. S.; Pawlik, Th D.; Baetzold, R. C.

2000-10-01

By using a combination of multifrequency EPR spectroscopy, ENDOR spectroscopy and calculations of structure and energy, the reactivities of photo-generated holes in microcrystalline AgBr and AgCl dispersions (photographic emulsions) have been followed in detail. Progress has been facilitated by the use of both gelatin and polyvinyl alcohol (PVA) as peptizers. The initial trapped hole centres produced by band-gap excitation have been identified. In AgBr, this species is [(Br4)3-.V], a neutral complex formed from hole trapping by the four nearest neighbours of a surface Ag+ vacancy (=V). [(Br4)3-.V] reacts with gelatin to produce a transient organic radical at the grain's surface. It does not, however, react with PVA. The formation of the oxidized gelatin radical might involve atomic bromine as an intermediate. In AgCl, the well-known self-trapped hole centre (AgCl6)4- is the initial hole species. The hole diffuses by an electron exchange process until it is trapped by a silver ion on the grain's surface or within its penultimate layer of lattice ions. It is subsequently released from this Ag2+ site to be retrapped at a centre containing four equivalent Cl- ions. The precise identity of this defect has yet to be determined, but its decay also results in the oxidation of gelatin.

Seroprevalence of acute dengue in a Malaysian tertiary medical centre

PubMed Central

Ding, Chuan Hun; Rashid, Zetti Zainol; Rahman, Md. Mostafizur; Khang, NanFeng; Low, Wan Ngor; Hussin, Nurabrar; Marzuki, Melissa Iqlima; Jaafar, Alyaa Nadhira; Roslan, Nurul Ain’ Nabilla; Chandrasekaran, Terukumar

2016-01-01

Objectives: The aims of this study were to determine the seroprevalence of acute dengue in Universiti Kebangsaan Malaysia (UKM) Medical Centre and its correlation with selected haematological and biochemical parameters. Methods: This cross-sectional study was conducted from January to June 2015. A patient was serologically diagnosed with acute dengue if the dengue virus IgG, IgM or NS-1 antigen was reactive. Results: Out of 1,774 patients suspected to have acute dengue, 1,153 were serologically diagnosed with the infection, resulting in a seroprevalence of 64.9%. Dengue-positive patients had a lower mean platelet count (89 × 109/L) compared to the dengue-negative patients (171 × 109/L) (p<0.0001). The mean total white cell count was also lower in the dengue-positive cases (4.7 × 109/L vs. 7.2 × 109/L; p<0.0001). The mean haematocrit was higher in patients with acute dengue (42.5% vs. 40.0%; p<0.0001). Likewise, the serum alanine transaminase level was also higher in patients with acute dengue (108 U/L vs. 54 U/L; p<0.0001). Conclusions: Dengue is very prevalent in UKM Medical Centre as most patients suspected to have acute dengue had serological evidence of the infection. The platelet count was the single most likely parameter to be abnormal (i.e. low) in patients with acute dengue. PMID:27182269

Modification of Agility Running Technique in Reaction to a Defender in Rugby Union

PubMed Central

Wheeler, Keane W.; Sayers, Mark G.L.

2010-01-01

Three-dimensional kinematic analysis examined agility running technique during pre-planned and reactive performance conditions specific to attacking ball carries in rugby union. The variation to running technique of 8 highly trained rugby union players was compared between agility conditions (pre-planned and reactive) and also agility performance speeds (fast, moderate and slow). Kinematic measures were used to determine the velocity of the centre of mass (COM) in the anteroposterior (running speed) and mediolateral (lateral movement speed) planes. The position of foot-strike and toe-off was also examined for the step prior to the agility side- step (pre-change of direction phase) and then the side-step (change of direction phase). This study demonstrated that less lateral movement speed towards the intended direction change occurred during reactive compared to pre-planned conditions at pre-change of direction (0.08 ± 0.28 m·s-1 and 0.42 ± 0.25 m·s-1, respectively) and change of direction foot-strikes (0.25 ± 0.42 m·s-1 and 0.69 ± 0.43 m·s-1, respectively). Less lateral movement speed during reactive conditions was associated with greater lateral foot displacement (44.52 ± 6.10% leg length) at the change of direction step compared to pre-planned conditions (41.35 ± 5.85%). Importantly, the anticipation abilities during reactive conditions provided a means to differentiate between speeds of agility performance, with faster performances displaying greater lateral movement speed at the change of direction foot- strike (0.52 ± 0.34 m·s-1) compared to moderate (0.20 ± 0.37 m·s-1) and slow (-0.08 ± 0.31 m·s-1). The changes to running technique during reactive conditions highlight the need to incorporate decision-making in rugby union agility programs. Key points Changes to running technique occur when required to make a decision. Fast agility performers use different stepping strategies in reactive conditions. Decision-making must be incorporated in agility training programs. PMID:24149639

Large File Transfers from Space Using Multiple Ground Terminals and Delay-Tolerant Networking

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Paulsen, Phillip; Stewart, Dave; Eddy, Wesley; McKim, James; Taylor, John; Lynch, Scott; Heberle, Jay; Northam, James; Jackson, Chris;

A reaction cell with sample laser heating for in situ soft X-ray absorption spectroscopy studies under environmental conditions.

PubMed

Escudero, Carlos; Jiang, Peng; Pach, Elzbieta; Borondics, Ferenc; West, Mark W; Tuxen, Anders; Chintapalli, Mahati; Carenco, Sophie; Guo, Jinghua; Salmeron, Miquel

2013-05-01

A miniature (1 ml volume) reaction cell with transparent X-ray windows and laser heating of the sample has been designed to conduct X-ray absorption spectroscopy studies of materials in the presence of gases at atmospheric pressures. Heating by laser solves the problems associated with the presence of reactive gases interacting with hot filaments used in resistive heating methods. It also facilitates collection of a small total electron yield signal by eliminating interference with heating current leakage and ground loops. The excellent operation of the cell is demonstrated with examples of CO and H2 Fischer-Tropsch reactions on Co nanoparticles.

Molecular basis of pollen-related food allergy: identification of a second cross-reactive IgE epitope on Pru av 1, the major cherry (Prunus avium) allergen.

PubMed

Wiche, Regina; Gubesch, Michaela; König, Herbert; Fötisch, Kay; Hoffmann, Andreas; Wangorsch, Andrea; Scheurer, Stephan; Vieths, Stefan

2005-01-01

Birch (Betula verrucosa) pollen-associated food allergy is a well-characterized syndrome, which is due to the cross-reactivity of IgE antibodies to homologous allergens in various foods. One crossreacting area on the major birch pollen allergen Bet v 1 and its homologue in cherry (Prunus avium) Pru av 1 has already been identified. This is the so-called 'P-loop' region, which encompasses amino acid residues around position 45 and is found on the two virtually identical tertiary protein structures. We tried to determine an additional IgE cross-reacting patch on Pru av 1 and Bet v 1. The putative IgE-binding region on Pru av 1 was localized with a mAb (monoclonal antibody) that was generated against Bet v 1, and cross-reacts with several Bet v 1 homologues in food and inhibits the binding of patients' IgE to Pru av 1. mAb reactivity pattern was analysed and amino acid positions 28 and 108 of Pru av 1 were selected and mutated by site-directed mutagenesis. The Pru av 1 mutants were produced as recombinant proteins and characterized for their folding, mAb- and IgE-binding capacity and allergenic potency with a cellular assay using the humanized rat basophilic leukaemia cell line RBL-25/30. Amino acid position 28 is involved in a second major IgE-binding region on Pru av 1 and probably on Bet v 1. The identification of this second major IgE-binding region is an essential prerequisite to understand the phenomenon of cross-reactivity and its clinical consequences, and to produce hypoallergenic proteins for an improved immunotherapy of type I allergy.

Probing the quantum coherence of a nanomechanical resonator using a superconducting qubit: II. Implementation

NASA Astrophysics Data System (ADS)

Blencowe, M. P.; Armour, A. D.

2008-09-01

We describe a possible implementation of the nanomechanical quantum superposition generation and detection scheme described in the preceding, companion paper (Armour A D and Blencowe M P 2008 New. J. Phys. 10 095004). The implementation is based on the circuit quantum electrodynamics (QED) set-up, with the addition of a mechanical degree of freedom formed out of a suspended, doubly-clamped segment of the superconducting loop of a dc SQUID located directly opposite the centre conductor of a coplanar waveguide (CPW). The relative merits of two SQUID based qubit realizations are addressed, in particular a capacitively coupled charge qubit and inductively coupled flux qubit. It is found that both realizations are equally promising, with comparable qubit-mechanical resonator mode as well as qubit-microwave resonator mode coupling strengths.

Application of digital control techniques for satellite medium power DC-DC converters

NASA Astrophysics Data System (ADS)

Skup, Konrad R.; Grudzinski, Pawel; Nowosielski, Witold; Orleanski, Piotr; Wawrzaszek, Roman

2010-09-01

The objective of this paper is to present a work concerning a digital control loop system for satellite medium power DC-DC converters that is done in Space Research Centre. The whole control process of a described power converter bases on a high speed digital signal processing. The paper presents a development of a FPGA digital controller for voltage mode stabilization that was implemented using VHDL. The described controllers are a classical digital PID controller and a bang-bang controller. The used converter for testing is a simple model of 5-20 W, 200 kHz buck power converter. A high resolution digital PWM approach is presented. Additionally a simple and effective solution of filtering of an analog-to-digital converter output is presented.

C-reactive protein point-of-care testing and antibiotic prescribing for acute respiratory tract infections in rural primary health centres of North Ethiopia: a cross-sectional study.

PubMed

Yebyo, Henock; Medhanyie, Araya Abrha; Spigt, Mark; Hopstaken, Rogier

2016-01-14

Unjustified antibiotic prescribing for acute upper respiratory infections (URTIs) is probably more common in poor-resource settings where physicians are scarce. Introducing C-reactive protein (CRP) point-of-care testing in such settings could reduce the misuse of antibiotics, which could avert antibiotic resistance. However, information useful for the applicability of CRP test in resource-limited settings is lacking. This study aimed to elicit the frequency of antibiotic prescribing and distribution of CRP levels in remote, rural settings in Ethiopia. We included 414 patients with acute URTIs from four health centres. Health professionals recorded the clinical features of the patients, but the laboratory professionals measured the CRP levels of all patients at the point of care. The most prominent respiratory causes for consultation were acute URTIs combined (44.4%), and lower respiratory tract infections-pneumonia (29.71%) and acute bronchitis (25.84%). The CRP distribution was <20 mg/l, 20-99 mg/l and 100 mg/l or more in 66.6%, 27.9% and 5.5% of the patients, respectively. The CRP levels were significantly different among these clinical diagnoses (X(2)=114.3, P<0.001, d.f.=4). A wide range of antibiotics was administered for 87.8% of the patients, regardless of the diagnostic or prognostic nature of their diseases. Antibiotic prescribing for acute URTIs in the rural areas of Ethiopia is unduly high, with high proportions of mild, self-limiting illness, mostly URTIs. Implementation of CRP point-of-care testing in such resource-constrained settings, with low- or middle-grade healthcare professionals, could help reconcile the inappropriate use of antibiotics by withholding from patients who do not benefit from antibiotic treatment.

C-reactive protein point-of-care testing and antibiotic prescribing for acute respiratory tract infections in rural primary health centres of North Ethiopia: a cross-sectional study

PubMed Central

Yebyo, Henock; Medhanyie, Araya Abrha; Spigt, Mark; Hopstaken, Rogier

2016-01-01

Unjustified antibiotic prescribing for acute upper respiratory infections (URTIs) is probably more common in poor-resource settings where physicians are scarce. Introducing C-reactive protein (CRP) point-of-care testing in such settings could reduce the misuse of antibiotics, which could avert antibiotic resistance. However, information useful for the applicability of CRP test in resource-limited settings is lacking. This study aimed to elicit the frequency of antibiotic prescribing and distribution of CRP levels in remote, rural settings in Ethiopia. We included 414 patients with acute URTIs from four health centres. Health professionals recorded the clinical features of the patients, but the laboratory professionals measured the CRP levels of all patients at the point of care. The most prominent respiratory causes for consultation were acute URTIs combined (44.4%), and lower respiratory tract infections—pneumonia (29.71%) and acute bronchitis (25.84%). The CRP distribution was <20 mg/l, 20–99 mg/l and 100 mg/l or more in 66.6%, 27.9% and 5.5% of the patients, respectively. The CRP levels were significantly different among these clinical diagnoses (X2=114.3, P<0.001, d.f.=4). A wide range of antibiotics was administered for 87.8% of the patients, regardless of the diagnostic or prognostic nature of their diseases. Antibiotic prescribing for acute URTIs in the rural areas of Ethiopia is unduly high, with high proportions of mild, self-limiting illness, mostly URTIs. Implementation of CRP point-of-care testing in such resource-constrained settings, with low- or middle-grade healthcare professionals, could help reconcile the inappropriate use of antibiotics by withholding from patients who do not benefit from antibiotic treatment. PMID:26769226

Australasian disasters of national significance: an epidemiological analysis, 1900-2012.

PubMed

Bradt, David A; Bartley, Bruce; Hibble, Belinda A; Varshney, Kavita

2015-04-01

A regional epidemiological analysis of Australasian disasters in the 20th century to present was undertaken to examine trends in disaster epidemiology; to characterise the impacts on civil society through disaster policy, practice and legislation; and to consider future potential limitations in national disaster resilience. A surveillance definition of disaster was developed conforming to the Centre for Research on the Epidemiology of Disasters (CRED) criteria (≥10 deaths, ≥100 affected, or declaration of state emergency or appeal for international assistance). The authors then applied economic and legislative inclusion criteria to identify additional disasters of national significance. The surveillance definition yielded 165 disasters in the period, from which 65 emerged as disasters of national significance. There were 38 natural disasters, 22 technological disasters, three offshore terrorist attacks and two domestic mass shootings. Geographic analysis revealed that states with major population centres experienced the vast majority of disasters of national significance. Timeline analysis revealed an increasing incidence of disasters since the 1980s, which peaked in the period 2005-2009. Recent seasonal bushfires and floods have incurred the highest death toll and economic losses in Australasian history. Reactive hazard-specific legislation emerged after all terrorist acts and after most disasters of national significance. Timeline analysis reveals an increasing incidence in natural disasters over the past 15 years, with the most lethal and costly disasters occurring in the past 3 years. Vulnerability to disaster in Australasia appears to be increasing. Reactive legislation is a recurrent feature of Australasian disaster response that suggests legislative shortsightedness and a need for comprehensive all-hazards model legislation in the future. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Bookshelf faulting and transform motion between rift segments of the Northern Volcanic Zone, Iceland

NASA Astrophysics Data System (ADS)

Green, R. G.; White, R. S.; Greenfield, T. S.

2013-12-01

Plate spreading is segmented on length scales from 10 - 1,000 kilometres. Where spreading segments are offset, extensional motion has to transfer from one segment to another. In classical plate tectonics, mid-ocean ridge spreading centres are offset by transform faults, but smaller 'non-transform' offsets exist between slightly overlapping spreading centres which accommodate shear by a variety of geometries. In Iceland the mid-Atlantic Ridge is raised above sea level by the Iceland mantle plume, and is divided into a series of segments 20-150 km long. Using microseismicity recorded by a temporary array of 26 three-component seismometers during 2009-2012 we map bookshelf faulting between the offset Askja and Kverkfjöll rift segments in north Iceland. The micro-earthquakes delineate a series of sub-parallel strike-slip faults. Well constrained fault plane solutions show consistent left-lateral motion on fault planes aligned closely with epicentral trends. The shear couple across the transform zone causes left-lateral slip on the series of strike-slip faults sub-parallel to the rift fabric, causing clockwise rotations about a vertical axis of the intervening rigid crustal blocks. This accommodates the overall right-lateral transform motion in the relay zone between the two overlapping volcanic rift segments. The faults probably reactivated crustal weaknesses along the dyke intrusion fabric (parallel to the rift axis) and have since rotated ˜15° clockwise into their present orientation. The reactivation of pre-existing rift-parallel weaknesses is in contrast with mid-ocean ridge transform faults, and is an important illustration of a 'non-transform' offset accommodating shear between overlapping spreading segments.

Orbital-specific mapping of the ligand exchange dynamics of Fe(CO)5 in solution.

PubMed

Wernet, Ph; Kunnus, K; Josefsson, I; Rajkovic, I; Quevedo, W; Beye, M; Schreck, S; Grübel, S; Scholz, M; Nordlund, D; Zhang, W; Hartsock, R W; Schlotter, W F; Turner, J J; Kennedy, B; Hennies, F; de Groot, F M F; Gaffney, K J; Techert, S; Odelius, M; Föhlisch, A

2015-04-02

Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site that need to be controlled to optimize complexes for photocatalytic hydrogen production and selective carbon-hydrogen bond activation. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst with an electron deficiency at the Fe centre, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16 - 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.

Orbital-specific mapping of the ligand exchange dynamics of Fe(CO)5 in solution

NASA Astrophysics Data System (ADS)

Wernet, Ph.; Kunnus, K.; Josefsson, I.; Rajkovic, I.; Quevedo, W.; Beye, M.; Schreck, S.; Grübel, S.; Scholz, M.; Nordlund, D.; Zhang, W.; Hartsock, R. W.; Schlotter, W. F.; Turner, J. J.; Kennedy, B.; Hennies, F.; de Groot, F. M. F.; Gaffney, K. J.; Techert, S.; Odelius, M.; Föhlisch, A.

2015-04-01

Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site that need to be controlled to optimize complexes for photocatalytic hydrogen production and selective carbon-hydrogen bond activation. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst with an electron deficiency at the Fe centre, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16,17,18,19 and 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.

Ranitidine-induced anaphylaxis: clinical features, cross-reactivity, and skin testing.

PubMed

Park, K H; Pai, J; Song, D-G; Sim, D W; Park, H J; Lee, J-H; Jeong, K Y; Pan, C-H; Shin, I; Park, J-W

2016-04-01

Histamine H2 receptor antagonists are commonly prescribed medications and are known to be well tolerated. However, 99 cases of ranitidine-induced anaphylaxis occurred in Korea from 2007 to 2014. The purpose of this study was to determine the incidence, clinical features, and diagnostic methods for ranitidine-induced anaphylaxis. Ranitidine-related pharmacovigilance data from 2007 to 2014 were reviewed. Adverse drug reactions with causal relationships were selected, and clinical manifestations, outcomes, and drug-related information were assessed. For further investigation, 8 years of pharmacovigilance data were collected at a single centre. Twenty-three patients participated in in vivo and in vitro studies. Skin tests, oral provocation tests, and laboratory tests were performed, including tests using other kinds of histamine H2 receptor antagonists. Over 7 years, 584 patients suffered adverse reactions to ranitidine. The most common manifestation was cutaneous symptoms. Among them, 99 patients (17.0%) experienced anaphylaxis. In a single-centre study, skin prick tests were positive in 91.7% of ranitidine-induced anaphylaxis patients (11/12); the optimal concentration was 20 mg/mL. Detection of ranitidine-specific immunoglobulin E failed. Cimetidine and proton pump inhibitors showed no cross-reactivity with ranitidine based on the skin prick test, oral provocation test, or clinical determination. Surprisingly, 82.6% of patients reintroduced ranitidine and re-experienced the same adverse reactions because ranitidine was not considered the culprit drug. Although ranitidine is known as a safe drug, it can also cause diverse adverse reactions, including anaphylaxis. This study demonstrates the need to pay attention to adverse reactions to ranitidine and consider ranitidine as a cause of anaphylaxis. © 2016 John Wiley & Sons Ltd.

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

PubMed Central

Mordi, Natalie A; Mordi, Ify R; Singh, Jagdeep S; Baig, Fatima; Choy, Anna-Maria; McCrimmon, Rory J; Struthers, Allan D; Lang, Chim C

2017-01-01

Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer-reviewed journal. Trial registration number NCT03226457; Pre-results. PMID:29042392

A User Guide to PARET/ANL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, A. P.; Dionne, B.; Marin-Lafleche, A.

2015-01-01

PARET was originally created in 1969 at what is now Idaho National Laboratory (INL), to analyze reactivity insertion events in research and test reactor cores cooled by light or heavy water, with fuel composed of either plates or pins. The use of PARET is also appropriate for fuel assemblies with curved fuel plates when their radii of curvatures are large with respect to the fuel plate thickness. The PARET/ANL version of the code has been developed at Argonne National Laboratory (ANL) under the sponsorship of the U.S. Department of Energy/NNSA, and has been used by the Reactor Conversion Program tomore » determine the expected transient behavior of a large number of reactors. PARET/ANL models the various fueled regions of a reactor core as channels. Each of these channels consists of a single flat fuel plate/pin (including cladding and, optionally, a gap) with water coolant on each side. In slab geometry the coolant channels for a given fuel plate are of identical dimensions (mirror symmetry), but they can be of different thickness in each channel. There can be many channels, but each channel is independent and coupled only through reactivity feedback effects to the whole core. The time-dependent differential equations that represent the system are replaced by an equivalent set of finite-difference equations in space and time, which are integrated numerically. PARET/ANL uses fundamentally the same numerical scheme as RELAP5 for the time-integration of the point-kinetics equations. The one-dimensional thermal-hydraulic model includes temperature-dependent thermal properties of the solid materials, such as heat capacity and thermal conductivity, as well as the transient heat production and heat transfer from the fuel meat to the coolant. Temperature- and pressure-dependent thermal properties of the coolant such as enthalpy, density, thermal conductivity, and viscosity are also used in determining parameters such as friction factors and heat transfer coefficients. The code first determines the steady-state solution for the initial state. Then the solution of the transient is obtained by integration in time and space. Multiple heat transfer, DNB and flow instability correlations are available. The code was originally developed to model reactors cooled by an open loop, which was adequate for rapid transients in pool-type cores. An external loop model appropriate for Miniature Neutron Source Reactors (MNSR’s) was also added to PARET/ANL to model natural circulation within the vessel, heat transfer from the vessel to pool and heat loss by evaporation from the pool. PARET/ANL also contains models for decay heat after shutdown, control rod reactivity versus time or position, time-dependent pump flow, and loss-of-flow event with flow reversal as well as logic for trips on period, power, and flow. Feedback reactivity effects from coolant density changes and temperature changes are represented by tables. Feedback reactivity from fuel heat-up (Doppler Effect) is represented by a four-term polynomial in powers of fuel temperature. Photo-neutrons produced in beryllium or in heavy water may be included in the point-kinetics equations by using additional delayed neutron groups.« less

Well-Defined Heterobimetallic Reactivity at Unsupported Ruthenium-Indium Bonds.

PubMed

Riddlestone, Ian M; Rajabi, Nasir A; Macgregor, Stuart A; Mahon, Mary F; Whittlesey, Michael K

2018-02-01

The hydride complex [Ru(IPr) 2 (CO)H][BAr F 4 ], 1, reacts with InMe 3 with loss of CH 4 to form [Ru(IPr) 2 (CO)(InMe)(Me)][BAr F 4 ], 4, featuring an unsupported Ru-In bond with unsaturated Ru and In centres. 4 reacts with H 2 to give [Ru(IPr) 2 (CO)(η 2 -H 2 )(InMe)(H)][BAr F 4 ], 5, while CO induces formation of the indyl complex [Ru(IPr) 2 (CO) 3 (InMe 2 )][BAr F 4 ], 7. These observations highlight the ability of Me to shuttle between Ru and In centres and are supported by DFT calculations on the mechanism of formation of 4 and its reactions with H 2 and CO. An analysis of Ru-In bonding in these species is also presented. Reaction of 1 with GaMe 3 also involves CH 4 loss but, in contrast to its In congener, sees IPr transfer from Ru to Ga to give a gallyl complex featuring an η 6 interaction of one aryl substituent with Ru. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Poliomyelitis case surveillance data management in Burkina Faso].

PubMed

Drabo, Koiné Maxime; Nana, Félicité; Kouassi, Kouassi Lazare; Konfé, Salifou; Hien, Hervé; Saizonou, Jacques; Ouedraogo, Tinoaga Laurent

2015-01-01

The global initiative for poliomyelitis eradication can only remain relevant if survey systems are regularly assessed. In order to identify shortcomings and to propose improvement, the data collection and transmission during case investigation were assessed in the Banfora health district in Burkina Faso. The survey targeted six (6) primary health centres, the district laboratory and the national laboratory, all involved in the poliomyelitis surveillance system. Data from registers, forms documenting suspected cases, stool sample forms and weekly reports were collected by means of a data grid. Data from actors involved in the poliomyelitis case investigation system were collected by means of an individual questionnaire. The reactivity of investigating suspected cases was satisfactory with a median alert questionnaire notification time of 18 hours. The completeness of the reporting system was satisfactory. Nevertheless, the promptness of data management by primary heath centres and the national laboratory remained unsatisfactory. Evaluation of data management revealed logistic and organization shortcomings. The overall efficacy of the poliomyelitis surveillance could be improved by using management tools for laboratory supplies, collecting data related to the homes of suspected cases and implementing a cold chain maintenance plan.

The E. coli 16S rRNA binding site of ribosomal protein S15: higher-order structure in the absence and in the presence of the protein.

PubMed Central

Mougel, M; Philippe, C; Ebel, J P; Ehresmann, B; Ehresmann, C

1988-01-01

We have investigated in detail the secondary and tertiary structures of E. coli 16S rRNA binding site of protein S15 using a variety of enzymatic and chemical probes. RNase T1 and nuclease S1 were used to probe unpaired nucleotides and RNase V1 to monitor base-paired or stacked nucleotides. Bases were probed with dimethylsulfate (at A(N-1), C(N-3) and G(N-7)), with 1-cyclohexyl-3 (2-(1-methylmorpholino)-ethyl)-carboiimide-p- toluenesulfonate (at U(N-3) and G(N-1)) and with diethylpyrocarbonate (at A(N-7)). The RNA region corresponding to nucleotides 652 to 753 was tested within: (1) the complete 16S rRNA molecule; (2) a 16S rRNA fragment corresponding to nucleotides 578 to 756 obtained by transcription in vitro; (3) the S15-16S rRNA complex; (4) the S15-fragment complex. Cleavage and modification sites were detected by primer extension with reverse transcriptase. Our results show that: (1) The synthetized fragment folds into the same overall secondary structure as in the complete 16S rRNA, with the exception of the large asymmetrical internal loop (nucleotides 673-676/714-733) which is fully accessible in the fragment while it appears conformationally heterogeneous in the 16S rRNA; (2) the reactivity patterns of the S15-16S rRNA and S15-fragment complexes are identical; (3) the protein protects defined RNA regions, located in the large interior loop and in the 3'-end strand of helix [655-672]-[734-751]; (4) the protein also causes enhanced chemical reactivity and enzyme accessibility interpreted as resulting from a local conformational rearrangement, induced by S15 binding. Images PMID:2453025

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

PubMed Central

Yang, Lu; Chen, Xufeng; Simet, Samantha M.; Hu, Guoku; Cai, Yu; Niu, Fang; Kook, Yeonhee

2016-01-01

Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell–substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2–related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension. PMID:27391108

Virtual Machine Language 2.1

NASA Technical Reports Server (NTRS)

Riedel, Joseph E.; Grasso, Christopher A.

2012-01-01

VML (Virtual Machine Language) is an advanced computing environment that allows spacecraft to operate using mechanisms ranging from simple, time-oriented sequencing to advanced, multicomponent reactive systems. VML has developed in four evolutionary stages. VML 0 is a core execution capability providing multi-threaded command execution, integer data types, and rudimentary branching. VML 1 added named parameterized procedures, extensive polymorphism, data typing, branching, looping issuance of commands using run-time parameters, and named global variables. VML 2 added for loops, data verification, telemetry reaction, and an open flight adaptation architecture. VML 2.1 contains major advances in control flow capabilities for executable state machines. On the resource requirements front, VML 2.1 features a reduced memory footprint in order to fit more capability into modestly sized flight processors, and endian-neutral data access for compatibility with Intel little-endian processors. Sequence packaging has been improved with object-oriented programming constructs and the use of implicit (rather than explicit) time tags on statements. Sequence event detection has been significantly enhanced with multi-variable waiting, which allows a sequence to detect and react to conditions defined by complex expressions with multiple global variables. This multi-variable waiting serves as the basis for implementing parallel rule checking, which in turn, makes possible executable state machines. The new state machine feature in VML 2.1 allows the creation of sophisticated autonomous reactive systems without the need to develop expensive flight software. Users specify named states and transitions, along with the truth conditions required, before taking transitions. Transitions with the same signal name allow separate state machines to coordinate actions: the conditions distributed across all state machines necessary to arm a particular signal are evaluated, and once found true, that signal is raised. The selected signal then causes all identically named transitions in all present state machines to be taken simultaneously. VML 2.1 has relevance to all potential space missions, both manned and unmanned. It was under consideration for use on Orion.

HIV-1 Cross-Reactive Primary Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates

PubMed Central

Wang, Yimeng; O'Dell, Sijy; Turner, Hannah L.; Chiang, Chi-I; Lei, Lin; Guenaga, Javier; Wilson, Richard; Martinez-Murillo, Paola; Doria-Rose, Nicole; Ward, Andrew B.; Mascola, John R.; Wyatt, Richard T.; Karlsson Hedestam, Gunilla B.

2017-01-01

ABSTRACT Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates elicit predominantly tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP.664, a native Env trimer mimetic, as a sorting probe to isolate monoclonal Abs (MAbs). We found striking genetic and functional convergence of the SOSIP-sorted Ig repertoire, with predominant VH4 or VH5 gene family usage and Env V3 specificity. Of these vaccine-elicited V3-specific MAbs, nearly 20% (6/33) displayed cross-reactive tier 2 virus neutralization, which recapitulated the serum neutralization capacity. Substantial similarities in binding specificity, neutralization breadth and potency, and sequence/structural homology were observed between selected macaque cross-reactive V3 NAbs elicited by vaccination and prototypic V3 NAbs derived from natural infections in humans, highlighting the convergence of this subset of primate V3-specific B cell repertories. Our study demonstrated that cross-reactive primary virus neutralizing B cell lineages could be elicited by vaccination as detected using a standardized panel of tier 2 viruses. Whether these lineages could be expanded to acquire increased breadth and potency of neutralization merits further investigation. IMPORTANCE Elicitation of antibody responses capable of neutralizing diverse HIV-1 primary virus isolates (designated broadly neutralizing antibodies [bNAbs]) remains a high priority for the vaccine field. bNAb responses were so far observed only in response to natural infection within a subset of individuals. To achieve this goal, an improved understanding of vaccine-elicited responses, including at the monoclonal Ab level, is essential. Here, we isolated and characterized a panel of vaccine-elicited cross-reactive neutralizing MAbs targeting the Env V3 loop that moderately neutralized several primary viruses and recapitulated the serum neutralizing antibody response. Striking similarities between the cross-reactive V3 NAbs elicited by vaccination in macaques and natural infections in humans illustrate commonalities between the vaccine- and infection-induced responses to V3 and support the feasibility of exploring the V3 epitope as a HIV-1 vaccine target in nonhuman primates. PMID:28835491

Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures.

PubMed

Howe, Charles L; Kaptzan, Tatiana; Magaña, Setty M; Ayers-Ringler, Jennifer R; LaFrance-Corey, Reghann G; Lucchinetti, Claudia F

2014-05-01

Neuromyelitis optica (NMO) is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin-4 (AQP4) water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte-enriched cultures and treatment with NMO patient-derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin-2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease-specific, as serum from patients with relapsing-remitting multiple sclerosis, Sjögren's, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development. Copyright © 2014 Wiley Periodicals, Inc.

ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis

PubMed Central

Shi, Y; Nikulenkov, F; Zawacka-Pankau, J; Li, H; Gabdoulline, R; Xu, J; Eriksson, S; Hedström, E; Issaeva, N; Kel, A; Arnér, E S J; Selivanova, G

2014-01-01

Rescue of the p53 tumor suppressor is an attractive cancer therapy approach. However, pharmacologically activated p53 can induce diverse responses ranging from cell death to growth arrest and DNA repair, which limits the efficient application of p53-reactivating drugs in clinic. Elucidation of the molecular mechanisms defining the biological outcome upon p53 activation remains a grand challenge in the p53 field. Here, we report that concurrent pharmacological activation of p53 and inhibition of thioredoxin reductase followed by generation of reactive oxygen species (ROS), result in the synthetic lethality in cancer cells. ROS promote the activation of c-Jun N-terminal kinase (JNK) and DNA damage response, which establishes a positive feedback loop with p53. This converts the p53-induced growth arrest/senescence to apoptosis. We identified several survival oncogenes inhibited by p53 in JNK-dependent manner, including Mcl1, PI3K, eIF4E, as well as p53 inhibitors Wip1 and MdmX. Further, we show that Wip1 is one of the crucial executors downstream of JNK whose ablation confers the enhanced and sustained p53 transcriptional response contributing to cell death. Our study provides novel insights for manipulating p53 response in a controlled way. Further, our results may enable new pharmacological strategy to exploit abnormally high ROS level, often linked with higher aggressiveness in cancer, to selectively kill cancer cells upon pharmacological reactivation of p53. PMID:24413150

XMM-Newton observations of the Galactic Centre Region - II. The soft-thermal emission

NASA Astrophysics Data System (ADS)

Heard, V.; Warwick, R. S.

2013-09-01

We have extended our earlier study of the X-ray emission emanating from the central 100 pc × 100 pc region of our Galaxy to an investigation of several features prominent in the soft X-ray (2-4.5 keV) band. We focus on three specific structures: a putative bipolar outflow from the vicinity of Sgr A*; a high surface brightness region located roughly 12 arcmin (25 pc) to the north-east of Sgr A* and a lower surface brightness extended loop feature seen to the south of Sgr A*. We show, unequivocally, that all three structures are thermal in nature and have similar temperatures (kT ≈ 1 keV). The inferred X-ray luminosities lie in the range (2-10) × 1034 erg s-1. In the case of the bipolar feature we suggest that the hot plasma is produced by the shock heating of the winds from massive stars within the Central Cluster, possibly collimated by the Circumnuclear Disc. Alternatively the outflow may be driven by outbursts on Sgr A*, which follow tidal disruption events occurring at a rate of roughly one every 4000 yr. The north-east enhancement is centred on a candidate pulsar wind nebula which has a relatively hard non-thermal X-ray spectrum. We suggest that the coincident soft-thermal emission traces the core of a new thermal-composite supernova remnant, designated as SNR G0.13-0.12. There is no clear evidence for an associated radio shell but such a feature may be masked by the bright emission of the nearby Radio Arc and other filamentary structures. SNR G0.13-0.12 is very likely interacting with the nearby molecular cloud, G0.11-0.11, and linked to the Fermi source, 2FGL J1746.4-2851c. Finally we explore a previous suggestion that the elliptically shaped X-ray loop to the south of Sgr A*, of maximum extent ˜45 pc, represents the shell of a superbubble located in the GC region. Although plausible, the interpretation of this feature in terms a coherent physical structure awaits confirmation.

Engagement, resilience and empathy in nursing assistants.

PubMed

Navarro-Abal, Yolanda; López-López, M José; Climent-Rodríguez, José A

To analyse the levels of engagement, resilience and empathy, and the relationship between them, in a sample of nursing assistants working in different private institutions in Huelva. A transversal, descriptive study. The sample comprised 128 nursing assistants working in private health centres of Huelva. They were given the following instruments: resilience scale Wagnild and Young, Interpersonal Reactivity Index and Utrech Work Engagement Scale. There is a relationship between the cognitive and emotional components of engagement and empathy. Certain sociodemographic variables associated with the organisation of work and working conditions are associated with level of engagement. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Evaluation of Baseline CD4+ T Cell Counts and ART Requirement in Newly Diagnosed HIV Seropositive Individuals in a Tertiary Care Hospital of Northern India.

PubMed

Bhattar, Sonali; Mehra, Bhanu; Bhalla, Preena; Rawat, Deepti

2016-11-01

Antiretroviral Therapy (ART) has changed the outlook of Human Immune-deficiency Virus (HIV)/Acquired Immuno Deficiency Syndrome (AIDS) patients worldwide. To analyse the trends in baseline CD4+ T cell counts and ART requirements in newly diagnosed HIV seropositive individuals in a Tertiary care hospital of Northern India. Out of 1263 HIV seropositive clients identified from January 2012 to June 2014, the baseline CD4+ T cell counts of only those 470 clients were analysed, who registered at the linked ART centre. The mean baseline CD4+ count of the study group was 249.77±216.0cells/mm 3 and that of male and female were 300.31±240.47cells/mm 3 and 232.38±204.25cells/mm 3 respectively. A total of 259 of 334 (77.54%) HIV reactive males, 83 of 130 (63.85%) HIV reactive females and overall 348 of 470 (74.04%) required antiretroviral treatment on enrolment. In the present study, about three-fourth of newly diagnosed HIV positive Indian patients required initiation of ART at registration. The relatively low baseline CD4+ T cell counts in this population highlights the need for timely baseline CD4+ counts testing of HIV positive patients and the urgency of initiating treatment in HIV reactive individuals in Indian health care settings.

Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies.

PubMed

Haraburda, Ewelina; Torres, Óscar; Parella, Teodor; Solà, Miquel; Pla-Quintana, Anna

2014-04-22

Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Uncoupling protein-3 lowers reactive oxygen species production in isolated mitochondria

PubMed Central

Toime, Laurence J.; Brand, Martin D.

2010-01-01

Mitochondria are the major cellular producers of reactive oxygen species (ROS), and mitochondrial ROS production increases steeply with increased protonmotive force. The uncoupling proteins (UCP1, UCP2 and UCP3) and adenine nucleotide translocase induce proton leak in response to exogenously added fatty acids, superoxide or lipid peroxidation products. “Mild uncoupling” by these proteins may provide a negative feedback loop to decrease protonmotive force and attenuate ROS production. Using wild type and Ucp3−/− mice, we found that native UCP3 actively lowers the rate of ROS production in isolated energized skeletal muscle mitochondria, in the absence of exogenous activators. The estimated specific activity of UCP3 in lowering ROS production was 90 to 500 times higher than that of the adenine nucleotide translocase. The mild uncoupling hypothesis was tested by measuring whether the effect of UCP3 on ROS production could be mimicked by chemical uncoupling. A chemical uncoupler mimicked the effect of UCP3 at early time points after mitochondrial energization, in support of the mild uncoupling hypothesis. However, at later time points the uncoupler did not mimic UCP3, suggesting that UCP3 can also affect on ROS production through a membrane potential-independent mechanism. PMID:20493945

Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity

PubMed Central

Dunn, Steven M.; Rizkallah, Pierre J.; Baston, Emma; Mahon, Tara; Cameron, Brian; Moysey, Ruth; Gao, Feng; Sami, Malkit; Boulter, Jonathan; Li, Yi; Jakobsen, Bent K.

