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Sample records for two-hit model oxidative

  1. Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations.

    Science.gov (United States)

    Monte, Aline Santos; Mello, Bruna Stefânia Ferreira; Borella, Vládia Célia Moreira; da Silva Araujo, Tatiane; da Silva, Francisco Eliclécio Rodrigues; Sousa, Francisca Cléa F de; de Oliveira, Antônio Carlos Pinheiro; Gama, Clarissa Severino; Seeman, Mary V; Vasconcelos, Silvânia Maria Mendes; Lucena, David Freitas De; Macêdo, Danielle

    2017-07-28

    Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. A Two-Hit Model of Autism: Adolescence as the Second Hit

    Science.gov (United States)

    Picci, Giorgia; Scherf, K. Suzanne

    2015-01-01

    Adolescence brings dramatic changes in behavior and neural organization. Unfortunately, for some 30% of individuals with autism, there is marked decline in adaptive functioning during adolescence. We propose a two-hit model of autism. First, early perturbations in neural development function as a “first hit” that sets up a neural system that is “built to fail” in the face of a second hit. Second, the confluence of pubertal hormones, neural reorganization, and increasing social demands during adolescence provides the “second hit” that interferes with the ability to transition into adult social roles and levels of adaptive functioning. In support of this model, we review evidence about adolescent-specific neural and behavioral development in autism. We conclude with predictions and recommendations for empirical investigation about several domains in which developmental trajectories for individuals with autism may be uniquely deterred in adolescence. PMID:26609500

  3. Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

    Science.gov (United States)

    Cucinotta, Francis A.; Ponomarev, Artem

    2009-01-01

    A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

  4. Chronic Porcine Two-Hit Model with Hemorrhagic Shock and textitPseudomonas aeruginosa Sepsis

    OpenAIRE

    Eissner, B.;Matz, K.;Smorodchenko, A.;Röschmann, A.;Specht, B. U. v.

    2016-01-01

    Background: Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as ‘first hit’ followed by a Pseudomonas aeruginosa infusion as ‘second hit’. Materials and Methods: Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic...

  5. Selective histone deacetylase 6 inhibition prolongs survival in a lethal two-hit model.

    Science.gov (United States)

    Cheng, Xin; Liu, Zhengcai; Liu, Baoling; Zhao, Ting; Li, Yongqing; Alam, Hasan B

    2015-07-01

    Hemorrhagic shock (HS) followed by a subsequent insult ("second hit") often initiates an exaggerated systemic inflammatory response and multiple organ failure. We have previously demonstrated that valproic acid, a pan histone deacetylase inhibitor, could improve survival in a rodent "two-hit" model. In the present study, our goal was to determine whether selective inhibition of histone deacetylase 6 with Tubastatin A (Tub-A) could prolong survival in a two-hit model where HS was followed by sepsis from cecal ligation and puncture (CLP). C57Bl/6J mice were subjected to sublethal HS (30% blood loss) and then randomly divided into two groups (n = 13 per group) such as Tub-A group (treatment) and vehicle (VEH) group (control). The Tub-A group was given an intraperitoneal injection of Tub-A (70 mg/kg) dissolved in dimethyl sulfoxide (DMSO). The VEH group was injected with DMSO (1 μl/g body weight). After 24 h, all mice were subjected CLP followed immediately by another dose of Tub-A or DMSO. Survival was monitored for 10 d. In a parallel study, peritoneal irrigation fluid and liver tissue from Tub-A- or DMSO-treated mice were collected 3 h after CLP. Enzyme-linked immunosorbent assay was performed to quantify activity of the myeloperoxidase and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in the peritoneal irrigation fluid. RNA was isolated from the liver tissue, and real-time polymerase chain reaction was performed to measure relative messenger RNA levels of TNF-α and IL-6. Treatment with Tub-A significantly improved survival compared with that of the control (69.2% versus 15.4%). In addition, Tub-A significantly suppressed myeloperoxidase activity (169.9 ± 8.4 ng/mL versus 70.4 ± 17.4 ng/mL; P hit model. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Effects of panaxadiol saponins on contents of TNF-α and IL-6 in two-hit rat models with hemorrhage and lipopolysaech

    International Nuclear Information System (INIS)

    Yu Zhenxiang; Ding Yanhua; Li Lu; Zhao Xuejian

    2005-01-01

    Objective: To explore the changes of serum TNF-α and IL-6 contents in the two-hit rat models with hemorrhage and lipopolysaech (LPS) and the effects of panaxadiol saponins (PDS) on TNF-α and contents IL-6. Methods: Adult Wistar rats were randomly divided into 5 groups: sham operational group (S), hemorrhage group (H), two-hit group with hemorrhage and LPS groups (HL), Dexamethasone pretreatment group (HLD), PDS pretreatment group (HLP). The rat models were made by hemorrhagic shock as the first hit and with endotoxin as the second hit. Then the rats were killed after 6 h. The contents of serum TNF-α and IL-6 in rats were measured by radioimmunoassay. Results: The serum TNF-α and IL-6 contents in HL group were increased significantly compared with S group or H group (P<0.001). The TNF-α and IL-6 contents in HLP group and HLD group were significantly lower than those in HL group (P<0.01). Conclusion: LPS can increase significantly the contents of serum TNF-α and IL-6 in rats with hemorrhagic shock. PDS can inhibit the release of serum TNF-α and IL-6, and has the same effects with DEX to protect against the tissue injuries of two-hit rats with hemorrhage and LPS. (authors)

  7. Mixed Hitting-Time Models

    NARCIS (Netherlands)

    Abbring, J.H.

    2009-01-01

    We study mixed hitting-time models, which specify durations as the first time a Levy process (a continuous-time process with stationary and independent increments) crosses a heterogeneous threshold. Such models of substantial interest because they can be reduced from optimal-stopping models with

  8. Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells.

    Science.gov (United States)

    Song, Jia-Le; Zhao, Xin; Wang, Qiang; Zhang, Ting

    2013-05-01

    Reactive oxygen species (ROS)-induced pancreatic β cell death affects insulin secretion and is important in the pathogenesis of diabetes. Lagerstroemia speciosa, a traditional folk medicine, has been used for t he prevention and treatment of diabetes. However, whether Lagerstroemia speciosa has a cytoprotective effect on pancreatic β cells remains to be elucidated. The present study aimed to investigate the cytoprotective effects of hot water extracts from Lagerstroemia speciosa leaves (LWE) on 3-morpholinosydnonimine (SIN-1)-induced oxidative damage in Syrian hamster pancreatic insulinoma HIT-T15 cells. The HIT-T15 cells were first treated with SIN-1 (50 µM) for 24 h and then co-incubated with LWE for 48 h. SIN-1 significantly decreased HIT-T15 cell viability (PHIT-T15 cells in a dose‑dependent manner. To further investigate the protective effects of LWE on SIN-1‑induced oxidative stress in HIT-T15 cells, the cellular levels of ROS, lipid peroxidation and endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px), were determined. LWE decreased the intracellular levels of ROS and lipid peroxidation, and increased the activities of antioxidant enzymes. These results suggest that LWE has a cytoprotective effect against SIN-1‑induced oxidative stress in HIT-T15 cells through the inhibition of lipid peroxidation, a decrease in ROS levels and an increase in antioxidant enzyme activity. In addition, LWE increased insulin secretion in SIN-1-treated HIT-T15 cells. Our results suggested that LWE were effective in the treatment of diabetes. Further studies are required to study the anti-diabetic molecular mechanism in a cell model.

  9. Possilibity of estimating payoff matrix from model for hit phenomena

    International Nuclear Information System (INIS)

    Ishii, Akira; Sakaidani, Shota; Iwanaga, Saori

    2016-01-01

    The conflicts of topics on social media is considered using an extended mathematical model based on the mathematical model for hit phenomena that has been used to analyze entertainment hits. The social media platform used in this study was blog. The calculation results shows examples of strong conflict, weak conflict, and no conflict cases. Since the conflict of two topics can be considered in the framework of game theory, the results can be used to determine each matrix element of the payoff matrix of game theory.

  10. Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel

    Directory of Open Access Journals (Sweden)

    Ralph A. Pietrofesa

    2016-06-01

    Full Text Available Spaceflight occasionally requires multiple extravehicular activities (EVA that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10 were exposed to >95% O2 for 8 h only (O2, 0.25 Gy ionizing γ-radiation (IR only, or a double-hit combination of both challenges (O2 + IR followed by 16 h of normoxia (ambient air containing 21% O2 and 5% CO2 (1 cycle = 24 h, 2 cycles = 48 h. Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05 decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP, apoptotic (cleaved caspase-3 and BAX, and antioxidant (HO-1 and Nqo1 proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O2 + IR exacerbated cell death and DNA damage compared to individual exposures O2 or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia

  11. A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

    Science.gov (United States)

    Davis, Justin; Eyre, Harris; Jacka, Felice N; Dodd, Seetal; Dean, Olivia; McEwen, Sarah; Debnath, Monojit; McGrath, John; Maes, Michael; Amminger, Paul; McGorry, Patrick D; Pantelis, Christos; Berk, Michael

    2016-01-01

    Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype—the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders. PMID:27073049

  12. Two-fluid (plasma-neutral) Extended-MHD simulations of spheromak configurations in the HIT-SI experiment with PSI-Tet

    Science.gov (United States)

    Sutherland, D. A.; Hansen, C. J.; Jarboe, T. R.

    2017-10-01

    A self-consistent, two-fluid (plasma-neutral) dynamic neutral model has been implemented into the 3-D, Extended-MHD code PSI-Tet. A monatomic, hydrogenic neutral fluid reacts with a plasma fluid through elastic scattering collisions and three inelastic collision reactions: electron-impact ionization, radiative recombination, and resonant charge-exchange. Density, momentum, and energy are evolved for both the plasma and neutral species. The implemented plasma-neutral model in PSI-Tet is being used to simulate decaying spheromak configurations in the HIT-SI experimental geometry, which is being compare to two-photon absorption laser induced fluorescence measurements (TALIF) made on the HIT-SI3 experiment. TALIF is used to measure the absolute density and temperature of monatomic deuterium atoms. Neutral densities on the order of 1015 m-3 and neutral temperatures between 0.6-1.7 eV were measured towards the end of decay of spheromak configurations with initial toroidal currents between 10-12 kA. Validation results between TALIF measurements and PSI-Tet simulations with the implemented dynamic neutral model will be presented. Additionally, preliminary dynamic neutral simulations of the HIT-SI/HIT-SI3 spheromak plasmas sustained with inductive helicity injection will be presented. Lastly, potential benefits of an expansion of the two-fluid model into a multi-fluid model that includes multiple neutral species and tracking of charge states will be discussed.

  13. A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis.

    Science.gov (United States)

    Davis, Justin; Eyre, Harris; Jacka, Felice N; Dodd, Seetal; Dean, Olivia; McEwen, Sarah; Debnath, Monojit; McGrath, John; Maes, Michael; Amminger, Paul; McGorry, Patrick D; Pantelis, Christos; Berk, Michael

    2016-06-01

    Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype-the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Hit Dexter: A Machine-Learning Model for the Prediction of Frequent Hitters.