2006-01-01

The mammalian α/β T cell receptor (TCR) repertoire plays a pivotal role in adaptive immunity by recognizing short, processed, peptide antigens bound in the context of a highly diverse family of cell-surface major histocompatibility complexes (pMHCs). Despite the extensive TCR–MHC interaction surface, peptide-independent cross-reactivity of native TCRs is generally avoided through cell-mediated selection of molecules with low inherent affinity for MHC. Here we show that, contrary to expectations, the germ line-encoded complementarity determining regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the MHC surface and not the bound peptide, can be engineered to yield soluble low nanomolar affinity ligands that retain a surprisingly high degree of specificity for the cognate pMHC target. Structural investigation of one such CDR2 mutant implicates shape complementarity of the mutant CDR2 contact interfaces as being a key determinant of the increased affinity. Our results suggest that manipulation of germ line CDR2 loops may provide a useful route to the production of high-affinity TCRs with therapeutic and diagnostic potential. PMID:16600963

Insights into the regioselectivity and RNA-binding affinity of HIV-1 nucleocapsid protein from linear-scaling quantum methods.

PubMed

Khandogin, Jana; Musier-Forsyth, Karin; York, Darrin M

2003-07-25

Human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NC) plays several important roles in the viral life-cycle and presents an attractive target for rational drug design. Here, the macromolecular reactivity of NC and its binding to RNA is characterized through determination of electrostatic and chemical descriptors derived from linear-scaling quantum calculations in solution. The computational results offer a rationale for the experimentally observed susceptibility of the Cys49 thiolate toward small-molecule electrophilic agents, and support the recently proposed stepwise protonation mechanism of the C-terminal Zn-coordination complex. The distinctive binding mode of NC to SL2 and SL3 stem-loops of the HIV-1 genomic RNA packaging signal is studied on the basis of protein side-chain contributions to the electrostatic binding energies. These results indicate the importance of several basic residues in the 3(10) helical region and the N-terminal zinc finger, and rationalize the presence of several evolutionarily conserved residues in NC. The combined reactivity and RNA-binding study provides new insights that may contribute toward the structure-based design of anti-HIV therapies.

On-board closed-loop congestion control for satellite based packet switching networks

NASA Technical Reports Server (NTRS)

Chu, Pong P.; Ivancic, William D.; Kim, Heechul

1993-01-01

NASA LeRC is currently investigating a satellite architecture that incorporates on-board packet switching capability. Because of the statistical nature of packet switching, arrival traffic may fluctuate and thus it is necessary to integrate congestion control mechanism as part of the on-board processing unit. This study focuses on the closed-loop reactive control. We investigate the impact of the long propagation delay on the performance and propose a scheme to overcome the problem. The scheme uses a global feedback signal to regulate the packet arrival rate of ground stations. In this scheme, the satellite continuously broadcasts the status of its output buffer and the ground stations respond by selectively discarding packets or by tagging the excessive packets as low-priority. The two schemes are evaluated by theoretical queuing analysis and simulation. The former is used to analyze the simplified model and to determine the basic trends and bounds, and the later is used to assess the performance of a more realistic system and to evaluate the effectiveness of more sophisticated control schemes. The results show that the long propagation delay makes the closed-loop congestion control less responsive. The broadcasted information can only be used to extract statistical information. The discarding scheme needs carefully-chosen status information and reduction function, and normally requires a significant amount of ground discarding to reduce the on-board packet loss probability. The tagging scheme is more effective since it tolerates more uncertainties and allows a larger margin of error in status information. It can protect the high-priority packets from excessive loss and fully utilize the downlink bandwidth at the same time.

Examining System-Wide Impacts of Solar PV Control Systems with a Power Hardware-in-the-Loop Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Tess L.; Fuller, Jason C.; Schneider, Kevin P.

2014-10-11

High penetration levels of distributed solar PV power generation can lead to adverse power quality impacts such as excessive voltage rise, voltage flicker, and reactive power values that result in unacceptable voltage levels. Advanced inverter control schemes have been proposed that have the potential to mitigate many power quality concerns. However, closed-loop control may lead to unintended behavior in deployed systems as complex interactions can occur between numerous operating devices. In order to enable the study of the performance of advanced control schemes in a detailed distribution system environment, a Hardware-in-the-Loop (HIL) platform has been developed. In the HIL system,more » GridLAB-D, a distribution system simulation tool, runs in real-time mode at the Pacific Northwest National Laboratory (PNNL) and supplies power system parameters at a point of common coupling to hardware located at the National Renewable Energy Laboratory (NREL). Hardware inverters interact with grid and PV simulators emulating an operational distribution system and power output from the inverters is measured and sent to PNNL to update the real-time distribution system simulation. The platform is described and initial test cases are presented. The platform is used to study the system-wide impacts and the interactions of controls applied to inverters that are integrated into a simulation of the IEEE 8500-node test feeder, with inverters in either constant power factor control or active volt/VAR control. We demonstrate that this HIL platform is well-suited to the study of advanced inverter controls and their impacts on the power quality of a distribution feeder. Additionally, the results from HIL are used to validate GridLAB-D simulations of advanced inverter controls.« less

Examining System-Wide Impacts of Solar PV Control Systems with a Power Hardware-in-the-Loop Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Tess L.; Fuller, Jason C.; Schneider, Kevin P.

2014-06-08

High penetration levels of distributed solar PV power generation can lead to adverse power quality impacts, such as excessive voltage rise, voltage flicker, and reactive power values that result in unacceptable voltage levels. Advanced inverter control schemes have been developed that have the potential to mitigate many power quality concerns. However, local closed-loop control may lead to unintended behavior in deployed systems as complex interactions can occur between numerous operating devices. To enable the study of the performance of advanced control schemes in a detailed distribution system environment, a test platform has been developed that integrates Power Hardware-in-the-Loop (PHIL) withmore » concurrent time-series electric distribution system simulation. In the test platform, GridLAB-D, a distribution system simulation tool, runs a detailed simulation of a distribution feeder in real-time mode at the Pacific Northwest National Laboratory (PNNL) and supplies power system parameters at a point of common coupling. At the National Renewable Energy Laboratory (NREL), a hardware inverter interacts with grid and PV simulators emulating an operational distribution system. Power output from the inverters is measured and sent to PNNL to update the real-time distribution system simulation. The platform is described and initial test cases are presented. The platform is used to study the system-wide impacts and the interactions of inverter control modes—constant power factor and active Volt/VAr control—when integrated into a simulated IEEE 8500-node test feeder. We demonstrate that this platform is well-suited to the study of advanced inverter controls and their impacts on the power quality of a distribution feeder. Additionally, results are used to validate GridLAB-D simulations of advanced inverter controls.« less

Structural analysis of a highly glycosylated and unliganded gp120-based antigen using mass spectrometry†

PubMed Central

Wang, Liwen; Qin, Yali; Ilchenko, Serguei; Bohon, Jen; Shi, Wuxian; Cho, Michael W.; Takamoto, Keiji; Chance, Mark R.

2010-01-01

Structural characterization of the HIV envelope protein gp120 is very important to provide an understanding of the protein's immunogenicity and it's binding to cell receptors. So far, crystallographic structure determination of gp120 with an intact V3 loop (in the absence of CD4 co-receptor or antibody) has not been achieved. The third variable region (V3) of the gp120 is immunodominant and contains glycosylation signatures that are essential for co-receptor binding and viral entry to T-cells. In this study, we characterized the structure of the outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila S2 cells utilizing mass spectrometry-based approaches. We mapped the glycosylation sites and calculated glycosylation occupancy of gp120-OD8; eleven sites from fifteen glycosylation motifs were determined as having high mannose or hybrid glycosylation structures. The specific glycan moieties of nine glycosylation sites from eight unique glycopeptides were determined by a combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein footprinting coupled with mass spectrometry analysis was employed to provide detailed information on protein structure of gp120-OD8 by directly identifying accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120-OD8 experimental footprinting data with a homology model derived from the ligated CD4/ gp120-OD8 crystal structure revealed a flexible V3 loop structure where the V3 tip may provide contacts with the rest of the protein while residues in the V3 base remain solvent accessible. In addition, the data illustrate interactions between specific sugar moieties and amino acid side chains potentially important to the gp120-OD8 structure. PMID:20825246

Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics

PubMed Central

Smirnov, Ivan; Carletti, Eugénie; Kurkova, Inna; Nachon, Florian; Nicolet, Yvain; Mitkevich, Vladimir A.; Débat, Hélène; Avalle, Bérangère; Belogurov, Alexey A.; Kuznetsov, Nikita; Reshetnyak, Andrey; Masson, Patrick; Tonevitsky, Alexander G.; Ponomarenko, Natalia; Makarov, Alexander A.; Friboulet, Alain; Tramontano, Alfonso; Gabibov, Alexander

2011-01-01

Igs offer a versatile template for combinatorial and rational design approaches to the de novo creation of catalytically active proteins. We have used a covalent capture selection strategy to identify biocatalysts from within a human semisynthetic antibody variable fragment library that uses a nucleophilic mechanism. Specific phosphonylation at a single tyrosine within the variable light-chain framework was confirmed in a recombinant IgG construct. High-resolution crystallographic structures of unmodified and phosphonylated Fabs display a 15-Å-deep two-chamber cavity at the interface of variable light (VL) and variable heavy (VH) fragments having a nucleophilic tyrosine at the base of the site. The depth and structure of the pocket are atypical of antibodies in general but can be compared qualitatively with the catalytic site of cholinesterases. A structurally disordered heavy chain complementary determining region 3 loop, constituting a wall of the cleft, is stabilized after covalent modification by hydrogen bonding to the phosphonate tropinol moiety. These features and presteady state kinetics analysis indicate that an induced fit mechanism operates in this reaction. Mutations of residues located in this stabilized loop do not interfere with direct contacts to the organophosphate ligand but can interrogate second shell interactions, because the H3 loop has a conformation adjusted for binding. Kinetic and thermodynamic parameters along with computational docking support the active site model, including plasticity and simple catalytic components. Although relatively uncomplicated, this catalytic machinery displays both stereo- and chemical selectivity. The organophosphate pesticide paraoxon is hydrolyzed by covalent catalysis with rate-limiting dephosphorylation. This reactibody is, therefore, a kinetically selected protein template that has enzyme-like catalytic attributes. PMID:21896761

A Mutation within the Extended X Loop Abolished Substrate-induced ATPase Activity of the Human Liver ATP-binding Cassette (ABC) Transporter MDR3*

PubMed Central

Kluth, Marianne; Stindt, Jan; Dröge, Carola; Linnemann, Doris; Kubitz, Ralf; Schmitt, Lutz

2015-01-01

The human multidrug resistance protein 3 (MDR3/ABCB4) belongs to the ubiquitous family of ATP-binding cassette (ABC) transporters and is located in the canalicular membrane of hepatocytes. There it flops the phospholipids of the phosphatidylcholine (PC) family from the inner to the outer leaflet. Here, we report the characterization of wild type MDR3 and the Q1174E mutant, which was identified previously in a patient with progressive familial intrahepatic cholestasis type 3 (PFIC-3). We expressed different variants of MDR3 in the yeast Pichia pastoris, purified the proteins via tandem affinity chromatography, and determined MDR3-specific ATPase activity in the presence or absence of phospholipids. The ATPase activity of wild type MDR3 was stimulated 2-fold by liver PC or 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine lipids. Furthermore, the cross-linking of MDR3 with a thiol-reactive fluorophore blocked ATP hydrolysis and exhibited no PC stimulation. Similarly, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin lipids did not induce an increase of wild type MDR3 ATPase activity. The phosphate analogues beryllium fluoride and aluminum fluoride led to complete inhibition of ATPase activity, whereas orthovanadate inhibited exclusively the PC-stimulated ATPase activity of MDR3. The Q1174E mutation is located in the nucleotide-binding domain in direct proximity of the leucine of the ABC signature motif and extended the X loop, which is found in ABC exporters. Our data on the Q1174E mutant demonstrated basal ATPase activity, but PC lipids were incapable of stimulating ATPase activity highlighting the role of the extended X loop in the cross-talk of the nucleotide-binding domain and the transmembrane domain. PMID:25533467

Reliable design of a closed loop supply chain network under uncertainty: An interval fuzzy possibilistic chance-constrained model

NASA Astrophysics Data System (ADS)

Vahdani, Behnam; Tavakkoli-Moghaddam, Reza; Jolai, Fariborz; Baboli, Arman

2013-06-01

This article seeks to offer a systematic approach to establishing a reliable network of facilities in closed loop supply chains (CLSCs) under uncertainties. Facilities that are located in this article concurrently satisfy both traditional objective functions and reliability considerations in CLSC network designs. To attack this problem, a novel mathematical model is developed that integrates the network design decisions in both forward and reverse supply chain networks. The model also utilizes an effective reliability approach to find a robust network design. In order to make the results of this article more realistic, a CLSC for a case study in the iron and steel industry has been explored. The considered CLSC is multi-echelon, multi-facility, multi-product and multi-supplier. Furthermore, multiple facilities exist in the reverse logistics network leading to high complexities. Since the collection centres play an important role in this network, the reliability concept of these facilities is taken into consideration. To solve the proposed model, a novel interactive hybrid solution methodology is developed by combining a number of efficient solution approaches from the recent literature. The proposed solution methodology is a bi-objective interval fuzzy possibilistic chance-constraint mixed integer linear programming (BOIFPCCMILP). Finally, computational experiments are provided to demonstrate the applicability and suitability of the proposed model in a supply chain environment and to help decision makers facilitate their analyses.

2D Magnetic Texture Analysis of Co-Cu Films

NASA Astrophysics Data System (ADS)

Bayirli, Mehmet; Karaagac, Oznur; Kockar, Hakan; Alper, Mursel

2017-05-01

The magnetic textures for the produced magnetic materials are important concepts in accordance with technical applications. Therefore, the aim of this article is to determine 2D magnetic textures of electrodeposited Co-Cu films by the measurement of hysteresis loops at the incremented angles. For that, Co-Cu films were deposited with different Co2+ in the electrolyte. In addition, the easy-axis orientation in the films from the squareness values of the angles, Mp(β) obtained by the hysteresis loops have been numerically studied using the Fourier series analysis. The differences observed in the magnetic easy-axis distributions were attributed to changes of the incorporation of Co in the films with the change of Co2+ in the electrolyte. The coefficients of Fourier series (A0 and A2n ) were also computed for 2D films. It is seen that a systematic and small decrease in A0 and an obvious decrease in A2n (n=1) were observed with increasing incorporated Co in the films. Results imply that interactions cause slightly demagnetization effect accordance with higher incorporation of Co in the films. Furthermore, the crystal structure of the Co-Cu films analysed by X-ray diffraction revealed that the films have dominantly face-centred cubic structure. Film contents analysed by energy-dispersive X-ray spectroscopy and film morphologies observed by scanning electron microscope also support the magnetic texture analysis results found by numerical computation.

The FANTASTIC FOUR proteins influence shoot meristem size in Arabidopsis thaliana.

PubMed

Wahl, Vanessa; Brand, Luise H; Guo, Ya-Long; Schmid, Markus

2010-12-22

Throughout their lives plants produce new organs from groups of pluripotent cells called meristems, located at the tips of the shoot and the root. The size of the shoot meristem is tightly controlled by a feedback loop, which involves the homeodomain transcription factor WUSCHEL (WUS) and the CLAVATA (CLV) proteins. This regulatory circuit is further fine-tuned by morphogenic signals such as hormones and sugars. Here we show that a family of four plant-specific proteins, encoded by the FANTASTIC FOUR (FAF) genes, has the potential to regulate shoot meristem size in Arabidopsis thaliana. FAF2 and FAF4 are expressed in the centre of the shoot meristem, overlapping with the site of WUS expression. Consistent with a regulatory interaction between the FAF gene family and WUS, our experiments indicate that the FAFs can repress WUS, which ultimately leads to an arrest of meristem activity in FAF overexpressing lines. The finding that meristematic expression of FAF2 and FAF4 is under negative control by CLV3 further supports the hypothesis that the FAFs are modulators of the genetic circuit that regulates the meristem. This study reports the initial characterization of the Arabidopsis thaliana FAF gene family. Our data indicate that the FAF genes form a plant specific gene family, the members of which have the potential to regulate the size of the shoot meristem by modulating the CLV3-WUS feedback loop.

Photomagnetic studies on spin-crossover solid solutions containing two different metal complexes, [Fe(1-bpp)(2)](x)[M(terpy)2](1-x)[BF4]2 (M = Ru or Co).

PubMed

Chastanet, Guillaume; Tovee, Clare A; Hyett, Geoffrey; Halcrow, Malcolm A; Létard, Jean-François

2012-04-28

The photomagnetic properties of two series of spin-crossover solid solutions, [Fe(1-bpp)(2)](x)[Ru(terpy)(2)](1-x)(BF(4))(2) and [Fe(1-bpp)(2)](x)[Co(terpy)(2)](1-x)(BF(4))(2) (1-bpp = 2,6-bis[pyrazol-1-yl]pyridine), have been investigated. For all the materials, the evolution of the T(LIESST) value, the high-spin → low-spin relaxation parameters and the LITH loops were thoroughly studied. Interestingly in the Fe:Co series, along the photo-excitation, cobalt ions are concomitantly converted from low-spin to high-spin states with the iron centres, and also fully relax after light excitation. This journal is © The Royal Society of Chemistry 2012

Observations of Rotating Sunspots from TRACE

NASA Astrophysics Data System (ADS)

Brown, D. S.; Nightingale, R. W.; Alexander, D.; Schrijver, C. J.; Metcalf, T. R.; Shine, R. A.; Title, A. M.; Wolfson, C. J.

2003-09-01

Recent observations from TRACE in the photospheric white-light channel have shown sunspots that rotate up to 200° about their umbral centre over a period of 3 5 days. The corresponding loops in the coronal fan are often seen to twist and can erupt as flares. In an ongoing study, seven cases of rotating sunspots have been identified, two of which can be associated with sigmoid structures appearing in Yohkoh/SXT and six with events seen by GOES. This paper analyzes the rotation rates of the sunspots using TRACE white-light data. Observations from AR 9114 are presented in detail in the main text and a summary of the results for the remaining six sunspots is presented in Appendixes A F. Discussion of the key results, particularly common features, are presented, as well as possible mechanisms for sunspot rotation.

Design of a colicin E7 based chimeric zinc-finger nuclease

NASA Astrophysics Data System (ADS)

Németh, Eszter; Schilli, Gabriella K.; Nagy, Gábor; Hasenhindl, Christoph; Gyurcsik, Béla; Oostenbrink, Chris

2014-08-01

Colicin E7 is a natural bacterial toxin. Its nuclease domain (NColE7) enters the target cell and kills it by digesting the nucleic acids. The HNH-motif as the catalytic centre of NColE7 at the C-terminus requires the positively charged N-terminal loop for the nuclease activity—offering opportunities for allosteric control in a NColE7-based artificial nuclease. Accordingly, four novel zinc finger nucleases were designed by computational methods exploiting the special structural features of NColE7. The constructed models were subjected to MD simulations. The comparison of structural stability and functional aspects showed that these models may function as safely controlled artificial nucleases. This study was complemented by random mutagenesis experiments identifying potentially important residues for NColE7 function outside the catalytic region.

Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study.

PubMed

Rossetti, Andrea O; Tovar Quiroga, Diego F; Juan, Elsa; Novy, Jan; White, Roger D; Ben-Hamouda, Nawfel; Britton, Jeffrey W; Oddo, Mauro; Rabinstein, Alejandro A

2017-07-01

The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. Cohort study (April 2009 to March 2016). Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95% CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6-90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7-89.2%). This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.

The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling.

PubMed

Khan, Sumbul Jawed; Abidi, Syeda Nayab Fatima; Skinner, Andrea; Tian, Yuan; Smith-Bolton, Rachel K

2017-07-01

Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.

Docking, thermodynamics and molecular dynamics (MD) studies of a non-canonical protease inhibitor, MP-4, from Mucuna pruriens.

PubMed

Kumar, Ashish; Kaur, Harmeet; Jain, Abha; Nair, Deepak T; Salunke, Dinakar M

2018-01-12

Sequence and structural homology suggests that MP-4 protein from Mucuna pruriens belongs to Kunitz-type protease inhibitor family. However, biochemical assays showed that this protein is a poor inhibitor of trypsin. To understand the basis of observed poor inhibition, thermodynamics and molecular dynamics (MD) simulation studies on binding of MP-4 to trypsin were carried out. Molecular dynamics simulations revealed that temperature influences the spectrum of conformations adopted by the loop regions in the MP-4 structure. At an optimal temperature, MP-4 achieves maximal binding while above and below the optimum temperature, its functional activity is hampered due to unfavourable flexibility and relative rigidity, respectively. The low activity at normal temperature is due to the widening of the conformational spectrum of the Reactive Site Loop (RSL) that reduces the probability of formation of stabilizing contacts with trypsin. The unique sequence of the RSL enhances flexibility at ambient temperature and thus reduces its ability to inhibit trypsin. This study shows that temperature influences the function of a protein through modulation in the structure of functional domain of the protein. Modulation of function through appearance of new sequences that are more sensitive to temperature may be a general strategy for evolution of new proteins.

The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling

PubMed Central

Skinner, Andrea; Tian, Yuan

2017-01-01

Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth. PMID:28753614

Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea

PubMed Central

Kurosaki, Yohei; Magassouba, N’Faly; Oloniniyi, Olamide K.; Cherif, Mahamoud S.; Sakabe, Saori; Takada, Ayato; Hirayama, Kenji; Yasuda, Jiro

2016-01-01

Given the current absence of specific drugs or vaccines for Ebola virus disease (EVD), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. We have developed a rapid detection assay for Zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) and coupled with a novel portable isothermal amplification and detection platform. The RT-LAMP assay is based on primer sets that target the untranscribed trailer region or nucleoprotein coding region of the viral RNA. The test could specifically detect viral RNAs of Central and West African Ebola virus strains within 15 minutes with no cross-reactivity to other hemorrhagic fever viruses and arboviruses, which cause febrile disease. The assay was evaluated using a total of 100 clinical specimens (serum, n = 44; oral swab, n = 56) collected from suspected EVD cases in Guinea. The specificity of this diagnostic test was 100% for both primer sets, while the sensitivity was 100% and 97.9% for the trailer and nucleoprotein primer sets, respectively, compared with a reference standard RT-PCR test. These observations suggest that our diagnostic assay is useful for identifying EVD cases, especially in the field or in settings with insufficient infrastructure. PMID:26900929

Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease

PubMed Central

Labovsky, V; Smulski, C R; Gómez, K; Levy, G; Levin, M J

2007-01-01

Chronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against the C-terminal region of the ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with the second extracellular loop of β1-adrenergic receptor (β1-AR, peptide H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human β1-AR, the aim of this study was to investigate further the physical interaction between cChHD IgGs and the human β1-AR. Immunofluorescence assays demonstrated the binding of these antibodies to the receptor expressed on stably transfected cells, together with a β1-AR agonist-like effect. In addition, immunoadsorption of the serum samples from cChHD patients with a commercially available matrix, containing peptides representing the first and the second extracellular loop of the β1-AR, completely abolished reactivity against the H26R peptide and the physiological response to the receptor. The follow-up of this specificity after in vitro immunoadsorption procedures suggests that this treatment might be used to diminish significantly the serum levels of anti-β1-AR antibodies in patients with Chagas heart disease. PMID:17419712

Wireless technologies for closed-loop retinal prostheses.

PubMed

Ng, David C; Bai, Shun; Yang, Jiawei; Tran, Nhan; Skafidas, Efstratios

2009-12-01

In this paper, we discuss various technologies needed to develop retinal prostheses with wireless power and data telemetry operation. In addition to the need to communicate with the implanted device, supply of power to the retinal prosthesis is especially difficult. This is because, in the implanted state, the device is not fixed in position due to constant motion of the eye. Furthermore, a retinal prosthesis incorporating a high density electrode array of more than 1000 electrodes is expected to consume approximately 45 mW of power and require 300 kbps of image and stimulation data. The front end of the wireless power and data transmission, the antenna, needs to be small compared to the size of the eye. Also, the wireless module is expected to operate in the reactive near-field region due to small separation between the transmit and receive antennas compared to their size and corresponding operating wavelength. An inductive link is studied as a means to transfer power and for data telemetry between the implant and external unit. In this work, the use of integrated circuit and microfabrication technologies for implementing inductive links is discussed. A closed-loop approach is taken to improve performance and reach optimum operation condition. Design and simulation data are presented as the basis for development of viable wireless module prototypes.

Wireless technologies for closed-loop retinal prostheses

NASA Astrophysics Data System (ADS)

Ng, David C.; Bai, Shun; Yang, Jiawei; Tran, Nhan; Skafidas, Efstratios

2009-12-01

In this paper, we discuss various technologies needed to develop retinal prostheses with wireless power and data telemetry operation. In addition to the need to communicate with the implanted device, supply of power to the retinal prosthesis is especially difficult. This is because, in the implanted state, the device is not fixed in position due to constant motion of the eye. Furthermore, a retinal prosthesis incorporating a high density electrode array of more than 1000 electrodes is expected to consume approximately 45 mW of power and require 300 kbps of image and stimulation data. The front end of the wireless power and data transmission, the antenna, needs to be small compared to the size of the eye. Also, the wireless module is expected to operate in the reactive near-field region due to small separation between the transmit and receive antennas compared to their size and corresponding operating wavelength. An inductive link is studied as a means to transfer power and for data telemetry between the implant and external unit. In this work, the use of integrated circuit and microfabrication technologies for implementing inductive links is discussed. A closed-loop approach is taken to improve performance and reach optimum operation condition. Design and simulation data are presented as the basis for development of viable wireless module prototypes.

Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea.

PubMed

Kurosaki, Yohei; Magassouba, N'Faly; Oloniniyi, Olamide K; Cherif, Mahamoud S; Sakabe, Saori; Takada, Ayato; Hirayama, Kenji; Yasuda, Jiro

2016-02-01

Given the current absence of specific drugs or vaccines for Ebola virus disease (EVD), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. We have developed a rapid detection assay for Zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) and coupled with a novel portable isothermal amplification and detection platform. The RT-LAMP assay is based on primer sets that target the untranscribed trailer region or nucleoprotein coding region of the viral RNA. The test could specifically detect viral RNAs of Central and West African Ebola virus strains within 15 minutes with no cross-reactivity to other hemorrhagic fever viruses and arboviruses, which cause febrile disease. The assay was evaluated using a total of 100 clinical specimens (serum, n = 44; oral swab, n = 56) collected from suspected EVD cases in Guinea. The specificity of this diagnostic test was 100% for both primer sets, while the sensitivity was 100% and 97.9% for the trailer and nucleoprotein primer sets, respectively, compared with a reference standard RT-PCR test. These observations suggest that our diagnostic assay is useful for identifying EVD cases, especially in the field or in settings with insufficient infrastructure.

Design and validation of a GNC system for missions to asteroids: the AIM scenario

NASA Astrophysics Data System (ADS)

Pellacani, A.; Kicman, P.; Suatoni, M.; Casasco, M.; Gil, J.; Carnelli, I.

2017-12-01

Deep space missions, and in particular missions to asteroids, impose a certain level of autonomy that depends on the mission objectives. If the mission requires the spacecraft to perform close approaches to the target body (the extreme case being a landing scenario), the autonomy level must be increased to guarantee the fast and reactive response which is required in both nominal and contingency operations. The GNC system must be designed in accordance with the required level of autonomy. The GNC system designed and tested in the frame of ESA's Asteroid Impact Mission (AIM) system studies (Phase A/B1 and Consolidation Phase) is an example of an autonomous GNC system that meets the challenging objectives of AIM. The paper reports the design of such GNC system and its validation through a DDVV plan that includes Model-in-the-Loop and Hardware-in-the-Loop testing. Main focus is the translational navigation, which is able to provide online the relative state estimation with respect to the target body using exclusively cameras as relative navigation sensors. The relative navigation outputs are meant to be used for nominal spacecraft trajectory corrections as well as to estimate the collision risk with the asteroid and, if needed, to command the execution of a collision avoidance manoeuvre to guarantee spacecraft safety

Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea‐pigs

PubMed Central

Fabris, Frank; Yue, Yuankun; Qu, Yongxia; Chahine, Mohamed; Sobie, Eric; Lee, Peng; Wieczorek, Rosemary; Jiang, Xian‐Cheng; Capecchi, Pier‐Leopoldo; Laghi‐Pasini, Franco; Lazzerini, Pietro‐Enea

2016-01-01

Key points Channelopathies of autoimmune origin are novel and are associated with corrected QT (QTc) prolongation and complex ventricular arrhythmias.We have recently demonstrated that anti‐SSA/Ro antibodies from patients with autoimmune diseases and with QTc prolongation on the ECG target the human ether‐à‐go‐go‐related gene (HERG) K+ channel by inhibiting the corresponding current, I Kr, at the pore region.Immunization of guinea‐pigs with a peptide (E‐pore peptide) corresponding to the extracellular loop region connecting the S5 and S6 segments of the HERG channel induces high titres of antibodies that inhibit I Kr, lengthen the action potential and cause QTc prolongation on the surface ECG. In addition, anti‐SSA/Ro‐positive sera from patients with connective tissue diseases showed high reactivity to the E‐pore peptide.The translational impact is the development of a peptide‐based approach for the diagnosis and treatment of autoimmune‐associated long QT syndrome. Abstract We recently demonstrated that anti‐SSA/52 kDa Ro antibodies (Abs) from patients with autoimmune diseases and corrected QT (QTc) prolongation directly target and inhibit the human ether‐à‐go‐go‐related gene (HERG) K+ channel at the extracellular pore (E‐pore) region, where homology with SSA/52 kDa Ro antigen was demonstrated. We tested the hypothesis that immunization of guinea‐pigs with a peptide corresponding to the E‐pore region (E‐pore peptide) will generate pathogenic inhibitory Abs and cause QTc prolongation. Guinea‐pigs were immunized with a 31‐amino‐acid peptide corresponding to the E‐pore region of HERG. On days 10–62 after immunization, ECGs were recorded and blood was sampled for the detection of E‐pore peptide Abs. Serum samples from patients with autoimmune diseases were evaluated for reactivity to E‐pore peptide by enzyme‐linked immunosorbent assay (ELISA), and histology was performed on hearts using Masson's Trichrome. Inhibition of the HERG channel was assessed by electrophysiology and by computational modelling of the human ventricular action potential. The ELISA results revealed the presence of high titres of E‐pore peptide Abs and significant QTc prolongation after immunization. High reactivity to E‐pore peptide was found using anti‐SSA/Ro Ab‐positive sera from patients with QTc prolongation. Histological data showed no evidence of fibrosis in immunized hearts. Simulations of simultaneous inhibition of repolarizing currents by anti‐SSA/Ro Ab‐positive sera showed the predominance of the HERG channel in controlling action potential duration and the QT interval. These results are the first to demonstrate that inhibitory Abs to the HERG E‐pore region induce QTc prolongation in immunized guinea‐pigs by targeting the HERG channel independently from fibrosis. The reactivity of anti‐SSA/Ro Ab‐positive sera from patients with connective tissue diseases with the E‐pore peptide opens novel pharmacotherapeutic avenues in the diagnosis and management of autoimmune‐associated QTc prolongation. PMID:27296897

Behavior of medial gastrocnemius motor units during postural reactions to external perturbations after stroke.

PubMed

Pollock, C L; Ivanova, T D; Hunt, M A; Garland, S J

2015-10-01

This study investigated the behavior of medial gastrocnemius (GM) motor units (MU) during external perturbations in standing in people with chronic stroke. GM MUs were recorded in standing while anteriorly-directed perturbations were introduced by applying loads of 1% body mass (BM) at the pelvis every 25-40s until 5% BM was maintained. Joint kinematics, surface electromyography (EMG), and force platform measurements were assessed. Although external loads caused a forward progression of the anterior-posterior centre of pressure (APCOP), people with stroke decreased APCOP velocity and centre of mass (COM) velocity immediately following the highest perturbations, thereby limiting movement velocity in response to perturbations. MU firing rate did not increase with loading but the GM EMG magnitude increased, reflecting MU recruitment. MU inter spike interval (ISI) during the dynamic response was negatively correlated with COM velocity and hip angular velocity. The GM utilized primarily MU recruitment to maintain standing during external perturbations. The lack of MU firing rate modulation occurred with a change in postural central set. However, the relationship of MU firing rate with kinematic variables suggests underlying long-loop responses may be somewhat intact after stroke. People with stroke demonstrate alterations in postural control strategies which may explain MU behavior with external perturbations. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

UV-radiation-induced electron emission by hormones. Hypothesis for specific communication mechanisms

NASA Astrophysics Data System (ADS)

Getoff, Nikola

2009-11-01

The highlights of recently observed electron emission from electronically excited sexual hormones (17β-estradiol, progesterone, testosterone) and the phytohormone genistein in polar media are briefly reviewed. The electron yield, Q(e aq-), dependence from substrate concentration, hormone structure, polarity of solvent, absorbed energy and temperature are discussed. The hormones reactivity with e aq- and efficiency in electron transfer ensure them the ability to communicate with other biological systems in an organism. A hypothesis is presented for the explanation of the mechanisms of the distinct recognition of signals transmitted by electrons, originating from different types of hormones to receiving centres. Biological consequences of the electron emission in respect to cancer are mentioned.

Thermal decomposition of dolomite under CO2: insights from TGA and in situ XRD analysis.

PubMed

Valverde, Jose Manuel; Perejon, Antonio; Medina, Santiago; Perez-Maqueda, Luis A

2015-11-28

Thermal decomposition of dolomite in the presence of CO2 in a calcination environment is investigated by means of in situ X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The in situ XRD results suggest that dolomite decomposes directly at a temperature around 700 °C into MgO and CaO. Immediate carbonation of nascent CaO crystals leads to the formation of calcite as an intermediate product of decomposition. Subsequently, decarbonation of this poorly crystalline calcite occurs when the reaction is thermodynamically favorable and sufficiently fast at a temperature depending on the CO2 partial pressure in the calcination atmosphere. Decarbonation of this dolomitic calcite occurs at a lower temperature than limestone decarbonation due to the relatively low crystallinity of the former. Full decomposition of dolomite leads also to a relatively low crystalline CaO, which exhibits a high reactivity as compared to limestone derived CaO. Under CO2 capture conditions in the Calcium-Looping (CaL) process, MgO grains remain inert yet favor the carbonation reactivity of dolomitic CaO especially in the solid-state diffusion controlled phase. The fundamental mechanism that drives the crystallographic transformation of dolomite in the presence of CO2 is thus responsible for its fast calcination kinetics and the high carbonation reactivity of dolomitic CaO, which makes natural dolomite a potentially advantageous alternative to limestone for CO2 capture in the CaL technology as well as SO2in situ removal in oxy-combustion fluidized bed reactors.

Abrogation of Wip1 expression by RITA-activated p53 potentiates apoptosis induction via activation of ATM and inhibition of HdmX

PubMed Central

Spinnler, C; Hedström, E; Li, H; de Lange, J; Nikulenkov, F; Teunisse, A F A S; Verlaan-de Vries, M; Grinkevich, V; Jochemsen, A G; Selivanova, G

2011-01-01

Inactivation of the p53 tumour suppressor, either by mutation or by overexpression of its inhibitors Hdm2 and HdmX is the most frequent event in cancer. Reactivation of p53 by targeting Hdm2 and HdmX is therefore a promising strategy for therapy. However, Hdm2 inhibitors do not prevent inhibition of p53 by HdmX, which impedes p53-mediated apoptosis. Here, we show that p53 reactivation by the small molecule RITA leads to efficient HdmX degradation in tumour cell lines of different origin and in xenograft tumours in vivo. Notably, HdmX degradation occurs selectively in cancer cells, but not in non-transformed cells. We identified the inhibition of the wild-type p53-induced phosphatase 1 (Wip1) as the major mechanism important for full engagement of p53 activity accomplished by restoration of the ataxia telangiectasia mutated (ATM) kinase-signalling cascade, which leads to HdmX degradation. In contrast to previously reported transactivation of Wip1 by p53, we observed p53-dependent repression of Wip1 expression, which disrupts the negative feedback loop conferred by Wip1. Our study reveals that the depletion of both HdmX and Wip1 potentiates cell death due to sustained activation of p53. Thus, RITA is an example of a p53-reactivating drug that not only blocks Hdm2, but also inhibits two important negative regulators of p53 – HdmX and Wip1, leading to efficient elimination of tumour cells. PMID:21546907

Abrogation of Wip1 expression by RITA-activated p53 potentiates apoptosis induction via activation of ATM and inhibition of HdmX.

PubMed

Spinnler, C; Hedström, E; Li, H; de Lange, J; Nikulenkov, F; Teunisse, A F A S; Verlaan-de Vries, M; Grinkevich, V; Jochemsen, A G; Selivanova, G

2011-11-01

Inactivation of the p53 tumour suppressor, either by mutation or by overexpression of its inhibitors Hdm2 and HdmX is the most frequent event in cancer. Reactivation of p53 by targeting Hdm2 and HdmX is therefore a promising strategy for therapy. However, Hdm2 inhibitors do not prevent inhibition of p53 by HdmX, which impedes p53-mediated apoptosis. Here, we show that p53 reactivation by the small molecule RITA leads to efficient HdmX degradation in tumour cell lines of different origin and in xenograft tumours in vivo. Notably, HdmX degradation occurs selectively in cancer cells, but not in non-transformed cells. We identified the inhibition of the wild-type p53-induced phosphatase 1 (Wip1) as the major mechanism important for full engagement of p53 activity accomplished by restoration of the ataxia telangiectasia mutated (ATM) kinase-signalling cascade, which leads to HdmX degradation. In contrast to previously reported transactivation of Wip1 by p53, we observed p53-dependent repression of Wip1 expression, which disrupts the negative feedback loop conferred by Wip1. Our study reveals that the depletion of both HdmX and Wip1 potentiates cell death due to sustained activation of p53. Thus, RITA is an example of a p53-reactivating drug that not only blocks Hdm2, but also inhibits two important negative regulators of p53 - HdmX and Wip1, leading to efficient elimination of tumour cells.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang Liang; Wang Huiming, E-mail: hmwang_1960@yahoo.com.cn; Zhou Lin

FOXO3a, a well-known transcriptional regulator, controls a wide spectrum of biological processes. The Phosphoinositide-3-kinase (PI3K)/Akt signaling pathway inactivates FOXO3a via phosphorylation-induced nuclear exclusion and degradation. A loss or gain of FOXO3a activity has been correlated with efficiency of chemotherapies in various cancers including oral squamous cell carcinoma (OSCC). Therefore, in the current study, we have investigated the FOXO3a activity modulating and antitumor effects of rapamycin and cisplatin in OSCC cells. Cisplatin inhibited proliferation and induced apoptosis in a dose-dependent way in OSCC Tca8113 cells. Rapamycin alone had no effect on cell proliferation and apoptosis. Rapamycin downregulated the expression of S-phasemore » kinase associated protein-2 (Skp2) and increased the FOXO3a protein stability but induced the upregulation of feedback Akt activation-mediated FOXO3a phosphorylation. Cisplatin decreased the phosphorylation of FOXO3a via Akt inhibition. Rapamycin combined with cisplatin as its feedback Akt activation inhibitor revealed the most dramatic FOXO3a nuclear localization and reactivation with the prevention of its feedback loop and exposed significant synergistic effects of decreased cell proliferation and increased apoptosis in vitro and decreased tumor size in vivo. Furthermore, the downstream effects of FOXO3a reactivation were found to be accumulation of p27 and Bim. In conclusion, rapamycin/cisplatin combination therapy boosts synergistic antitumor effects through the significant FOXO3a reactivation in OSCC cells. These results may represent a novel mechanism by which rapamycin/cisplatin combination therapy proves to be a potent molecular-targeted strategy for OSCC.« less

Scrub typhus: audit of an outbreak.