    Science.gov (United States)

    Stork, Conrad; Wagner, Johannes; Friedrich, Nils-Ole; de Bruyn Kops, Christina; Šícho, Martin; Kirchmair, Johannes

    2018-03-20

    False-positive assay readouts caused by badly behaving compounds-frequent hitters, pan-assay interference compounds (PAINS), aggregators, and others-continue to pose a major challenge to experimental screening. There are only a few in silico methods that allow the prediction of such problematic compounds. We report the development of Hit Dexter, two extremely randomized trees classifiers for the prediction of compounds likely to trigger positive assay readouts either by true promiscuity or by assay interference. The models were trained on a well-prepared dataset extracted from the PubChem Bioassay database, consisting of approximately 311 000 compounds tested for activity on at least 50 proteins. Hit Dexter reached MCC and AUC values of up to 0.67 and 0.96 on an independent test set, respectively. The models are expected to be of high value, in particular to medicinal chemists and biochemists who can use Hit Dexter to identify compounds for which extra caution should be exercised with positive assay readouts. Hit Dexter is available as a free web service at http://hitdexter.zbh. uni-hamburg.de. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Powered two-wheeler drivers' risk of hitting a pedestrian in towns.

    Science.gov (United States)

    Clabaux, Nicolas; Fournier, Jean-Yves; Michel, Jean-Emmanuel

    2014-12-01

    The risk of collision between pedestrians and powered two-wheelers is poorly understood today. The objective of this research is to determine the risk for powered two-wheeler drivers of hitting and injuring a pedestrian per kilometer driven in towns and to compare this risk with that run by four-wheeled vehicle drivers. Using the bodily injury accidents recorded by the police on nine roads in the city of Marseille in 2011 and a campaign of observations of powered two-wheeler traffic, we estimated the risk per kilometer driven by powered two-wheeler drivers of hitting a pedestrian and compared it with the risk run by four-wheeled vehicle drivers. The results show that the risk for powered two-wheeler drivers of hitting and injuring a pedestrian is significantly higher than the risk run by four-wheeled vehicle drivers. On the nine roads studied, it is on average 3.33 times higher (95% CI: 1.63; 6.78). Taking four more years into account made it possible to consolidate these results and to tighten the confidence interval. There does indeed seem to be problems in the interactions between pedestrians and powered two-wheeler users in urban traffic. These interaction problems lead to a higher risk of hitting and injuring a pedestrian for powered two-wheeler drivers than for four-wheeled vehicle drivers. The analysis of the police reports suggests that part of this increased risk comes from filtering maneuvers by powered two-wheelers. Possible countermeasures deal with the urban street layout. Measures consisting in reducing the width and the number of traffic lanes to a strict minimum and installing medians or pedestrian islands could be an effective way for the prevention of urban accidents between pedestrians and powered two-wheelers. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

  16. The distribution of alpha hits per target cell: a parameter to improve risk assessment after inhalation exposure to actinide oxides

    International Nuclear Information System (INIS)

    Fritsch, P.

    2006-01-01

    After inhalation exposure to radionuclides, according to ICRP recommendations, the equivalent dose delivered to the different target regions of the respiratory tract corresponds to a mean value. Some actinide oxides have a very high specific activity, so that, the Annual Limit of Intake (A.L.I.) can be reached when only a few particles have been deposited. In this case, because of the short range of α radiation, only a small fraction of the tissues is irradiated, due to the presence of hot spots. Recently, animal studies have shown that, in the rat, for the same a dose delivered to the lungs, the risk for lung tumour induction varies over more than 1 order of magnitude, depending on the number of deposited particles. The aim of this work is to identify a parameter which could take into account heterogeneity of dose distribution for a realistic risk assessment from the result of a standard dose calculation. In vitro experiments have shown that, the risk for pre-neoplastic transformation per unit of dose gradually decreases when more than 1 α hit is received per target cell. This could be explained by a gradual increase of the ratio of cell death versus cell transformation. Thus, the distribution of the number of α hits per cell could be a useful parameter to improve dose calculation for a risk assessment purpose. The α hit distribution has been characterized in basal cells of the extra thoracic and bronchial epithelia irradiated from the sequestered regions (E.T. seq and B.B. seq ) after exposure inhalation to 1 A.L.I. of 238 U or 238-239 Pu oxide aerosols. Default parameters were used for calculation (aerosol size 5 μm, type S compounds, standard workers). In a first step, the number of particles deposited in the source regions and their activity was obtained after simulations which corresponded to a stochastic application of the ICRP 66 deposition model (the behaviour of each particle was taken into account, and for each particle size, the fraction deposited

  17. Effects of vagus nerve stimulation and vagotomy on systemic and pulmonary inflammation in a two-hit model in rats.

    Directory of Open Access Journals (Sweden)

    Matthijs Kox

    Full Text Available Pulmonary inflammation contributes to ventilator-induced lung injury. Sepsis-induced pulmonary inflammation (first hit may be potentiated by mechanical ventilation (MV, second hit. Electrical stimulation of the vagus nerve has been shown to attenuate inflammation in various animal models through the cholinergic anti-inflammatory pathway. We determined the effects of vagotomy (VGX and vagus nerve stimulation (VNS on systemic and pulmonary inflammation in a two-hit model. Male Sprague-Dawley rats were i.v. administered lipopolysaccharide (LPS and subsequently underwent VGX, VNS or a sham operation. 1 hour following LPS, MV with low (8 mL/kg or moderate (15 mL/kg tidal volumes was initiated, or animals were left breathing spontaneously (SP. After 4 hours of MV or SP, rats were sacrificed. Cytokine and blood gas analysis was performed. MV with 15, but not 8 mL/kg, potentiated the LPS-induced pulmonary pro-inflammatory cytokine response (TNF-α, IL-6, KC: p<0.05 compared to LPS-SP, but did not affect systemic inflammation or impair oxygenation. VGX enhanced the LPS-induced pulmonary, but not systemic pro-inflammatory cytokine response in spontaneously breathing, but not in MV animals (TNF-α, IL-6, KC: p<0.05 compared to SHAM, and resulted in decreased pO(2 (p<0.05 compared to sham-operated animals. VNS did not affect any of the studied parameters in both SP and MV animals. In conclusion, MV with moderate tidal volumes potentiates the pulmonary inflammatory response elicited by systemic LPS administration. No beneficial effects of vagus nerve stimulation performed following LPS administration were found. These results questions the clinical applicability of stimulation of the cholinergic anti-inflammatory pathway in systemically inflamed patients admitted to the ICU where MV is initiated.

  18. NIMROD Simulations of the HIT-SI and HIT-SI3 Devices

    Science.gov (United States)

    Morgan, Kyle; Jarboe, Tom; Hossack, Aaron; Chandra, Rian; Everson, Chris

    2017-10-01

    The Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI) experiment uses a set of inductively driven helicity injectors to apply non-axisymmetric current drive on the edge of the plasma, driving an axisymmetric spheromak equilibrium in a central confinement volume. Significant improvements have been made to extended MHD modeling of HIT-SI, with both the resolution of disagreement at high injector frequencies in HIT-SI in addition to successes with the new upgraded HIT-SI3 device. Previous numerical studies of HIT-SI, using a zero-beta eMHD model, focused on operations with a drive frequency of 14.5 kHz, and found reduced agreement with both the magnetic profile and current amplification at higher frequencies (30-70 kHz). HIT-SI3 has three helicity injectors which are able to operate with different mode structures of perturbations through the different relative temporal phasing of the injectors. Simulations that allow for pressure gradients have been performed in the parameter regimes of both devices using the NIMROD code and show improved agreement with experimental results, most notably capturing the observed Shafranov-shift due to increased beta observed at higher finj in HIT-SI and the variety of toroidal perturbation spectra available in HIT-SI3. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Award Number DE-FG02- 96ER54361.

  19. Anticipating mismatches of HIT investments: Developing a viability-fit model for e-health services.

    Science.gov (United States)

    Mettler, Tobias

    2016-01-01

    Albeit massive investments in the recent years, the impact of health information technology (HIT) has been controversial and strongly disputed by both research and practice. While many studies are concerned with the development of new or the refinement of existing measurement models for assessing the impact of HIT adoption (ex post), this study presents an initial attempt to better understand the factors affecting viability and fit of HIT and thereby underscores the importance of also having instruments for managing expectations (ex ante). We extend prior research by undertaking a more granular investigation into the theoretical assumptions of viability and fit constructs. In doing so, we use a mixed-methods approach, conducting qualitative focus group discussions and a quantitative field study to improve and validate a viability-fit measurement instrument. Our findings suggest two issues for research and practice. First, the results indicate that different stakeholders perceive HIT viability and fit of the same e-health services very unequally. Second, the analysis also demonstrates that there can be a great discrepancy between the organizational viability and individual fit of a particular e-health service. The findings of this study have a number of important implications such as for health policy making, HIT portfolios, and stakeholder communication. Copyright © 2015. Published by Elsevier Ireland Ltd.

  20. Effects of high-intensity interval versus continuous moderate-intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a rat model.

    Science.gov (United States)

    Lu, Kai; Wang, Li; Wang, Changying; Yang, Yuan; Hu, Dayi; Ding, Rongjing

    2015-08-01

    The optimal aerobic exercise training (AET) protocol for patients following myocardial infarction (MI) has remained under debate. The present study therefore aimed to compare the effects of continuous moderate-intensity training (CMT) and high-intensity interval training (HIT) on cardiac functional recovery, and to investigate the potential associated mechanisms in a post-MI rat model. Female Sprague Dawley rats (8-10 weeks old) undergoing MI or sham surgery were subsequently submitted to CMT or HIT, or kept sedentary for eight weeks. Prior to and following AET, echocardiographic parameters and exercise capacity of the rats were measured. Western blotting was used to evaluate the levels of apoptosis and associated signaling pathway protein expression. The concentrations of biomarkers of oxidative stress were also determined by ELISA assay. Messenger (m)RNA levels and activity of the key enzymes for glycolysis and fatty acid oxidation, as well as the rate of adenosine triphosphate (ATP) synthesis, were also measured. Compared with the MI group, exercise capacity and cardiac function were significantly improved following AET, particularly following HIT. Left ventricular ejection fraction and fraction shortening were further improved in the MI-HIT group in comparison to that of the MI-CMT group. The two forms of AET almost equally attenuated apoptosis of the post-infarction myocardium. CMT and HIT also alleviated oxidative stress by decreasing the concentration of malondialdehyde and increasing the concentration of superoxide dismutase and glutathione peroxidase (GPx). In particular, HIT induced a greater increase in the concentration of GPx than that of CMT. AET, and HIT in particular, significantly increased the levels of mRNA and the maximal activity of phosphofructokinase-1 and carnitine palmitoyl transferase-1, as well as the maximal ratio of ATP synthesis. In addition, compared with the MI group, the expression of signaling proteins PI3K, Akt, p38mapk and AMPK

  1. PageRank, HITS and a unified framework for link analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Chris; He, Xiaofeng; Husbands, Parry; Zha, Hongyuan; Simon, Horst

    2001-10-01

    Two popular webpage ranking algorithms are HITS and PageRank. HITS emphasizes mutual reinforcement between authority and hub webpages, while PageRank emphasizes hyperlink weight normalization and web surfing based on random walk models. We systematically generalize/combine these concepts into a unified framework. The ranking framework contains a large algorithm space; HITS and PageRank are two extreme ends in this space. We study several normalized ranking algorithms which are intermediate between HITS and PageRank, and obtain closed-form solutions. We show that, to first order approximation, all ranking algorithms in this framework, including PageRank and HITS, lead to same ranking which is highly correlated with ranking by indegree. These results support the notion that in web resource ranking indegree and outdegree are of fundamental importance. Rankings of webgraphs of different sizes and queries are presented to illustrate our analysis.

  2. Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially Available Devices and by Different Gain Analytical Methods.

    Science.gov (United States)

    Lee, Sang Hun; Yoo, Myung Hoon; Park, Jun Woo; Kang, Byung Chul; Yang, Chan Joo; Kang, Woo Suk; Ahn, Joong Ho; Chung, Jong Woo; Park, Hong Ju

    2018-06-01

    To evaluate whether video head impulse test (vHIT) gains are dependent on the measuring device and method of analysis. Prospective study. vHIT was performed in 25 healthy subjects using two devices simultaneously. vHIT gains were compared between these instruments and using five different methods of comparing position and velocity gains during head movement intervals. The two devices produced different vHIT gain results with the same method of analysis. There were also significant differences in the vHIT gains measured using different analytical methods. The gain analytic method that compares the areas under the velocity curve (AUC) of the head and eye movements during head movements showed lower vHIT gains than a method that compared the peak velocities of the head and eye movements. The former method produced the vHIT gain with the smallest standard deviation among the five procedures tested in this study. vHIT gains differ in normal subjects depending on the device and method of analysis used, suggesting that it is advisable for each device to have its own normal values. Gain calculations that compare the AUC of the head and eye movements during the head movements show the smallest variance.

  3. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    T N Hagawane

    2016-01-01

    Results: It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6 levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. Interpretation & conclusions: The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  4. Revealing the equivalence of two clonal survival models by principal component analysis

    International Nuclear Information System (INIS)

    Lachet, Bernard; Dufour, Jacques

    1976-01-01

    The principal component analysis of 21 chlorella cell survival curves, adjusted by one-hit and two-hit target models, lead to quite similar projections on the principal plan: the homologous parameters of these models are linearly correlated; the reason for the statistical equivalence of these two models, in the present state of experimental inaccuracy, is revealed [fr

  5. Multiple-hit parameter estimation in monolithic detectors.

    Science.gov (United States)

    Hunter, William C J; Barrett, Harrison H; Lewellen, Tom K; Miyaoka, Robert S

    2013-02-01

    We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%-12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied.

  6. Modeling distortion of HIT by an Actuator Disk in a periodic domain

    Science.gov (United States)

    Ghate, Aditya; Ghaisas, Niranjan; Lele, Sanjiva

    2017-11-01

    We study the distortion of incompressible, homogeneous isotropic turbulence (HIT) by a dragging actuator disk with a fixed thrust coefficient (under the large Reynolds number limit), using Large Eddy Simulation (LES). The HIT inflow is tailored to ensure that the largest length scales in the flow are smaller than the actuator disk diameter in order to minimize the meandering of the turbulent wake and isolate the length scales that undergo distortion. The numerical scheme (Fourier collocation with dealiasing) and the SGS closure (anisotropic minimum dissipation model) are carefully selected to minimize numerical artifacts expected due to the inviscid assumption. The LES is used to characterize the following 3 properties of the flow a) distortion of HIT due to the expanding streamtube resulting in strong anisotropy, b) turbulent pressure modulation across the actuator disk, and the c) turbulent wake state. Finally, we attempt to model the initial distortion and the pressure modulation using a WKB variant of RDT solved numerically using a set of discrete Gabor modes. Funding provided by Precourt Institute for Energy at Stanford University.

  7. An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

    Science.gov (United States)

    Bradley, Stuart

    2015-11-20

    Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

  8. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome.

    Science.gov (United States)

    Hagawane, T N; Gaikwad, R V; Kshirsagar, N A

    2016-05-01

    Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  9. Double-hit mouse model of cigarette smoke priming for acute lung injury.

    Science.gov (United States)

    Sakhatskyy, Pavlo; Wang, Zhengke; Borgas, Diana; Lomas-Neira, Joanne; Chen, Yaping; Ayala, Alfred; Rounds, Sharon; Lu, Qing

    2017-01-01

    Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals.

  10. Inflammation and the Two-Hit Hypothesis of Schizophrenia

    Science.gov (United States)

    Feigenson, Keith A.; Kusnecov, Alex W.; Silverstein, Steven M.

    2014-01-01

    The high societal and individual cost of schizophrenia necessitates finding better, more effective treatment, diagnosis, and prevention strategies. One of the obstacles in this endeavor is the diverse set of etiologies that comprises schizophrenia. A substantial body of evidence has grown over the last few decades to suggest that schizophrenia is a heterogeneous syndrome with overlapping symptoms and etiologies. At the same time, an increasing number of clinical, epidemiological, and experimental studies have shown links between schizophrenia and inflammatory conditions. In this review, we analyze the literature on inflammation and schizophrenia, with a particular focus on comorbidity, biomarkers, and environmental insults. We then identify several mechanisms by which inflammation could influence the development of schizophrenia via the two-hit hypothesis. Lastly, we note the relevance of these findings to clinical applications in the diagnosis, prevention, and treatment of schizophrenia. PMID:24247023

  11. Comparison of two mathematical models for describing heat-induced cell killing

    International Nuclear Information System (INIS)

    Roti Roti, J.L.; Henle, K.J.

    1980-01-01

    A computer-based minimization algorithm is utilized to obtain the optimum fits of two models to hyperthermic cell killing data. The models chosen are the multitarget, single-hit equation, which is in general use, and the linear-quadratic equation, which has been applied to cell killing by ionizing irradiation but not to heat-induced cell killing. The linear-quadratic equation fits hyperthermic cell killing data as well as the multitarget, single-hit equation. Both parameters of the linear-quadratic equation obey the Arrhenius law, whereas only one of the two parameters of the multitarget, single-hit equation obeys the Arrhenius law. Thus the linear-quadratic function can completely define cell killing as a function of both time and temperature. In addition, the linear-quadratic model will provide a simplified approach to the study of the synergism between heat and X irradiation

  12. A C++ object-oriented toolkit for track finding with k-dimensional hits

    International Nuclear Information System (INIS)

    Uiterwijk, J.W.E.; Panman, J.; Vyver, B. van de

    2006-01-01

    A library is described for the recognition of tracks in a set of hits. The hits are assumed to be k-dimensional points (k-d), with k>=1, of which a subset can be grouped into tracks by using short-range correlations. A connection graph between the hits is created by sorting the hits first in k-d space using one of the developed, fast, k-space containers. The track-finding algorithm considers any connection between two hits as a possible track seed and grows these seeds into longer track segments using a modified depth-first search of the connection graph. All hit-acceptance decisions are called via abstract methods of an acceptance criterion class which isolates the library from the application's hit and track model. An application is tuned for a particular tracking environment by creating a concrete implementation for the hit and track acceptance calculations. The implementer is free to trade tracking time for acceptance complexity (influencing efficiency) depending on the requirements of the particular application. Results for simulated data show that the track finding is both efficient and fast even for high noise environments

  13. 42 CFR 495.344 - Approval of the State Medicaid HIT plan, the HIT PAPD and update, the HIT IAPD and update, and...

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Approval of the State Medicaid HIT plan, the HIT PAPD and update, the HIT IAPD and update, and the annual HIT IAPD. 495.344 Section 495.344 Public... Requirements Specific to the Medicaid Program § 495.344 Approval of the State Medicaid HIT plan, the HIT PAPD...

  14. Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

    Science.gov (United States)

    Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens

    2016-01-01

    Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160596

  15. Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models.

    Science.gov (United States)

    Baeder, Desiree Y; Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens; Regoes, Roland R

    2016-05-26

    Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. © 2016 The Author(s).

  16. A double hit model for the distribution of time to AIDS onset

    Science.gov (United States)

    Chillale, Nagaraja Rao

    2013-09-01

    Incubation time is a key epidemiologic descriptor of an infectious disease. In the case of HIV infection this is a random variable and is probably the longest one. The probability distribution of incubation time is the major determinant of the relation between the incidences of HIV infection and its manifestation to Aids. This is also one of the key factors used for accurate estimation of AIDS incidence in a region. The present article i) briefly reviews the work done, points out uncertainties in estimation of AIDS onset time and stresses the need for its precise estimation, ii) highlights some of the modelling features of onset distribution including immune failure mechanism, and iii) proposes a 'Double Hit' model for the distribution of time to AIDS onset in the cases of (a) independent and (b) dependent time variables of the two markers and examined the applicability of a few standard probability models.

  17. 77 FR 32639 - HIT Standards Committee and HIT Policy Committee; Call for Nominations

    Science.gov (United States)

    2012-06-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee and HIT Policy Committee; Call for... Health Information Technology Policy Committee (HITPC). Name of Committees: HIT Standards Committee and HIT Policy Committee. General Function of the Committees: The HITSC is charged to provide...

  18. Hit Parade

    DEFF Research Database (Denmark)

    Backe, Hans-Joachim

    2017-01-01

    Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2017, ITU, Copenhagen, DK, Oct 13, 2017.......Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2017, ITU, Copenhagen, DK, Oct 13, 2017....

  19. Hit Parade

    DEFF Research Database (Denmark)

    Cermak, Daniel; Wrighton, Max Alexander; Backe, Hans-Joachim

    2016-01-01

    Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Demo Night, ITU, Copenhagen, DK, Oct 5, 2016.......Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Demo Night, ITU, Copenhagen, DK, Oct 5, 2016....

  20. Hit Parade

    DEFF Research Database (Denmark)

    Cermak, Daniel; Wrighton, Max Alexander; Backe, Hans-Joachim

    2016-01-01

    Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2016, Danish Science Ministry, Copenhagen, DK, Oct 14, 2016.......Daniel Cermak-Sassenrath, Max Alexander Wrighton, Hans-Joachim Backe. Hit Parade. Installation. Kulturnatten 2016, Danish Science Ministry, Copenhagen, DK, Oct 14, 2016....

  1. "Hit-and-Run" leaves its mark: catalyst transcription factors and chromatin modification.

    Science.gov (United States)

    Varala, Kranthi; Li, Ying; Marshall-Colón, Amy; Para, Alessia; Coruzzi, Gloria M

    2015-08-01

    Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome-wide evidence for a "Hit-and-Run" model of transcription. In this model, a master TF "hits" a target promoter to initiate a rapid response to a signal. As the "hit" is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the "run", the master TF "hits" other targets to propagate the response genome-wide. As such, a TF may act as a "catalyst" to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long-term adaptive behavior in the whole organism. This "Hit-and-Run" model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF-regulated and TF-bound genes, implicating transient TF-target binding. Here, we explore this "Hit-and-Run" model to suggest molecular mechanisms and its biological relevance. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

  2. Post-hit dynamics of price limit hits in the Chinese stock markets

    Science.gov (United States)

    Wu, Ting; Wang, Yue; Li, Ming-Xia

    2017-01-01

    Price limit trading rules are useful to cool off traders short-term trading mania on individual stocks. The price dynamics approaching the limit boards are known as the magnet effect. However, the price dynamics after opening price limit hits are not well investigated. Here, we provide a detailed analysis on the price dynamics after the hits of up-limit or down-limit is open based on all A-share stocks traded in the Chinese stock markets. A "W" shape is found in the expected return, which reveals high probability of a continuous price limit hit on the following day. We also find that price dynamics after opening limit hits are dependent on the market trends. The time span of continuously hitting the price limit is found to an influence factor of the expected profit after the limit hit is open. Our analysis provides a better understanding of the price dynamics around the limit boards and contributes potential practical values for investors.