PubMed

Krishna, Mani Ram; Vasuki, B; Nagaraju, K

2015-06-01

To document the epidemiological, clinical and laboratory profile of all children with scrub typhus at a tertiary care centre in Chennai between September 2010 and June 2011. The case records of all children admitted and diagnosed with scrub typhus between September 2010 and June 2011 were analysed to look for salient clinical and laboratory parameters. During the study period, 52 children were admitted with scrub typhus in the authors' hospital. The presenting complaints included fever in all cases. Other symptoms included swelling of legs (50 %) and vomiting (45 %). 13 % presented with CNS symptoms. The commonest physical findings included eschar (67 %), hepatomegaly (94 %), splenomegaly (73 %) and third spacing (67 %). Salient lab parameters included packed cell volume (PCV) <30 (48 %), leucocytosis (56 %), positive C-reactive protein (CRP) (92 %), hypoalbuminemia (79 %). Common complications included acute kidney injury (10 %) and peripheral gangrene (4 %). There was no mortality in the present case series. The clinical profile of children with scrub typhus in a tertiary care centre is reported. Eschar and hepatosplenomegaly with a high CRP value is helpful in diagnosis. All patients responded well to the treatment.

Distortions induced in double-stranded oligonucleotides by the binding of cis- or trans-diammine-dichloroplatinum(II) to the d(GTG) sequence.

PubMed Central

Anin, M F; Leng, M

1990-01-01

Conformational changes induced in double-stranded oligonucleotides by the binding of trans- or cis-diamminedichloro platinum(II) to the d(GTG) sequence have been characterized by means of melting temperatures, electrophoretic migrations in non-denaturing polyacrylamide gels, reactivities with the artificial nuclease Phenanthroline-copper and with chemical probes. The cis-platinum adduct behaves more as a centre of directed bend than as a hinge joint, the induced bend angle being of the order of 25-30 degrees. The double helix is locally denatured over 2 base pairs (corresponding to the platinated 5'G residue and the central T residue) and is distorted over 4-5 base pairs. The trans-platinum adduct behaves also more as a centre of directed bend than as a hinge joint, the induced bend angle being of the order of 60 degrees. The double helix is locally denatured over 4 base pairs (corresponding to the immediately 5'T residue adjacent to the adduct and to the three base residues of the adduct). Both the cis- and trans-platinum adducts decrease the thermal stability of the double helix. Images PMID:2388824

Influence of transition metal electronegativity on the oxygen storage capacity of perovskite oxides.

PubMed

Liu, Lu; Taylor, Daniel D; Rodriguez, Efrain E; Zachariah, Michael R

2016-08-16

The selection of highly efficient oxygen carriers (OCs) is a key step necessary for the practical development of chemical looping combustion (CLC). In this study, a series of ABO3 perovskites, where A = La, Ba, Sr, Ca and B = Cr, Mn, Fe, Co, Ni, Cu, are synthesized and tested in a fixed bed reactor for reactivity and stability as OCs with CH4 as the fuel. We find that the electronegativity of the transition metal on the B-site (λB), is a convenient descriptor for oxygen storage capacity (OSC) of our perovskite samples. By plotting OSC for total methane oxidation against λB, we observe an inverted volcano plot relationship. These results could provide useful guidelines for perovskite OC design and their other energy related applications.

RADON LEVELS AND ЕQUIVALENT DOSE RATES AT THE IRT-SOFIA RESEARCH REACTOR SITE.

PubMed

Krezhov, Kiril; Mladenov, Aleksander; Dimitrov, Dobromir

2018-06-11

Results from radon measurements by active sampling of indoor air in the buildings within the Nuclear Scientific Experimental and Educational Centre (NSEEC) protected site at the Institute for Nuclear Research and Nuclear Energy (INRNE) are presented. The inspected buildings included in this report are the IRT research reactor structure and several auxiliary formations wherein the laundry facilities and the gamma irradiator GOU-1 (60Co source) are installed as well as the Central Alarm Station (CAS) premises. Besides the reactor hall and the primary cooling loop area, special attention was given to the premises of the First Class Radiochemical Laboratory in the IRT reactor basement. Determination of radon concentration distribution in the premises of the constructions within the site is an important part of radiation surveillance during the operation and maintenance of the NSEEC facilities as well as for their involvement in the educational activities at INRNE.

Fermi bubbles: high latitude X-ray supersonic shell

NASA Astrophysics Data System (ADS)

Keshet, Uri; Gurwich, Ilya

2018-06-01

The nature of the bipolar, γ-ray Fermi bubbles (FB) is still unclear, in part because their faint, high-latitude X-ray counterpart has until now eluded a clear detection. We stack ROSAT data at varying distances from the FB edges, thus boosting the signal and identifying an expanding shell behind the southwest, southeast, and northwest edges, albeit not in the dusty northeast sector near Loop I. A Primakoff-like model for the underlying flow is invoked to show that the signals are consistent with halo gas heated by a strong, forward shock to ˜keV temperatures. Assuming ion-electron thermal equilibrium then implies a ˜1056 erg event near the Galactic centre ˜7 Myr ago. However, the reported high absorption-line velocities suggest a preferential shock-heating of ions, and thus more energetic (˜1057 erg), younger (≲ 3 Myr) FBs.

Newtonian CAFE: a new ideal MHD code to study the solar atmosphere

NASA Astrophysics Data System (ADS)

González-Avilés, J. J.; Cruz-Osorio, A.; Lora-Clavijo, F. D.; Guzmán, F. S.

2015-12-01

We present a new code designed to solve the equations of classical ideal magnetohydrodynamics (MHD) in three dimensions, submitted to a constant gravitational field. The purpose of the code centres on the analysis of solar phenomena within the photosphere-corona region. We present 1D and 2D standard tests to demonstrate the quality of the numerical results obtained with our code. As solar tests we present the transverse oscillations of Alfvénic pulses in coronal loops using a 2.5D model, and as 3D tests we present the propagation of impulsively generated MHD-gravity waves and vortices in the solar atmosphere. The code is based on high-resolution shock-capturing methods, uses the Harten-Lax-van Leer-Einfeldt (HLLE) flux formula combined with Minmod, MC, and WENO5 reconstructors. The divergence free magnetic field constraint is controlled using the Flux Constrained Transport method.

Unusual case of iron overload with cancer-mimicking abdominal splenosis.

PubMed

Marchi, Giacomo; Avesani, Giacomo; Zamò, Alberto; Girelli, Domenico

2018-05-16

A 48-year-old man, former alcohol abuser and drug addicted, was referred to our tertiary referral centre for iron disorders because of marked hyperferritinaemia. His clinical history revealed chronic hepatitis C, ß-thalassaemia trait and post-traumatic splenectomy at age of 22. MRI-estimated liver iron content was markedly elevated, while first-line genetic test for haemochromatosis was negative. Alpha-fetoprotein was increased but liver ultrasonography did not reveal focal liver lesions. Multiphasic contrast-enhanced CT confirmed this result but showed two abdominal masses (diameter of 9 cm and 7 cm, respectively) among bowel loops, strongly suspicious for cancer. However, biopsy of one of the masses led to the final diagnosis of abdominal splenosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Near East mtDNA haplotype variants in Roman cattle from Augusta Raurica, Switzerland, and in the Swiss Evolène breed.

PubMed

Schlumbaum, A; Turgay, M; Schibler, J

2006-08-01

Typical Near East mitochondrial haplotypes of the T2 lineage were found in one cattle metacarpus sample from the Roman period and in two present-day Evolène cattle in Switzerland. Sequences from eight additional Evolène and four Raetian Grey aligned to the European haplotype T3. Analysis of nucleotide diversity within the mitochondrial D-loop of both studied Swiss cattle breeds revealed high haplotype diversity and similar diversity to a European cattle reference group. Mitochondrial T3 haplotypes radiated star-like from two similarly frequent haplotypes, possibly indicating two different expansion routes. The breed structure of Evolène cattle can be explained either by an introduction of diverse female lineages from the domestication centre or by later admixture. The introduction of the Near East lineage to Switzerland must have happened during the Roman time or earlier.

A novel active disturbance rejection based tracking design for laser system with quadrant photodetector

NASA Astrophysics Data System (ADS)

Manojlović, Stojadin M.; Barbarić, Žarko P.; Mitrović, Srđan T.

2015-06-01

A new tracking design for laser systems with different arrangements of a quadrant photodetector, based on the principle of active disturbance rejection control is suggested. The detailed models of quadrant photodetector with standard add-subtract, difference-over-sum and diagonal-difference-over-sum algorithms for displacement signals are included in the control loop. Target moving, non-linearity of a photodetector, parameter perturbations and exterior disturbances are treated as a total disturbance. Active disturbance rejection controllers with linear extended state observers for total disturbance estimation and rejection are designed. Proposed methods are analysed in frequency domain to quantify their stability characteristics and disturbance rejection performances. It is shown through simulations, that tracking errors are effectively compensated, providing the laser spot positioning in the area near the centre of quadrant photodetector where the mentioned algorithms have the highest sensitivity, which provides tracking of the manoeuvring targets with high accuracy.

Seismic Reflection Images of Deep Lithospheric Faults and Thin Crust at the Actively Deforming Indo-Australian Plate Boundary in the Indian Ocean

NASA Astrophysics Data System (ADS)

Singh, S. C.; Carton, H.; Chauhan, A.; Dyment, J.; Cannat, M.; Hananto, N.; Hartoyo, D.; Tapponnier, P.; Davaille, A.

2007-12-01

Recently, we acquired deep seismic reflection data using a state-of-the-art technology of Schlumberger having a powerful source (10,000 cubic inch) and a 12 km long streamer along a 250 km long trench parallel line offshore Sumatra in the Indian Ocean deformation zone that provides seismic reflection image down to 40 km depth over the old oceanic lithosphere formed at Wharton spreading centre about 55-57 Ma ago. We observe deep penetrating faults that go down to 37 km depth (~24 km in the oceanic mantle), providing the first direct evidence for full lithospheric-scale deformation in an intra-plate oceanic domain. These faults dip NE and have dips between 25 and 40 degrees. The majority of faults are present in the mantle and are spaced at about 5 km, and do not seem cut through the Moho. We have also imaged active strike-slip fault zones that seem to be associated with the re-activation of ancient fracture zones, which is consistent with previous seismological and seafloor observations. The geometries of the deep penetrating faults neither seem to correspond to faulting associated with the plate bending at the subduction front nor with the re-activation of fracture zone that initiated about 7.5 Ma ago, and therefore, we suggest that these deep mantle faults were formed due to compressive stress at the beginning of the hard collision between India and Eurasia, soon after the cessation of seafloor spreading in the Wharton basin. We also find that the crust generated at the fast Wharton spreading centre 55-57 Ma ago is only 3.5-4.5 km thick, the thinnest crust ever observed in a fast spreading environment. We suggest that this extremely thin crust is due to 40-50°C lower than normal mantle temperature in this part of the Indian Ocean during its formation.

Time delays in the response to the Neisseria meningitidis serogroup C outbreak in Nigeria - 2017.

PubMed

Hassan, Assad; Mustapha, G U; Lawal, Bola B; Na'uzo, Aliyu M; Ismail, Raji; Womi-Eteng Oboma, Eteng; Oyebanji, Oyeronke; Agenyi, Jeremiah; Thomas, Chima; Balogun, Muhammad Shakir; Dalhat, Mahmood M; Nguku, Patrick; Ihekweazu, Chikwe

2018-01-01

Nigeria reports high rates of mortality linked with recurring meningococcal meningitis outbreaks within the African meningitis belt. Few studies have thoroughly described the response to these outbreaks to provide strong and actionable public health messages. We describe how time delays affected the response to the 2016/2017 meningococcal meningitis outbreak in Nigeria. Using data from Nigeria Centre for Disease Control (NCDC), National Primary Health Care Development Agency (NPHCDA), World Health Organisation (WHO), and situation reports of rapid response teams, we calculated attack and death rates of reported suspected meningococcal meningitis cases per week in Zamfara, Sokoto and Yobe states respectively, between epidemiological week 49 in 2016 and epidemiological week 25 in 2017. We identified when alert and epidemic thresholds were crossed and determined when the outbreak was detected and notified in each state. We examined response activities to the outbreak. There were 12,535 suspected meningococcal meningitis cases and 877 deaths (CFR: 7.0%) in the three states. It took an average time of three weeks before the outbreaks were detected and notified to NCDC. Four weeks after receiving notification, an integrated response coordinating centre was set up by NCDC and requests for vaccines were sent to International Coordinating Group (ICG) on vaccine provision. While it took ICG one week to approve the requests, it took an average of two weeks for approximately 41% of requested vaccines to arrive. On the average, it took nine weeks from the date the epidemic threshold was crossed to commencement of reactive vaccination in the three states. There were delays in detection and notification of the outbreak, in coordinating response activities, in requesting for vaccines and their arrival from ICG, and in initiating reactive vaccination. Reducing these delays in future outbreaks could help decrease the morbidity and mortality linked with meningococcal meningitis outbreaks.

The FANTASTIC FOUR proteins influence shoot meristem size in Arabidopsis thaliana

PubMed Central

2010-01-01

Background Throughout their lives plants produce new organs from groups of pluripotent cells called meristems, located at the tips of the shoot and the root. The size of the shoot meristem is tightly controlled by a feedback loop, which involves the homeodomain transcription factor WUSCHEL (WUS) and the CLAVATA (CLV) proteins. This regulatory circuit is further fine-tuned by morphogenic signals such as hormones and sugars. Results Here we show that a family of four plant-specific proteins, encoded by the FANTASTIC FOUR (FAF) genes, has the potential to regulate shoot meristem size in Arabidopsis thaliana. FAF2 and FAF4 are expressed in the centre of the shoot meristem, overlapping with the site of WUS expression. Consistent with a regulatory interaction between the FAF gene family and WUS, our experiments indicate that the FAFs can repress WUS, which ultimately leads to an arrest of meristem activity in FAF overexpressing lines. The finding that meristematic expression of FAF2 and FAF4 is under negative control by CLV3 further supports the hypothesis that the FAFs are modulators of the genetic circuit that regulates the meristem. Conclusion This study reports the initial characterization of the Arabidopsis thaliana FAF gene family. Our data indicate that the FAF genes form a plant specific gene family, the members of which have the potential to regulate the size of the shoot meristem by modulating the CLV3-WUS feedback loop. PMID:21176196

Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope

PubMed Central

Upadhyay, Chitra; Mayr, Luzia M.; Zhang, Jing; Kumar, Rajnish; Gorny, Miroslaw K.; Nádas, Arthur; Zolla-Pazner, Susan

2014-01-01

ABSTRACT Broadly neutralizing antibodies targeting the HIV-1 envelope (Env) are key components for protection against HIV-1. However, many cross-reactive epitopes are often occluded. This study investigates the mechanisms contributing to the masking of V2i (variable loop V2 integrin) epitopes compared to the accessibility of V3 epitopes. V2i are conformation-dependent epitopes encompassing the integrin α4β7-binding motif on the V1V2 loop of HIV-1 Env gp120. The V2i monoclonal antibodies (MAbs) display extensive cross-reactivity with gp120 monomers from many subtypes but neutralize only few viruses, indicating V2i's cryptic nature. First, we asked whether CD4-induced Env conformational changes affect V2i epitopes similarly to V3. CD4 treatment of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs but not to the V2i MAbs. Second, the contribution of N-glycans in masking V2i versus V3 epitopes was evaluated by testing the neutralization of pseudoviruses produced in the presence of a glycosidase inhibitor, kifunensine. Viruses grown in kifunensine were more sensitive to neutralization by V3 but not V2i MAbs. Finally, we evaluated the time-dependent dynamics of the V2i and V3 epitopes. Extending the time of virus-MAb interaction to 18 h before adding target cells increased virus neutralization by some V2i MAbs and all V3 MAbs tested. Consistent with this, V2i MAb binding to Env on the surface of transfected cells also increased in a time-dependent manner. Hence, V2i and V3 epitopes are highly dynamic, but distinct factors modulate the antibody accessibility of these epitopes. The study reveals the importance of the structural dynamics of V2i and V3 epitopes in determining HIV-1 neutralization by antibodies targeting these sites. IMPORTANCE Conserved neutralizing epitopes are present in the V1V2 and V3 regions of HIV-1 Env, but these epitopes are often occluded from Abs. This study reveals that distinct mechanisms contribute to the masking of V3 epitopes and V2i epitopes in the V1V2 domain. Importantly, V3 MAbs and some V2i MAbs display greater neutralization against relatively resistant HIV-1 isolates when the MAbs interact with the virus for a prolonged period of time. Given their highly immunogenic nature, V3 and V2i epitopes are valuable targets that would augment the efficacy of HIV vaccines. PMID:25165106

Uncoupling proteins and the control of mitochondrial reactive oxygen species production.

PubMed

Mailloux, Ryan J; Harper, Mary-Ellen

2011-09-15

Reactive oxygen species (ROS), natural by-products of aerobic respiration, are important cell signaling molecules, which left unchecked can severely impair cellular functions and induce cell death. Hence, cells have developed a series of systems to keep ROS in the nontoxic range. Uncoupling proteins (UCPs) 1-3 are mitochondrial anion carrier proteins that are purported to play important roles in minimizing ROS emission from the electron transport chain. The function of UCP1 in this regard is highly contentious. However, UCPs 2 and 3 are generally thought to be activated by ROS or ROS by-products to induce proton leak, thus providing a negative feedback loop for mitochondrial ROS production. In our laboratory, we have not only confirmed that ROS activate UCP2 and UCP3, but also demonstrated that UCP2 and UCP3 are controlled by covalent modification by glutathione. Furthermore, the reversible glutathionylation is required to activate/inhibit UCP2 and UCP3, but not UCP1. Hence, our findings are consistent with the notion that UCPs 2 and 3 are acutely activated by ROS, which then directly modulate the glutathionylation status of the UCP to decrease ROS emission and participate in cell signaling mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

Uncertainty analysis on reactivity and discharged inventory for a pressurized water reactor fuel assembly due to {sup 235,238}U nuclear data uncertainties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Da Cruz, D. F.; Rochman, D.; Koning, A. J.

2012-07-01

This paper discusses the uncertainty analysis on reactivity and inventory for a typical PWR fuel element as a result of uncertainties in {sup 235,238}U nuclear data. A typical Westinghouse 3-loop fuel assembly fuelled with UO{sub 2} fuel with 4.8% enrichment has been selected. The Total Monte-Carlo method has been applied using the deterministic transport code DRAGON. This code allows the generation of the few-groups nuclear data libraries by directly using data contained in the nuclear data evaluation files. The nuclear data used in this study is from the JEFF3.1 evaluation, and the nuclear data files for {sup 238}U and {supmore » 235}U (randomized for the generation of the various DRAGON libraries) are taken from the nuclear data library TENDL. The total uncertainty (obtained by randomizing all {sup 238}U and {sup 235}U nuclear data in the ENDF files) on the reactor parameters has been split into different components (different nuclear reaction channels). Results show that the TMC method in combination with a deterministic transport code constitutes a powerful tool for performing uncertainty and sensitivity analysis of reactor physics parameters. (authors)« less

Analysis of the Human Immunodeficiency Virus Type 1 gp41 Membrane Proximal External Region Arrayed on Hepatitis B Surface Antigen Particles

PubMed Central

Phogat, S; K, Svehla; M, Tang; A, Spadaccini; J, Muller; J, Mascola; Berkower; R, Wyatt

2009-01-01

Vaccine immunogens derived from the envelope glycoproteins of the human immunodeficiency virus type 1 (HIV-1) that elicit broad neutralizing antibodies remains an elusive goal. The highly conserved 30 amino acid membrane proximal external region (MPER) of HIV gp41 contains the hydrophobic epitopes for two rare HIV-1 broad cross-reactive neutralizing antibodies, 2F5 and 4E10. Both these antibodies possess relatively hydrophobic HCDR3 loops and demonstrate enhanced binding to their epitopes in the context of the native gp160 precursor envelope glycoprotein by the intimate juxtaposition of a lipid membrane. The Hepatitis B surface antigen (HBsAg) S1 protein forms nanoparticles that can be utilized both as an immunogenic array of the MPER and to provide the lipid environment needed for enhanced 2F5 and 4E10 binding. We show that recombinant HBsAg particles with MPER (HBsAg-MPER) appended at the C-terminus of the S1 protein are recognized by 2F5 and 4E10 with high affinity compared to positioning the MPER at the N-terminus or the extracellular loop (ECL) of S1. Addition of C-terminal hydrophobic residues derived from the HIV-1 Env transmembrane region further enhances recognition of the MPER by both 2F5 and 4E10. Delipidation of the HBsAg-MPER particles decreases 2F5 and 4E10 binding and subsequent reconstitution with synthetic lipids restores optimal binding. Inoculation of the particles into small animals raised cross-reactive antibodies that recognize both the MPER and HIV-1 gp160 envelope glycoproteins expressed on the cell surface; however, no neutralizing activity could be detected. Prime:boost immunization of the HBsAg-MPER particles in sequence with HIV envelope glycoprotein proteoliposomes (Env-PLs) did not raise neutralizing antibodies that could be mapped to the MPER region. However, the Env-PLs did raise anti-Env antibodies that had the ability to neutralize selected HIV-1 isolates. The first generation HBsAg-MPER particles represent a unique means to present HIV-1 envelope glycoprotein neutralizing determinants to the immune system. PMID:18155743

Engineering a Single Chain Fv Antibody to αvβ6 Integrin using the Specificity-Determining Loop of a Foot-and-Mouth Disease Virus

PubMed Central

Kogelberg, Heide; Tolner, Berend; Thomas, Gareth J.; Di Cara, Danielle; Minogue, Shane; Ramesh, Bala; Sodha, Serena; Marsh, Dan; Lowdell, Mark W.; Meyer, Tim; Begent, Richard H.J.; Hart, Ian; Marshall, John F; Chester, Kerry

2010-01-01

Summary The αvβ6 integrin is a promising target for cancer therapy. Its expression is up-regulated de novo on many types of carcinoma where it may activate transforming growth factor-β1 and transforming growth factor-β3, interact with the specific extracellular matrix proteins and promote migration and invasion of tumour cells. The viral protein 1 (VP1) coat protein of the O1 British field strain serotype of foot-and-mouth disease virus is a high-affinity ligand for αvβ6, and we recently reported that a peptide derived from VP1 exhibited αvβ6-specific binding in vitro and in vivo. We hypothesized that this peptide could confer binding specificity of an antibody to αvβ6. A 17-mer peptide of VP1 was inserted into the complementary-determining region H3 loop of MFE-23, a murine single-chain Fv (scFv) antibody reactive with carcinoembryonic antigen (CEA). The resultant scFv (B6-1) bound to αvβ6 but retained residual reactivity with CEA. This was eliminated by point mutation (Y100bP) in the variable heavy-chain domain to create an scFv (B6-2) that was as structurally stable as MFE-23 and reacted specifically with αvβ6 but not α5β1, αvβ3, αvβ5, αvβ8 or CEA. B6-2 was internalized into αvβ6-expressing cells and inhibited αvβ6-dependent migration of carcinoma cells. B6-2 was subsequently humanized. The humanized form (B6-3) was obtained as a non-covalent dimer from secretion in Pichia pastoris (115 mg/l) and was a potent inhibitor of αvβ6-mediated cell adhesion. Thus, we have used a rational stepwise approach to create a humanized scFv with therapeutic potential to block αvβ6-mediated cancer cell invasion or to deliver and internalize toxins specifically to αvβ6-expressing tumours. PMID:18656482

Co-infection of scrub typhus and leptospirosis in patients with pyrexia of unknown origin in Longding district of Arunachal Pradesh in 2013.

PubMed

Borkakoty, Biswajyoti; Jakharia, Aniruddha; Biswas, Dipankar; Mahanta, Jagadish

2016-01-01

Scrub typhus and leptospirosis are bacterial zoonotic disease causing high morbidity and mortality. The seasonal outbreak of pyrexia is common in Arunachal Pradesh (AP); many times the disease remains undiagnosed. An outbreak of pyrexia of unknown origin (PUO) occurred in Longding district of Arunachal Pradesh in 2013, with 108 deaths, which was investigated to elucidate the cause of illness. Blood samples from the affected region with acute pyrexia were collected, and screened for the malaria parasite, scrub typhus IgM and leptospira IgM. Scrub typhus IgM was reactive in 97% (30/31), and 25% (8/31) cases were co-infected with leptospira. Incidentally, scrub typhus reactive (67%) and leptospira co-infection (62.7%) were higher in females. Record of previous 3 years (2011-2013) from Longding, Community Health Centre showed an increase in indoor pyrexia cases by 2-fold or more during October and November. The present study is the first report of co-infection of scrub typhus with leptospirosis from Northeast India. Medical officers in this region should take scrub typhus and leptospirosis in their differential diagnosis of patients with PUO for early diagnosis and effective treatment.

Morphogenetic Mechanisms in the Cyclic Regeneration of Hair Follicles and Deer Antlers from Stem Cells

PubMed Central

Li, Chunyi; McMahon, Chris

2013-01-01

We have made comparisons between hair follicles (HFs) and antler units (AUs)—two seemingly unrelated mammalian organs. HFs are tiny and concealed within skin, whereas AUs are gigantic and grown externally for visual display. However, these two organs share some striking similarities. Both consist of permanent and cyclic/temporary components and undergo stem-cell-based organogenesis and cyclic regeneration. Stem cells of both organs reside in the permanent part and the growth centres are located in the temporary part of each respective organ. Organogenesis and regeneration of both organs depend on epithelial-mesenchymal interactions. Establishment of these interactions requires stem cells and reactive/niche cells (dermal papilla cells for HFs and epidermal cells for AUs) to be juxtaposed, which is achieved through destruction of the cyclic part to bring the reactive cells into close proximity to the respective stem cell niche. Developments of HFs and AUs are regulated by similar endocrine (particularly testosterone) and paracrine (particularly IGF1) factors. Interestingly, these two organs come to interplay during antlerogenesis. In conclusion, we believe that investigators from the fields of both HF and AU biology could greatly benefit from a comprehensive comparison between these two organs. PMID:24383056

Influence of smooth temperature variation on hotspot ignition

NASA Astrophysics Data System (ADS)

Reinbacher, Fynn; Regele, Jonathan David

2018-01-01

Autoignition in thermally stratified reactive mixtures originates in localised hotspots. The ignition behaviour is often characterised using linear temperature gradients and more recently constant temperature plateaus combined with temperature gradients. Acoustic timescale characterisation of plateau regions has been successfully used to characterise the type of mechanical disturbance that will be created from a plateau core ignition. This work combines linear temperature gradients with superelliptic cores in order to more accurately account for a local temperature maximum of finite size and the smooth temperature variation contained inside realistic hotspot centres. A one-step Arrhenius reaction is used to model a H2-air reactive mixture. Using the superelliptic approach a range of behaviours for temperature distributions are investigated by varying the temperature profile between the gradient only and plateau and gradient bounding cases. Each superelliptic case is compared to a respective plateau and gradient case where simple acoustic timescale characterisation may be performed. It is shown that hot spots equivalent with excitation-to-acoustic timescale ratios sufficiently greater than unity exhibit behaviour very similar to a simple plateau-gradient model. However, for larger hot spots with timescale ratios sufficiently less than unity the reaction behaviour is highly dependent on the smooth temperature profile contained within the core region.

Improved irradiation tolerance of reactive gas pulse sputtered TiN coatings with a hybrid architecture of multilayered and compositionally graded structures

NASA Astrophysics Data System (ADS)

Liang, Wei; Yang, Jijun; Zhang, Feifei; Lu, Chenyang; Wang, Lumin; Liao, Jiali; Yang, Yuanyou; Liu, Ning

2018-04-01

This study investigates the improved irradiation tolerance of reactive gas pulse (RGP) sputtered TiN coatings which has hybrid architecture of multilayered and compositionally graded structures. The multilayered RGP-TiN coating is composed of hexagonal close-packed Ti phase and face-centred cubic TiN phase sublayers, where the former sublayer has a compositionally graded structure and the latter one maintains constant stoichiometric atomic ratio of Ti:N. After 100 keV He ion irradiation, the RGP-TiN coating exhibits improved irradiation resistance compared with its single layered (SL) counterpart. The size and density of He bubbles are smaller in the RGP-TiN coating than in the SL-TiN coating. The irradiation-induced surface blistering of the coatings shows a similar tendency. Meanwhile, the irradiation hardening and adhesion strength of the RGP-TiN coatings were not greatly affected by He irradiation. Moreover, the irradiation damage tolerance of the coatings can be well tuned by changing the undulation period number of N2 gas flow rate. Detailed analysis suggested that this improved irradiation tolerance could be related to the combined contribution of the multilayered and compositionally graded structures.

Effect of surface Fe-S hybrid structure on the activity of the perfect and reduced α-Fe2O3(001) for chemical looping combustion

NASA Astrophysics Data System (ADS)

Xiao, Xianbin; Qin, Wu; Wang, Jianye; Li, Junhao; Dong, Changqing

2018-05-01

Sulfurization of the gradually reduced Fe2O3 surfaces is inevitable while Fe2O3 is used as an oxygen carrier (OC) for coal chemical looping combustion (CLC), which will result in formation of Fe-S hybrid structure on the surfaces. The Fe-S hybrid structure will directly alter the reactivity of the surfaces. Therefore, detailed properties of Fe-S hybrid structure over the perfect and reduced Fe2O3(001) surfaces, and its effect on the interfacial interactions, including CO oxidization and decomposition on the surfaces, were investigated by using density functional theory (DFT) calculations. The S atom prefers to chemically bind to Fe site with electron transfer from the surfaces to the S atom, and a deeper reduction of Fe2O3(001) leads to an increasing interaction between S and Fe. The formation of Fe-S hybrid structure alters the electronic properties of the gradually reduced Fe2O3(001) surfaces, promoting CO oxidation on the surfaces ranging from Fe2O3 to FeO, but depressing carbon deposition on the surfaces ranging from FeO to Fe. The sulfurized FeO acts as a watershed to realize relatively high CO oxidation rate and low carbon deposition. Results provided a fundamental understanding for controlling and optimizing the CLC processes.

Qualification and characterization of electronics of the fast neutron Hodoscope detectors using neutrons from CABRI core

NASA Astrophysics Data System (ADS)

Mirotta, S.; Guillot, J.; Chevalier, V.; Biard, B.

2018-01-01

The study of Reactivity Initiated Accidents (RIA) is important to determine up to which limits nuclear fuels can withstand such accidents without clad failure. The CABRI International Program (CIP), conducted by IRSN under an OECD/NEA agreement, has been launched to perform representative RIA Integral Effect Tests (IET) on real irradiated fuel rods in prototypical Pressurized Water Reactors (PWR) conditions. For this purpose, the CABRI experimental pulse reactor, operated by CEA in Cadarache, France, has been strongly renovated, and equipped with a pressurized water loop. The behavior of the test rod, located in that loop in the center of the driver core, is followed in real time during the power transients thanks to the hodoscope, a unique online fuel motion monitoring system, and one of the major distinctive features of CABRI. The hodoscope measures the fast neutrons emitted by the tested rod during the power pulse with a complete set of 153 Fission Chambers and 153 Proton Recoil Counters. During the CABRI facility renovation, the electronic chain of these detectors has been upgraded. In this paper, the performance of the new system is presented describing gain calibration methodology in order to get maximal Signal/Noise ratio for amplification modules, threshold tuning methodology for the discrimination modules (old and new ones), and linear detectors response limit versus different reactor powers for the whole electronic chain.

The CABRI fast neutron Hodoscope: Renovation, qualification program and first results following the experimental reactor restart

NASA Astrophysics Data System (ADS)

Chevalier, V.; Mirotta, S.; Guillot, J.; Biard, B.

2018-01-01

The CABRI experimental pulse reactor, located at the Cadarache nuclear research center, southern France, is devoted to the study of Reactivity Initiated Accidents (RIA). For the purpose of the CABRI International Program (CIP), managed and funded by IRSN, in the framework of an OECD/NEA agreement, a huge renovation of the facility has been conducted since 2003. The Cabri Water Loop was then installed to ensure prototypical Pressurized Water Reactor (PWR) conditions for testing irradiated fuel rods. The hodoscope installed in the CABRI reactor is a unique online fuel motion monitoring system, operated by IRSN and dedicated to the measurement of the fast neutrons emitted by the tested rod during the power pulse. It is one of the distinctive features of the CABRI reactor facility, which is operated by CEA. The system is able to determine the fuel motion, if any, with a time resolution of 1 ms and a spatial resolution of 3 mm. The hodoscope equipment has been upgraded as well during the CABRI facility renovation. This paper presents the main outcomes achieved with the hodoscope since October 2015, date of the first criticality of the CABRI reactor in its new Cabri Water Loop configuration. Results obtained during reactor commissioning phase functioning, either in steady-state mode (at low and high power, up to 23 MW) or in transient mode (start-up, possibly beyond 20 GW), are discussed.

Induction of a feed forward pro-apoptotic mechanistic loop by nitric oxide in a human breast cancer model.

PubMed

Sen, Suvajit; Kawahara, Brian; Fukuto, Jon; Chaudhuri, Gautam

2013-01-01

We have previously demonstrated that relatively high concentrations of NO [Nitric Oxide] as produced by activated macrophages induced apoptosis in the human breast cancer cell line, MDA-MB-468. More recently, we also demonstrated the importance of endogenous H2O2 in the regulation of growth in human breast cancer cells. In the present study we assessed the interplay between exogenously administered NO and the endogenously produced reactive oxygen species [ROS] in human breast cancer cells and evaluated the mechanism[s] in the induction of apoptosis. To this end we identified a novel mechanism by which NO down regulated endogenous hydrogen peroxide [H2O2] formation via the down-regulation of superoxide [O2 (.-)] and the activation of catalase. We further demonstrated the existence of a feed forward mechanistic loop involving protein phosphatase 2A [PP2A] and its downstream substrate FOXO1 in the induction of apoptosis and the synthesis of catalase. We utilized gene silencing of PP2A, FOXO1 and catalase to assess their relative importance and key roles in NO mediated apoptosis. This study provides the potential for a therapeutic approach in treating breast cancer by targeted delivery of NO where NO donors and activators of downstream players could initiate a self sustaining apoptotic cascade in breast cancer cells.

Induction of a Feed Forward Pro-Apoptotic Mechanistic Loop by Nitric Oxide in a Human Breast Cancer Model

PubMed Central

Sen, Suvajit; Kawahara, Brian; Fukuto, Jon; Chaudhuri, Gautam

2013-01-01

We have previously demonstrated that relatively high concentrations of NO [Nitric Oxide] as produced by activated macrophages induced apoptosis in the human breast cancer cell line, MDA-MB-468. More recently, we also demonstrated the importance of endogenous H2O2 in the regulation of growth in human breast cancer cells. In the present study we assessed the interplay between exogenously administered NO and the endogenously produced reactive oxygen species [ROS] in human breast cancer cells and evaluated the mechanism[s] in the induction of apoptosis. To this end we identified a novel mechanism by which NO down regulated endogenous hydrogen peroxide [H2O2] formation via the down-regulation of superoxide [O2 .−] and the activation of catalase. We further demonstrated the existence of a feed forward mechanistic loop involving protein phosphatase 2A [PP2A] and its downstream substrate FOXO1 in the induction of apoptosis and the synthesis of catalase. We utilized gene silencing of PP2A, FOXO1 and catalase to assess their relative importance and key roles in NO mediated apoptosis. This study provides the potential for a therapeutic approach in treating breast cancer by targeted delivery of NO where NO donors and activators of downstream players could initiate a self sustaining apoptotic cascade in breast cancer cells. PMID:23950968

Structures of Two Major Allergens, Bla g 4 and Per a 4, From Cockroaches and Their IgE Binding Epitopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Y.; Chan, S; Ong, T

2009-01-01

Inhalant allergens from cockroaches are an important cause of asthma to millions of individuals worldwide. Here we report for the first time the structures of two major cockroach allergens, Bla g 4 and Per a 4, that adopt a typical lipocalin fold but with distinct structural features as compared with other known lipocalin allergens. Both Bla g 4 and Per a 4 contain two long-range disulfide bonds linking the N and C termini to a beta-barrel. The C-terminal helix of Bla g 4 is bent and greatly extended toward the N terminus. Bla g 4 is found to be amore » monomer, whereas Per a 4 exists as a dimer in solution with a novel dimeric interface involving residues from loops at the top and bottom of the beta-barrel. Putative ligand binding sites of both allergens are determined by docking of the juvenile hormone III inside the beta-barrel and found to interact with the ligand using non-conserved residues. Bla g 4 and Per a 4 are found to be cross-reactive in sera IgE binding, at least in the Singaporean Chinese population tested. A major IgE binding epitope unique to Per a 4 is found on the loops at the bottom of the beta-barrel that may aid the development of hypoallergens for immunotherapy.« less

Crystal structure of the bacterial luciferase/flavin complex provides insight into the function of the beta subunit.

PubMed

Campbell, Zachary T; Weichsel, Andrzej; Montfort, William R; Baldwin, Thomas O

2009-07-07

Bacterial luciferase from Vibrio harveyi is a heterodimer composed of a catalytic alpha subunit and a homologous but noncatalytic beta subunit. Despite decades of enzymological investigation, structural evidence defining the active center has been elusive. We report here the crystal structure of V. harveyi luciferase bound to flavin mononucleotide (FMN) at 2.3 A. The isoalloxazine ring is coordinated by an unusual cis-Ala-Ala peptide bond. The reactive sulfhydryl group of Cys106 projects toward position C-4a, the site of flavin oxygenation. This structure also provides the first data specifying the conformations of a mobile loop that is crystallographically disordered in both prior crystal structures [(1995) Biochemistry 34, 6581-6586; (1996) J. Biol. Chem. 271, 21956 21968]. This loop appears to be a boundary between solvent and the active center. Within this portion of the protein, a single contact was observed between Phe272 of the alpha subunit, not seen in the previous structures, and Tyr151 of the beta subunit. Substitutions at position 151 on the beta subunit caused reductions in activity and total quantum yield. Several of these mutants were found to have decreased affinity for reduced flavin mononucleotide (FMNH(2)). These findings partially address the long-standing question of how the beta subunit stabilizes the active conformation of the alpha subunit, thereby participating in the catalytic mechanism.