  3. ANALYSIS MUSIC CONCERTS ADOPTING THE MATHEMATICAL MODEL OF HIT PHENOMENA

    OpenAIRE

    Kawahata Yasuko; Genda Etsuo; Ishii Akira

    2013-01-01

    A mathematical model for the hit phenomenon in entertainment within a society is presented as a stochastic process of interactions of human dynamics. In this paper, we analyzed music to the concert.Knowing the cost of advertising the concert is difficult. But exposure to the media of the artist can be seen. We tried to analysis of music concert itself by performing a prediction of reputation of artists during the concert tour from this exposure.In this paper, The world most pop...

  4. Eyewitness Identification Reforms: Are Suggestiveness-Induced Hits and Guesses True Hits?

    Science.gov (United States)

    Wells, Gary L; Steblay, Nancy K; Dysart, Jennifer E

    2012-05-01

    Research-based reforms for collecting eyewitness identification evidence (e.g., unbiased pre-lineup instructions, double-blind administration) have been proposed by psychologists and adopted in increasing numbers of jurisdictions across the United States. It is well known that reducing rates of mistaken identifications can also reduce accurate identification rates (hits). But the reforms are largely designed to reduce the suggestiveness of the procedures they are meant to replace. Accordingly, we argue that it is misleading to label any hits obtained because of suggestive procedures as "hits" and then saddle reforms with the charge that they reduce the rate of these illegitimate hits. Eyewitness identification evidence should be based solely on the independent memory of the witness, not aided by biased instructions, cues from lineup administrators, or the use of lineup fillers who make the suspect stand out. Failure to call out these hits as being illegitimate can give solace to those who are motivated to preserve the status quo. © The Author(s) 2012.

  5. Enhancing hit identification in Mycobacterium tuberculosis drug discovery using validated dual-event Bayesian models.

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    Full Text Available High-throughput screening (HTS in whole cells is widely pursued to find compounds active against Mycobacterium tuberculosis (Mtb for further development towards new tuberculosis (TB drugs. Hit rates from these screens, usually conducted at 10 to 25 µM concentrations, typically range from less than 1% to the low single digits. New approaches to increase the efficiency of hit identification are urgently needed to learn from past screening data. The pharmaceutical industry has for many years taken advantage of computational approaches to optimize compound libraries for in vitro testing, a practice not fully embraced by academic laboratories in the search for new TB drugs. Adapting these proven approaches, we have recently built and validated Bayesian machine learning models for predicting compounds with activity against Mtb based on publicly available large-scale HTS data from the Tuberculosis Antimicrobial Acquisition Coordinating Facility. We now demonstrate the largest prospective validation to date in which we computationally screened 82,403 molecules with these Bayesian models, assayed a total of 550 molecules in vitro, and identified 124 actives against Mtb. Individual hit rates for the different datasets varied from 15-28%. We have identified several FDA approved and late stage clinical candidate kinase inhibitors with activity against Mtb which may represent starting points for further optimization. The computational models developed herein and the commercially available molecules derived from them are now available to any group pursuing Mtb drug discovery.

  6. Sesame oil mitigates nutritional steatohepatitis via attenuation of oxidative stress and inflammation: a tale of two-hit hypothesis.

    Science.gov (United States)

    Periasamy, Srinivasan; Chien, Se-Ping; Chang, Po-Cheng; Hsu, Dur-Zong; Liu, Ming-Yie

    2014-02-01

    Nonalcoholic fatty liver disease, the most common chronic liver disorder worldwide, comprises conditions from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is associated with an increased risk of hepatocellular carcinoma. Sesame oil, a healthful food, increases resistance to oxidative stress, inflammation and protects against multiple organ injury in various animal models. We investigated the protective effect of sesame oil against nutritional steatohepatitis in mice. C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 28 days to induce NASH. Sesame oil (1 and 2 ml/kg) was treated from 22nd to 28th day. Body weight, steatosis, triglycerides, aspartate transaminase, alanine transaminase, nitric oxide, malondialdehyde, tumor necrosis factor-α, interlukin-6, interleukin-1β, leptin, and transforming growth factor-β1 (TGF-β1) were assessed after 28 days. All tested parameters were higher in MCD-fed mice than in normal control mice. Mice fed with MCD diet for 4 weeks showed severe liver injury with steatosis, oxidative stress, and necrotic inflammation. In sesame-oil-treated mice, all tested parameters were significantly attenuated compared with MCD-alone mice. Sesame oil inhibited oxidative stress, inflammatory cytokines, leptin, and TGF-β1 in MCD-fed mice. In addition, histological analysis showed that sesame oil provided significant protection against fibrotic collagen. We conclude that sesame oil protects against steatohepatitic fibrosis by decreasing oxidative stress, inflammatory cytokines, leptin and TGF-β1. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Throat hit in users of the electronic cigarette: An exploratory study.

    Science.gov (United States)

    Etter, Jean-François

    2016-02-01

    A cross-sectional survey on the Internet in 2012-2014 was used to study the "throat hit," the specific sensation in the throat felt by users of e-cigarettes. Participants were 1672 current users of e-cigarettes, visitors of Websites dedicated to e-cigarettes and to smoking cessation. It was assessed whether the strength of the throat hit was associated with the characteristics of e-cigarettes and e-liquids, modifications of the devices, patterns of use, reasons for use, satisfaction with e-cigarettes, dependence on e-cigarettes, smoking behavior, and perceived effects on smoking. The strongest throat hit was obtained by using better-quality models and liquids with high nicotine content. Those who reported a "very strong" throat hit used liquids with 17.3 mg/mL nicotine, versus 7.1 mg/mL for those reporting a "very weak" hit (p e-cigarette models that provide high levels of nicotine, a strong throat hit, high satisfaction, and more effects on smoking, but may also be addictive, and models than contain less nicotine and are less addictive, but produce a weaker throat hit, are less satisfactory, and are possibly less efficient at helping people quit smoking. This trade-off must be kept in mind when regulating e-cigarettes. (c) 2016 APA, all rights reserved).

  8. A fast online hit verification method for the single ion hit system at GSI

    International Nuclear Information System (INIS)

    Du, G.; Fischer, B.; Barberet, P.; Heiss, M.

    2006-01-01

    For a single ion hit facility built to irradiate specific targets inside biological cells, it is necessary to prove that the ions hit the selected targets reliably because the ion hits usually cannot be seen. That ability is traditionally tested either indirectly by aiming at pre-etched tracks in a nuclear track detector or directly by making the ion tracks inside cells visible using a stain coupled to special proteins produced in response to ion hits. However, both methods are time consuming and hits can be verified only after the experiment. This means that targeting errors in the experiment cannot be corrected during the experiment. Therefore, we have developed a fast online hit verification method that measures the targeting accuracy electronically with a spatial resolution of ±1 μm before cell irradiation takes place. (authors)

  9. HIT and brain reward function: A case of mistaken identity (theory).

    Science.gov (United States)

    Wright, Cory; Colombo, Matteo; Beard, Alexander

    2017-08-01

    This paper employs a case study from the history of neuroscience-brain reward function-to scrutinize the inductive argument for the so-called 'Heuristic Identity Theory' (HIT). The case fails to support HIT, illustrating why other case studies previously thought to provide empirical support for HIT also fold under scrutiny. After distinguishing two different ways of understanding the types of identity claims presupposed by HIT and considering other conceptual problems, we conclude that HIT is not an alternative to the traditional identity theory so much as a relabeling of previously discussed strategies for mechanistic discovery. Copyright © 2017. Published by Elsevier Ltd.

  10. Hit and target theories and the molecular theory of radiation action: Notes on the influence of radiation quality

    International Nuclear Information System (INIS)

    Dennis, J.A.

    1977-01-01

    The two target and two hit models are the simplest that can be invoked to explain the dependence of the response of eukaryotic cells on radiation quality. The formal mathematical developments of these two models are contrasted using the LET concept as a description of radiation quality. The two hit model is generalised in terms of event sizes in spherical volumes, as in the dual radiation action theory of Kellerer and Rossi. The effects of short tracks and oxygen enhancement are described. Biological damage is considered as originating in any one of a large number of sites within a cell as in the molecular theory of Chadwick and Leenhouts. Evidence from prokaryotic systems of the possible necessity for more complicated models of radiation action and, in particular, for the necessity to account for the dependence of repair and metabolic factors on radiation quality is cited. The 'track segment' and 'track structure' theories are briefly discussed as alternatives to LET for the description of radiation quality. It is suggested that it would be premature to apply the simple two target or two hit models as a basis for the specification of quality factor in radiological protection. The consequence of doing so would be that the current dose limits for gamma radiation would appear to be too high or that the limits for neutron radiation would appear to be too low. (author)

  11. Health Information Technology (HIT) Adaptation: Refocusing on the Journey to Successful HIT Implementation.

    Science.gov (United States)

    Yen, Po-Yin; McAlearney, Ann Scheck; Sieck, Cynthia J; Hefner, Jennifer L; Huerta, Timothy R

    2017-09-07

    In past years, policies and regulations required hospitals to implement advanced capabilities of certified electronic health records (EHRs) in order to receive financial incentives. This has led to accelerated implementation of health information technologies (HIT) in health care settings. However, measures commonly used to evaluate the success of HIT implementation, such as HIT adoption, technology acceptance, and clinical quality, fail to account for complex sociotechnical variability across contexts and the different trajectories within organizations because of different implementation plans and timelines. We propose a new focus, HIT adaptation, to illuminate factors that facilitate or hinder the connection between use of the EHR and improved quality of care as well as to explore the trajectory of changes in the HIT implementation journey as it is impacted by frequent system upgrades and optimizations. Future research should develop instruments to evaluate the progress of HIT adaptation in both its longitudinal design and its focus on adaptation progress rather than on one cross-sectional outcome, allowing for more generalizability and knowledge transfer. ©Po-Yin Yen, Ann Scheck McAlearney, Cynthia J Sieck, Jennifer L Hefner, Timothy R Huerta. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 07.09.2017.

  12. Mass transfer model for two-layer TBP oxidation reactions: Revision 1

    International Nuclear Information System (INIS)

    Laurinat, J.E.

    1994-01-01

    To prove that two-layer, TBP-nitric acid mixtures can be safely stored in the Canyon evaporators, it must be demonstrated that a runaway reaction between TBP and nitric acid will not occur. Previous bench-scale experiments showed that, at typical evaporator temperatures, this reaction is endothermic and therefore cannot run away, due to the loss of heat from evaporation of water in the organic layer. However, the reaction would be exothermic and could run away if the small amount of water in the organic layer evaporates before the nitric acid in this layer is consumed by the reaction. Provided that there is enough water in the aqueous layer, this would occur if the organic layer is sufficiently thick so that the rate of loss of water by evaporation exceeds the rate of replenishment due to mixing with the aqueous layer. Bubbles containing reaction products enhance the rate of transfer of water from the aqueous layer to the organic layer. These bubbles are generated by the oxidation of TBP and its reaction products in the organic layer and by the oxidation of butanol in the aqueous layer. Butanol is formed by the hydrolysis of TBP in the organic layer. For aqueous-layer bubbling to occur, butanol must transfer into the aqueous layer. Consequently, the rate of oxidation and bubble generation in the aqueous layer strongly depends on the rate of transfer of butanol from the organic to the aqueous layer. This report presents measurements of mass transfer rates for the mixing of water and butanol in two-layer, TBP-aqueous mixtures, where the top layer is primarily TBP and the bottom layer is comprised of water or aqueous salt solution. Mass transfer coefficients are derived for use in the modeling of two-layer TBP-nitric acid oxidation experiments

  13. Comparison of two lung clearance models based on the dissolution rates of oxidized depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Crist, K.C.

    1984-10-01

    An in-vitro dissolution study was conducted on two respirable oxidized depleted uranium samples. The dissolution rates generated from this study were then utilized in the International Commission on Radiological Protection Task Group lung clearance model and a lung clearance model proposed by Cuddihy. Predictions from both models based on the dissolution rates of the amount of oxidized depleted uranium that would be cleared to blood from the pulmonary region following an inhalation exposure were compared. It was found that the predictions made by both models differed considerably. The difference between the predictions was attributed to the differences in the way each model perceives the clearance from the pulmonary region. 33 references, 11 figures, 9 tables.

  14. Comparison of two lung clearance models based on the dissolution rates of oxidized depleted uranium

    International Nuclear Information System (INIS)

    Crist, K.C.

    1984-10-01

    An in-vitro dissolution study was conducted on two respirable oxidized depleted uranium samples. The dissolution rates generated from this study were then utilized in the International Commission on Radiological Protection Task Group lung clearance model and a lung clearance model proposed by Cuddihy. Predictions from both models based on the dissolution rates of the amount of oxidized depleted uranium that would be cleared to blood from the pulmonary region following an inhalation exposure were compared. It was found that the predictions made by both models differed considerably. The difference between the predictions was attributed to the differences in the way each model perceives the clearance from the pulmonary region. 33 references, 11 figures, 9 tables

  15. Dirty Hits

    OpenAIRE

    Clarke, Louise

    2010-01-01

    Issue 9 of the Saatchi Gallery Magazine: Art&Music is dedicated to Sex. The article Dirty Hits invited a cross-section of contemporary artists and musicians to answer: What makes a dirty hit? As one of the artists invited, I wrote an autobiographical piece to reveal how these fumbling, feral sexual experiences of my childhood landscape, along with irrational superstition and folk law inform my life and underpin my work. The article also included an artwork: Louise Clarke, Sip (2009)

  16. Quantum walks with infinite hitting times

    International Nuclear Information System (INIS)

    Krovi, Hari; Brun, Todd A.

    2006-01-01

    Hitting times are the average time it takes a walk to reach a given final vertex from a given starting vertex. The hitting time for a classical random walk on a connected graph will always be finite. We show that, by contrast, quantum walks can have infinite hitting times for some initial states. We seek criteria to determine if a given walk on a graph will have infinite hitting times, and find a sufficient condition, which for discrete time quantum walks is that the degeneracy of the evolution operator be greater than the degree of the graph. The set of initial states which give an infinite hitting time form a subspace. The phenomenon of infinite hitting times is in general a consequence of the symmetry of the graph and its automorphism group. Using the irreducible representations of the automorphism group, we derive conditions such that quantum walks defined on this graph must have infinite hitting times for some initial states. In the case of the discrete walk, if this condition is satisfied the walk will have infinite hitting times for any choice of a coin operator, and we give a class of graphs with infinite hitting times for any choice of coin. Hitting times are not very well defined for continuous time quantum walks, but we show that the idea of infinite hitting-time walks naturally extends to the continuous time case as well

  17. 77 FR 23250 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Science.gov (United States)

    2012-04-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

  18. 76 FR 25355 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Science.gov (United States)

    2011-05-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

  19. 78 FR 29134 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Science.gov (United States)

    2013-05-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy...

  20. Statistical properties and pre-hit dynamics of price limit hits in the Chinese stock markets.

    Science.gov (United States)

    Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

    2015-01-01

    Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders' short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners.

  1. Statistical Properties and Pre-Hit Dynamics of Price Limit Hits in the Chinese Stock Markets

    Science.gov (United States)

    Wan, Yu-Lei; Xie, Wen-Jie; Gu, Gao-Feng; Jiang, Zhi-Qiang; Chen, Wei; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

    2015-01-01

    Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders’ short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners. PMID:25874716

  2. Developing Health Information Technology (HIT) Programs and HIT Curriculum: The Southern Polytechnic State University Experience

    Science.gov (United States)

    Zhang, Chi; Reichgelt, Han; Rutherfoord, Rebecca H.; Wang, Andy Ju An

    2014-01-01

    Health Information Technology (HIT) professionals are in increasing demand as healthcare providers need help in the adoption and meaningful use of Electronic Health Record (EHR) systems while the HIT industry needs workforce skilled in HIT and EHR development. To respond to this increasing demand, the School of Computing and Software Engineering…

  3. Influence of ITO deposition and post annealing on HIT solar cell structures

    NARCIS (Netherlands)

    Zhang, D.; Tavakoliyaraki, A.; Wu, Y.; Van Swaaij, R.A.C.M.M.; Zeman, M.

    2011-01-01

    Heterojunction silicon with intrinsic thin layer (HIT) solar cells that combine advanced thin-film hydrogenated amorphous silicon (a-Si:H) and crystalline silicon (c-Si) technologies are promising because of the high performance at low cost. Due to the low conductivity of a-Si:H, indium tin oxide

  4. Evidence for Ancestral Programming of Resilience in a Two-Hit Stress Model

    Directory of Open Access Journals (Sweden)

    Jamshid Faraji

    2017-05-01

    Full Text Available In a continuously stressful environment, the effects of recurrent prenatal stress (PS may accumulate across generations and alter stress vulnerability and resilience. Here, we report in female rats that a family history of recurrent ancestral PS facilitates certain aspects of movement performance, and that these benefits are abolished by the experience of a second hit, induced by a silent ischemia during adulthood. Female F4-generation rats with and without a family history of cumulative multigenerational PS (MPS were tested for skilled motor function before and after the induction of a minor ischemic insult by endothelin-1 infusion into the primary motor cortex. MPS resulted in improved skilled motor abilities and blunted hypothalamic-pituitary-adrenal (HPA axis function compared to non-stressed rats. Deep sequencing revealed downregulation of miR-708 in MPS rats along with upregulation of its predicted target genes Mapk10 and Rasd2. Through miR-708 stress may regulate mitogen-activated protein kinase (MAPK pathway activity. Hair trace elemental analysis revealed an increased Na/K ratio, which suggests a chronic shift in adrenal gland function. The ischemic lesion activated the HPA axis in MPS rats only; the lesion, however, abolished the advantage of MPS in skilled reaching. The findings indicate that MPS generates adaptive flexibility in movement, which is challenged by a second stressor, such as a neuropathological condition. Thus, a second “hit” by a stressor may limit behavioral flexibility and neural plasticity associated with ancestral stress.

  5. Comparison of different two-pathway models for describing the combined effect of DO and nitrite on the nitrous oxide production by ammonia-oxidizing bacteria.

    Science.gov (United States)

    Lang, Longqi; Pocquet, Mathieu; Ni, Bing-Jie; Yuan, Zhiguo; Spérandio, Mathieu

    2017-02-01

    The aim of this work is to compare the capability of two recently proposed two-pathway models for predicting nitrous oxide (N 2 O) production by ammonia-oxidizing bacteria (AOB) for varying ranges of dissolved oxygen (DO) and nitrite. The first model includes the electron carriers whereas the second model is based on direct coupling of electron donors and acceptors. Simulations are confronted to extensive sets of experiments (43 batches) from different studies with three different microbial systems. Despite their different mathematical structures, both models could well and similarly describe the combined effect of DO and nitrite on N 2 O production rate and emission factor. The model-predicted contributions for nitrifier denitrification pathway and hydroxylamine pathway also matched well with the available isotopic measurements. Based on sensitivity analysis, calibration procedures are described and discussed for facilitating the future use of those models.

  6. Lead generation and examples opinion regarding how to follow up hits.

    Science.gov (United States)

    Orita, Masaya; Ohno, Kazuki; Warizaya, Masaichi; Amano, Yasushi; Niimi, Tatsuya

    2011-01-01

    In fragment-based drug discovery (FBDD), not only identifying the starting fragment hit to be developed but also generating a drug lead from that starting fragment hit is important. Converting fragment hits to leads is generally similar to a high-throughput screening (HTS) hits-to-leads approach in that properties associated with activity for a target protein, such as selectivity against other targets and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox), and physicochemical properties should be taken into account. However, enhancing the potency of the fragment hit is a key requirement in FBDD, unlike HTS, because initial fragment hits are generally weak. This enhancement is presently achieved by adding additional chemical groups which bind to additional parts of the target protein or by joining or combining two or more hit fragments; however, strategies for effecting greater improvements in effective activity are needed. X-ray analysis is a key technology attractive for converting fragments to drug leads. This method makes it clear whether a fragment hit can act as an anchor and provides insight regarding introduction of functional groups to improve fragment activity. Data on follow-up chemical synthesis of fragment hits has allowed for the differentiation of four different strategies: fragment optimization, fragment linking, fragment self-assembly, and fragment evolution. Here, we discuss our opinion regarding how to follow up on fragment hits, with a focus on the importance of fragment hits as an anchor moiety to so-called hot spots in the target protein using crystallographic data. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Verbs in the lexicon: Why is hitting easier than breaking?

    Science.gov (United States)

    McKoon, Gail; Love, Jessica

    2011-11-01

    Adult speakers use verbs in syntactically appropriate ways. For example, they know implicitly that the boy hit at the fence is acceptable but the boy broke at the fence is not. We suggest that this knowledge is lexically encoded in semantic decompositions. The decomposition for break verbs (e.g. crack, smash) is hypothesized to be more complex than that for hit verbs (e.g. kick, kiss). Specifically, the decomposition of a break verb denotes that "an entity changes state as the result of some external force" whereas the decomposition for a hit verb denotes only that "an entity potentially comes in contact with another entity." In this article, verbs of the two types were compared in a lexical decision experiment - Experiment 1 - and they were compared in sentence comprehension experiments with transitive sentences (e.g. the car hit the bicycle and the car broke the bicycle) - Experiments 2 and 3. In Experiment 1, processing times were shorter for the hit than the break verbs and in Experiments 2 and 3, processing times were shorter for the hit sentences than the break sentences, results that are in accord with the complexities of the postulated semantic decompositions.