Development of a Reverse Transcription Loop-Mediated Isothermal Amplification Method for the Rapid Detection of Subtype H7N9 Avian Influenza Virus

PubMed Central

Bao, Hongmei; Zhao, Yuhui; Wang, Yunhe; Xu, Xiaolong; Shi, Jianzhong; Zeng, Xianying; Wang, Xiurong; Chen, Hualan

2014-01-01

A novel influenza A (H7N9) virus has emerged in China. To rapidly detect this virus from clinical samples, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of the H7N9 virus. The minimum detection limit of the RT-LAMP assay was 0.01 PFU H7N9 virus, making this method 100-fold more sensitive to the detection of the H7N9 virus than conventional RT-PCR. The H7N9 virus RT-LAMP assays can efficiently detect different sources of H7N9 influenza virus RNA (from chickens, pigeons, the environment, and humans). No cross-reactive amplification with the RNA of other subtype influenza viruses or of other avian respiratory viruses was observed. The assays can effectively detect H7N9 influenza virus RNA in drinking water, soil, cloacal swab, and tracheal swab samples that were collected from live poultry markets, as well as human H7N9 virus, in less than 30 min. These results suggest that the H7N9 virus RT-LAMP assays were efficient, practical, and rapid diagnostic methods for the epidemiological surveillance and diagnosis of influenza A (H7N9) virus from different resource samples. PMID:24689044

Rapid detection of duck hepatitis A virus genotype C using reverse transcription loop-mediated isothermal amplification.

PubMed

Li, Chuanfeng; Chen, Zongyan; Meng, Chunchun; Liu, Guangqing

2014-02-01

A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was used and optimized to develop a rapid and sensitive detection system for duck hepatitis A virus genotype C (DHAV-C) RNA. A set of four specific primers was designed against highly conserved sequences located within the 3D gene from DHAV (strain GX1201). Under optimal reaction conditions, the sensitivity of DHAV-C-specific RT-LAMP was 100-fold higher than that of reverse transcriptase-polymerase chain reaction (RT-PCR), with a detection limit of 0.3pg (6.59×10(4) copies) per reaction. No cross-reactivity was observed from the samples of other duck viruses, which is in good accordance with RT-PCR. Furthermore, a positive reaction can be visually inspected by observing turbidity or color change after the addition of SYBR green I dye. The DHAV-C-specific RT-LAMP assay was applied to the samples and compared with RT-PCR. The positive-sample ratios were 26.7% (12 of 45) by RT-LAMP and 20% (9 of 45) by RT-PCR. Therefore, the newly developed RT-LAMP assay is a rapid, specific, sensitive, and cost-effective method of DHAV-C detection. This assay has potential applications in both clinical diagnosis and field surveillance of DHAV-C infection. Copyright © 2013. Published by Elsevier B.V.

Mapping of contact sites in complex formation between light-activated rhodopsin and transducin by covalent crosslinking: Use of a chemically preactivated reagent

PubMed Central

Itoh, Yoshiki; Cai, Kewen; Khorana, H. Gobind

2001-01-01

Contact sites in interaction between light-activated rhodopsin and transducin (T) have been investigated by using a chemically preactivated crosslinking reagent, N-succinimidyl 3-(2-pyridyldithio)propionate. The 3 propionyl-N-succinimidyl group in the reagent was attached by a disulfide exchange reaction to rhodopsin mutants containing single reactive cysteine groups in the cytoplasmic loops. Complex formation between the derivatized rhodopsin mutants and T was carried out by illumination at λ > 495 nm. Subsequent increase in pH (from 6 to 7.5 or higher) of the complex resulted in crosslinking of rhodopsin to the Tα subunit. Crosslinking to Tα was demonstrated for the rhodopsin mutants K141C, S240C, and K248C, and the crosslinked sites in Tα were identified for the rhodopsin mutant S240C. The peptides carrying the crosslinking moiety were isolated from the trypsin-digested peptide mixture, and their identification was carried out by matrix-assisted laser desorption ionization–time of flight mass spectrometry. The main site of crosslinking is within the peptide sequence, Leu-19–Arg-28 at the N-terminal region of Tα. The total results show that both the N and the C termini of Tα are in close vicinity to the third cytoplasmic loop of rhodopsin in the complex between rhodopsin and T. PMID:11320238

Molecular evolution of miraculin-like proteins in soybean Kunitz super-family.

PubMed

Selvakumar, Purushotham; Gahloth, Deepankar; Tomar, Prabhat Pratap Singh; Sharma, Nidhi; Sharma, Ashwani Kumar

2011-12-01

Miraculin-like proteins (MLPs) belong to soybean Kunitz super-family and have been characterized from many plant families like Rutaceae, Solanaceae, Rubiaceae, etc. Many of them possess trypsin inhibitory activity and are involved in plant defense. MLPs exhibit significant sequence identity (~30-95%) to native miraculin protein, also belonging to Kunitz super-family compared with a typical Kunitz family member (~30%). The sequence and structure-function comparison of MLPs with that of a classical Kunitz inhibitor have demonstrated that MLPs have evolved to form a distinct group within Kunitz super-family. Sequence analysis of new genes along with available MLP sequences in the literature revealed three major groups for these proteins. A significant feature of Rutaceae MLP type 2 sequences is the presence of phosphorylation motif. Subtle changes are seen in putative reactive loop residues among different MLPs suggesting altered specificities to specific proteases. In phylogenetic analysis, Rutaceae MLP type 1 and type 2 proteins clustered together on separate branches, whereas native miraculin along with other MLPs formed distinct clusters. Site-specific positive Darwinian selection was observed at many sites in both the groups of Rutaceae MLP sequences with most of the residues undergoing positive selection located in loop regions. The results demonstrate the sequence and thereby the structure-function divergence of MLPs as a distinct group within soybean Kunitz super-family due to biotic and abiotic stresses of local environment.

Development of a single-tube loop-mediated isothermal amplification assay for detection of four pathogens of bacterial meningitis.

PubMed

Huy, Nguyen Tien; Hang, Le Thi Thuy; Boamah, Daniel; Lan, Nguyen Thi Phuong; Van Thanh, Phan; Watanabe, Kiwao; Huong, Vu Thi Thu; Kikuchi, Mihoko; Ariyoshi, Koya; Morita, Kouichi; Hirayama, Kenji

2012-12-01

Several loop-mediated isothermal amplification (LAMP) assays have been developed to detect common causative pathogens of bacterial meningitis (BM). However, no LAMP assay is reported to detect Streptococcus agalactiae and Streptococcus suis, which are also among common pathogens of BM. Moreover, it is laborious and expensive by performing multiple reactions for each sample to detect bacterial pathogen. Thus, we aimed to design and develop a single-tube LAMP assay capable of detecting multiple bacterial species, based on the nucleotide sequences of the 16S rRNA genes of the bacteria. The nucleotide sequences of the 16S rRNA genes of main pathogens involved in BM were aligned to identify conserved regions, which were further used to design broad range specific LAMP assay primers. We successfully designed a set of broad range specific LAMP assay primers for simultaneous detection of four species including Staphylococcus aureus, Streptococcus pneumoniae, S. suis and S. agalactiae. The broad range LAMP assay was highly specific without cross-reactivity with other bacteria including Haemophilus influenzae, Neisseria meningitidis and Escherichia coli. The sensitivity of our LAMP assay was 100-1000 times higher compared with the conventional PCR assay. The bacterial species could be identified after digestion of the LAMP products with restriction endonuclease DdeI and HaeIII. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Real-time fluorescence loop-mediated isothermal amplification assay for direct detection of egg drop syndrome virus.

PubMed

Zheney, Makay; Kaziyev, Zhambul; Kassenova, Gulmira; Zhao, Lingna; Liu, Wei; Liang, Lin; Li, Gang

2018-02-13

Egg drop syndrome (EDS), caused by the adenovirus "egg drop syndrome virus" (EDSV) causes severe economic losses through reduced egg production in breeder and layer flocks. The diagnosis of EDSV has been done by molecular tools since its complete genome sequence was identified. In order to enhance the capabilities of the real-time fluorescence loop-mediated isothermal amplification (RealAmp) assay, we aimed to apply the method for direct detection of the EDSV without viral DNA extraction. In order to detect the presence of the EDSV DNA, three pairs of primers were designed, from the conserved region of fiber gene of the EDSV. For our assay, test and control samples were directly used in the reaction mixture in 10-fold serial dilution. The target DNA was amplified at 65 °C, which yield positive results in a relatively short period of 40-45 min. The method reported in this study is highly sensitive as compared to polymerase chain reaction (PCR) and showed no sign of cross-reactivity or false positive results. The RealAmp accomplished specific identification of EDSV among a variety of poultry disease viruses. The direct RealAmp can be used to detect the presence of EDSV. As our result showed, the RealAmp method could be suitable for the direct detection of other DNA viruses.

Reconstitution of a functional 7SK snRNP

PubMed Central

Brogie, John E.

2017-01-01

Abstract The 7SK small nuclear ribonucleoprotein (snRNP) plays a central role in RNA polymerase II elongation control by regulating the availability of active P-TEFb. We optimized conditions for analyzing 7SK RNA by SHAPE and demonstrated a hysteretic effect of magnesium on 7SK folding dynamics including a 7SK GAUC motif switch. We also found evidence that the 5΄ end pairs alternatively with two different regions of 7SK giving rise to open and closed forms that dictate the state of the 7SK motif. We then used recombinant P-TEFb, HEXIM1, LARP7 and MEPCE to reconstruct a functional 7SK snRNP in vitro. Stably associated P-TEFb was highly inhibited, but could still be released and activated by HIV-1 Tat. Notably, P-TEFb association with both in vitro-reconstituted and cellular snRNPs led to similar changes in SHAPE reactivities, confirming that 7SK undergoes a P-TEFb-dependent structural change. We determined that the xRRM of LARP7 binds to the 3΄ stem loop of 7SK and inhibits the methyltransferase activity of MEPCE through a C-terminal MEPCE interaction domain (MID). Inhibition of MEPCE is dependent on the structure of the 3΄ stem loop and the closed form of 7SK RNA. This study provides important insights into intramolecular interactions within the 7SK snRNP. PMID:28431135

High-output stoma after small-bowel resections for Crohn's disease.

PubMed

Tsao, Stephen K K; Baker, Melanie; Nightingale, Jeremy M D

2005-12-01

A 56-year-old Caucasian woman with a history of Crohn's disease and multiple bowel resections resulting in a loop jejunostomy was referred to our Nutritional Unit from a neighboring district general hospital for further management. She was first seen in October 2001, and initial assessment indicated that she was malnourished with fluid depletion, evidenced by the high volume of stomal fluid produced. There had been no sudden change in her medication, her Crohn's disease was quiescent and there was no evidence of any intra-abdominal sepsis. Despite a high calorific intake through her diet, she continued to lose weight. Serum urea and electrolytes; magnesium; C-reactive protein; full blood count; urinary spot sodium; anthropometric measurements. High-output stoma with malabsorption as a consequence of repeated small-bowel surgery. The patient was treated with oral hypotonic fluid restriction (0.5 l/day), 2 l of oral glucose-saline solution per day, high-dose oral antimotility agents (loperamide and codeine phosphate), a proton-pump inhibitor (omeprazole) and oral magnesium replacement. A year later, the patient's loop jejunostomy was closed and an end ileostomy fashioned, bringing an additional 35 cm of small bowel into continuity; macronutrient absorption improved but her problem of dehydration was only slightly reduced. She was stabilized on a twice-weekly subcutaneous magnesium and saline infusion and daily oral 1alpha-hydroxycholecalciferol.

Optical properties of zirconium oxynitride films: The effect of composition, electronic and crystalline structures

NASA Astrophysics Data System (ADS)

Carvalho, P.; Borges, J.; Rodrigues, M. S.; Barradas, N. P.; Alves, E.; Espinós, J. P.; González-Elipe, A. R.; Cunha, L.; Marques, L.; Vasilevskiy, M. I.; Vaz, F.

2015-12-01

This work is devoted to the investigation of zirconium oxynitride (ZrOxNy) films with varied optical responses prompted by the variations in their compositional and structural properties. The films were prepared by dc reactive magnetron sputtering of Zr, using Ar and a reactive gas mixture of N2 + O2 (17:3). The colour of the films changed from metallic-like, very bright yellow-pale and golden yellow, for low gas flows to red-brownish for intermediate gas flows. Associated to this colour change there was a significant decrease of brightness. With further increase of the reactive gas flow, the colour of the samples changed from red-brownish to dark blue or even to interference colourations. The variations in composition disclosed the existence of four different zones, which were found to be closely related with the variations in the crystalline structure. XRD analysis revealed the change from a B1 NaCl face-centred cubic zirconium nitride-type phase for films prepared with low reactive gas flows, towards a poorly crystallized over-stoichiometric nitride phase, which may be similar to that of Zr3N4 with some probable oxygen inclusions within nitrogen positions, for films prepared with intermediate reactive gas flows. For high reactive gas flows, the films developed an oxynitride-type phase, similar to that of γ-Zr2ON2 with some oxygen atoms occupying some of the nitrogen positions, evolving to a ZrO2 monoclinic type structure within the zone where films were prepared with relatively high reactive gas flows. The analysis carried out by reflected electron energy loss spectroscopy (REELS) revealed a continuous depopulation of the d-band and an opening of an energy gap between the valence band (2p) and the Fermi level close to 5 eV. The ZrN-based coatings (zone I and II) presented intrinsic colourations, with a decrease in brightness and a colour change from bright yellow to golden yellow, red brownish and dark blue. Associated to these changes, there was also a shift of the reflectivity minimum to lower energies, with the increase of the non-metallic content. The samples lying in the two last zones (zone III, oxynitride and zone IV, oxide films) revealed a typical semi-transparent-optical behaviour showing interference-like colourations only due to the complete depopulation of the d band at the Fermi level. The samples lying in these zones presented also an increase of the optical bandgap from 2 to 3.6 eV.

Radio Astronomers Get Their First Glimpse of Powerful Solar Storm

NASA Astrophysics Data System (ADS)

2001-08-01

Astronomers have made the first radio-telescope images of a powerful coronal mass ejection on the Sun, giving them a long-sought glimpse of hitherto unseen aspects of these potentially dangerous events. "These observations are going to provide us with a new and unique tool for deciphering the mechanisms of coronal mass ejections and how they are related to other solar events," said Tim Bastian, an astronomer at the National Science Foundation's National Radio Astronomy Observatory (NRAO) in Charlottesville, Virginia. Radio image of coronal mass ejection; circle indicates the size and location of the Sun. White dots are where radio spectral measurements were made. Bastian, along with Monique Pick, Alain Kerdraon and Dalmiro Maia of the Paris Observatory, and Angelos Vourlidas of the Naval Research Laboratory in Washington, D.C., used a solar radio telescope in Nancay, France, to study a coronal mass ejection that occurred on April 20, 1998. Their results will be published in the September 1 edition of the Astrophysical Journal Letters. Coronal mass ejections are powerful magnetic explosions in the Sun's corona, or outer atmosphere, that can blast billions of tons of charged particles into interplanetary space at tremendous speeds. If the ejection is aimed in the direction of Earth, the speeding particles interact with our planet's magnetic field to cause auroral displays, radio-communication blackouts, and potentially damage satellites and electric-power systems. "Coronal mass ejections have been observed for many years, but only with visible-light telescopes, usually in space. While previous radio observations have provided us with powerful diagnostics of mass ejections and associated phenomena in the corona, this is the first time that one has been directly imaged in wavelengths other than visible light," Bastian said. "These new data from the radio observations give us important clues about how these very energetic events work," he added. The radio images show an expanding set of loops similar to the loops seen at visible wavelengths. The radio loops, astronomers believe, indicate regions where electrons are being accelerated to nearly the speed of light at about the time the ejection process is getting started. The same ejection observed by the radio telescope also was observed by orbiting solar telescopes. Depending on what later radio observations show, the solar studies may reveal new insights into the physics of other astronomical phenomena. For example, shocks in the corona and the interplanetary medium accelerate electrons and ions, a process believed to occur in supernova remnants - the expanding debris from stellar explosions. The electrons also may be accelerated by processes associated with magnetic reconnection, a process that occurs in the Earth's magnetosphere. "The Sun is an excellent physics laboratory, and what it teaches us can then help us understand other astrophysical phenomena in the universe," Bastian said. The radio detection of a coronal mass ejection also means that warning of the potentially dangerous effects of these events could come from ground-based radio telescopes, rather than more-expensive orbiting observatories. "With solar radio telescopes strategically placed at three or four locations around the world, coronal mass ejections could be detected 24 hours a day to provide advance warning," Bastian said. The Nancay station for radio astronomy is a facility of the Paris Observatory. The Nancay Radioheliograph is funded by the French Ministry of Education, the Centre National de la Recherche Scientifique, and by the Region Centre. This research has also been supported by the Centre National d'Etudes Spatiales. The National Radio Astronomy Observatory is a facility of the National Science Foundation, operated under cooperative agreement by Associated Universities, Inc.

Real-time measurement of reactive gases (NO, NO2, O3, CO) at ERSA, Cape Corsica, a long term Observatory.

NASA Astrophysics Data System (ADS)

Pichon, Jean-Marc; Colomb, Aurelie; Gheusi, Francois; Sauvage, Stephane; Pont, Veronique; Tison, Emmanuel; Bordier, Florent; Grignion, Guillaume; Savelli, Jean-Luc; Dulac, Francois; Sciare, Jean; Nicolas, Jose; Bourrianne, Thierry; Bouvier, Laetitia

2013-04-01

Important efforts have been put in 2012 in order to implement the infrastructure and instrumentation for a fully equipped background monitoring station at Ersa, Cape Corsica, key location at the crossroads of dusty southerly airmasses and polluted outflows from the European continent. The ERSA observatory is a french initiative within the framework of CHARMEX (Chemistry-Aerosol Mediterranean Experiment (ChArMEx, http://charmex.lsce.ipsl.fr/) and CORSICA (Centre d'Observation Régional pour la Surveillance du Climat et de l'environnement Atmosphérique et océanographique en Méditerranée occidentale (http://www2.obs-mip.fr/corsica) . The measurements of the station include real-time measurement of reactive gases (O3, CO, NO, NO2), off-line VOC measurements (cylinders, cartridges), a broad spectrum of aerosol properties (chemical composition, ground optical properties, integrated and space-resolved optical properties , size distribution properties, mass, hygroscopicity as well as dry/wet depositions). Among all the parameters, reactive gases are recognized as precursors of ozone and aerosol. The primarily emitted nitrogen oxides (NOx=NO+NO2) have a substantial impact on radical chemistry, ozone (O3) formation and aerosol by their atmospheric oxidation to aerosol nitrate. Carbon monoxide (CO) is mostly primarily emitted from combustion processes, but it is also formed in substantial amounts from the oxidation of methane (CH4) and volatile organic compounds (VOCs). Due to its high global turn-over rates CO is a major O3 precursor, and it has a strong impact on the oxidizing capacity and thus indirectly on the concentration of the climate gas CH4. O3 is a climate gas itself, however, also strongly involved in NO/NO2 partitioning and oxidizing capacity, thus coupling back on several photochemical processes. Accordingly, impacts on climate are multiple and rather complex. The understanding requires high quality, long-term observations of these reactive species. We present here the first measurement of reactive gases (O3, CO, NO, NO2) obtained at ERSA, the new monitoring station at Cape Corsica.

Associations of temporal and energetic characteristics of behavior with depressive symptoms: A population-based longitudinal study within Strelau's Regulative Theory of Temperament.

PubMed

Hintsa, T; Wesolowska, K; Elovainio, M; Strelau, J; Pulkki-Råback, L; Keltikangas-Järvinen, L

2016-06-01

Individual dispositions have previously been associated with increased risk for depressive symptoms. The direction of the association has been found to be sometimes reciprocal. We examined whether temperament traits are associated with depressive symptoms and whether depressive symptoms contribute to changes in temperament. Participants (n=674-811) were from a population-based Young Finns Study. Temperament was assessed by a Finnish version of the Formal Characteristics of Behavior - Temperament Inventory. Depressive symptoms were assessed with modified BDI (mBDI) in 1997, 2001, 2007 and 2012, and BDI-II in 2012. Higher perseveration and emotional reactivity were associated with higher level of depressive symptoms, and higher endurance was associated with lower level of depressive symptoms in 2007 and 2012. These associations were independent of several potential confounders and baseline depressive symptoms. The results of cross-lagged structural equation modeling showed that the associations between temperament and depressive symptoms were reciprocal: briskness, endurance and activity decreased the risk for depressive symptoms while depressive symptoms decreased the level of these characteristics. Perseveration, emotional reactivity and depressive symptoms reinforced each other over time. The depressive symptoms scales we used are not meant for measuring clinically diagnosed depression. The relationships between temperament traits and depressive symptoms were not strong enough to provide a clinical basis for guiding treatment. Lower perseveration, lower emotional reactivity and higher endurance seem to be health protective temperament characteristics that reduce the risk for depressive symptoms. The reciprocal associations between temperament and depressive symptoms imply mutual health protective and health declining effects. Clinical relevance of the study is that enhancing positive loops and self-concept, and supporting individual stress management might be helpful in prevention of depressive symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Supplemental Reactor Physics Calculations and Analysis of ELF Mk 1A Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pope, Michael A.

2014-10-01

These calculations supplement previous the reactor physics work evaluating the Enhanced Low Enriched Uranium (LEU) Fuel (ELF) Mk 1A element. This includes various additional comparisons between the current Highly Enriched Uranium (HEU) and LEU along with further characterization of the performance of the ELF fuel. The excess reactivity to be held down at BOC for ELF Mk 1A fuel is estimated to be approximately $2.75 greater than with HEU for a typical cycle. This is a combined effect of the absence of burnable poison in the ELF fuel and the reduced neck shim worth in LEU fuel compared to HEU.more » Burnable poison rods were conceptualized for use in the small B positions containing Gd2O3 absorber. These were shown to provide $2.37 of negative reactivity at BOC and to burn out in less than half of a cycle. The worth of OSCCs is approximately the same between HEU and ELF Mk 1A (LEU) fuels in the representative loading evaluated. This was evaluated by rotating all banks simultaneously. The safety rod worth is relatively unchanged between HEU and ELF Mk 1A (LEU) fuels in the representative loading evaluated. However, this should be reevaluated with different loadings. Neutron flux, both total and fast (>1 MeV), is either the same or reduced upon changing from HEU to ELF Mk 1A (LEU) fuels in the representative loading evaluated. This is consistent with the well-established trend of lower neutron fluxes for a given power in LEU than HEU.The IPT loop void reactivity is approximately the same or less positive with ELF Mk 1A (LEU) fuel than HEU in the representative loading evaluated.« less

[Circumscribed palmar hypokeratosis (CPM): The diagnostic value of dermoscopy].

PubMed

Topin-Ruiz, S; Debarre, J-M; Blanchard, E; Kettani, S; Valmier, P-J; Martin, L; Le Corre, Y

2017-03-01

Circumscribed palmar hypokeratosis (CPH) is a rare skin disease, first described in 2002, associated with sudden localized reduction of the corneal layer. In most cases, it presents as an isolated rounded erythematous palmar lesion on the thenar eminence. We describe the dermoscopic semiology of CPH in 3 cases. Three patients between the ages of 59 and 72 presented very limited erythematous lesions suggestive of CPH. Dermoscopic examination of these lesions provided similar findings. Biopsy, which was performed in one patient, confirmed the diagnosis of CPH. Two dermoscopic elements of CPH are characteristic: (1) the sides of the lesion have a "stair step" or "geological strata" type of configuration, and the thickness of the different strata varies; (2) the centre of the lesion showed a homogeneous erythematous area with a vascular pattern composed of dotted vessels of the superficial dermis and sometime vascular loops. These dermoscopic aspects are characteristic and enable CPH to be differentiated from Bowen's disease or porokeratosis of Mibelli. In Bowen's disease, there is no stair step like aspect to the sides of lesions; further, the centre of the lesion shows glomerular vessels (coiled vessels) and/or globular vessels (small red clods). In porokeratosis, peripheral keratotic "white track" structures comprise a single pigmented channel or a double white line. There is no "stair step" or central vascular pattern. The dermoscopic semiology of CPH is highly characteristic and enables differentiation from Bowen's disease and porokeratosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mechanical gating of a mechanochemical reaction cascade

NASA Astrophysics Data System (ADS)

Wang, Junpeng; Kouznetsova, Tatiana B.; Boulatov, Roman; Craig, Stephen L.

2016-11-01

Covalent polymer mechanochemistry offers promising opportunities for the control and engineering of reactivity. To date, covalent mechanochemistry has largely been limited to individual reactions, but it also presents potential for intricate reaction systems and feedback loops. Here we report a molecular architecture, in which a cyclobutane mechanophore functions as a gate to regulate the activation of a second mechanophore, dichlorocyclopropane, resulting in a mechanochemical cascade reaction. Single-molecule force spectroscopy, pulsed ultrasonication experiments and DFT-level calculations support gating and indicate that extra force of >0.5 nN needs to be applied to a polymer of gated gDCC than of free gDCC for the mechanochemical isomerization gDCC to proceed at equal rate. The gating concept provides a mechanism by which to regulate stress-responsive behaviours, such as load-strengthening and mechanochromism, in future materials designs.

Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallace, Bret D.; Wang, Hongwei; Lane, Kimberly T.

2011-08-12

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial {beta}-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial {beta}-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial {beta}-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally,more » oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.« less

Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme

PubMed Central

Wallace, Bret D.; Wang, Hongwei; Lane, Kimberly T.; Scott, John E.; Orans, Jillian; Koo, Ja Seol; Venkatesh, Madhukumar; Jobin, Christian; Yeh, Li-An; Mani, Sridhar; Redinbo, Matthew R.

2011-01-01

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11–induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy. PMID:21051639

Alleviating cancer drug toxicity by inhibiting a bacterial enzyme.

PubMed

Wallace, Bret D; Wang, Hongwei; Lane, Kimberly T; Scott, John E; Orans, Jillian; Koo, Ja Seol; Venkatesh, Madhukumar; Jobin, Christian; Yeh, Li-An; Mani, Sridhar; Redinbo, Matthew R

2010-11-05

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.

The real-world navigator

NASA Technical Reports Server (NTRS)

Balabanovic, Marko; Becker, Craig; Morse, Sarah K.; Nourbakhsh, Illah R.

1994-01-01

The success of every mobile robot application hinges on the ability to navigate robustly in the real world. The problem of robust navigation is separable from the challenges faced by any particular robot application. We offer the Real-World Navigator as a solution architecture that includes a path planner, a map-based localizer, and a motion control loop that combines reactive avoidance modules with deliberate goal-based motion. Our architecture achieves a high degree of reliability by maintaining and reasoning about an explicit description of positional uncertainty. We provide two implementations of real-world robot systems that incorporate the Real-World Navigator. The Vagabond Project culminated in a robot that successfully navigated a portion of the Stanford University campus. The Scimmer project developed successful entries for the AIAA 1993 Robotics Competition, placing first in one of the two contests entered.

Research on Experiment of Islanding Protection Device of Grid-connected Photovoltaic System Based on RTDS

NASA Astrophysics Data System (ADS)

Zhou, Ning; Yang, Jia; Cheng, Zheng; Chen, Bo; Su, Yong Chun; Shu, Zhan; Zou, Jin

2017-06-01

Solar photovoltaic power generation is the power generation using solar cell module converting sunlight into DC electric energy. In the paper an equivalent model of solar photovoltaic power generation system is built in RTDS. The main circuit structure of the two-stage PV grid-connected system consists of the DC-DC, DC-AC circuit. The MPPT (Maximum Power Point Tracking) control of the PV array is controlled by adjusting the duty ratio of the DC-DC circuit. The proposed control strategy of constant voltage/constant reactive power (V/Q) control is successfully implemented grid-connected control of the inverter when grid-connected operation. The closed-loop experiment of islanding protection device of photovoltaic power plant on RTDS, verifies the correctness of the simulation model, and the experimental verification can be applied to this type of device.

Adaptive super-twisting sliding mode control for a three-phase single-stage grid-connected differential boost inverter based photovoltaic system.

PubMed

Pati, Akshaya K; Sahoo, N C

2017-07-01

This paper presents an adaptive super-twisting sliding mode control (STC) along with double-loop control for voltage tracking performance of three-phase differential boost inverter and DC-link capacitor voltage regulation in grid-connected PV system. The effectiveness of the proposed control strategies are demonstrated under realistic scenarios such as variations in solar insolation, load power demand, grid voltage, and transition from grid-connected to standalone mode etc. Additional supplementary power quality control functions such as harmonic compensation, and reactive power management are also investigated with the proposed control strategy. The results are compared with conventional proportional-integral controller, and PWM sliding mode controller. The system performance is evaluated in simulation and in real-time. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel.

PubMed

Yamada, Toshiki; Krzeminski, Mickael; Bozoky, Zoltan; Forman-Kay, Julie D; Strange, Kevin

2016-11-01

Eukaryotic CLC anion channels and transporters are homodimeric proteins composed of multiple α-helical membrane domains and large cytoplasmic C-termini containing two cystathionine-β-synthase domains (CBS1 and CBS2) that dimerize to form a Bateman domain. The Bateman domains of adjacent CLC subunits interact to form a Bateman domain dimer. The functions of CLC CBS and Bateman domains are poorly understood. We utilized the Caenorhabditis elegans CLC-1/2/Ka/Kb anion channel homolog CLH-3b to characterize the regulatory roles of CLC cytoplasmic domains. CLH-3b activity is reduced by phosphorylation or deletion of a 14-amino-acid activation domain (AD) located on the linker connecting CBS1 and CBS2. We demonstrate here that phosphorylation-dependent reductions in channel activity require an intact Bateman domain dimer and concomitant phosphorylation or deletion of both ADs. Regulation of a CLH-3b AD deletion mutant is reconstituted by intracellular perfusion with recombinant 14-amino-acid AD peptides. The sulfhydryl reactive reagent 2-(trimethylammonium)ethyl methanethiosulfonate bromide (MTSET) alters in a phosphorylation-dependent manner the activity of channels containing single cysteine residues that are engineered into the short intracellular loop connecting membrane α-helices H and I (H-I loop), the AD, CBS1, and CBS2. In contrast, MTSET has no effect on channels in which cysteine residues are engineered into intracellular regions that are dispensable for regulation. These studies together with our previous work suggest that binding and unbinding of the AD to the Bateman domain dimer induces conformational changes that are transduced to channel membrane domains via the H-I loop. Our findings provide new, to our knowledge, insights into the roles of CLC Bateman domains and the structure-function relationships that govern the regulation of CLC protein activity by diverse ligands and signaling pathways. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Transposon Mutagenesis of the Zika Virus Genome Highlights Regions Essential for RNA Replication and Restricted for Immune Evasion.

PubMed

Fulton, Benjamin O; Sachs, David; Schwarz, Megan C; Palese, Peter; Evans, Matthew J

2017-08-01

The molecular constraints affecting Zika virus (ZIKV) evolution are not well understood. To investigate ZIKV genetic flexibility, we used transposon mutagenesis to add 15-nucleotide insertions throughout the ZIKV MR766 genome and subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants replicated, which likely reflects a high degree of functional constraints on the genome. The NS1 gene exhibited distinct mutational tolerances at different stages of the screen. This result may define regions of the NS1 protein that are required for the different stages of the viral life cycle. The ZIKV structural genes showed the highest degree of insertional tolerance. Although the envelope (E) protein exhibited particular flexibility, the highly conserved envelope domain II (EDII) fusion loop of the E protein was intolerant of transposon insertions. The fusion loop is also a target of pan-flavivirus antibodies that are generated against other flaviviruses and neutralize a broad range of dengue virus and ZIKV isolates. The genetic restrictions identified within the epitopes in the EDII fusion loop likely explain the sequence and antigenic conservation of these regions in ZIKV and among multiple flaviviruses. Thus, our results provide insights into the genetic restrictions on ZIKV that may affect the evolution of this virus. IMPORTANCE Zika virus recently emerged as a significant human pathogen. Determining the genetic constraints on Zika virus is important for understanding the factors affecting viral evolution. We used a genome-wide transposon mutagenesis screen to identify where mutations were tolerated in replicating viruses. We found that the genetic regions involved in RNA replication were mostly intolerant of mutations. The genes coding for structural proteins were more permissive to mutations. Despite the flexibility observed in these regions, we found that epitopes bound by broadly reactive antibodies were genetically constrained. This finding may explain the genetic conservation of these epitopes among flaviviruses. Copyright © 2017 American Society for Microbiology.

A mutation within the extended X loop abolished substrate-induced ATPase activity of the human liver ATP-binding cassette (ABC) transporter MDR3.

PubMed

Kluth, Marianne; Stindt, Jan; Dröge, Carola; Linnemann, Doris; Kubitz, Ralf; Schmitt, Lutz

2015-02-20

The human multidrug resistance protein 3 (MDR3/ABCB4) belongs to the ubiquitous family of ATP-binding cassette (ABC) transporters and is located in the canalicular membrane of hepatocytes. There it flops the phospholipids of the phosphatidylcholine (PC) family from the inner to the outer leaflet. Here, we report the characterization of wild type MDR3 and the Q1174E mutant, which was identified previously in a patient with progressive familial intrahepatic cholestasis type 3 (PFIC-3). We expressed different variants of MDR3 in the yeast Pichia pastoris, purified the proteins via tandem affinity chromatography, and determined MDR3-specific ATPase activity in the presence or absence of phospholipids. The ATPase activity of wild type MDR3 was stimulated 2-fold by liver PC or 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine lipids. Furthermore, the cross-linking of MDR3 with a thiol-reactive fluorophore blocked ATP hydrolysis and exhibited no PC stimulation. Similarly, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin lipids did not induce an increase of wild type MDR3 ATPase activity. The phosphate analogues beryllium fluoride and aluminum fluoride led to complete inhibition of ATPase activity, whereas orthovanadate inhibited exclusively the PC-stimulated ATPase activity of MDR3. The Q1174E mutation is located in the nucleotide-binding domain in direct proximity of the leucine of the ABC signature motif and extended the X loop, which is found in ABC exporters. Our data on the Q1174E mutant demonstrated basal ATPase activity, but PC lipids were incapable of stimulating ATPase activity highlighting the role of the extended X loop in the cross-talk of the nucleotide-binding domain and the transmembrane domain. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Role of Loop-Clamping Side Chains in Catalysis by Triosephosphate Isomerase.

PubMed

Zhai, Xiang; Amyes, Tina L; Richard, John P

2015-12-09

The side chains of Y208 and S211 from loop 7 of triosephosphate isomerase (TIM) form hydrogen bonds to backbone amides and carbonyls from loop 6 to stabilize the caged enzyme-substrate complex. The effect of seven mutations [Y208T, Y208S, Y208A, Y208F, S211G, S211A, Y208T/S211G] on the kinetic parameters for TIM catalyzed reactions of the whole substrates dihydroxyacetone phosphate and d-glyceraldehyde 3-phosphate [(k(cat)/K(m))(GAP) and (k(cat)/K(m))DHAP] and of the substrate pieces glycolaldehyde and phosphite dianion (k(cat)/K(HPi)K(GA)) are reported. The linear logarithmic correlation between these kinetic parameters, with slope of 1.04 ± 0.03, shows that most mutations of TIM result in an identical change in the activation barriers for the catalyzed reactions of whole substrate and substrate pieces, so that the transition states for these reactions are stabilized by similar interactions with the protein catalyst. The second linear logarithmic correlation [slope = 0.53 ± 0.16] between k(cat) for isomerization of GAP and K(d)(⧧) for phosphite dianion binding to the transition state for wildtype and many mutant TIM-catalyzed reactions of substrate pieces shows that ca. 50% of the wildtype TIM dianion binding energy, eliminated by these mutations, is expressed at the wildtype Michaelis complex, and ca. 50% is only expressed at the wildtype transition state. Negative deviations from this correlation are observed when the mutation results in a decrease in enzyme reactivity at the catalytic site. The main effect of Y208T, Y208S, and Y208A mutations is to cause a reduction in the total intrinsic dianion binding energy, but the effect of Y208F extends to the catalytic site.

Overcoming Antigenic Diversity by Enhancing the Immunogenicity of Conserved Epitopes on the Malaria Vaccine Candidate Apical Membrane Antigen-1

PubMed Central

Dutta, Sheetij; Dlugosz, Lisa S.; Drew, Damien R.; Ge, Xiopeng; Ababacar, Diouf; Rovira, Yazmin I.; Moch, J. Kathleen; Shi, Meng; Long, Carole A.; Foley, Michael; Beeson, James G.; Anders, Robin F.; Miura, Kazutoyo; Haynes, J. David; Batchelor, Adrian H.

2013-01-01

Malaria vaccine candidate Apical Membrane Antigen-1 (AMA1) induces protection, but only against parasite strains that are closely related to the vaccine. Overcoming the AMA1 diversity problem will require an understanding of the structural basis of cross-strain invasion inhibition. A vaccine containing four diverse allelic proteins 3D7, FVO, HB3 and W2mef (AMA1 Quadvax or QV) elicited polyclonal rabbit antibodies that similarly inhibited the invasion of four vaccine and 22 non-vaccine strains of P. falciparum. Comparing polyclonal anti-QV with antibodies against a strain-specific, monovalent, 3D7 AMA1 vaccine revealed that QV induced higher levels of broadly inhibitory antibodies which were associated with increased conserved face and domain-3 responses and reduced domain-2 response. Inhibitory monoclonal antibodies (mAb) raised against the QV reacted with a novel cross-reactive epitope at the rim of the hydrophobic trough on domain-1; this epitope mapped to the conserved face of AMA1 and it encompassed the 1e-loop. MAbs binding to the 1e-loop region (1B10, 4E8 and 4E11) were ∼10-fold more potent than previously characterized AMA1-inhibitory mAbs and a mode of action of these 1e-loop mAbs was the inhibition of AMA1 binding to its ligand RON2. Unlike the epitope of a previously characterized 3D7-specific mAb, 1F9, the 1e-loop inhibitory epitope was partially conserved across strains. Another novel mAb, 1E10, which bound to domain-3, was broadly inhibitory and it blocked the proteolytic processing of AMA1. By itself mAb 1E10 was weakly inhibitory but it synergized with a previously characterized, strain-transcending mAb, 4G2, which binds close to the hydrophobic trough on the conserved face and inhibits RON2 binding to AMA1. Novel inhibition susceptible regions and epitopes, identified here, can form the basis for improving the antigenic breadth and inhibitory response of AMA1 vaccines. Vaccination with a few diverse antigenic proteins could provide universal coverage by redirecting the immune response towards conserved epitopes. PMID:24385910

Cognitive reactivity to sad mood provocation and the prediction of depressive relapse.

PubMed

Segal, Zindel V; Kennedy, Sidney; Gemar, Michael; Hood, Karyn; Pedersen, Rebecca; Buis, Tom

2006-07-01

Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further understanding of factors predisposing to relapse/recurrence in recovered patients may help to shorten the potentially lifelong course of depression.