  8. An explanation for the multiplicative and the additive dose-effect relationship with the single-hit model

    International Nuclear Information System (INIS)

    Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

    1997-01-01

    For solid tumors and for leukemia the excess cancer rate after a single radiation dose D is different. The multiplicative model describes the excess solid tumor probability rate which is proportional to the background rate of cancer and dependent on dose D. The additive model describes the excess probability rate for leukaemia which is proportional to the dose D but unrelated to the spontaneous rate of cancer. A second great difference between the two models is the duration of the increased cancer probability rate. The multiplicative mode predicts that the additional cancer risk persist the whole lifetime after exposure and the additive model predicts excess risk over a period of time. With the Single-hit model (SHM) which is a multistage cancer model both dose-response relationships can be described. It will be shown that only small differences in the derivation will lead to the different relationships. We then analyze the incidence data of leukemia (1950-1987) and of all solid tumors (1958-1987) of the atomic bomb survivors. (author)

  9. Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background.

    Science.gov (United States)

    Farkas, József; Kovács, László Á; Gáspár, László; Nafz, Anna; Gaszner, Tamás; Ujvári, Balázs; Kormos, Viktória; Csernus, Valér; Hashimoto, Hitoshi; Reglődi, Dóra; Gaszner, Balázs

    2017-06-23

    Major depression is a common cause of chronic disability. Despite decades of efforts, no equivocally accepted animal model is available for studying depression. We tested the validity of a new model based on the three-hit concept of vulnerability and resilience. Genetic predisposition (hit 1, mutation of pituitary adenylate cyclase-activating polypeptide, PACAP gene), early-life adversity (hit 2, 180-min maternal deprivation, MD180) and chronic variable mild stress (hit 3, CVMS) were combined. Physical, endocrinological, behavioral and functional morphological tools were used to validate the model. Body- and adrenal weight changes as well as corticosterone titers proved that CVMS was effective. Forced swim test indicated increased depression in CVMS PACAP heterozygous (Hz) mice with MD180 history, accompanied by elevated anxiety level in marble burying test. Corticotropin-releasing factor neurons in the oval division of the bed nucleus of the stria terminalis showed increased FosB expression, which was refractive to CVMS exposure in wild-type and Hz mice. Urocortin1 neurons became over-active in CMVS-exposed PACAP knock out (KO) mice with MD180 history, suggesting the contribution of centrally projecting Edinger-Westphal nucleus to the reduced depression and anxiety level of stressed KO mice. Serotoninergic neurons of the dorsal raphe nucleus lost their adaptation ability to CVMS in MD180 mice. In conclusion, the construct and face validity criteria suggest that MD180 PACAP HZ mice on CD1 background upon CVMS may be used as a reliable model for the three-hit theory. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. The SVT Hit Buffer

    International Nuclear Information System (INIS)

    Belforte, S.; Dell'Orso, M.; Donati, S.

    1996-01-01

    The Hit Buffer is part of the Silicon Vertex Tracker, a trigger processor dedicated to the reconstruction of particle trajectories in the Silicon Vertex Detector and the Central Tracking Chamber of the Collider Detector at Fermilab. The Hit Buffer is a high speed data-traffic node, where thousands of words are received in arbitrary order and simultaneously organized in an internal structured data base, to be later promptly retrieved and delivered in response to specific requests. The Hit Buffer is capable of processing data at a rate of 25 MHz, thanks to the use of special fast devices like Cache-Tag RAMs and high performance Erasable Programmable Logic Devices from the XILINX XC7300 family

  11. Mass transfer model for two-layer TBP oxidation reactions

    International Nuclear Information System (INIS)

    Laurinat, J.E.

    1994-01-01

    To prove that two-layer, TBP-nitric acid mixtures can be safely stored in the canyon evaporators, it must be demonstrated that a runaway reaction between TBP and nitric acid will not occur. Previous bench-scale experiments showed that, at typical evaporator temperatures, this reaction is endothermic and therefore cannot run away, due to the loss of heat from evaporation of water in the organic layer. However, the reaction would be exothermic and could run away if the small amount of water in the organic layer evaporates before the nitric acid in this layer is consumed by the reaction. Provided that there is enough water in the aqueous layer, this would occur if the organic layer is sufficiently thick so that the rate of loss of water by evaporation exceeds the rate of replenishment due to mixing with the aqueous layer. This report presents measurements of mass transfer rates for the mixing of water and butanol in two-layer, TBP-aqueous mixtures, where the top layer is primarily TBP and the bottom layer is comprised of water or aqueous salt solution. Mass transfer coefficients are derived for use in the modeling of two-layer TBP-nitric acid oxidation experiments. Three cases were investigated: (1) transfer of water into the TBP layer with sparging of both the aqueous and TBP layers, (2) transfer of water into the TBP layer with sparging of just the TBP layer, and (3) transfer of butanol into the aqueous layer with sparging of both layers. The TBP layer was comprised of 99% pure TBP (spiked with butanol for the butanol transfer experiments), and the aqueous layer was comprised of either water or an aluminum nitrate solution. The liquid layers were air sparged to simulate the mixing due to the evolution of gases generated by oxidation reactions. A plastic tube and a glass frit sparger were used to provide different size bubbles. Rates of mass transfer were measured using infrared spectrophotometers provided by SRTC/Analytical Development

  12. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis.

    Science.gov (United States)

    Padmanabhan, Anand; Jones, Curtis G; Bougie, Daniel W; Curtis, Brian R; McFarland, Janice G; Wang, Demin; Aster, Richard H

    2015-01-01

    Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain "delayed HIT" seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. © 2015 by The American Society of Hematology.

  13. Single-hit mechanism of tumour cell killing by radiation.

    Science.gov (United States)

    Chapman, J D

    2003-02-01

    To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells

  14. How I treat double-hit lymphoma.

    Science.gov (United States)

    Friedberg, Jonathan W

    2017-08-03

    The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 . These lymphomas, which occur in hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

  15. Computational Physics' Greatest Hits

    Science.gov (United States)

    Bug, Amy

    2011-03-01

    The digital computer, has worked its way so effectively into our profession that now, roughly 65 years after its invention, it is virtually impossible to find a field of experimental or theoretical physics unaided by computational innovation. It is tough to think of another device about which one can make that claim. In the session ``What is computational physics?'' speakers will distinguish computation within the field of computational physics from this ubiquitous importance across all subfields of physics. This talk will recap the invited session ``Great Advances...Past, Present and Future'' in which five dramatic areas of discovery (five of our ``greatest hits'') are chronicled: The physics of many-boson systems via Path Integral Monte Carlo, the thermodynamic behavior of a huge number of diverse systems via Monte Carlo Methods, the discovery of new pharmaceutical agents via molecular dynamics, predictive simulations of global climate change via detailed, cross-disciplinary earth system models, and an understanding of the formation of the first structures in our universe via galaxy formation simulations. The talk will also identify ``greatest hits'' in our field from the teaching and research perspectives of other members of DCOMP, including its Executive Committee.

  16. Statistics of hits to bone cell nuclei

    International Nuclear Information System (INIS)

    Kruglikov, I.L.; Polig, E.; Jee, W.S.S.

    1993-01-01

    The statistics of hits to the nuclei of bone cells irradiated from alpha sources labeling bone tissue is described. It is shown that the law of remodeling of a bone structural unit (BSU), which describes the distribution of quiescence periodes of this unit, affects the statistics of hits. It the irradiation of bone cells occurs during the whole cell cycle, the mean number of hits is independent of the law of remodeling. In this case the variance of hits has the minimum value for constant quiescence periods of BSUs (deterministic remodeling) and the maximum value for exponentially distributed quiescence periods (random remodeling). For the first generation of bone cells, i.e. for the cells which existed at the moment of the uptake of the nuclide, the mean number of hits depends on the law of remodeling. For random remodeling the mean number is equal to the mean value for the complete remodeling cycle. For deterministic remodeling the mean is only half this value. For the first generation of bone cells, changing the law of remodeling from random to deterministic increases the probability of no hits to the nuclei of bone cells. For the same mean value of hits, the difference does not exceed 13.3% of the total number of cells. For the subsequent generations of bone cells, such a change of the law of remodeling decreases the probability of no hits up to 20.4% of the total number of cells. (orig.)

  17. Recent Improvements in the SHIELD-HIT Code

    DEFF Research Database (Denmark)

    Hansen, David Christoffer; Lühr, Armin Christian; Herrmann, Rochus

    2012-01-01

    Purpose: The SHIELD-HIT Monte Carlo particle transport code has previously been used to study a wide range of problems for heavy-ion treatment and has been benchmarked extensively against other Monte Carlo codes and experimental data. Here, an improved version of SHIELD-HIT is developed concentra......Purpose: The SHIELD-HIT Monte Carlo particle transport code has previously been used to study a wide range of problems for heavy-ion treatment and has been benchmarked extensively against other Monte Carlo codes and experimental data. Here, an improved version of SHIELD-HIT is developed...

  18. Thermal oxidation of silicon with two oxidizing species

    International Nuclear Information System (INIS)

    Vild-Maior, A.A.; Filimon, S.

    1979-01-01

    A theoretical model for the thermal oxidation of silicon in wet oxygen is presented. It is shown that the presence of oxygen in the oxidation furnace has an important effect when the water temperature is not too high (less than about 65 deg C). The model is in good agreement with the experimental data. (author)

  19. Nedley Depression Hit Hypothesis

    OpenAIRE

    Nedley, Neil; Ramirez, Francisco E.

    2014-01-01

    Depression is often diagnosed using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. We propose how certain lifestyle choices and non-modifiable factors can predict the development of depression. We identified 10 cause categories (hits or ?blows? to the brain) and theorize that four or more active hits could trigger a depression episode. Methods. A sample of 4271 participants from our community-based program (70% female; ages 17-94 years) was assessed ...

  20. Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward streptozotocin-treated mice and HIT-T15 pancreatic β cells.

    Science.gov (United States)

    Joo, Hye-Eun; Lee, Hyo-Jung; Sohn, Eun Jung; Lee, Min-Ho; Ko, Hyun-Suk; Jeong, Soo-Jin; Lee, Hyo-Jeong; Kim, Sung-Hoon

    2013-01-01

    The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

  1. Current insights into the laboratory diagnosis of HIT.

    Science.gov (United States)

    Bakchoul, T; Zöllner, H; Greinacher, A

    2014-06-01

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune-mediated disorders, the currently available laboratory tests for anti-PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations. © 2014 John Wiley & Sons Ltd.

  2. Constructive Technology Assessment for HIT development

    DEFF Research Database (Denmark)

    Høstgaard, Anna Marie Balling; Bertelsen, Pernille; Petersen, Lone Stub

    2013-01-01

    Experience and time has shown a need for new evaluation methods for evaluating Health Information Technology (HIT), as summative evaluation methods fail to accommodate the rapid and constant changes in HIT over time and to involve end-users, which has been recognized as an important success facto...... during all the phases in the process. Thereby anumber of problems were prevented to occur later on.Thus, the CTA method and its framework are useful for evaluators and project-management in order to facilitate and support successful HIT development....

  3. Double-hit lymphoma demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-hit translocations, MYC/BCL-2 and IRF4/BCL-2.

    Science.gov (United States)

    Tabata, Rie; Yasumizu, Ryoji; Tabata, Chiharu; Kojima, Masaru

    2013-01-01

    Here, we report a rare case of double-hit lymphoma, demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2. The present case had a rare abnormal chromosome, t(6;14;18)(p25;q32;q21), independently, in addition to known dual-hit chromosomal abnormalities, t(14;18)(q32;q21) and t(8;22)(q24;q11.2). Lymph node was characterized by a follicular and diffuse growth pattern with variously sized neoplastic follicles. The intrafollicular area was composed of centrocytes with a few centroblasts and the interfollicular area was occupied by uniformly spread medium- to large-sized lymphocytes. CD23 immunostaining demonstrated a disrupted follicular dendritic cell meshwork. The intrafollicular tumor cells had a germinal center phenotype with the expression of surface IgM, CD10, Bcl-2, Bcl-6, and MUM1/IRF4. However, the interfollicular larger cells showed plasmacytic differentiation with diminished CD20, Bcl-2, Bcl-6, and positive intracytoplasmic IgM, and co-expression of MUM1/IRF4 and CD138 with increased Ki-67-positive cells (> 90%). MUM1/IRF4 has been found to induce c-MYC expression, and in turn, MYC transactivates MUM1/IRF4, creating a positive autoregulatory feedback loop. On the other hand, MUM1/IRF4 functions as a tumor suppressor in c-MYC-induced B-cell leukemia. The present rare case arouses interest in view of the possible "dual" activation of both c-MYC and MUM1/IRF4 through two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2.

  4. Improved process for calculating the probability of being hit by crashing aircraft by the Balfanz-model

    International Nuclear Information System (INIS)

    Hennings, W.

    1988-01-01

    For calculating the probability of being hit by crashing military aircraft on different buildings, a model was introduced, which has already been used in the conventional fields. In the context of converting the research reactor BER II, this model was also used in the nuclear field. The report introduces this model and shows the application to a vertical cylinder as an example. Compared to the previous model, an exact and also simpler solution of the model attempt for determining the shade surface for different shapes of buildings is derived. The problems of the distribution of crashes given by the previous model is treated via the vertical angle and an attempt to solve these problems is given. (orig./HP) [de

  5. Simplified validation of borderline hits of database searches

    OpenAIRE

    Thomas, Henrik; Shevchenko, Andrej

    2008-01-01

    Along with unequivocal hits produced by matching multiple MS/MS spectra to database sequences, LC-MS/MS analysis often yields a large number of hits of borderline statistical confidence. To simplify their validation, we propose to use rapid de novo interpretation of all acquired MS/MS spectra and, with the help of a simple software tool, display the candidate sequences together with each database search hit. We demonstrate that comparing hit database sequences and independent de novo interpre...

  6. Simulation of injector dynamics during steady inductive helicity injection current drive in the HIT-SI experiment

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, C., E-mail: hansec@uw.edu [PSI-Center, University of Washington, Seattle, Washington 98195 (United States); Columbia University, New York, New York 10027 (United States); Marklin, G. [PSI-Center, University of Washington, Seattle, Washington 98195 (United States); Victor, B. [HIT-SI Group, University of Washington, Seattle, Washington 98195 (United States); Akcay, C. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Jarboe, T. [HIT-SI Group, University of Washington, Seattle, Washington 98195 (United States); PSI-Center, University of Washington, Seattle, Washington 98195 (United States)

    2015-04-15

    We present simulations of inductive helicity injection in the Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI) device that treats the entire plasma volume in a single dynamic MHD model. A new fully 3D numerical tool, the PSI-center TETrahedral mesh code, was developed that provides the geometric flexibility required for this investigation. Implementation of a zero-β Hall MHD model using PSI-TET will be presented including formulation of a new self-consistent magnetic boundary condition for the wall of the HIT-SI device. Results from simulations of HIT-SI are presented focusing on injector dynamics that are investigated numerically for the first time. Asymmetries in the plasma loading between the two helicity injectors and progression of field reversal in each injector are observed. Analysis indicates cross-coupling between injectors through confinement volume structures. Injector impedance is found to scale with toroidal current at fixed density, consistent with experimental observation. Comparison to experimental data with an injector drive frequency of 14.5 kHz shows good agreement with magnetic diagnostics. Global mode structures from Bi-Orthogonal decomposition agree well with experimental data for the first four modes.

  7. 78 FR 29135 - HIT Standards Committee Advisory Meeting

    Science.gov (United States)

    2013-05-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting AGENCY: Office of...: HIT Standards Committee. General Function of the Committee: To provide recommendations to the National... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy Committee...

  8. Reduction of multiple hits in atom probe tomography

    International Nuclear Information System (INIS)

    Thuvander, Mattias; Kvist, Anders; Johnson, Lars J.S.; Weidow, Jonathan; Andrén, Hans-Olof

    2013-01-01

    The accuracy of compositional measurements using atom probe tomography is often reduced because some ions are not recorded when several ions hit the detector in close proximity to each other and within a very short time span. In some cases, for example in analysis of carbides, the multiple hits result in a preferential loss of certain elements, namely those elements that frequently field evaporate in bursts or as dissociating molecules. In this paper a method of reducing the effect of multiple hits is explored. A fine metal grid was mounted a few millimeters behind the local electrode, effectively functioning as a filter. This resulted in a decrease in the overall detection efficiency, from 37% to about 5%, but also in a decrease in the fraction of multiple hits. In an analysis of tungsten carbide the fraction of ions originating from multiple hits decreased from 46% to 10%. As a result, the measured carbon concentration increased from 48.2 at%to 49.8 at%, very close to the expected 50.0 at%. The characteristics of the multiple hits were compared for analyses with and without the grid filter. - Highlights: ► APT experiments have been performed with a reduced amount of multiple hits. ► The multiple hits were reduced by placing a grid behind the electrode. ► This resulted in improved carbon measurement of WC

  9. 42 CFR 495.340 - As-needed HIT PAPD update and as-needed HIT IAPD update requirements.

    Science.gov (United States)

    2010-10-01

    ... limited to any of the following: (a) A projected cost increase of $100,000 or more. (b) A schedule... implementation approach, or scope of activities beyond that approved in the HIT planning advance planning document or the HIT implementation advance planning document. (d) A change in implementation concept or a...

  10. On the Hitting Probability of Max-Stable Processes

    OpenAIRE

    Hofmann, Martin

    2012-01-01

    The probability that a max-stable process {\\eta} in C[0, 1] with identical marginal distribution function F hits x \\in R with 0 < F (x) < 1 is the hitting probability of x. We show that the hitting probability is always positive, unless the components of {\\eta} are completely dependent. Moreover, we consider the event that the paths of standard MSP hit some x \\in R twice and we give a sufficient condition for a positive probability of this event.

  11. Implementation of a rapid HIT immunoassay at a university hospital - Retrospective analysis of HIT laboratory orders in patients with thrombocytopenia.

    Science.gov (United States)

    Black, Anne; Heimerl, Susanne; Oertli, Linnéa; Wilczek, Wolf; Greinacher, Andreas; Spannagl, Michael; Herr, Wolfgang; Hart, Christina

    2017-10-01

    Heparin-induced thrombocytopenia (HIT) is a rare cause of thrombocytopenia and a potentially life-threatening adverse drug reaction. Clinical overdiagnosis of HIT results in costly laboratory tests and anticoagulation. Criteria and algorithms for diagnosis are established, but their translation into clinical practice is still challenging. In a retrospective approach we studied all HIT related laboratory test requests within four years and evaluated data before (1st period, 24month) and after (2nd period, 24month) replacing particle gel immunoassay (PaGIA) and enzyme-linked immunosorbent assay (ELISA) by a chemiluminescent immunoassay (CLIA). HIT was confirmed by heparin-induced platelet activation (HIPA) test. Clinical pretest probability for HIT using an implemented simplified 4Ts score and platelet count were evaluated. Costs for laboratory tests and alternative anticoagulation were calculated. In 1850 patients with suspected HIT, 2327 laboratory orders were performed. In 87.2% of these orders an intermediate/high simplified 4Ts score was found. Thrombocytopenia was present in 87.1%. After replacing PaGIA and ELISA by CLIA the number of immunological and functional laboratory tests was reduced by 38.2%. The number of positive HIT immunoassays declined from 22.6% to 6.0%, while the number of positive HIPA tests among positive immunological tests increased by 19%. Altogether, acute HIT was confirmed in 59 patients. A decline in the use of alternative anticoagulants was observed in the 2nd period. Our study shows that in a university hospital setting HIT is well-known, but diagnosis requires a precise laboratory confirmation. Replacing PaGIA and ELISA by CLIA did not influence laboratory order behavior but results in reduced overall costs for laboratory diagnostics and alternative anticoagulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Ultrathin Oxide Passivation Layer by Rapid Thermal Oxidation for the Silicon Heterojunction Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Youngseok Lee

    2012-01-01

    Full Text Available It is difficult to deposit extremely thin a-Si:H layer in heterojunction with intrinsic thin layer (HIT solar cell due to thermal damage and tough process control. This study aims to understand oxide passivation mechanism of silicon surface using rapid thermal oxidation (RTO process by examining surface effective lifetime and surface recombination velocity. The presence of thin insulating a-Si:H layer is the key to get high Voc by lowering the leakage current (I0 which improves the efficiency of HIT solar cell. The ultrathin thermal passivation silicon oxide (SiO2 layer was deposited by RTO system in the temperature range 500–950°C for 2 to 6 minutes. The thickness of the silicon oxide layer was affected by RTO annealing temperature and treatment time. The best value of surface recombination velocity was recorded for the sample treated at a temperature of 850°C for 6 minutes at O2 flow rate of 3 Lpm. A surface recombination velocity below 25 cm/s was obtained for the silicon oxide layer of 4 nm thickness. This ultrathin SiO2 layer was employed for the fabrication of HIT solar cell structure instead of a-Si:H, (i layer and the passivation and tunneling effects of the silicon oxide layer were exploited. The photocurrent was decreased with the increase of illumination intensity and SiO2 thickness.

  13. Dynamics of hepatic gene expression and serum cytokine profiles in single and double-hit burn and sepsis animal models

    Directory of Open Access Journals (Sweden)

    Rohit Rao

    2015-06-01

    Full Text Available We simulate the pathophysiology of severe burn trauma and burn-induced sepsis, using rat models of experimental burn injury and cecal ligation and puncture (CLP either individually (singe-hit model or in combination (double-hit model. The experimental burn injury simulates a systemic but sterile pro-inflammatory response, while the CLP simulates the effect of polymicrobial sepsis. Given the liver׳s central role in mediating the host immune response and onset of hypermetabolism after burn injury, elucidating the alterations in hepatic gene expression in response to injury can lead to a better understanding of the regulation of the inflammatory response, whereas circulating cytokine protein expression, reflects key systemic inflammatory mediators. In this article, we present both the hepatic gene expression and circulating cytokine/chemokine protein expression data for the above-mentioned experimental model to gain insights into the temporal dynamics of the inflammatory and hypermetabolic response following burn and septic injury. This data article supports results discussed in research articles (Yang et al., 2012 [1,4]; Mattick et al. 2012, 2013 [2,3]; Nguyen et al., 2014 [5]; Orman et al., 2011, 2012 [6–8].

  14. HIT or miss: the application of health care information technology to managing uncertainty in clinical decision making.