ESEEM of industrial silica-bearing powders: reactivity of defects during wet processing in the ceramics production

NASA Astrophysics Data System (ADS)

Romanelli, Maurizio; Di Benedetto, Francesco; Fornaciai, Gabriele; Innocenti, Massimo; Montegrossi, Giordano; Pardi, Luca A.; Zoleo, Alfonso; Capacci, Fabio

2015-05-01

A study is undertaken to ascertain whether changes in the speciation of inorganic radicals are occurring during the ceramic industrial production that involves abundant silica powders as raw material. Industrial dusts were sampled in two ceramic firms, immediately after the wet mixing stage, performed with the aid of a relevant pressure. The dusts were then characterised by means of X-ray diffraction, analysis of the trace elements through chemical methods, granulometry, continuous-wave electron paramagnetic resonance (EPR) and pulsed electron spin echo envelope modulation (ESEEM) spectroscopies. The results of the characterisation point to a relevant change in the speciation of the two samples; namely, a prevailing contribution due to an inorganic radical different from that pertaining to pure quartz is pointed out. The combined interpretation of EPR and ESEEM data suggests the attribution of the main paramagnetic contribution to the A-centre in kaolinite, a constituent that is added to pure quartz at the initial stage of the ceramic production. In one of the two samples, a second weak EPR signal is attributed to the quartz's hAl species. By taking into account the relative quantities of quartz and kaolinite mixed in the two samples, and the relative abundances of the two radical species, we propose that the partial or complete suppression of the hAl species in favour of the A-centre of kaolinite has occurred. Although this change is apparently fostered by the mixture between quartz and another radical-bearing raw material, kaolinite, the suppression of the hAl centre of quartz is ascribed to the role played by the pressure and the wet environment during the industrial mixing procedure. This suppression provides a net change of radical speciation associated with quartz, when this phase is in contact with workers' respiratory system.

Ultraviolet-B radiation applied to detached peach fruit: A study of free radical generation by EPR spin trapping.

PubMed

Sgherri, C; Scattino, C; Pinzino, C; Tonutti, P; Ranieri, A M

2015-11-01

In peaches, phenolic compounds are the major sources of antioxidants, and cyanidin-3-O-glucoside is the main anthocyanin present, above all in the skin. Anthocyanin content has been shown to increase after UV-B irradiation, which may be very harmful for all biological organisms due to the induction of the generation of reactive oxygen species (ROS). Peach fruits (cv. 'Suncrest') were exposed during post-harvest to supplemental ultraviolet-B radiation. A spin-trapping technique was used to monitor the generation of free radicals under UV-B, and 5-(diethoxy-phosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO) was used as the spin trap. The flesh of peaches was essentially unaffected by the treatment, whereas the skin was responsive at the end of the treatment, accumulating ascorbate, flavonoids, cyanidin-3-O-glucoside, and showing a higher antioxidant activity. The levels of stable free radicals were also lower at the end of treatment. Carbon-centred radicals contributed the most to the total amounts of free radicals, whereas hydroxyl radicals and oxygen-centred free radicals contributed minimally. The carbon-centred free radical identified was the same as the one obtained after irradiation of authentic cyanidin-3-O-glucoside. During UV-B treatment cyanidin-3-O-glucoside increased and was capable of radicalization protecting the other organic molecules of the cell from oxidation. ROS, among which hydroxyl radicals, were thus maintained to minimal levels. This ability of cyanidin-3-O-glucoside displayed the mechanism underlined the tolerance to UV-B irradiation indicating that shelf life can be prolonged by the presence of anthocyanins. Thus, UV-B technique results a good approach to induce antioxidant production in peach fruits increasing their nutraceutical properties. Copyright © 2015. Published by Elsevier Masson SAS.

Obesity and addiction: neurobiological overlaps.

PubMed

Volkow, N D; Wang, G-J; Tomasi, D; Baler, R D

2013-01-01

Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

Spatial Dependence of DNA Damage in Bacteria due to Low-Temperature Plasma Application as Assessed at the Single Cell Level

NASA Astrophysics Data System (ADS)

Privat-Maldonado, Angela; O'Connell, Deborah; Welch, Emma; Vann, Roddy; van der Woude, Marjan W.

2016-10-01

Low temperature plasmas (LTPs) generate a cocktail of reactive nitrogen and oxygen species (RNOS) with bactericidal activity. The RNOS however are spatially unevenly distributed in the plasma. Here we test the hypothesis that this distribution will affect the mechanisms underpinning plasma bactericidal activity focussing on the level of DNA damage in situ. For the first time, a quantitative, single cell approach was applied to assess the level of DNA damage in bacteria as a function of the radial distance from the centre of the plasma jet. Salmonella enterica on a solid, dry surface was treated with two types of LTP: an atmospheric-pressure dielectric barrier discharge plasma jet (charged and neutral species) and a radio-frequency atmospheric-pressure plasma jet (neutral species). In both cases, there was an inverse correlation between the degree of DNA damage and the radial distance from the centre of the plasma, with the highest DNA damage occurring directly under the plasma. This trend was also observed with Staphylococcus aureus. LTP-generated UV radiation was eliminated as a contributing factor. Thus valuable mechanistic information can be obtained from assays on biological material, which can inform the development of LTP as a complementary or alternative therapy for (topical) bacterial infections.

Spatial Dependence of DNA Damage in Bacteria due to Low-Temperature Plasma Application as Assessed at the Single Cell Level

PubMed Central

Privat-Maldonado, Angela; O’Connell, Deborah; Welch, Emma; Vann, Roddy; van der Woude, Marjan W.

2016-01-01

Low temperature plasmas (LTPs) generate a cocktail of reactive nitrogen and oxygen species (RNOS) with bactericidal activity. The RNOS however are spatially unevenly distributed in the plasma. Here we test the hypothesis that this distribution will affect the mechanisms underpinning plasma bactericidal activity focussing on the level of DNA damage in situ. For the first time, a quantitative, single cell approach was applied to assess the level of DNA damage in bacteria as a function of the radial distance from the centre of the plasma jet. Salmonella enterica on a solid, dry surface was treated with two types of LTP: an atmospheric-pressure dielectric barrier discharge plasma jet (charged and neutral species) and a radio-frequency atmospheric-pressure plasma jet (neutral species). In both cases, there was an inverse correlation between the degree of DNA damage and the radial distance from the centre of the plasma, with the highest DNA damage occurring directly under the plasma. This trend was also observed with Staphylococcus aureus. LTP-generated UV radiation was eliminated as a contributing factor. Thus valuable mechanistic information can be obtained from assays on biological material, which can inform the development of LTP as a complementary or alternative therapy for (topical) bacterial infections. PMID:27759098

Seismic &Infrasound Integrated Array "Apatity". Techniques, data processing, first results of observations.

NASA Astrophysics Data System (ADS)

Vinogradov, Y.; Baryshnikov, A.

2003-04-01

Since September 2001 3 infrasound membrane type sensors "K-304 AM" have been installed on the territory seismic array "Apatity" near the lake Imandra. A seismic array comprising 11 short-period sensors (type "Geotech S-500"), disposed on small and large circle (0.4 and 1 km diameter). Infrasound sensors located on small circle near the seismograths. All data are digitized at the array site and transmitted in real time to a processing center in Apatity to the Kola Regional Seismological Centre (KRSC). Common complex we are called - Seismic &Infrasound Integrated Array (SISIA) "Apatity". To support temporary storage the transmitting data in a disk loop and access to the data "NEWNORAC" program was created. This program replaced "NORAC" system developed by Norwegian Institute NORSAR, which was in use in KRSC before. A program package EL (event locator) for display and processing of the data has been modified. Now it includes the following : - quick access to the data stored in the disk loop (last two weeks); - data convertation from disk loop format to CSS 3.0 format; - data filtering using bandpass, highpass, lowpass, adaptive or rejector filters; - calculation of spectra and sonograms (spectral diagrams); - seismic events location with plotting on a map; - calculation of backazimuth and apparent velocity of acoustic wave by similar parts of wave recordings; - loading and processing CSS 3.0 seismic and acoustic data from KRSC archive. To store the acoustic data permanently the program BARCSS was made. It rewrites the data from the disk loop to KRSC archive in CSS 3.0 format. For comparison of acoustic noise level with wind we use data from meteorological station in Kandalaksha city, sampling rate is 3 hours. During the period from October 2001 to October 2002 more than 745 seismic events, which basically connected with mine technical activity of the large mining enterprises at the Kola Peninsula, were registered. The most part of events, caused by ground explosions, was registered by infrasound part of SISIA "Apatity". Their sources were at distances from 38 to 220 km. The result of observations during the first 1 year enabled us to estimate frequency range and main directions of arrivals of acoustic waves and noise level in the place of observations. In accordance with the results and relief a 4-rays wind-noise-reducing pipe array would be install at all 3 sensors at May 2003, for improvement the delectability during windy conditions. A schemes of the SISIA "Apatity", data transmitting and processing and samples of detected signals are shown in the presentation.

CAX1 suppresses Cd-induced generation of reactive oxygen species in Arabidopsis halleri.

PubMed

Ahmadi, Hassan; Corso, Massimiliano; Weber, Michael; Verbruggen, Nathalie; Clemens, Stephan

2018-06-07

The molecular analysis of metal hyperaccumulation in species such as Arabidopsis halleri offers the chance to gain insights into metal homeostasis and into the evolution of adaptation to extreme habitats. A prerequisite of metal hyperaccumulation is metal hypertolerance. Genetic analysis of a backcross population derived from A. lyrata x A. halleri crosses revealed three quantitative trait loci (QTLs) for Cd hypertolerance. A candidate gene for Cdtol2 is AhCAX1, encoding a vacuolar Ca 2+ /H + antiporter. We developed a method for the transformation of vegetatively propagated A. halleri plants and generated AhCAX1-silenced lines. Upon Cd 2+ exposure several-fold higher accumulation of reactive oxygen species (ROS) was detectable in roots of AhCAX1-silenced plants. In accordance with the dependence of Cdtol2 on external Ca 2+ concentration, this phenotype was exclusively observed in low Ca 2+ conditions. The effects of external Ca 2+ on Cd accumulation cannot explain the phenotype as they were not influenced by the genotype. Our data strongly support the hypothesis that higher expression of CAX1 in A. halleri relative to other Arabidopsis species represents a Cd hypertolerance factor. We propose a function of AhCAX1 in preventing a positive feedback loop of Cd-elicited ROS production triggering further Ca 2+ -dependent ROS accumulation. This article is protected by copyright. All rights reserved.

Publisher Correction: Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons.

PubMed

Hervera, Arnau; De Virgiliis, Francesco; Palmisano, Ilaria; Zhou, Luming; Tantardini, Elena; Kong, Guiping; Hutson, Thomas; Danzi, Matt C; Perry, Rotem Ben-Tov; Santos, Celio X C; Kapustin, Alexander N; Fleck, Roland A; Del Río, José Antonio; Carroll, Thomas; Lemmon, Vance; Bixby, John L; Shah, Ajay M; Fainzilber, Mike; Di Giovanni, Simone

2018-03-08

In the version of this Article originally published, the affiliations for Roland A. Fleck and José Antonio Del Río were incorrect due to a technical error that resulted in affiliations 8 and 9 being switched. The correct affiliations are: Roland A. Fleck: 8 Centre for Ultrastructural Imaging, Kings College London, London, UK. José Antonio Del Río: 2 Cellular and Molecular Neurobiotechnology, Institute for Bioengineering of Catalonia, Barcelona, Spain; 9 Department of Cell Biology, Physiology and Immunology, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; 10 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. This has now been amended in all online versions of the Article.

Geodynamic model for the development of the Cameroon Hot Line (Equatorial Africa)

NASA Astrophysics Data System (ADS)

Nkono, Collin; Féménias, Olivier; Demaiffe, Daniel

2014-12-01

This work proposes a new geodynamic model for the development of the Cameroon Hot Line (CHL) in Equatorial Africa. It is based on the analysis of the distribution of lineaments and of magmatic bodies (Paleogene anorogenic ring-complexes and Neogene volcanic centres). Two successive geodynamic models are proposed to explain the distribution of the Cainozoic to recent magmatic activity. They are both sinistral. The first one, during the Paleogene, developed around the N ∼ 70°E direction while the second one (Neogene) is oriented around the N ∼ 130°E direction. The two periods are separated by a short transition. The emplacement follows the local reactivation of pre-existing (Pan-African) faults in relation to the collision between the Afro-Arabian and Eurasian plates, during the Alpine history.

AI based HealthCare Platform for Real Time, Predictive and Prescriptive Analytics using Reactive Programming

NASA Astrophysics Data System (ADS)

Kaur, Jagreet; Singh Mann, Kulwinder, Dr.

2018-01-01

AI in Healthcare needed to bring real, actionable insights and Individualized insights in real time for patients and Doctors to support treatment decisions., We need a Patient Centred Platform for integrating EHR Data, Patient Data, Prescriptions, Monitoring, Clinical research and Data. This paper proposes a generic architecture for enabling AI based healthcare analytics Platform by using open sources Technologies Apache beam, Apache Flink Apache Spark, Apache NiFi, Kafka, Tachyon, Gluster FS, NoSQL- Elasticsearch, Cassandra. This paper will show the importance of applying AI based predictive and prescriptive analytics techniques in Health sector. The system will be able to extract useful knowledge that helps in decision making and medical monitoring in real-time through an intelligent process analysis and big data processing.

A review on chitosan centred scaffolds and their applications in tissue engineering.

PubMed

Ahmed, Shakeel; Annu; Sheikh, Javed; Ali, Akbar

2018-05-03

The diversity and availability of biopolymer and increased clinical demand for safe scaffolds lead to an increased interest in fabricating scaffolds in order to achieve fruitful progress in tissue engineering. Due to biocompatibility, biodegradability, inherent antimicrobial character, chitosan has drawn ample consideration in recent years. Chitosan is a biopolymer obtained by de-acetylation of chitin extracted from shells of crustaceans and fungi. Due to the presence of reactive functionality in the molecular chain chitosan can be modified either chemically or physically to fabricate the tailor-made scaffolds having desired properties for tissue engineering centered applications. In this review chitosan, its properties and role either virgin, chemically or physically modified, 2D or 3D scaffolds for tissue engineering application have been highlighted. Copyright © 2017. Published by Elsevier B.V.

Behaviour of fractional loop delay zero crossing digital phase locked loop (FR-ZCDPLL)

NASA Astrophysics Data System (ADS)

Nasir, Qassim

2018-01-01

This article analyses the performance of the first-order zero crossing digital phase locked loops (FR-ZCDPLL) when fractional loop delay is added to loop. The non-linear dynamics of the loop is presented, analysed and examined through bifurcation behaviour. Numerical simulation of the loop is conducted to proof the mathematical analysis of the loop operation. The results of the loop simulation show that the proposed FR-ZCDPLL has enhanced the performance compared to the conventional zero crossing DPLL in terms of wider lock range, captured range and stable operation region. In addition, extensive experimental simulation was conducted to find the optimum loop parameters for different loop environmental conditions. The addition of the fractional loop delay network in the conventional loop also reduces the phase jitter and its variance especially when the signal-to-noise ratio is low.

Hyporheic less-mobile porosity and solute transport in porous media

NASA Astrophysics Data System (ADS)

MahmoodPoorDehkordy, F.; Briggs, M. A.; Day-Lewis, F. D.; Scruggs, C.; Singha, K.; Zarnetske, J. P.; Lane, J. W., Jr.; Bagtzoglou, A. C.

2017-12-01

Solute transport and reactive processes are strongly influenced by hydrodynamic exchange with the hyporheic zone. Contaminant transport and redox zonation in the hyporheic zone and near-stream aquifer can be impacted by the exchange between mobile and less-mobile porosity zones in heterogeneous porous media. Less-mobile porosity zones can be created by fine materials with tight pore throats (e.g. clay, organics) and in larger, well-connected pores down gradient of flow obstructions (e.g. sand behind cobbles). Whereas fluid sampling is primarily responsive to the more-mobile domain, tracking solute tracer dynamics by geoelectrical methods provides direct information about both more- and less-mobile zones. During tracer injection through porous media of varied pore connectivity, a lag between fluid and bulk electrical conductivity is observed, creating a hysteresis loop when plotted in conductivity space. Thus, the combination of simultaneous fluid and bulk electrical conductivity measurements enables a much improved quantification of less-mobile solute dynamics compared to traditional fluid-only sampling approaches. We have demonstrated the less-mobile porosity exchange in laboratory-scale column experiments verified by simulation models. The experimental approach has also been applied to streambed sediments in column and reach-scale field experiments and verified using numerical simulation. Properties of the resultant hysteresis loops can be used to estimate exchange parameters of less-mobile porosity. Our integrated approach combining field experiments, laboratory experiments, and numerical modeling provides new insights into the effect of less-mobile porosity on solute transport in the hyporheic zone.

The development of loop-mediated isothermal amplification (LAMP) assays for the rapid authentication of five forbidden vegetables in strict vegetarian diets

PubMed Central

Lee, Meng-Shiou; Su, Ting-Ying; Lien, Yi-Yang; Sheu, Shyang-Chwen

2017-01-01

Plant-based food ingredients such as garlic, Chinese leek, Chinese onion, green onion and onion are widely used in many cuisines around the world. However, these ingredients known as the “five forbidden vegetables” (FFVs) are not allowed in some vegetarian diets. In this study, a loop-mediated isothermal amplification (LAMP) assay was developed for the detection of FFVs using five respective LAMP primer sets. The specific primers targeted the ITS1-5.8S-ITS2 nuclear ribosomal DNA sequence regions among the five vegetables. The results demonstrated that the identification of FFVs using the newly developed LAMP assay is more sensitive than the traditional PCR method. Using pepper, basil, parsley, chili and ginger as references, established LAMP primer sets showed high specificity for the identification of the FFV species. Moreover, when FFVs were mixed with other plant ingredients at different ratios (100:0, 50:50, 20:80, 10:90, 5:95, 2:98, and 1:99), no cross-reactivity was evident using LAMP. Finally, genomic DNAs extracted from boiled and steamed FFVs in processed foods were used as templates; the performance of the LAMP reaction was not influenced using validated LAMP primers. Not only can FFV ingredients be identified but commercial foods containing FFVs can also be authenticated. This LAMP method will be useful for the authentication of FFVs in practical food markets in the future. PMID:28290475

Crystal structure of NTPDase2 in complex with the sulfoanthraquinone inhibitor PSB-071.

PubMed

Zebisch, Matthias; Baqi, Younis; Schäfer, Petra; Müller, Christa E; Sträter, Norbert

2014-03-01

In many vertebrate tissues CD39-like ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) act in concert with ecto-5'-nucleotidase (e5NT, CD73) to convert extracellular ATP to adenosine. Extracellular ATP is a cytotoxic, pro-inflammatory signalling molecule whereas its product adenosine constitutes a universal and potent immune suppressor. Interference with these ectonucleotidases by use of small molecule inhibitors or inhibitory antibodies appears to be an effective strategy to enhance anti-tumour immunity and suppress neoangiogenesis. Here we present the first crystal structures of an NTPDase catalytic ectodomain in complex with the Reactive Blue 2 (RB2)-derived inhibitor PSB-071. In both of the two crystal forms presented the inhibitor binds as a sandwich of two molecules at the nucleoside binding site. One of the molecules is well defined in its orientation. Specific hydrogen bonds are formed between the sulfonyl group and the nucleoside binding loop. The methylphenyl side chain functionality that improved NTPDase2-specificity is sandwiched between R245 and R394, the latter of which is exclusively found in NTPDase2. The second molecule exhibits great in-plane rotational freedom and could not be modelled in a specific orientation. In addition to this structural insight into NTPDase inhibition, the observation of the putative membrane interaction loop (MIL) in two different conformations related by a 10° rotation identifies the MIL as a dynamic section of NTPDases that is potentially involved in regulation of catalysis. Copyright © 2014 Elsevier Inc. All rights reserved.

Oral rice-based vaccine induces passive and active immunity against enterotoxigenic E. coli-mediated diarrhea in pigs.

PubMed

Takeyama, Natsumi; Yuki, Yoshikazu; Tokuhara, Daisuke; Oroku, Kazuki; Mejima, Mio; Kurokawa, Shiho; Kuroda, Masaharu; Kodama, Toshiaki; Nagai, Shinya; Ueda, Susumu; Kiyono, Hiroshi

2015-09-22

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in both neonatal and weaned pigs. Because the cholera toxin B subunit (CTB) has a high level of amino acid identity to the ETEC heat-labile toxin (LT) B-subunit (LTB), we selected MucoRice-CTB as a vaccine candidate against ETEC-induced pig diarrhea. When pregnant sows were orally immunized with MucoRice-CTB, increased amounts of antigen-specific IgG and IgA were produced in their sera. CTB-specific IgG was secreted in the colostrum and transferred passively to the sera of suckling piglets. IgA antibodies in the colostrum and milk remained high with a booster dose after farrowing. Additionally, when weaned minipigs were orally immunized with MucoRice-CTB, production of CTB-specific intestinal SIgA, as well as systemic IgG and IgA, was induced. To evaluate the cross-protective effect of MucoRice-CTB against ETEC diarrhea, intestinal loop assay with ETEC was conducted. The fluid volume accumulated in the loops of minipigs immunized with MucoRice-CTB was significantly lower than that in control minipigs, indicating that MucoRice-CTB-induced cross-reactive immunity could protect weaned pigs from diarrhea caused by ETEC. MucoRice-CTB could be a candidate oral vaccine for inducing both passive and active immunity to protect both suckling and weaned piglets from ETEC diarrhea. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functionally Similar WRKY Proteins Regulate Vacuolar Acidification in Petunia and Hair Development in Arabidopsis

PubMed Central

de Vries, Michel

2016-01-01

The WD40 proteins ANTHOCYANIN11 (AN11) from petunia (Petunia hybrida) and TRANSPARENT TESTA GLABRA1 (TTG1) from Arabidopsis thaliana and associated basic helix-loop-helix (bHLH) and MYB transcription factors activate a variety of differentiation processes. In petunia petals, AN11 and the bHLH protein AN1 activate, together with the MYB protein AN2, anthocyanin biosynthesis and, together with the MYB protein PH4, distinct genes, such as PH1 and PH5, that acidify the vacuole. To understand how AN1 and AN11 activate anthocyanin biosynthetic and PH genes independently, we isolated PH3. We found that PH3 is a target gene of the AN11-AN1-PH4 complex and encodes a WRKY protein that can bind to AN11 and is required, in a feed-forward loop, together with AN11-AN1-PH4 for transcription of PH5. PH3 is highly similar to TTG2, which regulates hair development, tannin accumulation, and mucilage production in Arabidopsis. Like PH3, TTG2 can bind to petunia AN11 and the Arabidopsis homolog TTG1, complement ph3 in petunia, and reactivate the PH3 target gene PH5. Our findings show that the specificity of WD40-bHLH-MYB complexes is in part determined by interacting proteins, such as PH3 and TTG2, and reveal an unanticipated similarity in the regulatory circuitry that controls petunia vacuolar acidification and Arabidopsis hair development. PMID:26977085

Limestone calcination under calcium-looping conditions for CO2 capture and thermochemical energy storage in the presence of H2O: an in situ XRD analysis.

PubMed

Valverde, Jose Manuel; Medina, Santiago

2017-03-15

This work reports an in situ XRD analysis of whether the calcination/carbonation behavior of natural limestone (CaCO 3 ) is affected by the addition of H 2 O to the calciner at a very low concentration under relevant Calcium-Looping (CaL) conditions for CO 2 capture in coal fired power plants (CFPP) and Thermochemical Energy Storage (TCES) in Concentrated Solar Power plants (CSP). Previous studies have demonstrated that the presence of steam in the calciner at a high concentration yields a significant increase in the reaction rate. However, a further undesired consequence is the serious deterioration of the CaO mechanical strength, which would lead to particle attrition and mass loss in any CaL process based on the use of circulating fluidized beds. The results presented in this manuscript on the time evolution of the wt% and crystallite size of the phases involved in the calcination/carbonation reactions indicate that the calcination rate is still notably increased by the presence of H 2 O at very low concentrations whereas the reactivity toward carbonation and crystal structure of the formed CaO are not essentially affected, which suggests that the CaO mechanical strength is not impaired. Thus, the benefit of using steam for calcination in the CaL process could be still retained while at the same time particle attrition would not be promoted.

The development of loop-mediated isothermal amplification (LAMP) assays for the rapid authentication of five forbidden vegetables in strict vegetarian diets.

PubMed

Lee, Meng-Shiou; Su, Ting-Ying; Lien, Yi-Yang; Sheu, Shyang-Chwen

2017-03-14

Plant-based food ingredients such as garlic, Chinese leek, Chinese onion, green onion and onion are widely used in many cuisines around the world. However, these ingredients known as the "five forbidden vegetables" (FFVs) are not allowed in some vegetarian diets. In this study, a loop-mediated isothermal amplification (LAMP) assay was developed for the detection of FFVs using five respective LAMP primer sets. The specific primers targeted the ITS1-5.8S-ITS2 nuclear ribosomal DNA sequence regions among the five vegetables. The results demonstrated that the identification of FFVs using the newly developed LAMP assay is more sensitive than the traditional PCR method. Using pepper, basil, parsley, chili and ginger as references, established LAMP primer sets showed high specificity for the identification of the FFV species. Moreover, when FFVs were mixed with other plant ingredients at different ratios (100:0, 50:50, 20:80, 10:90, 5:95, 2:98, and 1:99), no cross-reactivity was evident using LAMP. Finally, genomic DNAs extracted from boiled and steamed FFVs in processed foods were used as templates; the performance of the LAMP reaction was not influenced using validated LAMP primers. Not only can FFV ingredients be identified but commercial foods containing FFVs can also be authenticated. This LAMP method will be useful for the authentication of FFVs in practical food markets in the future.

Structural basis of trypsin inhibition and entomotoxicity of cospin, serine protease inhibitor involved in defense of Coprinopsis cinerea fruiting bodies.

PubMed

Sabotič, Jerica; Bleuler-Martinez, Silvia; Renko, Miha; Avanzo Caglič, Petra; Kallert, Sandra; Štrukelj, Borut; Turk, Dušan; Aebi, Markus; Kos, Janko; Künzler, Markus

2012-02-03

Cospin (PIC1) from Coprinopsis cinerea is a serine protease inhibitor with biochemical properties similar to those of the previously characterized fungal serine protease inhibitors, cnispin from Clitocybe nebularis and LeSPI from Lentinus edodes, classified in the family I66 of the MEROPS protease inhibitor classification. In particular, it exhibits a highly specific inhibitory profile as a very strong inhibitor of trypsin with K(i) in the picomolar range. Determination of the crystal structure revealed that the protein has a β-trefoil fold. Site-directed mutagenesis and mass spectrometry results have confirmed Arg-27 as the reactive binding site for trypsin inhibition. The loop containing Arg-27 is positioned between the β2 and β3 strands, distinguishing cospin from other β-trefoil-fold serine protease inhibitors in which β4-β5 or β5-β6 loops are involved in protease inhibition. Biotoxicity assays of cospin on various model organisms revealed a strong and specific entomotoxic activity against Drosophila melanogaster. The inhibitory inactive R27N mutant was not entomotoxic, associating toxicity with inhibitory activity. Along with the abundance of cospin in fruiting bodies of C. cinerea and the lack of trypsin-like proteases in the C. cinerea genome, these results suggest that cospin and its homologs are effectors of a fungal defense mechanism against fungivorous insects that function by specific inhibition of serine proteases in the insect gut.

Investigating the development of less-mobile porosity in realistic hyporheic zone sediments with COMSOL Multiphysics

NASA Astrophysics Data System (ADS)

MahmoodPoorDehkordy, F.; Briggs, M. A.; Day-Lewis, F. D.; Bagtzoglou, A. C.

2017-12-01

Although hyporheic zones are often modeled at the reach scale as homogeneous "boxes" of exchange, heterogeneity caused by variations of pore sizes and connectivity is not uncommon. This heterogeneity leads to the creation of more- and less-mobile zones of hydraulic exchange that influence reactive solute transport processes. Whereas fluid sampling is generally sensitive to more-mobile zones, geoelectrical measurement is sensitive to ionic tracer dynamics in both less- and more-mobile zones. Heterogeneity in pore connectivity leads to a lag between fluid and bulk electrical conductivity (EC) resulting in a hysteresis loop, observed during tracer breakthrough tests, that contains information about the less-mobile porosity attributes of the medium. Here, we present a macro-scale model of solute transport and electrical conduction developed using COMSOL Multiphysics. The model is used to simulate geoelectrical monitoring of ionic transport for bed sediments based on (1) a stochastic sand-and-cobble mixture and (2) a dune feature with strong permeability layering. In both of these disparate sediment types, hysteresis between fluid and bulk EC is observed, and depends in part on fluid flux rate through the model domain. Using the hysteresis loop, the ratio of less-mobile to mobile porosity and mass-transfer coefficient are estimated graphically. The results indicate the presence and significance of less-mobile porosity in the hyporheic zones and demonstrate the capability of the proposed model to detect heterogeneity in flow processes and estimate less-mobile zone parameters.

Development of Electrical Capacitance Sensors for Accident Tolerant Fuel (ATF) Testing at the Transient Reactor Test (TREAT) Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Maolong; Ryals, Matthew; Ali, Amir

2016-08-01

A variety of instruments are being developed and qualified to support the Accident Tolerant Fuels (ATF) program and future transient irradiations at the Transient Reactor Test (TREAT) facility at Idaho National Laboratory (INL). The University of New Mexico (UNM) is working with INL to develop capacitance-based void sensors for determining the timing of critical boiling phenomena in static capsule fuel testing and the volume-averaged void fraction in flow-boiling in-pile water loop fuel testing. The static capsule sensor developed at INL is a plate-type configuration, while UNM is utilizing a ring-type capacitance sensor. Each sensor design has been theoretically and experimentallymore » investigated at INL and UNM. Experiments are being performed at INL in an autoclave to investigate the performance of these sensors under representative Pressurized Water Reactor (PWR) conditions in a static capsule. Experiments have been performed at UNM using air-water two-phase flow to determine the sensitivity and time response of the capacitance sensor under a flow boiling configuration. Initial measurements from the capacitance sensor have demonstrated the validity of the concept to enable real-time measurement of void fraction. The next steps include designing the cabling interface with the flow loop at UNM for Reactivity Initiated Accident (RIA) ATF testing at TREAT and further characterization of the measurement response for each sensor under varying conditions by experiments and modeling.« less

Influence of smooth temperature variation on hotspot ignition

DOE PAGES

Reinbacher, Fynn; Regele, Jonathan David

2017-10-06

Autoignition in thermally stratified reactive mixtures originates in localised hotspots. The ignition behaviour is often characterised using linear temperature gradients and more recently constant temperature plateaus combined with temperature gradients. Acoustic timescale characterisation of plateau regions has been successfully used to characterise the type of mechanical disturbance that will be created from a plateau core ignition. This work combines linear temperature gradients with superelliptic cores in order to more accurately account for a local temperature maximum of finite size and the smooth temperature variation contained inside realistic hotspot centres. A one-step Arrhenius reaction is used to model a H 2–airmore » reactive mixture. Using the superelliptic approach a range of behaviours for temperature distributions are investigated by varying the temperature profile between the gradient only and plateau and gradient bounding cases. Each superelliptic case is compared to a respective plateau and gradient case where simple acoustic timescale characterisation may be performed. It is shown that hot spots equivalent with excitation-to-acoustic timescale ratios sufficiently greater than unity exhibit behaviour very similar to a simple plateau-gradient model. Furthermore, for larger hot spots with timescale ratios sufficiently less than unity the reaction behaviour is highly dependent on the smooth temperature profile contained within the core region.« less

A new reactive atom plasma technology (RAPT) for precision machining: the etching of ULE optical surfaces

NASA Astrophysics Data System (ADS)

Fanara, Carlo; Shore, Paul; Nicholls, John R.; Lyford, Nicholas; Sommer, Phil; Fiske, Peter

2006-06-01

The next generation of 30-100 metre diameter extremely large telescopes (ELTs) requires large numbers of hexagonal primary mirror segments. As part of the Basic Technology programme run jointly by UCL and Cranfield University, a reactive atomic plasma technology (RAP(tm)) emerged from the US Lawrence Livermore National Laboratory (LLNL), is employed for the finishing of these surfaces. Results are presented on this novel etching technology. The Inductively Coupled Plasma (ICP) operated at atmospheric pressure using argon, activates the chemical species injected through its centre and promotes the fluorine-based chemical reactions at the surface. Process assessment trials on Ultra Low Expansion (ULE(tm)) plates, previously ground at high material removal rates, have been conducted. The quality of the surfaces produced on these samples using the RAP process are discussed. Substantial volumetric material removal rates of up to 0.446(21) mm 3/s at the highest process speed (1,200 mm/min) were found to be possible without pre-heating the substrate. The influences of power transfer, process speed and gas concentration on the removal rates have been determined. The suitability of the RAP process for revealing and removing sub-surface damage induced by high removal rate grinding is discussed. The results on SiC samples are reported elsewhere in this conference.

Validation of reactive gases and aerosols in the MACC global analysis and forecast system

NASA Astrophysics Data System (ADS)

Eskes, H.; Huijnen, V.; Arola, A.; Benedictow, A.; Blechschmidt, A.-M.; Botek, E.; Boucher, O.; Bouarar, I.; Chabrillat, S.; Cuevas, E.; Engelen, R.; Flentje, H.; Gaudel, A.; Griesfeller, J.; Jones, L.; Kapsomenakis, J.; Katragkou, E.; Kinne, S.; Langerock, B.; Razinger, M.; Richter, A.; Schultz, M.; Schulz, M.; Sudarchikova, N.; Thouret, V.; Vrekoussis, M.; Wagner, A.; Zerefos, C.

2015-11-01

The European MACC (Monitoring Atmospheric Composition and Climate) project is preparing the operational Copernicus Atmosphere Monitoring Service (CAMS), one of the services of the European Copernicus Programme on Earth observation and environmental services. MACC uses data assimilation to combine in situ and remote sensing observations with global and regional models of atmospheric reactive gases, aerosols, and greenhouse gases, and is based on the Integrated Forecasting System of the European Centre for Medium-Range Weather Forecasts (ECMWF). The global component of the MACC service has a dedicated validation activity to document the quality of the atmospheric composition products. In this paper we discuss the approach to validation that has been developed over the past 3 years. Topics discussed are the validation requirements, the operational aspects, the measurement data sets used, the structure of the validation reports, the models and assimilation systems validated, the procedure to introduce new upgrades, and the scoring methods. One specific target of the MACC system concerns forecasting special events with high-pollution concentrations. Such events receive extra attention in the validation process. Finally, a summary is provided of the results from the validation of the latest set of daily global analysis and forecast products from the MACC system reported in November 2014.

Influence of smooth temperature variation on hotspot ignition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinbacher, Fynn; Regele, Jonathan David

Autoignition in thermally stratified reactive mixtures originates in localised hotspots. The ignition behaviour is often characterised using linear temperature gradients and more recently constant temperature plateaus combined with temperature gradients. Acoustic timescale characterisation of plateau regions has been successfully used to characterise the type of mechanical disturbance that will be created from a plateau core ignition. This work combines linear temperature gradients with superelliptic cores in order to more accurately account for a local temperature maximum of finite size and the smooth temperature variation contained inside realistic hotspot centres. A one-step Arrhenius reaction is used to model a H 2–airmore » reactive mixture. Using the superelliptic approach a range of behaviours for temperature distributions are investigated by varying the temperature profile between the gradient only and plateau and gradient bounding cases. Each superelliptic case is compared to a respective plateau and gradient case where simple acoustic timescale characterisation may be performed. It is shown that hot spots equivalent with excitation-to-acoustic timescale ratios sufficiently greater than unity exhibit behaviour very similar to a simple plateau-gradient model. Furthermore, for larger hot spots with timescale ratios sufficiently less than unity the reaction behaviour is highly dependent on the smooth temperature profile contained within the core region.« less

Livermore Compiler Analysis Loop Suite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hornung, R. D.

2013-03-01

LCALS is designed to evaluate compiler optimizations and performance of a variety of loop kernels and loop traversal software constructs. Some of the loop kernels are pulled directly from "Livermore Loops Coded in C", developed at LLNL (see item 11 below for details of earlier code versions). The older suites were used to evaluate floating-point performances of hardware platforms prior to porting larger application codes. The LCALS suite is geared toward assissing C++ compiler optimizations and platform performance related to SIMD vectorization, OpenMP threading, and advanced C++ language features. LCALS contains 20 of 24 loop kernels from the older Livermoremore » Loop suites, plus various others representative of loops found in current production appkication codes at LLNL. The latter loops emphasize more diverse loop constructs and data access patterns than the others, such as multi-dimensional difference stencils. The loops are included in a configurable framework, which allows control of compilation, loop sampling for execution timing, which loops are run and their lengths. It generates timing statistics for analysis and comparing variants of individual loops. Also, it is easy to add loops to the suite as desired.« less

Silk gland-specific proteinase inhibitor serpin16 from the Bombyx mori shows cysteine proteinase inhibitory activity.

PubMed

Guo, Peng-Chao; Dong, Zhaoming; Xiao, Li; Li, Tao; Zhang, Yan; He, Huawei; Xia, Qingyou; Zhao, Ping

2015-01-30

Serpins (serine proteinase inhibitors) are widely distributed in different species and are well known for their inhibitory activities towards serine proteinases. Here, we report the functional characterization of Bombyx mori serpin16. Expression analysis showed that serpin16 was specifically expressed at high levels in the silk gland at both the transcriptional and translational levels. Moreover, homology modeling and multi-sequence alignment suggested that serpin16 had a canonical serpin fold, but it contained a unique reactive center loop, which was obviously shorter than that of typical serpins. Inhibitory activity analyses revealed that the target proteinase of serpin18 is a cysteine proteinase, rather than a serine proteinase. Furthermore, a Michaelis complex model of serpin16 with its target proteinase was constructed to explain the structural basis of how serpin16 recognizes the cysteine proteinase and its target specificity. Copyright © 2014 Elsevier Inc. All rights reserved.

Responses of the rotifer Brachionus plicatilis to flame retardant (BDE-47) stress.

PubMed

Jian, Xiaoyang; Tang, Xuexi; Xu, Ningning; Sha, Jingjing; Wang, You

2017-03-15

A series of short-term toxicological tests were conducted on the rotifer Brachionus plicatilis to assess the toxicity of the flame retardant 2,2',4,4'-tetrabrominated biphenyl ether (BDE-47). BDE-47 increased mortality, morphological damage, and altered population dynamics and fecundity of rotifer. Antioxidant enzymes were differentially changed to maintain the balance between antioxidant and pro-oxidant activity. However, with increases in the concentration of BDE-47, the metabolic and antioxidant activity decreased. Moreover, the reactive oxygen species (ROS) and malondialdehyde contents increased and the ratio between glutathione and glutathione-SH decreased, indicating oxidative stress. The addition of the ROS-inhibitor N-acetylcysteine alleviated the degree of damage and stimulated the activity of xenobiotic-metabolizing and antioxidant system, which suggested that ROS were the most important loop in the stress response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural insights into the interaction of a monoclonal antibody and Nodal peptides by STD-NMR spectroscopy.

PubMed

Calvanese, Luisa; Focà, Annalia; Sandomenico, Annamaria; Focà, Giuseppina; Caporale, Andrea; Doti, Nunzianna; Iaccarino, Emanuela; Leonardi, Antonio; D'Auria, Gabriella; Ruvo, Menotti; Falcigno, Lucia

2017-12-15

Nodal is a growth factor expressed during early embryonic development, but reactivated in several advanced-stage cancers. Targeting of Nodal signaling, which occurs via the binding to Cripto-1 co-receptor, results in inhibition of cell aggressiveness and reduced tumor growth. The Nodal binding region to Cripto-1 was identified and targeted with a high affinity monoclonal antibody (3D1). By STD-NMR technique, we investigated the interaction of Nodal fragments with 3D1 with the aim to elucidate at atomic level the interaction surface. Data indicate with high accuracy the antibody-antigen contact atoms and confirm the information previously obtained by immune-enzymatic methods. Main residues contacted by 3D1 are P46, V47, E49 and E50, which belong to the Nodal loop involved in the interaction with the co-receptor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18

PubMed Central

Guo, Peng-Chao; Dong, Zhaoming; Zhao, Ping; Zhang, Yan; He, Huawei; Tan, Xiang; Zhang, Weiwei; Xia, Qingyou

2015-01-01

Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development. PMID:26148664

Multimodal Excitatory Interfaces with Automatic Content Classification

NASA Astrophysics Data System (ADS)

Williamson, John; Murray-Smith, Roderick

We describe a non-visual interface for displaying data on mobile devices, based around active exploration: devices are shaken, revealing the contents rattling around inside. This combines sample-based contact sonification with event playback vibrotactile feedback for a rich and compelling display which produces an illusion much like balls rattling inside a box. Motion is sensed from accelerometers, directly linking the motions of the user to the feedback they receive in a tightly closed loop. The resulting interface requires no visual attention and can be operated blindly with a single hand: it is reactive rather than disruptive. This interaction style is applied to the display of an SMS inbox. We use language models to extract salient features from text messages automatically. The output of this classification process controls the timbre and physical dynamics of the simulated objects. The interface gives a rapid semantic overview of the contents of an inbox, without compromising privacy or interrupting the user.

Attachment of reporter groups to specific, selected cytidine residues in RNA using a bisulfite-catalyzed transamination reaction.

PubMed Central

Draper, D E

1984-01-01

Bisulfite catalyzes transamination of cytidine at the N4 position; the suitability of this reaction for attaching reporter groups to selected cytidine residues in RNA molecules has been investigated. Poly(C) is nearly quantitatively converted to the poly (N4 aminoethyl-C) derivative after 3 hrs at 42 degrees C with ethylene diamine (pK1 = 7.6) and bisulfite. This derivative reacts quantitatively with N-hydroxysuccinimide esters; the linkage of a fluorescent dye, nitrobenzofurazan, to cytidine by this reaction is demonstrated. To direct the bisulfite reaction to selected cytidines within a large RNA molecule, the RNA is hybridized to complementary DNA containing a deletion. Only the cytidines in the single strand RNA loop (corresponding to the DNA deletion) are reactive. Two cytidines in the middle of a 340 base RNA fragment from 16S ribosomal RNA have been modified by this technique. Images PMID:6198634

Top-down cortical input during NREM sleep consolidates perceptual memory.

PubMed

Miyamoto, D; Hirai, D; Fung, C C A; Inutsuka, A; Odagawa, M; Suzuki, T; Boehringer, R; Adaikkan, C; Matsubara, C; Matsuki, N; Fukai, T; McHugh, T J; Yamanaka, A; Murayama, M

2016-06-10

During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation. Copyright © 2016, American Association for the Advancement of Science.

System identification from closed-loop data with known output feedback dynamics

NASA Technical Reports Server (NTRS)

Phan, Minh; Juang, Jer-Nan; Horta, Lucas G.; Longman, Richard W.

1992-01-01

This paper presents a procedure to identify the open loop systems when it is operating under closed loop conditions. First, closed loop excitation data are used to compute the system open loop and closed loop Markov parameters. The Markov parameters, which are the pulse response samples, are then used to compute a state space representation of the open loop system. Two closed loop configurations are considered in this paper. The closed loop system can have either a linear output feedback controller or a dynamic output feedback controller. Numerical examples are provided to illustrate the proposed closed loop identification method.

Harnessing speckle for a sub-femtometre resolved broadband wavemeter and laser stabilization

PubMed Central

Metzger, Nikolaus Klaus; Spesyvtsev, Roman; Bruce, Graham D.; Miller, Bill; Maker, Gareth T.; Malcolm, Graeme; Mazilu, Michael; Dholakia, Kishan

2017-01-01

The accurate determination and control of the wavelength of light is fundamental to many fields of science. Speckle patterns resulting from the interference of multiple reflections in disordered media are well-known to scramble the information content of light by complex but linear processes. However, these patterns are, in fact, exceptionally rich in information about the illuminating source. We use a fibre-coupled integrating sphere to generate wavelength-dependent speckle patterns, in combination with algorithms based on the transmission matrix method and principal component analysis, to realize a broadband and sensitive wavemeter. We demonstrate sub-femtometre wavelength resolution at a centre wavelength of 780 nm, and a broad calibrated measurement range from 488 to 1,064 nm. This compares favourably to the performance of conventional wavemeters. Using this speckle wavemeter as part of a feedback loop, we stabilize a 780 nm diode laser to achieve a linewidth better than 1 MHz. PMID:28580938

Rare top quark decays at a 100 TeV proton-proton collider: t → bWZ and t→ hc

NASA Astrophysics Data System (ADS)

Papaefstathiou, Andreas; Tetlalmatzi-Xolocotzi, Gilberto

2018-03-01

We investigate extremely rare top quark decays at a future proton-proton collider with centre-of-mass energy of 100 TeV. We focus on two decay modes: radiative decay with a Z boson, t → b WZ, and flavour-changing neutral decay with a Higgs boson, t → h c, the former being kinematically suppressed with a branching ratio of O(10^{-6}) (Altarelli et al., Phys Lett B 502:125-132, 2001), and the latter highly loop-suppressed, with a branching ratio of O(10^{-15}) (Aguilar-Saavedra, Acta Phys Polon B 35:2695-2710, 2004). We find that t → b WZ will be very challenging to observe in top quark pair production, even within well-motivated beyond-the-standard model scenarios. For the mode t→ h c we find a stronger sensitivity than that obtained by any future LHC measurement by at least one order of magnitude.

David Price--Pioneer of digital ICP monitoring, neurosurgeon and teacher.

PubMed

Czosnyka, Marek; Kirollos, Ramez; van Hille, Philip

2015-06-01

In early 1970s first personal desk-top computers started to be available in hospitals. Mr Price was one of the pioneers introducing his own software to identify Marmarou's model of CSF space during infusion studies to diagnose patients suffering from hydrocephalus. His closed-loop control system for infusion of mannitol to manage patients at risk of intracranial hypertension was designed in 1977. The system worked successfully for 10 years in Pinderfields Hospital in Wakefield, UK. In the middle 1980's he initiated international cooperation with Children's Health Centre in Poland in long-term computer-assisted monitoring and analysis of ICP. Software designed in a course of this cooperation paved the way for contemporary package of ICM+ (Intensive Care Monitor, University of Cambridge, UK). Our scientific portfolio from these years (1985-1995) contains hundreds of head injured patients with waveform ICP analysis, introduction of compensatory reserve index RAP, few highly cited papers. Now, we understand ICP much better thanks to David's personal passion and extremely friendly support.

Breaking the 'detox-loop' for alcoholics with social detoxification.

PubMed

Richman, A; Neumann, B

1984-01-01

A significant number of alcoholics do not respond to detoxification as a step on the way to rehabilitation. Instead, they periodically 'dry out' and subsequently return to alcohol abuse. They do not accept the responsibilities inherent in the sick role (cooperation in order to improve status of health by entering and continuing treatment), although they do accept the privileges (care, shelter and asylum). Repeated detoxifications (within medical and non-medical settings) of persons who do not commit themselves to entering rehabilitation, are of minimum benefit to the patient and absorb resources which could be better used by those more amendable to treatment. An appropriate level of care--social detoxification--should be provided for ' detox - loopers '. Such a model can focus on the alcoholic's social welfare needs. Social detoxification provides both respite and basic care. The door to ongoing rehabilitation through professional services, as well as self-help groups, can remain open, without being the main objective of the centre.

High brilliant thermal and cold moderator for the HBS neutron source project Jülich

NASA Astrophysics Data System (ADS)

Cronert, T.; Dabruck, J. P.; Doege, P. E.; Bessler, Y.; Klaus, M.; Hofmann, M.; Zakalek, P.; Rücker, U.; Lange, C.; Butzek, M.; Hansen, W.; Nabbi, R.; Brückel, T.

2016-09-01

The proposed High Brilliance Neutron Source (HBS), recognized within the Helmholtz Association of German Research Centres, will optimize the entire chain from particle source through particle accelerator, target, moderator, reflector, shielding, beam extraction, beam transport all the way to the detector, utilizing the nuclear Be(p,n) or Be(d,n) reaction in the lower MeV energy range. A D2O moderating reflector prototype (MRP) and a cold source were constructed and build according to MCNP parameter studies. The MRP was tested in a feasibility study at the TREFF instrument at MLZ (Garching). Cold beam extraction from the flux maximum within the moderator based on liquid para H2 and other cold moderators will be tested by energy spectroscopy via TOF-method. Different ratios of liquid ortho/para H2 will be fed to the cold moderator. The ratio will be controlled by feeding from reservoires of natural liquid H2 and a storage loop with an ortho/para converter and determined via online heat capacity measurement.

Stimulus learning and response learning by observation in the European starling, in a two-object/two-action test.

PubMed

Campbell; Heyes; Goldsmith

1999-07-01

Juvenile European starlings, Sturnus vulgaris, were allowed to observe a conspecific demonstrator using its beak to remove one of two distinctively coloured objects (i.e. a red or a black plug) from a hole in the lid of a plastic box. Both plugs could be removed by either pulling up on a loop of string inserted through the centre of the plug, or pushing down on the plug. When subsequently allowed access to the plugs, and rewarded with food for all removal responses, regardless of the object to which they were made and their direction, observer birds removed the same plug in the same direction as their demonstrator. These results suggest that the two-object/two-action paradigm is a valuable procedure for testing for the simultaneous effects of learning about a stimulus and a response, an object and an action, through conspecific observation. Copyright 1999 The Association for the Study of Animal Behaviour.

TOGA COARE Satellite data summaries available on the World Wide Web

NASA Technical Reports Server (NTRS)

Chen, S. S.; Houze, R. A., Jr.; Mapes, B. E.; Brodzick, S. R.; Yutler, S. E.

1995-01-01

Satellite data summary images and analysis plots from the Tropical Ocean Global Atmosphere Coupled Ocean-Atmosphere Response Experiment (TOGA COARE), which were initially prepared in the field at the Honiara Operations Center, are now available on the Internet via World Wide Web browsers such as Mosaic. These satellite data summaries consist of products derived from the Japanese Geosynchronous Meteorological Satellite IR data: a time-size series of the distribution of contiguous cold cloudiness areas, weekly percent high cloudiness (PHC) maps, and a five-month time-longitudinal diagram illustrating the zonal motion of large areas of cold cloudiness. The weekly PHC maps are overlaid with weekly mean 850-hPa wind calculated from the European Centre for Medium-Range Weather Forecasts (ECMWF) global analysis field and can be viewed as an animation loop. These satellite summaries provide an overview of spatial and temporal variabilities of the cloud population and a large-scale context for studies concerning specific processes of various components of TOGA COARE.

High Torque-to-Inertia Servo System for Stabilizing Sensor Systems. Candidate Systems Include Missile Guidance, Surveillance, and Tracking

DTIC Science & Technology

1980-04-01

specifications ... 3-10 25. Typical isolation curve ... 3-12 26. Servo amp/motor/load frequency response (inner gimbal) ... 4-3 27. Slave loop ( open loop...slave loop ( open loop) frequency response (inner gimbal) . . . 4-4 30. Slave loop (closed loop) frequency response (inner gimbal) ... 4-5 3 . Slave...loop inner gimbal time response ... 4-5 32. Servo amp/motor/load frequency response (outer gimbal) ... 4-6 33. Slave loop ( open loop) uncompensated

Coronal Loops: Observations and Modeling of Confined Plasma.

PubMed

Reale, Fabio

Coronal loops are the building blocks of the X-ray bright solar corona. They owe their brightness to the dense confined plasma, and this review focuses on loops mostly as structures confining plasma. After a brief historical overview, the review is divided into two separate but not independent parts: the first illustrates the observational framework, the second reviews the theoretical knowledge. Quiescent loops and their confined plasma are considered and, therefore, topics such as loop oscillations and flaring loops (except for non-solar ones, which provide information on stellar loops) are not specifically addressed here. The observational section discusses the classification, populations, and the morphology of coronal loops, its relationship with the magnetic field, and the loop stranded structure. The section continues with the thermal properties and diagnostics of the loop plasma, according to the classification into hot, warm, and cool loops. Then, temporal analyses of loops and the observations of plasma dynamics, hot and cool flows, and waves are illustrated. In the modeling section, some basics of loop physics are provided, supplying fundamental scaling laws and timescales, a useful tool for consultation. The concept of loop modeling is introduced and models are divided into those treating loops as monolithic and static, and those resolving loops into thin and dynamic strands. More specific discussions address modeling the loop fine structure and the plasma flowing along the loops. Special attention is devoted to the question of loop heating, with separate discussion of wave (AC) and impulsive (DC) heating. Large-scale models including atmosphere boxes and the magnetic field are also discussed. Finally, a brief discussion about stellar coronal loops is followed by highlights and open questions.

Improvement of logistics education from the point of view environmental management

NASA Astrophysics Data System (ADS)

Bányai, Á.

2009-04-01

The paper briefly presents the influence of environmental management on the improvement of the logistics education and research structure of the Department of Materials Handling and Logistics at the University of Miskolc, Hungary. The logistics, as an integrated science offers a very good possibility to demonstrate the effect of new innovative knowledge on the migration of the priorities of education and research of sciences. The importance of logistics in the field of recycling (or in wider sense in the field of environmental management) can be justified by the high proportion of logistic costs (as investment and operation costs) and these costs show that optimum logistic solutions are able to decrease the financial outcomes and lead to the establishment of a profitable system. Technological change constantly creates new demands on both education and research. The most important objective of the department is to create a unique logistics education in the country. For this reason the department offered up-to-date integrated knowledge at all level: undergraduate, master degree and PhD education. The integration of logistics means traditionally the joint use of technology of material handling, method of material flow, technology method of traffic, information technology, management sciences, production technology, marketing, market research, technology of services, mathematics and optimization, communication technology, system engineering, electronics and automation, mechatronics [1, 3]. The education and research portfolio of the department followed this tradition till 1993. The new lectures in the field of sustainability (logistics of recycling, logistics of quality management and recycling, closed loop economy, EU logistics or global logistics) became more and more important in the logistics education. The results of fast developments in closed loop economy, recycling, waste management, environmental protection are more and more used in the industry and this effected a revolutionary change in the education and research structure of logistics [2]. The European Community policy in the environment sectors aims at a high level of protection. Four principles were defined: the precautionary principle, the principle that preventive action should be taken, that environmental damages should as a priority be rectified at source and that the polluter should pay. All of these four principles have a very strong logistics background, especially in the field of import/export operations, traffic/transportation, inventory control, materials handling, fleet operations, customer service, supply chain management, distribution, strategic planning, warehousing, information systems of logistics, purchasing. These facts effect the development of different topics of logistics in each field of the education of the department: collection logistics of used products (especially WEEE), optimization of collection systems, design and control of disassembly systems, distribution of fractions of disassembled used products, design and control of recycling parks, possibilities of virtual networks in the field of recycling logistics, integration of logistics, recycling and total quality management, identification systems and recycling, etc. Within the framework of different supports our department has the opportunity to take part in European networks and research projects in the field of sustainability, environmental protection, recycling and closed loop economy. One of the biggest networks was developed within the framework of a Brite-Euram project entitled ‘Closing the loop from the product design to the end of life technologies'. The importance of logistics is certified by the fact, that this network defined the milestones of the improvement of an economically beneficial closed loop economy as quality aspects, communication and marketing, logistics and qualification. Within the frame of this project the logistics focused on the improvement of technologies (disassembly, reuse, refurbishment, remanufacturing and recycling), collection systems, and development of the concept for collection logistics and pre-disassembly, market survey in waste management. The Regional Knowledge Centre of Mechatronics and Logistics Systems was established in 2005. The overall objective of Knowledge Centre is to develop knowledge-intensive mechatronics and logistics systems in the leading edge of the world and to integrate the results in the economy and society through utilising the knowledge. The realisation of the objective requires the establishment and operation of a networking system of relations between those involved in sciences, the economy and society. The knowledge centre is a "knowledge integration tool" of the university in the field of mechanical engineering, and plays an important part in the intensification of the integration of the philosophy of sustainability into the related sciences. The program of the knowledge centre is focused on three well definable strategic fields, which are the vertical elements of the model. These are the R&D programs: world of products, materials and technologies, and integrated systems. The programs cover the implementation of seven, internationally competitive, application-oriented part tasks. These seven part tasks and the sustainability are closely related. The realisation of the part tasks through networking offers considerable results and economical-ecological benefits, forth for the participants and the region. The activities include basic and applied research, experimental development, technology transfer, as well as education and training and preparing the new scientific generation. The horizontal elements of the model are given by the utilisation of knowledge that can be interpreted in different dimensions: technical/engineering, legal, sustainability, economic, and social. The program relies on the continuation of existing relations in networks, and its regional nature is embodied in the cooperation of the higher education institutes and companies of the three counties. This publication was supported by the National Office for Research and Technology within the frame of Pázmány Péter programme. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the National Office for Research and Technology. Literature: [1] J. Cselényi, Gy. Fischer, J. Murvai, B. Mang: Typical models of the recycling logistics of worn out product. Proceedings of XIV. International Conference on Material Handling and Warehousing in Belgrade, 1996. pp. 138-143. [2] R. Knoth, M. Hoffmann, B. Kopacek, P. Kopacek: A logistic concept to improve the re-usability of electric and electronic equipment, Electronics and the Environment, 2001. Proceedings of the 2001 IEEE International Symposium. 2001. pp. 115 - 118. [3] L. Cser, B. Mang: Cleaner Technologies and Recycling in Hungary. Proceedings of Int. Workshop on Environmental Conscious Manufacturing in Hertogenbosch, The Netherlands, 1997. pp. 48-56.

Silica fractionation and reactivity in soils

NASA Astrophysics Data System (ADS)

Unzué Belmonte, Dácil; Barão, Lúcia; Vandevenne, Floor; Schoelynck, Jonas; Struyf, Eric; Meire, Patrick

2014-05-01

The Si cycle is a globally important biogeochemical cycle, with strong connections to other biogeochemical cycles, including C. Silica is taken up by plants to form protective structures called phytoliths, which become a part of the soil and contribute strongly to soil Si cycling upon litter burial. Different silica fractions are found in soils, with phytoliths among the most easily soluble, especially compared to silicate minerals. A whole set of secondary non-biogenic fractions exist, that also have a high reactivity (adsorbed Si, reactive secondary minerals…). A good characterization of the different fractions of reactive silica is crucial to move forward knowledge on ecosystem Si cycling, which has been recognized in the last decade as crucial for terrestrial Si fluxes. A new method to analyze the different fractions of silica in soils has been described by Koning et al. (2002) and adapted by our research team (Barão et al. 2013). Using a continuous extraction of Si and aluminum in 0.5M NaOH, biogenic and non-biogenic reactive fractions are separated based on their Si/Al ratios and their reactivity in NaOH. Applying this new method I will investigate three emerging ideas on how humans can affect directly terrestrial Si fluxes. -Land use. I expect strong silica fractionation and reactivity differences in different land uses. These effects due to agricultural and forestry management have already been shown earlier in temperate soils (Vandevenne et al. 2012). Now we will test this hypothesis in recently deforested soils, in the south of Brazil. 'Pristine' forest, managed forest and tobacco field soils (with and without rotation crops) will be studied. This research belongs to an interdisciplinary project on soils and global change. -Fire. According to the IPCC report, extreme events such as fires (number and intensity) would increase due to climate change. We analyzed litter from spruce forest, beech forest and peat soils at two burning levels, after 350°C and 550°C burnings. The first results showed differences in silica fractions between treatments and between soil types. This project is a close collaboration with University of Dresden. -Fertilization. Humans use fertilizers to increase crops growth and to avoid plagues affecting soil biogeochemistry. We set up a greenhouse experiment where olivine (a relatively easily weatherable silicate mineral) fertilization is applied to two crops (barley and wheat), at two rain application regimes (daily rain and weekly heavy rain) and with different fertilizer grain sizes. The aim of this project is to investigate how olivine application affects Si fractionation and reactivity in the soil profile. Barão, L., Clymans, W., Vandevenne, F., Meire, P., Conley, D.J. and Struyf, E. Pedogenic and biogenic amorphous Si distribution along a temperate land use gradient. Submitted, European Journal of Soil Science, 2013. Koning, E., Epping, E., and Van Raaphorst, W.: Determining bio- genic silica in marine samples by tracking silicate and aluminium concentrations in alkaline leaching solutions, Aquat. Geochem., 8, 37-67, 2002. Vandevenne, F.I., Struyf, E., Clymans, W. & Meire, P. 2012. Agricultural silica harvest: have humans created a new and important loop in the global silica cycle? Frontiers in Ecology and the Environment 10: 243-248.

Coupled dual loop absorption heat pump

DOEpatents

Sarkisian, Paul H.; Reimann, Robert C.; Biermann, Wendell J.

1985-01-01

A coupled dual loop absorption system which utilizes two separate complete loops. Each individual loop operates at three temperatures and two pressures. This low temperature loop absorber and condenser are thermally coupled to the high temperature loop evaporator, and the high temperature loop condenser and absorber are thermally coupled to the low temperature generator.

Introduction to Loop Heat Pipes

NASA Technical Reports Server (NTRS)

Ku, Jentung

2015-01-01

This is the presentation file for the short course Introduction to Loop Heat Pipes, to be conducted at the 2015 Thermal Fluids and Analysis Workshop, August 3-7, 2015, Silver Spring, Maryland. This course will discuss operating principles and performance characteristics of a loop heat pipe. Topics include: 1) pressure profiles in the loop; 2) loop operating temperature; 3) operating temperature control; 4) loop startup; 4) loop shutdown; 5) loop transient behaviors; 6) sizing of loop components and determination of fluid inventory; 7) analytical modeling; 8) examples of flight applications; and 9) recent LHP developments.

Cosmology and astrophysics from relaxed galaxy clusters - III. Thermodynamic profiles and scaling relations

NASA Astrophysics Data System (ADS)

Mantz, A. B.; Allen, S. W.; Morris, R. G.; Schmidt, R. W.

2016-03-01

This is the third in a series of papers studying the astrophysics and cosmology of massive, dynamically relaxed galaxy clusters. Our sample comprises 40 clusters identified as being dynamically relaxed and hot (I.e. massive) in Papers I and II of this series. Here we consider the thermodynamics of the intracluster medium, in particular the profiles of density, temperature and related quantities, as well as integrated measurements of gas mass, average temperature, total luminosity and centre-excluded luminosity. We fit power-law scaling relations of each of these quantities as a function of redshift and cluster mass, which can be measured precisely and with minimal bias for these relaxed clusters using hydrostatic arguments. For the thermodynamic profiles, we jointly model the density and temperature and their intrinsic scatter as a function of radius, thus also capturing the behaviour of the gas pressure and entropy. For the integrated quantities, we also jointly fit a multidimensional intrinsic covariance. Our results reinforce the view that simple hydrodynamical models provide a good description of relaxed clusters outside their centres, but that additional heating and cooling processes are important in the inner regions (radii r ≲ 0.5 r2500 ≈ 0.15 r500). The thermodynamic profiles remain regular, with small intrinsic scatter, down to the smallest radii where deprojection is straightforward (˜20 kpc); within this radius, even the most relaxed systems show clear departures from spherical symmetry. Our results suggest that heating and cooling are continuously regulated in a tight feedback loop, allowing the cluster atmosphere to remain stratified on these scales.

The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

NASA Technical Reports Server (NTRS)

Pickard, B. G.; Ding, J. P.

1993-01-01

Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

Reactive lymphoid hyperplasia of the liver in a patient with multiple carcinomas: a case report and brief review.

PubMed

Sato, K; Ueda, Y; Yokoi, M; Hayashi, K; Kosaka, T; Katsuda, S

2006-09-01

A rare case of reactive lymphoid hyperplasia (RLH) of the liver in a 75-year-old woman admitted to hospital for surgical treatment of gastric, caecal and colon carcinomas is described here. Two nodular lesions in the left and right lobes of the liver were clinically diagnosed as metastatic tumours by computed tomography of the abdomen. A demarcating grey-white mass of size 1.4 cm was observed in a partially resected liver specimen. On examining the lesion microscopically, it was found to be composed of hyperplastic lymphoid follicles, lymphocytes, plasma cells, other inflammatory cells and interlaced hyalinised fibrous tissues. In the portal tracts around the lesion, chronic inflammatory cell infiltrates were seen, but no interface hepatitis or lymphoid follicle was observed. No evidence of monoclonality was observed by immunohistochemistry for B and T cell markers, in situ hybridisation for kappa and lambda light chains, and polymerase chain reaction analysis of immunoglobulin heavy chains or T cell receptor beta and gamma gene rearrangements. Bcl-2 immunoreactivity was not observed in the germinal centre. Epstein-Barr virus (EBV) antigen (latent membrane protein-1) and EBV-encoded small RNAs were not detected. A proliferation neither of myofibroblasts nor of cells positive for follicular dendritic cell markers was observed. RLH, formerly known as pseudolymphoma, has been reported of the liver in only 14 cases and is considered to be a differential diagnosis of small nodular lesions of the liver. That RLH has an inflammatory reactive nature, not a neoplastic disposition, and that EBV does not participate in the pathogenesis of RLH is supported by this case.

A Bimetallic Nickel–Gallium Complex Catalyzes CO 2 Hydrogenation via the Intermediacy of an Anionic d 10 Nickel Hydride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cammarota, Ryan C.; Vollmer, Matthew V.; Xie, Jing

Large-scale CO2 hydrogenation could offer a renewable stream of industrially important C1 chemicals while reducing CO2 emissions. Critical to this opportunity is the requirement for inexpensive catalysts based on earth-abundant metals instead of precious metals. We report a nickel-gallium complex featuring a Ni(0)→Ga(III) bond that shows remarkable catalytic activity for hydrogenating CO2 to formate at ambient temperature (3150 turnovers, turnover frequency = 9700 h-1), compared with prior homogeneous Ni-centred catalysts. The Lewis acidic Ga(III) ion plays a pivotal role by stabilizing reactive catalytic intermediates, including a rare anionic d10 Ni hydride. The structure of this reactive intermediate shows a terminalmore » Ni-H, for which the hydride donor strength rivals those of precious metal-hydrides. Collectively, our experimental and computational results demonstrate that modulating a transition metal center via a direct interaction with a Lewis acidic support can be a powerful strategy for promoting new reactivity paradigms in base-metal catalysis. The work was supported as part of the Inorganometallic Catalysis Design Center, an Energy Frontier Research Center funded by the U.S. Department of Energy (DOE), Office of Science, Basic Energy Sciences under Award DE-SC0012702. R.C.C. and M.V.V. were supported by DOE Office of Science Graduate Student Research and National Science Foundation Graduate Research Fellowship programs, respectively. J.C.L., S.A.B., and A.M.A. were supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

The aetiology of anaemia during pregnancy: a study to evaluate the contribution of iron deficiency and common infections in pregnant Ugandan women.

PubMed

Baingana, Rhona K; Enyaru, John K; Tjalsma, Harold; Swinkels, Dorine W; Davidsson, Lena

2015-06-01

To describe the aetiology of anaemia in pregnant Ugandan women and explore Fe deficiency and common infections as contributors to anaemia in this population. Cross-sectional study in which Hb, ferritin, transferrin receptor (sTfR), C-reactive protein, α-1 acid glycoprotein, hepcidin, malaria, hookworm infestation, syphilis and Helicobacter pylori infection were assessed. Antenatal care clinic at Kawempe Health Centre, Kampala, Uganda. HIV-negative women (n 151) in their first or second pregnancy at 10-16 weeks' gestation. The prevalence of anaemia was 29·1 %. Fe deficiency was 40·4 % and 14·6 % based on ferritin 8·3 μg/ml. The prevalence of Fe-deficiency anaemia was 9·3 % based on ferritin 8·3 μg/ml. Hepcidin concentration was positively correlated with ferritin concentration (n 151, r=0·578, P1 g/l and/or C-reactive protein >5 mg/l. Malaria parasitaemia (OR=6·85; 95 % CI 1·25, 37·41, P=0·026) and Fe deficiency defined using sTfR (OR=5·58; 95 % CI 1·26, 24·80, P=0·024) were independently and positively associated with anaemia. Population-attributable risk factors for anaemia for raised C-reactive protein, Fe deficiency defined by sTfR >8·3 μg/ml and presence of malaria parasites were 41·6 (95 % CI 11·1, 72·2) %, 13·5 (95 % CI 2·0, 25·0) % and 12·0 (95 % CI 1·4, 22·6) %, respectively. Infections and inflammation are of greater significance than Fe deficiency in the aetiology of anaemia in pregnant Ugandan women during the first trimester.

Methods of preparation and modification of advanced zero-valent iron nanoparticles, their properties and application in water treatment technologies

NASA Astrophysics Data System (ADS)

Filip, Jan; Kašlík, Josef; Medřík, Ivo; Petala, Eleni; Zbořil, Radek; Slunský, Jan; Černík, Miroslav; Stavělová, Monika

2014-05-01

Zero-valent iron nanoparticles are commonly used in modern water treatment technologies. Compared to conventionally-used macroscopic iron or iron microparticles, the using of nanoparticles has the advantages given mainly by their generally large specific surface area (it drives their high reactivity and/or sorption capacity), small dimensions (it allows their migration e.g. in ground water), and particular physical and chemical properties. Following the applications of zero-valent iron particles in various pilot tests, there arose several critical suggestions for improvements of used nanomaterials and for development of new generation of reactive nanomaterials. In the presentation, the methods of zero-valent iron nanoparticles synthesis will be summarized with a special attention paid to the thermally-induced solid-state reaction allowing preparation of zero-valent iron nanoparticles in an industrial scale. Moreover, the method of thermal reduction of iron-oxide precursors enables to finely tune the critical parameters (mainly particle size and morphology, specific surface area, surface chemistry of nanoparticles etc.) of resulting zero-valet iron nanoparticles. The most important trends of advanced nanoparticles development will be discussed: (i) surface modification of nanomaterilas, (ii) development of nanocomposites and (iii) development of materials for combined reductive-sorption technologies. Laboratory testing of zero-valent iron nanoparticles reactivity and migration will be presented and compared with the field observations: the advanced zero-valent iron nanoparticles were used for groundwater treatment at the locality contaminated by chlorinated hydrocarbons (VC, DCE, TCE and PCE) and reacted nanoparticles were extracted from the sediments for their fate assessment. The authors gratefully acknowledge the support by the Technology Agency of the Czech Republic "Competence Centres" (project No. TE01020218) and the EU FP7 (project NANOREM).

Utility of the Determine Syphilis TP rapid test in commercial sex venues in Peru.

PubMed

Campos, P E; Buffardi, A L; Chiappe, M; Buendía, C; Garcia, P J; Carcamo, C P; Garnett, G; White, P; Holmes, K K

2006-12-01

This study sought to evaluate the utility of the Determine Syphilis TP test performed in Peruvian commercial sex venues for the detection of active syphilis; and determine the feasibility of integrating rapid syphilis testing for female sex workers (FSW) into existing health outreach services. We tested 3586 female sex workers for syphilis by Determine in the field using whole blood fingerstick, and by rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) in a central laboratory in Lima using sera. 97.4% of the FSW offered rapid syphilis testing participated; and among those who tested positive, 87% visited the local health centre for treatment. More than twice as many specimens were RPR reactive using serum in Lima (5.7%) than tested positive by whole blood Determine in the field (2.8%), and although most were confirmed by TPHA, only a small proportion (0.7%) were RPR reactive at >or=1:8 dilutions, and likely indicating active syphilis. Sensitivity, specificity and positive predictive value of the Determine Syphilis TP test in whole blood when compared to serum RPR reactivity at any dilution confirmed by TPHA as the gold standard were 39.3%, 99.2% and 71.4%, respectively. Sensitivity improved to 64.0% when using serum RPR >or=1:8 confirmed by TPHA. Invalid tests were rare (0.3%). Rapid syphilis testing in sex work venues proved feasible, but Determine using whole blood obtained by fingerstick was substantially less sensitive than reported in previous laboratory-based studies using serum. Although easy to perform in outreach venues, the utility of this rapid syphilis test was relatively low in settings where a large proportion of the targeted population has been previously tested and treated.

Utility of the Determine Syphilis TP rapid test in commercial sex venues in Peru

PubMed Central

Campos, P E; Buffardi, A L; Chiappe, M; Buendía, C; Garcia, P J; Carcamo, C P; Garnett, G; White, P

2006-01-01

Objectives This study sought to evaluate the utility of the Determine Syphilis TP test performed in Peruvian commercial sex venues for the detection of active syphilis; and determine the feasibility of integrating rapid syphilis testing for female sex workers (FSW) into existing health outreach services. Methods We tested 3586 female sex workers for syphilis by Determine in the field using whole blood fingerstick, and by rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) in a central laboratory in Lima using sera. Results 97.4% of the FSW offered rapid syphilis testing participated; and among those who tested positive, 87% visited the local health centre for treatment. More than twice as many specimens were RPR reactive using serum in Lima (5.7%) than tested positive by whole blood Determine in the field (2.8%), and although most were confirmed by TPHA, only a small proportion (0.7%) were RPR reactive at ⩾1:8 dilutions, and likely indicating active syphilis. Sensitivity, specificity and positive predictive value of the Determine Syphilis TP test in whole blood when compared to serum RPR reactivity at any dilution confirmed by TPHA as the gold standard were 39.3%, 99.2% and 71.4%, respectively. Sensitivity improved to 64.0% when using serum RPR ⩾1:8 confirmed by TPHA. Invalid tests were rare (0.3%). Conclusions Rapid syphilis testing in sex work venues proved feasible, but Determine using whole blood obtained by fingerstick was substantially less sensitive than reported in previous laboratory‐based studies using serum. Although easy to perform in outreach venues, the utility of this rapid syphilis test was relatively low in settings where a large proportion of the targeted population has been previously tested and treated. PMID:17116642

Specific Stimuli Induce Specific Adaptations: Sensorimotor Training vs. Reactive Balance Training

PubMed Central

Freyler, Kathrin; Krause, Anne; Gollhofer, Albert; Ritzmann, Ramona

2016-01-01

Typically, balance training has been used as an intervention paradigm either as static or as reactive balance training. Possible differences in functional outcomes between the two modalities have not been profoundly studied. The objective of the study was to investigate the specificity of neuromuscular adaptations in response to two balance intervention modalities within test and intervention paradigms containing characteristics of both profiles: classical sensorimotor training (SMT) referring to a static ledger pivoting around the ankle joint vs. reactive balance training (RBT) using externally applied perturbations to deteriorate body equilibrium. Thirty-eight subjects were assigned to either SMT or RBT. Before and after four weeks of intervention training, postural sway and electromyographic activities of shank and thigh muscles were recorded and co-contraction indices (CCI) were calculated. We argue that specificity of training interventions could be transferred into corresponding test settings containing properties of SMT and RBT, respectively. The results revealed that i) postural sway was reduced in both intervention groups in all test paradigms; magnitude of changes and effect sizes differed dependent on the paradigm: when training and paradigm coincided most, effects were augmented (P<0.05). ii) These specificities were accompanied by segmental modulations in the amount of CCI, with a greater reduction within the CCI of thigh muscles after RBT compared to the shank muscles after SMT (P<0.05). The results clearly indicate the relationship between test and intervention specificity in balance performance. Hence, specific training modalities of postural control cause multi-segmental and context-specific adaptations, depending upon the characteristics of the trained postural strategy. In relation to fall prevention, perturbation training could serve as an extension to SMT to include the proximal segment, and thus the control of structures near to the body’s centre of mass, into training. PMID:27911944

An optimal open/closed-loop control method with application to a pre-stressed thin duralumin plate

NASA Astrophysics Data System (ADS)

Nadimpalli, Sruthi Raju

The excessive vibrations of a pre-stressed duralumin plate, suppressed by a combination of open-loop and closed-loop controls, also known as open/closed-loop control, is studied in this thesis. The two primary steps involved in this process are: Step (I) with an assumption that the closed-loop control law is proportional, obtain the optimal open-loop control by direct minimization of the performance measure consisting of energy at terminal time and a penalty on open-loop control force via calculus of variations. If the performance measure also involves a penalty on closed-loop control effort then a Fourier based method is utilized. Step (II) the energy at terminal time is minimized numerically to obtain optimal values of feedback gains. The optimal closed-loop control gains obtained are used to describe the displacement and the velocity of open-loop, closed-loop and open/closed-loop controlled duralumin plate.

Functional evaluation of carbohydrate-centred glycoclusters by enzyme-linked lectin assay: ligands for concanavalin A.

PubMed

Köhn, Maja; Benito, Juan M; Ortiz Mellet, Carmen; Lindhorst, Thisbe K; García Fernández, José M

2004-06-07

The affinities of the mannose-specific lectin concanavalin A (Con A) towards D-glucose-centred mannosyl clusters differing in the anomeric configuration of the monosaccharide core, nature of the bridging functional groups and valency, have been measured by a competitive enzyme-linked lectin assay. Pentavalent thioether-linked ligands (5 and 7) were prepared by radical addition of 2,3,4,6-tetra-O-acetyl-1-thio-alpha-D-mannopyranose to the corresponding penta-O-allyl-alpha- or -beta-D-glucopyranose, followed by deacetylation. The distinct reactivity of the anomeric position in the D-glucose scaffold was exploited in the preparation of a tetravalent cluster (10) that keeps a reactive aglyconic group for further manipulation, including incorporation of a reporter group or attachment to a solid support. Hydroboration of the double bonds in the penta-O-allyl-alpha-D-glucopyranose derivative and replacement of the hydroxy groups with amine moieties gave a suitable precursor for the preparation of pentavalent and 15-valent mannosides through the thiourea-bridging reaction (17 and 20, respectively). The diastereomeric 1-thiomannose-coated clusters 5 and 7 were demonstrated to be potent ligands for Con A, with IC(50) values for the inhibition of the Con A-yeast mannan association indicative of 6.4- and 5.5-fold increases in binding affinity (valency-corrected values), respectively, relative to the value for methyl alpha-D-mannopyranoside. The tetravalent cluster 10 exhibited a valency-corrected relative lectin-binding potency virtually identical to that of the homologous pentavalent mannoside 7. In sharp contrast, replacement of the 1-thiomannose wedges of 5 with alpha-D-mannopyranosylthioureido units (17) virtually abolished any multivalent or statistic effects, with a dramatic decrease of binding affinity. The 15-valent ligand 20, possessing classical O-glycosidic linkages, exhibited a twofold increase in lectin affinity relative to the penta-O-(thioglycoside) 5; it is less efficient based on the number of mannose units. The results illustrate the potential of carbohydrates as polyfunctional platforms for glycocluster construction and underline the importance of careful design of the overall architecture in optimising glycocluster recognition by specific lectins.

Evaluation of different jumping tests in defining position-specific and performance-level differences in high level basketball players

PubMed Central

Pehar, Miran; Sekulic, Damir; Sisic, Nedim; Spasic, Miodrag; Uljevic, Ognjen; Krolo, Ante; Sattler, Tine

2017-01-01

The importance of jumping ability in basketball is well known, but there is an evident lack of studies that have examined different jumping testing protocols in basketball players at advanced levels. The aim of this study was to assess the applicability of different tests of jumping capacity in identifying differences between (i) playing position and (ii) competitive levels of professional players. Participants were 110 male professional basketball players (height: 194.92±8.09 cm; body mass: 89.33±10.91 kg; 21.58±3.92 years of age; Guards, 49; Forwards, 22; Centres, 39) who competed in the first (n = 58) and second division (n = 52). The variables included anthropometrics and jumping test performance. Jumping performances were evaluated by the standing broad jump (SBJ), countermovement jump (CMJ), reactive strength index (RSI), repeated reactive strength ability (RRSA) and four running vertical jumps: maximal jump with (i) take-off from the dominant leg and (ii) non-dominant leg, lay-up shot jump with take-off from the (iii) dominant leg and (iv) non-dominant leg. First-division players were taller (ES: 0.76, 95%CI: 0.35-1.16, moderate differences), heavier (0.69, 0.29-1.10), had higher maximal reach height (0.67, 0.26-1.07, moderate differences), and had lower body fat % (-0.87, -1.27-0.45, moderate differences) than second-division players. The playing positions differed significantly in three of four running jump achievements, RSI and RRSA, with Centres being least successful. The first-division players were superior to second-division players in SBJ (0.63, 0.23-1.03; 0.87, 0.26-1.43; 0.76, 0.11-1.63, all moderate differences, for total sample, Guards, and Forwards, respectively). Running vertical jumps and repeated jumping capacity can be used as valid measures of position-specific jumping ability in basketball. The differences between playing levels in vertical jumping achievement can be observed by assessing vertical jump scores together with differences in anthropometric indices between levels. PMID:29158620

The M358R variant of α{sub 1}-proteinase inhibitor inhibits coagulation factor VIIa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheffield, William P., E-mail: sheffiel@mcmaster.ca; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario; Bhakta, Varsha

The naturally occurring M358R mutation of the plasma serpin α{sub 1}-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg–Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg–Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assaysmore » of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10{sup 2} M{sup −1}sec{sup −1}. We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin. - Highlights: • The inhibitory specificity of the serpin alpha-1-proteinase inhibitor (API) is sharply altered in the M358R variant. • API M358R forms denaturation-resistant complexes with coagulation factor VIIa at a rate accelerated by tissue factor but unaffected by heparin. • Complex formation was shown by gel-based assays and quantified kinetically by inhibition of FVIIa-dependent amidolysis.« less

The COBATEST network: a platform to perform monitoring and evaluation of HIV community-based testing practices in Europe and conduct operational research.

PubMed

Fernàndez-López, L; Reyes-Urueña, J; Agustí, C; Kustec, T; Klavs, I; Casabona, C

2016-01-01

The European project "HIV community-based testing practices in Europe" (HIV-COBATEST) has contributed to the establishment of a network of community-based voluntary counselling and testing services (CBVCTs) that monitors and evaluates HIV testing activity in the communities. The objective of this paper is to describe the data that have been collected during 2014 by the COBATEST network in order to provide an insight into testing activity of CBVCTs in Europe. Members of the CBVCT network share common instruments for data collection and data entry. The network has a common database that allows global data analysis and comparison between different centres. In 2014, 40 CBVCTs of 18 European countries were participating in the network, and, from those, 20 CBVCTs were using the common COBATEST data collection tools. In these 20 CBVCTs, a total of 9266 HIV screening tests were performed on 8554 people, of which 1.58% (135/8554) were reactive and 51.1% (69/135) confirmed positive. Five cases were false positives, and 84.1% (58/69) of the confirmed positive cases were linked to care. Most of the tested individuals were men (70.8%), between 21 and 35 years of age (57.6%) and natives (67.1%). A higher proportion of men who had sex with men (MSM) (38.8%; 3267/8554) were tested compared to heterosexual men (27.7%) and women (23.5%). Rapid blood test was used in 78.5% of the cases and mostly performed in CBVCT offices (88.3%). Among sex workers (SWs), the percentage of reactive screening tests was particularly high (4.0%), especially among male SWs (7.7%) as compared to other risk groups, such as MSM (3.1%). The COBATEST network contributes to the availability of standardized information about the activity and impact of CBVCT centres in Europe. This information and standardized tools can help improve these services and inform decision-makers to better contextualize these interventions within their national HIV-prevention programmes.

Regulative Loops, Step Loops and Task Loops

ERIC Educational Resources Information Center

VanLehn, Kurt

2016-01-01

This commentary suggests a generalization of the conception of the behavior of tutoring systems, which the target article characterized as having an outer loop that was executed once per task and an inner loop that was executed once per step of the task. A more general conception sees these two loops as instances of regulative loops, which…

Closed-Loop Control Better than Open-Loop Control of Profofol TCI Guided by BIS: A Randomized, Controlled, Multicenter Clinical Trial to Evaluate the CONCERT-CL Closed-Loop System

PubMed Central

Zhang, Xuena; Wu, Anshi; Yao, Shanglong; Xue, Zhanggang; Yue, Yun

2015-01-01

Background The CONCERT-CL closed-loop infusion system designed by VERYARK Technology Co., Ltd. (Guangxi, China) is an innovation using TCI combined with closed-loop controlled intravenous anesthesia under the guide of BIS. In this study we performed a randomized, controlled, multicenter study to compare closed-loop control and open-loop control of propofol by using the CONCERT-CL closed-loop infusion system. Methods 180 surgical patients from three medical centers undergone TCI intravenous anesthesia with propofol and remifentanil were randomly assigned to propofol closed-loop group and propofol opened-loop groups. Primary outcome was global score (GS, GS = (MDAPE+Wobble)/% of time of bispectral index (BIS) 40-60). Secondary outcomes were doses of the anesthetics and emergence time from anesthesia, such as, time to tracheal extubation. Results There were 89 and 86 patients in the closed-loop and opened-loop groups, respectively. GS in the closed-loop groups (22.21±8.50) were lower than that in the opened-loop group (27.19±15.26) (p=0.009). The higher proportion of time of BIS between 40 and 60 was also observed in the closed-loop group (84.11±9.50%), while that was 79.92±13.17% in the opened-loop group, (p=0.016). No significant differences in propofol dose and time of tracheal extubation were observed. The frequency of propofol regulation in the closed-loop group (31.55±9.46 times/hr) was obverse higher than that in the opened-loop group (6.84±6.21 times/hr) (p=0.000). Conclusion The CONCERT-CL closed-loop infusion system can automatically regulate the TCI of propofol, maintain the BIS value in an adequate range and reduce the workload of anesthesiologists better than open-loop system. Trial Registration ChiCTR ChiCTR-OOR-14005551 PMID:25886041

Suppressing Transients In Digital Phase-Locked Loops

NASA Technical Reports Server (NTRS)

Thomas, J. B.

1993-01-01

Loop of arbitrary order starts in steady-state lock. Method for initializing variables of digital phase-locked loop reduces or eliminates transients in phase and frequency typically occurring during acquisition of lock on signal or when changes made in values of loop-filter parameters called "loop constants". Enables direct acquisition by third-order loop without prior acquisition by second-order loop of greater bandwidth, and eliminates those perturbations in phase and frequency lock occurring when loop constants changed by arbitrarily large amounts.

Equilibrium models of coronal loops that involve curvature and buoyancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindman, Bradley W.; Jain, Rekha, E-mail: hindman@solarz.colorado.edu

2013-12-01

We construct magnetostatic models of coronal loops in which the thermodynamics of the loop is fully consistent with the shape and geometry of the loop. This is achieved by treating the loop as a thin, compact, magnetic fibril that is a small departure from a force-free state. The density along the loop is related to the loop's curvature by requiring that the Lorentz force arising from this deviation is balanced by buoyancy. This equilibrium, coupled with hydrostatic balance and the ideal gas law, then connects the temperature of the loop with the curvature of the loop without resorting to amore » detailed treatment of heating and cooling. We present two example solutions: one with a spatially invariant magnetic Bond number (the dimensionless ratio of buoyancy to Lorentz forces) and the other with a constant radius of the curvature of the loop's axis. We find that the density and temperature profiles are quite sensitive to curvature variations along the loop, even for loops with similar aspect ratios.« less

Observations of simultaneous coronal loop shrinkage and expansion during the decay phase of a solar flare

NASA Astrophysics Data System (ADS)

Khan, J. I.; Fletcher, L.; Nitta, N. V.

2006-07-01

We report what we believe are the first direct and unambiguous observations of simultaneous coronal magnetic flux loop shrinkage and expansion during the decay phase of a solar flare. The retracting and expanding loops were observed nearly face-on (i.e., with the loop major axis approximately orthogonal to the line of sight) in emission in imaging data from the Yohkoh Soft X-ray Telescope (SXT). The retracting loop is observed to shrink with a speed of 118 ± 66 km s-1. The faint outward moving loop-like feature occurred ~200´´ above the shrinking loop during the time of the shrinking loop. We estimate the speed of the outward moving loop was ~129 ± 74 km s-1. We interpret the shrinking loop and simultaneous outward moving loop as direct evidence for reconnected magnetic field lines during a flare.

Earth System Chemistry integrated Modelling (ESCiMo) with the Modular Earth Submodel System (MESSy) version 2.51

NASA Astrophysics Data System (ADS)

Jöckel, Patrick; Tost, Holger; Pozzer, Andrea; Kunze, Markus; Kirner, Oliver; Brenninkmeijer, Carl A. M.; Brinkop, Sabine; Cai, Duy S.; Dyroff, Christoph; Eckstein, Johannes; Frank, Franziska; Garny, Hella; Gottschaldt, Klaus-Dirk; Graf, Phoebe; Grewe, Volker; Kerkweg, Astrid; Kern, Bastian; Matthes, Sigrun; Mertens, Mariano; Meul, Stefanie; Neumaier, Marco; Nützel, Matthias; Oberländer-Hayn, Sophie; Ruhnke, Roland; Runde, Theresa; Sander, Rolf; Scharffe, Dieter; Zahn, Andreas

2016-03-01

Three types of reference simulations, as recommended by the Chemistry-Climate Model Initiative (CCMI), have been performed with version 2.51 of the European Centre for Medium-Range Weather Forecasts - Hamburg (ECHAM)/Modular Earth Submodel System (MESSy) Atmospheric Chemistry (EMAC) model: hindcast simulations (1950-2011), hindcast simulations with specified dynamics (1979-2013), i.e. nudged towards ERA-Interim reanalysis data, and combined hindcast and projection simulations (1950-2100). The manuscript summarizes the updates of the model system and details the different model set-ups used, including the on-line calculated diagnostics. Simulations have been performed with two different nudging set-ups, with and without interactive tropospheric aerosol, and with and without a coupled ocean model. Two different vertical resolutions have been applied. The on-line calculated sources and sinks of reactive species are quantified and a first evaluation of the simulation results from a global perspective is provided as a quality check of the data. The focus is on the intercomparison of the different model set-ups. The simulation data will become publicly available via CCMI and the Climate and Environmental Retrieval and Archive (CERA) database of the German Climate Computing Centre (DKRZ). This manuscript is intended to serve as an extensive reference for further analyses of the Earth System Chemistry integrated Modelling (ESCiMo) simulations.

Ylide Ligands as Building Blocks for Bioactive Group 11 Metal Complexes.

PubMed

Gimeno, M Concepción; Johnson, Alice; Marzo, Isabel

2018-05-22

The reactivity of the phosphonium salt, (cyanomethyl)triphenylphosphonium chloride, and the ylide, triphenylphosphoniumcyanomethylide, towards group eleven metal complexes is described. Mononuclear neutral gold(I) and gold(III) complexes of the type [AuX{CH(CN)PPh3}] or [AuX3{CH(CN)PPh3}], and cationic derivatives such as [AuL{CH(CN)PPh3}]X have been prepared. Surprisingly the cationic gold species could only be prepared with ligands with a large steric hindrance such as bulky NHCs or the JohnPhos phosphine, in contrast with silver and copper derivatives which have dimeric structures with coordination to the cyano group of the ylide. Bis(ylide)metal complexes have been synthesised in which a different structure is observed for gold compared to copper and silver. While gold shows mononuclear species, the silver complex presents a bidimensional polymeric structure as a result of further coordination of the silver centre to the nitrogen of the cyano group. These complexes possess two chiral centres and the gold compound is obtained as a mixture of diastereoisomers, whereas the copper and silver derivatives afford only one diastereroisomer. These compounds were screened for the in vitro cytotoxic activity against the human lung carcinoma cell line (A549). The IC50 values reveal an excellent cytotoxic activity for these metal complexes compared with cisplatin. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular dynamics simulations of electrostatics and hydration distributions around RNA and DNA motifs

NASA Astrophysics Data System (ADS)

Marlowe, Ashley E.; Singh, Abhishek; Semichaevsky, Andrey V.; Yingling, Yaroslava G.

2009-03-01

Nucleic acid nanoparticles can self-assembly through the formation of complementary loop-loop interactions or stem-stem interactions. Presence and concentration of ions can significantly affect the self-assembly process and the stability of the nanostructure. In this presentation we use explicit molecular dynamics simulations to examine the variations in cationic distributions and hydration environment around DNA and RNA helices and loop-loop interactions. Our simulations show that the potassium and sodium ionic distributions are different around RNA and DNA motifs which could be indicative of ion mediated relative stability of loop-loop complexes. Moreover in RNA loop-loop motifs ions are consistently present and exchanged through a distinct electronegative channel. We will also show how we used the specific RNA loop-loop motif to design a RNA hexagonal nanoparticle.

LoopX: A Graphical User Interface-Based Database for Comprehensive Analysis and Comparative Evaluation of Loops from Protein Structures.

PubMed

Kadumuri, Rajashekar Varma; Vadrevu, Ramakrishna

2017-10-01

Due to their crucial role in function, folding, and stability, protein loops are being targeted for grafting/designing to create novel or alter existing functionality and improve stability and foldability. With a view to facilitate a thorough analysis and effectual search options for extracting and comparing loops for sequence and structural compatibility, we developed, LoopX a comprehensively compiled library of sequence and conformational features of ∼700,000 loops from protein structures. The database equipped with a graphical user interface is empowered with diverse query tools and search algorithms, with various rendering options to visualize the sequence- and structural-level information along with hydrogen bonding patterns, backbone φ, ψ dihedral angles of both the target and candidate loops. Two new features (i) conservation of the polar/nonpolar environment and (ii) conservation of sequence and conformation of specific residues within the loops have also been incorporated in the search and retrieval of compatible loops for a chosen target loop. Thus, the LoopX server not only serves as a database and visualization tool for sequence and structural analysis of protein loops but also aids in extracting and comparing candidate loops for a given target loop based on user-defined search options.

Top3-Rmi1 dissolve Rad51-mediated D-loops by a topoisomerase-based mechanism

PubMed Central

Fasching, Clare L.; Cejka, Petr; Kowalczykowski, Stephen C.; Heyer, Wolf-Dietrich

2015-01-01

Summary The displacement loop (D-loop) is the DNA strand invasion product formed during homologous recombination. Disruption of nascent D-loops represents a mechanism of anti-recombination. During Synthesis-Dependent Strand Annealing D-loop disruption after extension of the invading strand is an integral step of the pathway and ensures a non-crossover outcome. The proteins implicated in D-loop disruption are DNA motor proteins/helicases acting by migrating DNA junctions. Here we report an unanticipated mechanism of D-loop dissolution mediated by DNA topoisomerase 3 (Top3) and dependent on its catalytic activity. D-loop dissolution catalyzed by yeast Top3 is highly specific for yeast Rad51/Rad54-mediated D-loops, whereas protein-free D-loops or D-loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also the human Topoisomerase IIIα-RMI1–RMI2 complex is capable of dissolving D-loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is in part a result of unprocessed D-loops. PMID:25699708

Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops

PubMed Central

Phan, Andy; Mailey, Katherine; Saeki, Jessica; Gu, Xiaobo

2017-01-01

Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 × 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites. PMID:28213527

Current systems of coronal loops in 3D MHD simulations

NASA Astrophysics Data System (ADS)

Warnecke, J.; Chen, F.; Bingert, S.; Peter, H.

2017-11-01

Aims: We study the magnetic field and current structure associated with a coronal loop. Through this we investigate to what extent the assumptions of a force-free magnetic field break down and where they might be justified. Methods: We analyze a three-dimensional (3D) magnetohydrodynamic (MHD) model of the solar corona in an emerging active region with the focus on the structure of the forming coronal loops. The lower boundary of this simulation is taken from a model of an emerging active region. As a consequence of the emerging magnetic flux and the horizontal motions at the surface a coronal loop forms self-consistently. We investigate the current density along magnetic field lines inside (and outside) this loop and study the magnetic and plasma properties in and around this loop. The loop is defined as the bundle of field lines that coincides with enhanced emission in extreme UV. Results: We find that the total current along the emerging loop changes its sign from being antiparallel to parallel to the magnetic field. This is caused by the inclination of the loop together with the footpoint motion. Around the loop, the currents form a complex non-force-free helical structure. This is directly related to a bipolar current structure at the loop footpoints at the base of the corona and a local reduction of the background magnetic field (I.e., outside the loop) caused by the plasma flow into and along the loop. Furthermore, the locally reduced magnetic pressure in the loop allows the loop to sustain a higher density, which is crucial for the emission in extreme UV. The action of the flow on the magnetic field hosting the loop turns out to also be responsible for the observed squashing of the loop. Conclusions: The complex magnetic field and current system surrounding it can only be modeled in 3D MHD models where the magnetic field has to balance the plasma pressure. A one-dimensional coronal loop model or a force-free extrapolation cannot capture the current system and the complex interaction of the plasma and the magnetic field in the coronal loop, despite the fact that the loop is under low-β conditions.

THE CORONAL LOOP INVENTORY PROJECT: EXPANDED ANALYSIS AND RESULTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmelz, J. T.; Christian, G. M.; Chastain, R. A., E-mail: jschmelz@usra.edu

We have expanded upon earlier work that investigates the relative importance of coronal loops with isothermal versus multithermal cross-field temperature distributions. These results are important for determining if loops have substructure in the form of unresolved magnetic strands. We have increased the number of loops targeted for temperature analysis from 19 to 207 with the addition of 188 new loops from multiple regions. We selected all loop segments visible in the 171 Å images of the Atmospheric Imaging Assembly (AIA) that had a clean background. Eighty-six of the new loops were rejected because they could not be reliably separated frommore » the background in other AIA filters. Sixty-one loops required multithermal models to reproduce the observations. Twenty-eight loops were effectively isothermal, that is, the plasma emission to which AIA is sensitive could not be distinguished from isothermal emission, within uncertainties. Ten loops were isothermal. Also, part of our inventory was one small flaring loop, one very cool loop whose temperature distribution could not be constrained by the AIA data, and one loop with inconclusive results. Our survey can confirm an unexpected result from the pilot study: we found no isothermal loop segments where we could properly use the 171-to-193 ratio method, which would be similar to the analysis done for many loops observed with TRACE and EIT. We recommend caution to observers who assume the loop plasma is isothermal, and hope that these results will influence the direction of coronal heating models and the effort modelers spend on various heating scenarios.« less

Three-phase Four-leg Inverter LabVIEW FPGA Control Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

In the area of power electronics control, Field Programmable Gate Arrays (FPGAs) have the capability to outperform their Digital Signal Processor (DSP) counterparts due to the FPGA’s ability to implement true parallel processing and therefore facilitate higher switching frequencies, higher control bandwidth, and/or enhanced functionality. National Instruments (NI) has developed two platforms, Compact RIO (cRIO) and Single Board RIO (sbRIO), which combine a real-time processor with an FPGA. The FPGA can be programmed with a subset of the well-known LabVIEW graphical programming language. The use of cRIO and sbRIO for power electronics control has developed over the last few yearsmore » to include control of three-phase inverters. Most three-phase inverter topologies include three switching legs. The addition of a fourth-leg to natively generate the neutral connection allows the inverter to serve single-phase loads in a microgrid or stand-alone power system and to balance the three-phase voltages in the presence of significant load imbalance. However, the control of a four-leg inverter is much more complex. In particular, instead of standard two-dimensional space vector modulation (SVM), the inverter requires three-dimensional space vector modulation (3D-SVM). The candidate software implements complete control algorithms in LabVIEW FPGA for a three-phase four-leg inverter. The software includes feedback control loops, three-dimensional space vector modulation gate-drive algorithms, advanced alarm handling capabilities, contactor control, power measurements, and debugging and tuning tools. The feedback control loops allow inverter operation in AC voltage control, AC current control, or DC bus voltage control modes based on external mode selection by a user or supervisory controller. The software includes the ability to synchronize its AC output to the grid or other voltage-source before connection. The software also includes provisions to allow inverter operation in parallel with other voltage regulating devices on the AC or DC buses. This flexibility allows the Inverter to operate as a stand-alone voltage source, connected to the grid, or in parallel with other controllable voltage sources as part of a microgrid or remote power system. In addition, as the inverter is expected to operate under severe unbalanced conditions, the software includes algorithms to accurately compute real and reactive power for each phase based on definitions provided in the IEEE Standard 1459: IEEE Standard Definitions for the Measurement of Electric Power Quantities Under Sinusoidal, Nonsinusoidal, Balanced, or Unbalanced Conditions. Finally, the software includes code to output analog signals for debugging and for tuning of control loops. The software fits on the Xilinx Virtex V LX110 FPGA embedded in the NI cRIO-9118 FPGA chassis, and with a 40 MHz base clock, supports a modulation update rate of 40 MHz, user-settable switching frequencies and synchronized control loop update rates of tens of kHz, and reference waveform generation, including Phase Lock Loop (PLL), update rate of 100 kHz.« less

Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism.

PubMed

Fasching, Clare L; Cejka, Petr; Kowalczykowski, Stephen C; Heyer, Wolf-Dietrich

2015-02-19

The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also, the human Topoisomerase IIIa-RMI1-RMI2 complex is capable of dissolving D loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops. Copyright © 2015 Elsevier Inc. All rights reserved.

On the nature of fast sausage waves in coronal loops

NASA Astrophysics Data System (ADS)

Bahari, Karam

2018-05-01

The effect of the parameters of coronal loops on the nature of fast sausage waves are investigated. To do this three models of the coronal loop considered, a simple loop model, a current-carrying loop model and a model with radially structured density called "Inner μ" profile. For all the models the Magnetohydrodynamic (MHD) equations solved analytically in the linear approximation and the restoring forces of oscillations obtained. The ratio of the magnetic tension force to the pressure gradient force obtained as a function of the distance from the axis of the loop. In the simple loop model for all values of the loop parameters the fast sausages wave have a mixed nature of Alfvénic and fast MHD waves, in the current-carrying loop model with thick annulus and low density contrast the fast sausage waves can be considered as purely Alfvénic wave in the core region of the loop, and in the "Inner μ" profile for each set of the parameters of the loop the wave can be considered as a purely Alfvénic wave in some regions of the loop.

Performance of loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria among malaria suspected pregnant women in Northwest Ethiopia.

PubMed

Tegegne, Banchamlak; Getie, Sisay; Lemma, Wossenseged; Mohon, Abu Naser; Pillai, Dylan R

2017-01-19

Malaria is a major public health problem and an important cause of maternal and infant morbidity in sub-Saharan Africa, including Ethiopia. Early and accurate diagnosis of malaria with effective treatment is the best strategy for prevention and control of complications during pregnancy and infant morbidity and mortality. However, laboratory diagnosis has relied on the identification of malaria parasites and parasite antigens in peripheral blood using Giemsa-stained microscopy or rapid diagnostic tests (RDTs) which lack analytical and clinical sensitivity. The aim of this study was to evaluate the performance of loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria among malaria suspected pregnant women in Northwest Ethiopia. A cross sectional study was conducted from January to April 2016. Pregnant women (n = 87) suspected of having malaria at six health centres were enrolled. A venous blood sample was collected from each study subject, and analysed for Plasmodium parasites by microscopy, RDT, and LAMP. Diagnostic accuracy outcome measures (sensitivity, specificity, predictive values, and Kappa scores) of microscopy, RDT and LAMP were compared to nested polymerase chain reaction (nPCR) as the gold standard. Specimen processing and reporting times were documented. Using nPCR as the gold standard technique, the sensitivity of microscopy and RDT was 90 and 70%, and the specificity was 98.7 and 97.4%, respectively. LAMP assay was 100% sensitive and 93.5% specific compared to nPCR. This study showed higher sensitivity of LAMP compared to microscopy and RDT for the detection of malaria in pregnancy. Increased sensitivity and ease of use with LAMP in point-of-care testing for malaria in pregnancy was noted. LAMP warrants further evaluation in intermittent screening and treatment programmes in pregnancy.

How to find home backwards? Navigation during rearward homing of Cataglyphis fortis desert ants.

PubMed

Pfeffer, Sarah E; Wittlinger, Matthias

2016-07-15

Cataglyphis ants are renowned for their impressive navigation skills, which have been studied in numerous experiments during forward locomotion. However, the ants' navigational performance during backward homing when dragging large food loads has not been investigated until now. During backward locomotion, the odometer has to deal with unsteady motion and irregularities in inter-leg coordination. The legs' sensory feedback during backward walking is not just a simple reversal of the forward stepping movements: compared with forward homing, ants are facing towards the opposite direction during backward dragging. Hence, the compass system has to cope with a flipped celestial view (in terms of the polarization pattern and the position of the sun) and an inverted retinotopic image of the visual panorama and landmark environment. The same is true for wind and olfactory cues. In this study we analyze for the first time backward-homing ants and evaluate their navigational performance in channel and open field experiments. Backward-homing Cataglyphis fortis desert ants show remarkable similarities in the performance of homing compared with forward-walking ants. Despite the numerous challenges emerging for the navigational system during backward walking, we show that ants perform quite well in our experiments. Direction and distance gauging was comparable to that of the forward-walking control groups. Interestingly, we found that backward-homing ants often put down the food item and performed foodless search loops around the left food item. These search loops were mainly centred around the drop-off position (and not around the nest position), and increased in length the closer the ants came to their fictive nest site. © 2016. Published by The Company of Biologists Ltd.

Development of a pilot-scale 1 for Legionella elimination in biofilm in hot water network: heat shock treatment evaluation.

PubMed

Farhat, M; Trouilhé, M-C; Briand, E; Moletta-Denat, M; Robine, E; Frère, J

2010-03-01

(i) To develop an analytical tool in order to evaluate the effectiveness of anti-Legionella treatment in biofilm and (ii) study the fate of Legionella populations in water and biofilm after applying a heat shock treatment. A pilot-scale unit simulating a hot water system was built and designed by the Scientific and Technical Building Centre (CSTB, France). At the end of the contamination period, a stable cultivable Legionella spp. concentration of 5x10(5) CFU l(-1) was obtained. Two heat shock treatments (70 degrees C for 30 min) were applied. The results showed that the first treatment had a transitional effect on the abatement of Legionella concentrations, while the second treatment had no detectable effect on Legionella populations in water and biofilm. The DAPI (4',6'-diamidino-2-phenylindole), Legionella PCR and GVPC (glycocolle vancomycin pyrophosphate cycloheximide) counts measured in the dead leg water of the Test Loop were 1, 2 and 2 log units higher than results found in the Test Loop water. Moreover, Legionella spp. count in tap water was about 10(4) GU l(-1). These analyses revealed that they are responsible for the rapid recolonization as well as the uncomplete destroyed biofilm. In addition, a resistance test was conducted and showed that Legionella in the second heat shock treatment was not thermo-resistant but thermo-acclimated. Thermal disinfection does not seem to be efficient enough to eliminate Legionella when it is used as a curative treatment. This work could help water managers for a better management of water network and for a better control of Legionella.

Anisotropic magnetic switching along hard [1 1 0]-type axes in Er-doped DyFe2/YFe2 thin films

NASA Astrophysics Data System (ADS)

Stenning, G. B. G.; Bowden, G. J.; van der Laan, G.; Figueroa, A. I.; Bencok, P.; Steadman, P.; Hesjedal, T.

2017-10-01

Epitaxial-grown DyFe2/YFe2 multilayer thin films form an ideal model system for the study of magnetic exchange springs. Here the DyFe2 (YFe2) layers are magnetically hard (soft). In the presence of a magnetic field, exchange springs form in the YFe2 layers. Recently, it has been demonstrated that placing small amounts of Er into the centre of the YFe2 springs generates substantial changes in magnetic behavior. In particular, (i) the number of exchange-spring states is increased dramatically, (ii) the resulting domain-wall states cannot simply be described as either Néel or Bloch walls, (iii) the Er and Dy magnetic loops are strikingly different, and (iv) it is possible to engineer Er-induced magnetic exchange-spring collapse. Here, results are presented for Er-doped (1 1 0)-oriented DyFe2 (60 Å/YFe2(240 Å)15 multilayer films, at 100 K in fields of up to 12 T. In particular, we contrast magnetic loops for fields applied along seemingly equivalent hard-magnetic [1 1 0]-type axes. MBE-grown cubic Laves thin films offer the unique feature of allowing to apply the magnetic field along (i) a hard out-of-plane [1 1 0]-axis (the growth axis) and (ii) a similar hard in-plane [ 1 bar 10 ] -axis. Differences are found and attributed to the competition between the crystal-field interaction at the Er site and the long-range dipole-dipole interaction. In particular, the out-of-plane [1 1 0] Er results show the existence of a new magnetic exchange spring state, which would be very difficult to identify without the aid of element-specific technique of X-ray magnetic circular dichroism (XMCD).

A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations.

PubMed

Schweikardt, Thorsten; Olivares, Concepción; Solano, Francisco; Jaenicke, Elmar; García-Borrón, José Carlos; Decker, Heinz

2007-10-01

Tyrosinases are the first and rate-limiting enzymes in the synthesis of melanin pigments responsible for colouring hair, skin and eyes. Mutation of tyrosinases often decreases melanin production resulting in albinism, but the effects are not always understood at the molecular level. Homology modelling of mouse tyrosinase based on recently published crystal structures of non-mammalian tyrosinases provides an active site model accounting for loss-of-function mutations. According to the model, the copper-binding histidines are located in a helix bundle comprising four densely packed helices. A loop containing residues M374, S375 and V377 connects the CuA and CuB centres, with the peptide oxygens of M374 and V377 serving as hydrogen acceptors for the NH-groups of the imidazole rings of the copper-binding His367 and His180. Therefore, this loop is essential for the stability of the active site architecture. A double substitution (374)MS(375) --> (374)GG(375) or a single M374G mutation lead to a local perturbation of the protein matrix at the active site affecting the orientation of the H367 side chain, that may be unable to bind CuB reliably, resulting in loss of activity. The model also accounts for loss of function in two naturally occurring albino mutations, S380P and V393F. The hydroxyl group in S380 contributes to the correct orientation of M374, and the substitution of V393 for a bulkier phenylalanine sterically impedes correct side chain packing at the active site. Therefore, our model explains the mechanistic necessity for conservation of not only active site histidines but also adjacent amino acids in tyrosinase.

Were they in the loop during automated driving? Links between visual attention and crash potential.

PubMed

Louw, Tyron; Madigan, Ruth; Carsten, Oliver; Merat, Natasha

2017-08-01

A proposed advantage of vehicle automation is that it relieves drivers from the moment-to-moment demands of driving, to engage in other, non-driving related, tasks. However, it is important to gain an understanding of drivers' capacity to resume manual control, should such a need arise. As automation removes vehicle control-based measures as a performance indicator, other metrics must be explored. This driving simulator study, conducted under the European Commission (EC) funded AdaptIVe project, assessed drivers' gaze fixations during partially-automated (SAE Level 2) driving, on approach to critical and non-critical events. Using a between-participant design, 75 drivers experienced automation with one of five out-of-the-loop (OOTL) manipulations, which used different levels of screen visibility and secondary tasks to induce varying levels of engagement with the driving task: 1) no manipulation, 2) manipulation by light fog, 3) manipulation by heavy fog, 4) manipulation by heavy fog plus a visual task, 5) no manipulation plus an n-back task. The OOTL manipulations influenced drivers' first point of gaze fixation after they were asked to attend to an evolving event. Differences resolved within one second and visual attention allocation adapted with repeated events, yet crash outcome was not different between OOTL manipulation groups. Drivers who crashed in the first critical event showed an erratic pattern of eye fixations towards the road centre on approach to the event, while those who did not demonstrated a more stable pattern. Automated driving systems should be able to direct drivers' attention to hazards no less than 6 seconds in advance of an adverse outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

NOAA GOES Geostationary Satellite Server

Science.gov Websites

Size West CONUS IR Image MPEG | Loop Visible Full Size West CONUS VIS Image MPEG | Loop Water Vapor Full Size West Conus WV Image MPEG | Loop Alaska Infrared Full Size Alaska IR Image Loop | Color Infrared Full Size Hawaii IR Image Loop | Color Visible Full Size Hawaii VIS Image Loop Water Vapor Full

Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops.

PubMed

Phan, Andy; Mailey, Katherine; Saeki, Jessica; Gu, Xiaobo; Schroeder, Susan J

2017-05-01

Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 × 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites. © 2017 Phan et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Sequence-structure relationships in RNA loops: establishing the basis for loop homology modeling.

PubMed

Schudoma, Christian; May, Patrick; Nikiforova, Viktoria; Walther, Dirk

2010-01-01

The specific function of RNA molecules frequently resides in their seemingly unstructured loop regions. We performed a systematic analysis of RNA loops extracted from experimentally determined three-dimensional structures of RNA molecules. A comprehensive loop-structure data set was created and organized into distinct clusters based on structural and sequence similarity. We detected clear evidence of the hallmark of homology present in the sequence-structure relationships in loops. Loops differing by <25% in sequence identity fold into very similar structures. Thus, our results support the application of homology modeling for RNA loop model building. We established a threshold that may guide the sequence divergence-based selection of template structures for RNA loop homology modeling. Of all possible sequences that are, under the assumption of isosteric relationships, theoretically compatible with actual sequences observed in RNA structures, only a small fraction is contained in the Rfam database of RNA sequences and classes implying that the actual RNA loop space may consist of a limited number of unique loop structures and conserved sequences. The loop-structure data sets are made available via an online database, RLooM. RLooM also offers functionalities for the modeling of RNA loop structures in support of RNA engineering and design efforts.

Performance evaluation of reactive and proactive routing protocol in IEEE 802.11 ad hoc network

NASA Astrophysics Data System (ADS)

Hamma, Salima; Cizeron, Eddy; Issaka, Hafiz; Guédon, Jean-Pierre

2006-10-01

Wireless technology based on the IEEE 802.11 standard is widely deployed. This technology is used to support multiple types of communication services (data, voice, image) with different QoS requirements. MANET (Mobile Adhoc NETwork) does not require a fixed infrastructure. Mobile nodes communicate through multihop paths. The wireless communication medium has variable and unpredictable characteristics. Furthermore, node mobility creates a continuously changing communication topology in which paths break and new one form dynamically. The routing table of each router in an adhoc network must be kept up-to-date. MANET uses Distance Vector or Link State algorithms which insure that the route to every host is always known. However, this approach must take into account the adhoc networks specific characteristics: dynamic topologies, limited bandwidth, energy constraints, limited physical security, ... Two main routing protocols categories are studied in this paper: proactive protocols (e.g. Optimised Link State Routing - OLSR) and reactive protocols (e.g. Ad hoc On Demand Distance Vector - AODV, Dynamic Source Routing - DSR). The proactive protocols are based on periodic exchanges that update the routing tables to all possible destinations, even if no traffic goes through. The reactive protocols are based on on-demand route discoveries that update routing tables only for the destination that has traffic going through. The present paper focuses on study and performance evaluation of these categories using NS2 simulations. We have considered qualitative and quantitative criteria. The first one concerns distributed operation, loop-freedom, security, sleep period operation. The second are used to assess performance of different routing protocols presented in this paper. We can list end-to-end data delay, jitter, packet delivery ratio, routing load, activity distribution. Comparative study will be presented with number of networking context consideration and the results show the appropriate routing protocol for two kinds of communication services (data and voice).

Closed and open conformations of the lid domain induce different patterns of human pancreatic lipase antigenicity and immunogenicity.

PubMed

Halimi, Hubert; De Caro, Josiane; Carrière, Frédéric; De Caro, Alain

2005-12-01

Epitope mapping was performed on human pancreatic lipase (HPL) using the SPOTscan method. A set of 146 short (12 amino acid residues) synthetic overlapping peptides covering the entire amino acid sequence of HPL were used to systematically assess the immunoreactivity of antisera raised in rabbits against native HPL, HPL without a lid (HPL(-lid)) and HPL covalently inhibited by diethyl p-nitrophenyl phosphate (DP-HPL). In the latter form of HPL, the lid domain controlling the access to the active site was assumed to exist in the open conformation. All the anti-lipase sera were tested in a direct ELISA, anti-HPL serum showing the greatest antibody titer. Although from the structural point of view, the differences between the various forms of HPL were restricted to the lid domain, differences in the antigenic properties of HPL were observed with the SPOTscan method, and the anti-DP-HPL antibodies showed the strongest reactivity. Most of the peptide stretches recognized included amino acid residues which are accessible at the surface of the lipase, except for those located near the active site. Two small peptides (T173-P180, V199-A207) were identified in the vicinity of the active site, their antipeptide antibodies were produced and their reactivity towards the various forms of HPL was tested in a double sandwich ELISA. No reactivity was observed under these conditions. Two antipeptide antibodies directed against two other selected peptides, P208-V221 (belonging to the beta9 loop) and I245-F258 (belonging to the lid domain) were prepared and found to react much more strongly with DP-HPL than with HPL or HPL(-lid) in a double sandwich ELISA. These antibodies should provide useful tools for monitoring the conformational changes taking place during the opening of the HPL lid domain.

A paradigm shift towards low-nitrifying production systems: the role of biological nitrification inhibition (BNI).

PubMed

Subbarao, G V; Sahrawat, K L; Nakahara, K; Rao, I M; Ishitani, M; Hash, C T; Kishii, M; Bonnett, D G; Berry, W L; Lata, J C

2013-07-01

Agriculture is the single largest geo-engineering initiative that humans have initiated on planet Earth, largely through the introduction of unprecedented amounts of reactive nitrogen (N) into ecosystems. A major portion of this reactive N applied as fertilizer leaks into the environment in massive amounts, with cascading negative effects on ecosystem health and function. Natural ecosystems utilize many of the multiple pathways in the N cycle to regulate N flow. In contrast, the massive amounts of N currently applied to agricultural systems cycle primarily through the nitrification pathway, a single inefficient route that channels much of this reactive N into the environment. This is largely due to the rapid nitrifying soil environment of present-day agricultural systems. In this Viewpoint paper, the importance of regulating nitrification as a strategy to minimize N leakage and to improve N-use efficiency (NUE) in agricultural systems is highlighted. The ability to suppress soil nitrification by the release of nitrification inhibitors from plant roots is termed 'biological nitrification inhibition' (BNI), an active plant-mediated natural function that can limit the amount of N cycling via the nitrification pathway. The development of a bioassay using luminescent Nitrosomonas to quantify nitrification inhibitory activity from roots has facilitated the characterization of BNI function. Release of BNIs from roots is a tightly regulated physiological process, with extensive genetic variability found in selected crops and pasture grasses. Here, the current status of understanding of the BNI function is reviewed using Brachiaria forage grasses, wheat and sorghum to illustrate how BNI function can be utilized for achieving low-nitrifying agricultural systems. A fundamental shift towards ammonium (NH4(+))-dominated agricultural systems could be achieved by using crops and pastures with high BNI capacities. When viewed from an agricultural and environmental perspective, the BNI function in plants could potentially have a large influence on biogeochemical cycling and closure of the N loop in crop-livestock systems.

A paradigm shift towards low-nitrifying production systems: the role of biological nitrification inhibition (BNI)

PubMed Central

Subbarao, G. V.; Sahrawat, K. L.; Nakahara, K.; Rao, I. M.; Ishitani, M.; Hash, C. T.; Kishii, M.; Bonnett, D. G.; Berry, W. L.; Lata, J. C.

2013-01-01

Background Agriculture is the single largest geo-engineering initiative that humans have initiated on planet Earth, largely through the introduction of unprecedented amounts of reactive nitrogen (N) into ecosystems. A major portion of this reactive N applied as fertilizer leaks into the environment in massive amounts, with cascading negative effects on ecosystem health and function. Natural ecosystems utilize many of the multiple pathways in the N cycle to regulate N flow. In contrast, the massive amounts of N currently applied to agricultural systems cycle primarily through the nitrification pathway, a single inefficient route that channels much of this reactive N into the environment. This is largely due to the rapid nitrifying soil environment of present-day agricultural systems. Scope In this Viewpoint paper, the importance of regulating nitrification as a strategy to minimize N leakage and to improve N-use efficiency (NUE) in agricultural systems is highlighted. The ability to suppress soil nitrification by the release of nitrification inhibitors from plant roots is termed ‘biological nitrification inhibition’ (BNI), an active plant-mediated natural function that can limit the amount of N cycling via the nitrification pathway. The development of a bioassay using luminescent Nitrosomonas to quantify nitrification inhibitory activity from roots has facilitated the characterization of BNI function. Release of BNIs from roots is a tightly regulated physiological process, with extensive genetic variability found in selected crops and pasture grasses. Here, the current status of understanding of the BNI function is reviewed using Brachiaria forage grasses, wheat and sorghum to illustrate how BNI function can be utilized for achieving low-nitrifying agricultural systems. A fundamental shift towards ammonium (NH4+)-dominated agricultural systems could be achieved by using crops and pastures with high BNI capacities. When viewed from an agricultural and environmental perspective, the BNI function in plants could potentially have a large influence on biogeochemical cycling and closure of the N loop in crop–livestock systems. PMID:23118123

Preconceptual design of a fluoride high temperature salt-cooled engineering demonstration reactor: Motivation and overview

DOE PAGES

Qualls, A. Louis; Betzler, Benjamin R.; Brown, Nicholas R.; ...

2016-12-21

Engineering demonstration reactors are nuclear reactors built to establish proof of concept for technology options that have never been built. Examples of engineering demonstration reactors include Peach Bottom 1 for high temperature gas-cooled reactors (HTGRs) and Experimental Breeder Reactor-II (EBR-II) for sodium-cooled fast reactors. Historically, engineering demonstrations have played a vital role in advancing the technology readiness level of reactor technologies. Our paper details a preconceptual design for a fluoride salt-cooled engineering demonstration reactor. The fluoride salt-cooled high-temperature reactor (FHR) demonstration reactor (DR) is a concept for a salt-cooled reactor with 100 megawatts of thermal output (MWt). It would usemore » tristructural-isotropic (TRISO) particle fuel within prismatic graphite blocks. FLiBe (2 7LiF-BeF2) is the reference primary coolant. The FHR DR is designed to be small, simple, and affordable. Development of the FHR DR is a necessary intermediate step to enable near-term commercial FHRs. The design philosophy of the FHR DR was focused on safety, near-term deployment, and flexibility. Lower risk technologies are purposely included in the initial FHR DR design to ensure that the reactor can be built, licensed, and operated as an engineering demonstration with minimal risk and cost. These technologies include TRISO particle fuel, replaceable core structures, and consistent structural material selection for core structures and the primary and intermediate loops, and tube-and-shell primary-to-intermediate heat exchangers. Important capabilities to be demonstrated by building and operating the FHR DR include fabrication and operation of high temperature reactors; heat exchanger performance (including passive decay heat removal); pump performance; and reactivity control; salt chemistry control to maximize vessel life; tritium management; core design methodologies; salt procurement, handling, maintenance and ultimate disposal. It is recognized that non-nuclear separate and integral test efforts (e.g., heated salt loops or loops using simulant fluids) are necessary to develop the technologies that will be demonstrated in the FHR DR.« less

Preconceptual design of a fluoride high temperature salt-cooled engineering demonstration reactor: Motivation and overview

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qualls, A. Louis; Betzler, Benjamin R.; Brown, Nicholas R.

Engineering demonstration reactors are nuclear reactors built to establish proof of concept for technology options that have never been built. Examples of engineering demonstration reactors include Peach Bottom 1 for high temperature gas-cooled reactors (HTGRs) and Experimental Breeder Reactor-II (EBR-II) for sodium-cooled fast reactors. Historically, engineering demonstrations have played a vital role in advancing the technology readiness level of reactor technologies. Our paper details a preconceptual design for a fluoride salt-cooled engineering demonstration reactor. The fluoride salt-cooled high-temperature reactor (FHR) demonstration reactor (DR) is a concept for a salt-cooled reactor with 100 megawatts of thermal output (MWt). It would usemore » tristructural-isotropic (TRISO) particle fuel within prismatic graphite blocks. FLiBe (2 7LiF-BeF2) is the reference primary coolant. The FHR DR is designed to be small, simple, and affordable. Development of the FHR DR is a necessary intermediate step to enable near-term commercial FHRs. The design philosophy of the FHR DR was focused on safety, near-term deployment, and flexibility. Lower risk technologies are purposely included in the initial FHR DR design to ensure that the reactor can be built, licensed, and operated as an engineering demonstration with minimal risk and cost. These technologies include TRISO particle fuel, replaceable core structures, and consistent structural material selection for core structures and the primary and intermediate loops, and tube-and-shell primary-to-intermediate heat exchangers. Important capabilities to be demonstrated by building and operating the FHR DR include fabrication and operation of high temperature reactors; heat exchanger performance (including passive decay heat removal); pump performance; and reactivity control; salt chemistry control to maximize vessel life; tritium management; core design methodologies; salt procurement, handling, maintenance and ultimate disposal. It is recognized that non-nuclear separate and integral test efforts (e.g., heated salt loops or loops using simulant fluids) are necessary to develop the technologies that will be demonstrated in the FHR DR.« less

Radiation Enhanced Absorption of Frank Loops by Nanovoids in Cu

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Youxing; Zhang, Xinghang; Wang, Jian

Neutron and heavy ion irradiation generally induces voids in metallic materials, and continuous radiations typically result in void swelling and mechanical failure of the irradiated materials. Recent experiments showed that nanovoids in nanotwinned copper could act as sinks for radiation-induced Frank loops, significantly mitigating radiation damage [Y. Chen et al., Nat. Commun. 6:7036 (2015)]. In this paper, we report on structural evolution of Frank loops under cascades and address the role of nanovoids in absorbing Frank loops in detail by using molecular dynamics simulations. Results show that a stand-alone Frank loop is stable under cascades. When Frank loops are adjacentmore » to nanovoids, the diffusion of a group of atoms from the loop into nanovoids is accomplished via the formation and propagation of dislocation loops. The loop-nanovoid interactions result in the shrinkage of the nanovoids and the Frank loops.« less

Radiation Enhanced Absorption of Frank Loops by Nanovoids in Cu

DOE PAGES

Chen, Youxing; Zhang, Xinghang; Wang, Jian

2016-11-01

Neutron and heavy ion irradiation generally induces voids in metallic materials, and continuous radiations typically result in void swelling and mechanical failure of the irradiated materials. Recent experiments showed that nanovoids in nanotwinned copper could act as sinks for radiation-induced Frank loops, significantly mitigating radiation damage [Y. Chen et al., Nat. Commun. 6:7036 (2015)]. In this paper, we report on structural evolution of Frank loops under cascades and address the role of nanovoids in absorbing Frank loops in detail by using molecular dynamics simulations. Results show that a stand-alone Frank loop is stable under cascades. When Frank loops are adjacentmore » to nanovoids, the diffusion of a group of atoms from the loop into nanovoids is accomplished via the formation and propagation of dislocation loops. The loop-nanovoid interactions result in the shrinkage of the nanovoids and the Frank loops.« less

Conformational Sampling in Template-Free Protein Loop Structure Modeling: An Overview

PubMed Central

Li, Yaohang

2013-01-01

Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a “mini protein folding problem” under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized. PMID:24688696

Conformational sampling in template-free protein loop structure modeling: an overview.

PubMed

Li, Yaohang

2013-01-01

Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a "mini protein folding problem" under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized.

Run-time parallelization and scheduling of loops

NASA Technical Reports Server (NTRS)

Saltz, Joel H.; Mirchandaney, Ravi; Crowley, Kay

1990-01-01

Run time methods are studied to automatically parallelize and schedule iterations of a do loop in certain cases, where compile-time information is inadequate. The methods presented involve execution time preprocessing of the loop. At compile-time, these methods set up the framework for performing a loop dependency analysis. At run time, wave fronts of concurrently executable loop iterations are identified. Using this wavefront information, loop iterations are reordered for increased parallelism. Symbolic transformation rules are used to produce: inspector procedures that perform execution time preprocessing and executors or transformed versions of source code loop structures. These transformed loop structures carry out the calculations planned in the inspector procedures. Performance results are presented from experiments conducted on the Encore Multimax. These results illustrate that run time reordering of loop indices can have a significant impact on performance. Furthermore, the overheads associated with this type of reordering are amortized when the loop is executed several times with the same dependency structure.

Mortality among British Columbians testing for hepatitis C antibody.

PubMed

Yu, Amanda; Spinelli, John J; Cook, Darrel A; Buxton, Jane A; Krajden, Mel

2013-04-02

Hepatitis C virus (HCV) infection is a major preventable and treatable cause of morbidity and mortality. The ability to link population based centralized laboratory HCV testing data with administrative databases provided a unique opportunity to compare mortality between HCV seronegative and seropositive individuals. Through the use of laboratory testing patterns and results, the objective of this study was to differentiate the viral effects of mortality due to HCV infection from risk behaviours/activities that are associated with acquisition of HCV infection. Serological testing data from the British Columbia (BC) Centre for Disease Control Public Health Microbiology and Reference Laboratory from 1992-2004 were linked to the BC Vital Statistics Agency death registry. Four groups of HCV testers were defined by their HCV antibody (anti-HCV) testing patterns: single non-reactive (SNR); serial multiple tested non-reactive (MNR); reactive at initial testing (REAC); and seroconverter (SERO) (previously seronegative followed by reactive, a marker for incident infection). Standardized mortality ratios (SMRs) were calculated to compare the relative risk of all cause and disease specific mortality to that of the BC population for each serological group. Time dependent Cox proportional hazard regression was used to compare hazard ratios (HRs) among HCV serological groups. All anti-HCV testers had higher SMRs than the BC population. Referent to the SNR group, the REAC group had higher risks for liver (HR: 9.62; 95% CI=8.55-10.87) and drug related mortality (HR: 13.70; 95% CI=11.76-16.13). Compared to the REAC group, the SERO group had a lower risk for liver (HR: 0.53; 95% CI=0.24-0.99), but a higher risk for drug related mortality (HR: 1.54; 95% CI=1.12-2.05). These findings confirm that individuals who test anti-HCV positive have increased mortality related to progressive liver disease, and that a substantial proportion of the mortality is attributable to drug use and risk behaviours/activities associated with HCV acquisition. Mortality reduction in HCV infected individuals will require comprehensive prevention programming to reduce the harms due to behaviours/activities which relate to HCV acquisition, as well as HCV treatment to prevent progression of chronic liver disease.

On higher order discrete phase-locked loops.

NASA Technical Reports Server (NTRS)

Gill, G. S.; Gupta, S. C.

1972-01-01

An exact mathematical model is developed for a discrete loop of a general order particularly suitable for digital computation. The deterministic response of the loop to the phase step and the frequency step is investigated. The design of the digital filter for the second-order loop is considered. Use is made of the incremental phase plane to study the phase error behavior of the loop. The model of the noisy loop is derived and the optimization of the loop filter for minimum mean-square error is considered.

On the routing protocol influence on the resilience of wireless sensor networks to jamming attacks.

PubMed

Del-Valle-Soto, Carolina; Mex-Perera, Carlos; Monroy, Raul; Nolazco-Flores, Juan Arturo

2015-03-27

In this work, we compare a recently proposed routing protocol, the multi-parent hierarchical (MPH) protocol, with two well-known protocols, the ad hoc on-demand distance vector (AODV) and dynamic source routing (DSR). For this purpose, we have developed a simulator, which faithfully reifies the workings of a given protocol, considering a fixed, reconfigurable ad hoc network given by the number and location of participants, and general network conditions. We consider a scenario that can be found in a large number of wireless sensor network applications, a single sink node that collects all of the information generated by the sensors. The metrics used to compare the protocols were the number of packet retransmissions, carrier sense multiple access (CSMA) inner loop retries, the number of nodes answering the queries from the coordinator (sink) node and the energy consumption. We tested the network under ordinary (without attacks) conditions (and combinations thereof) and when it is subject to different types of jamming attacks (in particular, random and reactive jamming attacks), considering several positions for the jammer. Our results report that MPH has a greater ability to tolerate such attacks than DSR and AODV, since it minimizes and encapsulates the network segment under attack. The self-configuring capabilities of MPH derived from a combination of a proactive routes update, on a periodic-time basis, and a reactive behavior provide higher resilience while offering a better performance (overhead and energy consumption) than AODV and DSR, as shown in our simulation results.

Discovery of Specific Inhibitors for Intestinal E. coli   β-Glucuronidase through In Silico Virtual Screening

PubMed Central

Cheng, Ta-Chun; Cheng, Kai-Wen; Leu, Yu-Lin; Chuang, Chih-Hung; Huang, Chien-Chaio; Hsieh, Yuan-Chin; Chang, Long-Sen; Cheng, Tian-Lu

2015-01-01

Glucuronidation is a major metabolism process of detoxification for carcinogens, 4-(methylnitrosamino)-1-(3-pyridy)-1-butanone (NNK) and 1,2-dimethylhydrazine (DMH), of reactive oxygen species (ROS). However, intestinal E. coli    β-glucuronidase (eβG) has been considered pivotal to colorectal carcinogenesis. Specific inhibition of eβG may prevent reactivating the glucuronide-carcinogen and protect the intestine from ROS-mediated carcinogenesis. In order to develop specific eβG inhibitors, we found that 59 candidate compounds obtained from the initial virtual screening had high inhibition specificity against eβG but not human βG. In particular, we found that compounds 7145 and 4041 with naphthalenylidene-benzenesulfonamide (NYBS) are highly effective and selective to inhibit eβG activity. Compound 4041  (IC50 = 2.8 μM) shows a higher inhibiting ability than compound 7145  (IC50 = 31.6 μM) against eβG. Furthermore, the molecular docking analysis indicates that compound 4041 has two hydrophobic contacts to residues L361 and I363 in the bacterial loop, but 7145 has one contact to L361. Only compound 4041 can bind to key residue (E413) at active site of eβG via hydrogen-bonding interactions. These novel NYBS-based eβG specific inhibitors may provide as novel candidate compounds, which specifically inhibit eβG to reduce eβG-based carcinogenesis and intestinal injury. PMID:25839056

Discovery of specific inhibitors for intestinal E. coli  β-glucuronidase through in silico virtual screening.

PubMed

Cheng, Ta-Chun; Chuang, Kuo-Hsiang; Roffler, Steve R; Cheng, Kai-Wen; Leu, Yu-Lin; Chuang, Chih-Hung; Huang, Chien-Chaio; Kao, Chien-Han; Hsieh, Yuan-Chin; Chang, Long-Sen; Cheng, Tian-Lu; Chen, Chien-Shu

2015-01-01

Glucuronidation is a major metabolism process of detoxification for carcinogens, 4-(methylnitrosamino)-1-(3-pyridy)-1-butanone (NNK) and 1,2-dimethylhydrazine (DMH), of reactive oxygen species (ROS). However, intestinal E. coli   β-glucuronidase (eβG) has been considered pivotal to colorectal carcinogenesis. Specific inhibition of eβG may prevent reactivating the glucuronide-carcinogen and protect the intestine from ROS-mediated carcinogenesis. In order to develop specific eβG inhibitors, we found that 59 candidate compounds obtained from the initial virtual screening had high inhibition specificity against eβG but not human βG. In particular, we found that compounds 7145 and 4041 with naphthalenylidene-benzenesulfonamide (NYBS) are highly effective and selective to inhibit eβG activity. Compound 4041  (IC50 = 2.8 μM) shows a higher inhibiting ability than compound 7145  (IC50 = 31.6 μM) against eβG. Furthermore, the molecular docking analysis indicates that compound 4041 has two hydrophobic contacts to residues L361 and I363 in the bacterial loop, but 7145 has one contact to L361. Only compound 4041 can bind to key residue (E413) at active site of eβG via hydrogen-bonding interactions. These novel NYBS-based eβG specific inhibitors may provide as novel candidate compounds, which specifically inhibit eβG to reduce eβG-based carcinogenesis and intestinal injury.

Claudin-2-mediated cation and water transport share a common pore

PubMed Central

Rosenthal, Rita; Günzel, Dorothee; Krug, Susanne M.; Schulzke, Jörg-Dieter; Fromm, Michael; Yu, Alan S.L.

2016-01-01

Aim Claudin-2 is a tight junction protein typically located in “leaky” epithelia exhibiting large paracellular permeabilities like small intestine and proximal kidney tubule. Former studies revealed that claudin-2 forms paracellular channels for small cations like sodium and potassium and also paracellular channels for water. This study analyzes whether the diffusive transport of sodium and water occurs through a common pore of the claudin-2 channel. Methods Wild-type claudin-2 and different claudin-2 mutants were expressed in MDCK I kidney tubule cells using an inducible system. Ion and water permeability and the effect of blocking reagents on both were investigated on different clones of the mutants. Results Neutralization of a negatively charged cation interaction site in the pore with the mutation, D65N, decreased both, sodium permeability and water permeability. Claudin-2 mutants (I66C and S68C) with substitution of the pore-lining amino acids with cysteine were used to test the effect of steric blocking of the claudin-2 pore by thiol-reactive reagents. Addition of thiol-reactive reagents to these mutants simultaneously decreased conductance and water permeability. Remarkably, all experimental perturbations caused parallel changes in ion conductance and water permeability, disproving different or independent passage pathways. Conclusion Our results indicate that claudin-2-mediated cation and water transport are frictionally coupled and share a common pore. This pore is lined and determined in permeability by amino acid residues of the first extracellular loop of claudin-2. PMID:27359349

Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections

PubMed Central

Kam, Yiu-Wing; Lee, Cheryl Yi-Pin; Teo, Teck-Hui; Howland, Shanshan W.; Amrun, Siti Naqiah; See, Peter; Kng, Nicholas Qing-Rong; Huber, Roland G.; Xu, Mei-Hui; Tan, Heng-Liang; Choo, Andre; Ginhoux, Florent; Fink, Katja; Wang, Cheng-I; Ng, Lisa F.P.

2017-01-01

Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a conformation-specific epitope on the E monomer, and a quaternary epitope on the virion surface. The most potent ZIKV-neutralizing mAb (SIgN-3C) was assessed in 2 type I interferon receptor–deficient (IFNAR–/–) mouse models of ZIKV infection. Treatment of adult nonpregnant mice with SIgN-3C rescued mice from virus-induced weight loss and mortality. The SIgN-3C variant with Leu-to-Ala mutations in the Fc region (SIgN-3C-LALA) did not induce antibody-dependent enhancement (ADE) in vitro but provided similar levels of protection in vivo. In pregnant ZIKV-infected IFNAR–/– mice, treatment with SIgN-3C or SIgN-3C-LALA significantly reduced viral load in the fetal organs and placenta and abrogated virus-induced fetal growth retardation. Therefore, SIgN-3C-LALA holds promise as a ZIKV prophylactic and therapeutic agent. PMID:28422757

Crosslinked basement membrane-based coatings enhance glucose sensor function and continuous glucose monitoring in vivo.

PubMed

Klueh, Ulrike; Ludzinska, Izabela; Czajkowski, Caroline; Qiao, Yi; Kreutzer, Donald L

2018-01-01

Overcoming sensor-induced tissue reactions is an essential element of achieving successful continuous glucose monitoring (CGM) in the management of diabetes, particularly when used in closed loop technology. Recently, we demonstrated that basement membrane (BM)-based glucose sensor coatings significantly reduced tissue reactions at sites of device implantation. However, the biocompatible BM-based biohydrogel sensor coating rapidly degraded over a less than a 3-week period, which effectively eliminated the protective sensor coating. In an effort to increase the stability and effectiveness of the BM coating, we evaluated the impact of crosslinking BM utilizing glutaraldehyde as a crosslinking agent, designated as X-Cultrex. Sensor performance (nonrecalibrated) was evaluated for the impact of these X-Cultrex coatings in vitro and in vivo. Sensor performance was assessed over a 28-day time period in a murine CGM model and expressed as mean absolute relative difference (MARD) values. Tissue reactivity of Cultrex-coated, X-Cultrex-coated, and uncoated glucose sensors was evaluated over a 28-day time period in vivo using standard histological techniques. These studies demonstrated that X-Cultrex-based sensor coatings had no effect on glucose sensor function in vitro. In vivo, glucose sensor performance was significantly enhanced following X-Cultrex coating throughout the 28-day study. Histological evaluations of X-Cultrex-treated sensors demonstrated significantly less tissue reactivity when compared to uncoated sensors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 7-16, 2018. © 2017 Wiley Periodicals, Inc.

A Power Hardware-in-the-Loop Platform with Remote Distribution Circuit Cosimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmintier, Bryan; Lundstrom, Blake; Chakraborty, Sudipta

2015-04-01

This paper demonstrates the use of a novel cosimulation architecture that integrates hardware testing using Power Hardware-in-the-Loop (PHIL) with larger-scale electric grid models using off-the-shelf, non-PHIL software tools. This architecture enables utilities to study the impacts of emerging energy technologies on their system and manufacturers to explore the interactions of new devices with existing and emerging devices on the power system, both without the need to convert existing grid models to a new platform or to conduct in-field trials. The paper describes an implementation of this architecture for testing two residential-scale advanced solar inverters at separate points of common coupling.more » The same hardware setup is tested with two different distribution feeders (IEEE 123 and 8500 node test systems) modeled using GridLAB-D. In addition to simplifying testing with multiple feeders, the architecture demonstrates additional flexibility with hardware testing in one location linked via the Internet to software modeling in a remote location. In testing, inverter current, real and reactive power, and PCC voltage are well captured by the co-simulation platform. Testing of the inverter advanced control features is currently somewhat limited by the software model time step (1 sec) and tested communication latency (24 msec). Overshoot induced oscillations are observed with volt/VAR control delays of 0 and 1.5 sec, while 3.4 sec and 5.5 sec delays produced little or no oscillation. These limitations could be overcome using faster modeling and communication within the same co-simulation architecture.« less

Xenoepitope substitution avoids deceptive imprinting and broadens the immune response to foot-and-mouth disease virus.

PubMed

Szczepanek, Steven M; Barrette, Roger W; Rood, Debra; Alejo, Diana; Silbart, Lawrence K

2012-04-01

Many RNA viruses encode error-prone polymerases which introduce mutations into B and T cell epitopes, providing a mechanism for immunological escape. When regions of hypervariability are found within immunodominant epitopes with no known function, they are referred to as "decoy epitopes," which often deceptively imprint the host's immune response. In this work, a decoy epitope was identified in the foot-and-mouth disease virus (FMDV) serotype O VP1 G-H loop after multiple sequence alignment of 118 isolates. A series of chimeric cyclic peptides resembling the type O G-H loop were prepared, each bearing a defined "B cell xenoepitope" from another virus in place of the native decoy epitope. These sequences were derived from porcine respiratory and reproductive syndrome virus (PRRSV), from HIV, or from a presumptively tolerogenic sequence from murine albumin and were subsequently used as immunogens in BALB/c mice. Cross-reactive antibody responses against all peptides were compared to a wild-type peptide and ovalbumin (OVA). A broadened antibody response was generated in animals inoculated with the PRRSV chimeric peptide, in which virus binding of serum antibodies was also observed. A B cell epitope mapping experiment did not reveal recognition of any contiguous linear epitopes, raising the possibility that the refocused response was directed to a conformational epitope. Taken together, these results indicate that xenoepitope substitution is a novel method for immune refocusing against decoy epitopes of RNA viruses such as FMDV as part of the rational design of next-generation vaccines.

Functionally Similar WRKY Proteins Regulate Vacuolar Acidification in Petunia and Hair Development in Arabidopsis.

PubMed

Verweij, Walter; Spelt, Cornelis E; Bliek, Mattijs; de Vries, Michel; Wit, Niek; Faraco, Marianna; Koes, Ronald; Quattrocchio, Francesca M

2016-03-01

The WD40 proteins ANTHOCYANIN11 (AN11) from petunia (Petunia hybrida) and TRANSPARENT TESTA GLABRA1 (TTG1) from Arabidopsis thaliana and associated basic helix-loop-helix (bHLH) and MYB transcription factors activate a variety of differentiation processes. In petunia petals, AN11 and the bHLH protein AN1 activate, together with the MYB protein AN2, anthocyanin biosynthesis and, together with the MYB protein PH4, distinct genes, such as PH1 and PH5, that acidify the vacuole. To understand how AN1 and AN11 activate anthocyanin biosynthetic and PH genes independently, we isolated PH3. We found that PH3 is a target gene of the AN11-AN1-PH4 complex and encodes a WRKY protein that can bind to AN11 and is required, in a feed-forward loop, together with AN11-AN1-PH4 for transcription of PH5. PH3 is highly similar to TTG2, which regulates hair development, tannin accumulation, and mucilage production in Arabidopsis. Like PH3, TTG2 can bind to petunia AN11 and the Arabidopsis homolog TTG1, complement ph3 in petunia, and reactivate the PH3 target gene PH5. Our findings show that the specificity of WD40-bHLH-MYB complexes is in part determined by interacting proteins, such as PH3 and TTG2, and reveal an unanticipated similarity in the regulatory circuitry that controls petunia vacuolar acidification and Arabidopsis hair development. © 2016 American Society of Plant Biologists. All rights reserved.

Development of Fluorescent Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) using Quenching Probes for the Detection of the Middle East Respiratory Syndrome Coronavirus.

PubMed

Shirato, Kazuya; Semba, Shohei; El-Kafrawy, Sherif A; Hassan, Ahmed M; Tolah, Ahmed M; Takayama, Ikuyo; Kageyama, Tsutomu; Notomi, Tsugunori; Kamitani, Wataru; Matsuyama, Shutoku; Azhar, Esam Ibraheem

2018-05-12

Clinical detection of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) in patients is achieved using genetic diagnostic methods, such as real-time RT-PCR assay. Previously, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of MERS-CoV [Virol J. 2014. 11:139]. Generally, amplification of RT-LAMP is monitored by the turbidity induced by precipitation of magnesium pyrophosphate with newly synthesized DNA. However, this mechanism cannot completely exclude the possibility of unexpected reactions. Therefore, in this study, fluorescent RT-LAMP assays using quenching probes (QProbes) were developed specifically to monitor only primer-derived signals. Two primer sets (targeting nucleocapsid and ORF1a sequences) were constructed to confirm MERS cases by RT-LAMP assay only. Our data indicate that both primer sets were capable of detecting MERS-CoV RNA to the same level as existing genetic diagnostic methods, and that both were highly specific with no cross-reactivity observed with other respiratory viruses. These primer sets were highly efficient in amplifying target sequences derived from different MERS-CoV strains, including camel MERS-CoV. In addition, the detection efficacy of QProbe RT-LAMP was comparable to that of real-time RT-PCR assay using clinical specimens from patients in Saudi Arabia. Altogether, these results indicate that QProbe RT-LAMP assays described here can be used as powerful diagnostic tools for rapid detection and surveillance of MERS-CoV infections. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Core Design Characteristics of the Fluoride Salt-Cooled High Temperature Demonstration Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Nicholas R; Qualls, A L; Betzler, Benjamin R

2016-01-01

Fluoride salt-cooled high temperature reactors (FHRs) are a promising reactor technology option with significant knowledge gaps to implementation. One potential approach to address those technology gaps is via a small-scale demonstration reactor with the goal of increasing the technology readiness level (TRL) of the overall system for the longer term. The objective of this paper is to outline a notional concept for such a system, and to address how the proposed concept would advance the TRL of FHR concepts. Development of the proposed FHR Demonstration Reactor (DR) will enable commercial FHR deployment through disruptive and rapid technology development and demonstration.more » The FHR DR will close remaining gaps to commercial viability. Lower risk technologies are included in the initial FHR DR design to ensure that the reactor can be built, licensed, and operated within an acceptable budget and schedule. Important capabilities that will be demonstrated by building and operating the FHR DR include core design methodologies; fabrication and operation of high temperature reactors; salt procurement, handling, maintenance, and ultimate disposal; salt chemistry control to maximize vessel life; tritium management; heat exchanger performance; pump performance; and reactivity control. The FHR DR is considered part of a broader set of FHR technology development and demonstration efforts, some of which are already underway. Nonreactor test efforts (e.g., heated salt loops or loops using simulant fluids) can demonstrate many technologies necessary for commercial deployment of FHRs. The FHR DR, however, fulfills a crucial role in FHR technology development by advancing the technical maturity and readiness level of the system as a whole.« less

Rapid detection of the Klebsiella pneumoniae carbapenemase (KPC) gene by loop-mediated isothermal amplification (LAMP).

PubMed

Nakano, Ryuichi; Nakano, Akiyo; Ishii, Yoshikazu; Ubagai, Tsuneyuki; Kikuchi-Ueda, Takane; Kikuchi, Hirotoshi; Tansho-Nagakawa, Shigeru; Kamoshida, Go; Mu, Xiaoqin; Ono, Yasuo

2015-03-01

Klebsiella pneumoniae carbapenemases (KPC), which are associated with resistance to carbapenem, have recently spread worldwide and have become a global concern. It is necessary to detect KPC-producing organisms in clinical settings to be able to control the spread of this resistance. We have developed a loop-mediated isothermal amplification (LAMP) method for rapid detection of KPC producers. LAMP primer sets were designed to recognize the homologous regions of blaKPC-2 to blaKPC-17 and could amplify blaKPC rapidly. The specificity and sensitivity of the primers in the LAMP reactions for blaKPC detection were determined. This LAMP assay was able to specifically detect KPC producers at 68 °C, and no cross-reactivity was observed for other types of β-lactamase (class A, B, C, or D) producers. The detection limit for this assay was found to be 10(0) CFU per tube, in 25 min, which was 10-fold more sensitive than a PCR assay for blaKPC detection. Then, the sensitivity of the LAMP reactions for blaKPC detection in human specimens (sputum samples, urine samples, fecal samples and blood samples) was analyzed; it was observed that the LAMP assay had almost the same sensitivity in these samples as when using purified DNA. The LAMP assay is easy to perform and rapid. It may therefore be routinely applied for detection of KPC producers in the clinical laboratory. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Solid waste management of a chemical-looping combustion plant using Cu-based oxygen carriers.

PubMed

García-Labiano, Francisco; Gayán, Pilar; Adánez, Juan; De Diego, Luis F; Forero, Carmen R

2007-08-15

Waste management generated from a Chemical-Looping Combustion (CLC) plant using copper-based materials is analyzed by two ways: the recovery and recycling of the used material and the disposal of the waste. A copper recovery process coupled to the CLC plant is proposed to avoid the loss of active material generated by elutriation from the system. Solid residues obtained from a 10 kWth CLC prototype operated during 100 h with a CuO-Al2O3 oxygen carrier prepared by impregnation were used as raw material in the recovery process. Recovering efficiencies of approximately 80% were obtained in the process, where the final products were an eluate of Cu(NO3)2 and a solid. The eluate was used for preparation of new oxygen carriers by impregnation, which exhibited high reactivity for reduction and oxidation reactions as well as adequate physical and chemical properties to be used in a CLC plant. The proposed recovery process largely decreases the amount of natural resources (Cu and Al203) employed in a CLC power plant as well as the waste generated in the process. To determine the stability of the different solid streams during deposition in a landfill, these were characterized with respect to their leaching behavior according to the European Union normative. The solid residue finally obtained in the CLC plant coupled to the recovery process (composed by Al2O3 and CuAl2O4) can be classified as a stable nonreactive hazardous waste acceptable at landfills for nonhazardous wastes.

Autoinhibition and signaling by the switch II motif in the G-protein chaperone of a radical B12 enzyme.

PubMed

Lofgren, Michael; Koutmos, Markos; Banerjee, Ruma

2013-10-25

MeaB is an accessory GTPase protein involved in the assembly, protection, and reactivation of 5'-deoxyadenosyl cobalamin-dependent methylmalonyl-CoA mutase (MCM). Mutations in the human ortholog of MeaB result in methylmalonic aciduria, an inborn error of metabolism. G-proteins typically utilize conserved switch I and II motifs for signaling to effector proteins via conformational changes elicited by nucleotide binding and hydrolysis. Our recent discovery that MeaB utilizes an unusual switch III region for bidirectional signaling with MCM raised questions about the roles of the switch I and II motifs in MeaB. In this study, we addressed the functions of conserved switch II residues by performing alanine-scanning mutagenesis. Our results demonstrate that the GTPase activity of MeaB is autoinhibited by switch II and that this loop is important for coupling nucleotide-sensitive conformational changes in switch III to elicit the multiple chaperone functions of MeaB. Furthermore, we report the structure of MeaB·GDP crystallized in the presence of AlFx(-) to form the putative transition state analog, GDP·AlF4(-). The resulting crystal structure and its comparison with related G-proteins support the conclusion that the catalytic site of MeaB is incomplete in the absence of the GTPase-activating protein MCM and therefore unable to stabilize the transition state analog. Favoring an inactive conformation in the absence of the client MCM protein might represent a strategy for suppressing the intrinsic GTPase activity of MeaB in which the switch II loop plays an important role.

Crystal structure of the cytoplasmic phosphatase and tensin homolog (PTEN)-like region of Ciona intestinalis voltage-sensing phosphatase provides insight into substrate specificity and redox regulation of the phosphoinositide phosphatase activity.

PubMed

Matsuda, Makoto; Takeshita, Kohei; Kurokawa, Tatsuki; Sakata, Souhei; Suzuki, Mamoru; Yamashita, Eiki; Okamura, Yasushi; Nakagawa, Atsushi

2011-07-01

Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) has a transmembrane voltage sensor domain and a cytoplasmic region sharing similarity to the phosphatase and tensin homolog (PTEN). It dephosphorylates phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate upon membrane depolarization. The cytoplasmic region is composed of a phosphatase domain and a putative membrane interaction domain, C2. Here we determined the crystal structures of the Ci-VSP cytoplasmic region in three distinct constructs, wild-type (248-576), wild-type (236-576), and G365A mutant (248-576). The crystal structure of WT-236 and G365A-248 had the disulfide bond between the catalytic residue Cys-363 and the adjacent residue Cys-310. On the other hand, the disulfide bond was not present in the crystal structure of WT-248. These suggest the possibility that Ci-VSP is regulated by reactive oxygen species as found in PTEN. These structures also revealed that the conformation of the TI loop in the active site of the Ci-VSP cytoplasmic region was distinct from the corresponding region of PTEN; Ci-VSP has glutamic acid (Glu-411) in the TI loop, orienting toward the center of active site pocket. Mutation of Glu-411 led to acquirement of increased activity toward phosphatidylinositol 3,5-bisphosphate, suggesting that this site is required for determining substrate specificity. Our results provide the basic information of the enzymatic mechanism of Ci-VSP.

A novel loop-mediated isothermal amplification-based test for detecting Neospora caninum DNA.

PubMed

Ramos, Andrea Estefanía; Muñoz, Marina; Cortés-Vecino, Jesús Alfredo; Barato, Paola; Patarroyo, Manuel Alfonso

2017-11-29

Neospora caninum is a cyst-forming, coccidian parasite which is known to cause neurological disorders in dogs and abortion and neonatal mortality in cows and other livestock. This study reports the development of a loop-mediated isothermal amplification (LAMP) assay based on the Neospora caninum Nc-5 gene and compares its efficacy for detecting DNA to that of a semi-nested PCR test. Six primers were designed based on the Nc-5 repeat region of N. caninum. Specific LAMP primers led to successful amplification of N. caninum DNA at 63 °C in 30 min. The LAMP assay was highly specific (i.e. it did not reveal cross-reactivity with other parasite species) and had a low N. caninum plasmid DNA limit of detection (1 fg), which is ten times higher than that for the semi-nested PCR. LAMP applicability was evaluated using a set of naturally-infected samples (59 from canine faeces and five from bovine abortions). Thirty-nine percent (25/64) of the naturally-infected samples were positive for N. caninum DNA by LAMP and 36% (23/64) by semi-nested PCR. However, the LAMP assay is much faster to perform than semi-nested PCR and provides results in 30 min. The optimized reaction conditions described in this study resulted in a sensitive, specific and rapid technique for detecting N. caninum DNA. Considering the advantages of LAMP for detecting N. caninum DNA, further assays aimed at testing its usefulness on a wider range of field samples are recommended.