    Science.gov (United States)

    Kazandjian, Vahé A; Lipitz-Snyderman, Allison

    2011-12-01

    To discuss the usefulness of health care information technology (HIT) in assisting care providers minimize uncertainty while simultaneously increasing efficiency of the care provided. An ongoing study of HIT, performance measurement (clinical and production efficiency) and their implications to the payment for care represents the design of this study. Since 2006, all Maryland hospitals have embarked on a multi-faceted study of performance measures and HIT adoption surveys, which will shape the health care payment model in Maryland, the last of the all-payor states, in 2011. This paper focuses on the HIT component of the Maryland care payment initiative. While the payment model is still under review and discussion, 'appropriateness' of care has been discussed as an important dimension of measurement. Within this dimension, the 'uncertainty' concept has been identified as associated with variation in care practices. Hence, the methods of this paper define how HIT can assist care providers in addressing the concept of uncertainty, and then provides findings from the first HIT survey in Maryland to infer the readiness of Maryland hospital in addressing uncertainty of care in part through the use of HIT. Maryland hospitals show noteworthy variation in their adoption and use of HIT. While computerized, electronic patient records are not commonly used among and across Maryland hospitals, many of the uses of HIT internally in each hospital could significantly assist in better communication about better practices to minimize uncertainty of care and enhance the efficiency of its production. © 2010 Blackwell Publishing Ltd.

  15. Novel HIT antibody detection method using Sonoclot® coagulation analyzer.

    Science.gov (United States)

    Wanaka, Keiko; Asada, Reiko; Miyashita, Kumiko; Kaneko, Makoto; Endo, Hirokazu; Yatomi, Yutaka

    2015-01-01

    Since heparin-induced thrombocytopenia (HIT), caused by the generation of antibodies against platelet factor 4 (PF4)/heparin complexes (HIT antibodies), may induce serious complications due to thrombosis, a prompt diagnosis is desirable. Functional tests with platelet activation to detect HIT antibodies are useful for diagnosis of HIT, in particular (14)C-selotonin release assay (SRA). However, they are complicated and so can be performed only in limited laboratories. We tested if a blood coagulation test using Sonoclot® analyzer can serve for the detection of HIT antibodies. A murine monoclonal antibody (HIT-MoAb) against PF4/heparin complexes was used as an alternative to human HIT antibodies. To the mixture of HIT-MoAb and heparin (0.5 U/mL, final), whole blood obtained from a healthy volunteer was added, and then the activated clotting time (ACT), clot rate (CR), and area under the curve (AUC) were measured with Sonoclot® analyzer for 30minutes. The HIT-MoAb (30 to 100μg/mL, final) concentration dependently suppressed the anticoagulation activity (prolongation of ACT and decrease of CR and AUC) of heparin. The suppression of anticoagulation effect of heparin by HIT-MoAb was demonstrated by measurements using Sonoclot® analyzer. This method may provide a new tool for screening of HIT antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Gorlin syndrome with an ovarian leiomyoma associated with a PTCH1 second hit.

    Science.gov (United States)

    Akizawa, Yoshika; Miyashita, Toshiyuki; Sasaki, Ryo; Nagata, Reiko; Aoki, Ryoko; Ishitani, Ken; Nagashima, Yoji; Matsui, Hideo; Saito, Kayoko

    2016-04-01

    We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS. © 2016 Wiley Periodicals, Inc.

  17. The validation of Huffaz Intelligence Test (HIT)

    Science.gov (United States)

    Rahim, Mohd Azrin Mohammad; Ahmad, Tahir; Awang, Siti Rahmah; Safar, Ajmain

    2017-08-01

    In general, a hafiz who can memorize the Quran has many specialties especially in respect to their academic performances. In this study, the theory of multiple intelligences introduced by Howard Gardner is embedded in a developed psychometric instrument, namely Huffaz Intelligence Test (HIT). This paper presents the validation and the reliability of HIT of some tahfiz students in Malaysia Islamic schools. A pilot study was conducted involving 87 huffaz who were randomly selected to answer the items in HIT. The analysis method used includes Partial Least Square (PLS) on reliability, convergence and discriminant validation. The study has validated nine intelligences. The findings also indicated that the composite reliabilities for the nine types of intelligences are greater than 0.8. Thus, the HIT is a valid and reliable instrument to measure the multiple intelligences among huffaz.

  18. MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

    Science.gov (United States)

    Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

    2018-05-21

    High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

  19. Development and psychometric evaluation of the Impact of Health Information Technology (I-HIT) scale.

    Science.gov (United States)

    Dykes, Patricia C; Hurley, Ann; Cashen, Margaret; Bakken, Suzanne; Duffy, Mary E

    2007-01-01

    The use of health information technology (HIT) for the support of communication processes and data and information access in acute care settings is a relatively new phenomenon. A means of evaluating the impact of HIT in hospital settings is needed. The purpose of this research was to design and psychometrically evaluate the Impact of Health Information Technology scale (I-HIT). I-HIT was designed to measure the perception of nurses regarding the ways in which HIT influences interdisciplinary communication and workflow patterns and nurses' satisfaction with HIT applications and tools. Content for a 43-item tool was derived from the literature, and supported theoretically by the Coiera model and by nurse informaticists. Internal consistency reliability analysis using Cronbach's alpha was conducted on the 43-item scale to initiate the item reduction process. Items with an item total correlation of less than 0.35 were removed, leaving a total of 29 items. Item analysis, exploratory principal component analysis and internal consistency reliability using Cronbach's alpha were used to confirm the 29-item scale. Principal components analysis with Varimax rotation produced a four-factor solution that explained 58.5% of total variance (general advantages, information tools to support information needs, information tools to support communication needs, and workflow implications). Internal consistency of the total scale was 0.95 and ranged from 0.80-0.89 for four subscales. I-HIT demonstrated psychometric adequacy and is recommended to measure the impact of HIT on nursing practice in acute care settings.

  20. Effect of high-intensity intermittent swimming training on fatty acid oxidation enzyme activity in rat skeletal muscle.

    Science.gov (United States)

    Terada, Shin; Tabata, Izumi; Higuchi, Mitsuru

    2004-02-01

    We previously reported that high-intensity exercise training significantly increased citrate synthase (CS) activity, a marker of oxidative enzyme, in rat skeletal muscle to a level equaling that attained after low-intensity prolonged exercise training (Terada et al., J Appl Physiol 90: 2019-2024, 2001). Since mitochondrial oxidative enzymes and fatty acid oxidation (FAO) enzymes are often increased simultaneously, we assessed the effect of high-intensity intermittent swimming training on FAO enzyme activity in rat skeletal muscle. Male Sprague-Dawley rats (3 to 4 weeks old) were assigned to a 10-day period of high-intensity intermittent exercise training (HIT), low-intensity prolonged exercise training (LIT), or sedentary control conditions. In the HIT group, the rats repeated fourteen 20 s swimming sessions with a weight equivalent to 14-16% of their body weight. Between the exercise sessions, a 10 s pause was allowed. Rats in the LIT group swam 6 h/day in two 3 h sessions separated by 45 min of rest. CS activity in the triceps muscle of rats in the HIT and LIT groups was significantly higher than that in the control rats by 36 and 39%, respectively. Furthermore, 3-beta hydroxyacyl-CoA dehydrogenase (HAD) activity, an important enzyme in the FAO pathway in skeletal muscle, was higher in the two training groups than in the control rats (HIT: 100%, LIT: 88%). No significant difference in HAD activity was observed between the two training groups. In conclusion, the present investigation demonstrated that high-intensity intermittent swimming training elevated FAO enzyme activity in rat skeletal muscle to a level similar to that attained after 6 h of low-intensity prolonged swimming exercise training.

  1. DEPDC5 takes a second hit in familial focal epilepsy.

    Science.gov (United States)

    Anderson, Matthew P

    2018-04-30

    Loss-of-function mutations in a single allele of the gene encoding DEP domain-containing 5 protein (DEPDC5) are commonly linked to familial focal epilepsy with variable foci; however, a subset of patients presents with focal cortical dysplasia that is proposed to result from a second-hit somatic mutation. In this issue of the JCI, Ribierre and colleagues provide several lines of evidence to support second-hit DEPDC5 mutations in this disorder. Moreover, the authors use in vivo, in utero electroporation combined with CRISPR-Cas9 technology to generate a murine model of the disease that recapitulates human manifestations, including cortical dysplasia-like changes, focal seizures, and sudden unexpected death. This study provides important insights into familial focal epilepsy and provides a preclinical model for evaluating potential therapies.

  2. MIDAS and HIT-6 French translation: reliability and correlation between tests.

    Science.gov (United States)

    Magnoux, E; Freeman, M A; Zlotnik, G

    2008-01-01

    The aim was to evaluate the test-retest reliability of the French translation of the Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT)-6 questionnaires as applied to episodic and chronic headaches and to assess the correlation between these two questionnaires. The MIDAS and HIT-6 questionnaires, which assess the degree of migraine-related functional disability, are widely used in headache treatment clinics. The French translation has not been checked for test-retest reliability. MIDAS involves recall, over the previous 3 months, of the number of days with functional disability with regard to work and to home and social life. HIT-6 involves a more subjective and general assessment of headache-related disability over the previous 4 weeks. We expect that there may be greater impact recall bias for chronic headaches than for episodic headaches and considered it important to be able to determine if the reliability of these questionnaires is equally good for these two patient populations. Given that both questionnaires have the same objective, that of assessing headache impact, it was thought useful to determine if their results might show a correlation and if they could thus be used interchangeably. The study was approved by an external ethics committee. The subjects were patients who regularly visit the Clinique de la Migraine de Montréal, which specializes in the treatment of headaches. The MIDAS and HIT-6 questionnaires were completed by the patients during their regular visit. Twelve days later, the same questionnaires were mailed with a prepaid return envelope. Sixty-five patients were required in both the episodic and chronic headache groups, assuming an 80% questionnaire return rate. One hundred and eighty-five patients were enrolled, and 143 completed the study, 75 with episodic headaches and 68 with chronic headaches. The questionnaire return rate was 78.9%. On average, questionnaires were completed a second time 21 days after the first

  3. Capture orbits around asteroids by hitting zero-velocity curves

    Science.gov (United States)

    Wang, Wei; Yang, Hongwei; Zhang, Wei; Ma, Guangfu

    2017-12-01

    The problem of capturing a spacecraft from a heliocentric orbit into a high parking orbit around binary asteroids is investigated in the current study. To reduce the braking Δ V, a new capture strategy takes advantage of the three-body gravity of the binary asteroid to lower the inertial energy before applying the Δ V. The framework of the circular restricted three-body problem (CR3BP) is employed for the binary asteroid system. The proposed capture strategy is based on the mechanism by which inertial energy can be decreased sharply near zero-velocity curves (ZVCs). The strategy has two steps, namely, hitting the target ZVC and raising the periapsis by a small Δ V at the apoapsis. By hitting the target ZVC, the positive inertial energy decreases and becomes negative. Using a small Δ V, the spacecraft inserts into a bounded orbit around the asteroid. In addition, a rotating mass dipole model is employed for elongated asteroids, which leads to dynamics similar to that of the CR3BP. With this approach, the proposed capture strategy can be applied to elongated asteroids. Numerical simulations validate that the proposed capture strategy is applicable for the binary asteroid 90 Antiope and the elongated asteroid 216 Kleopatra.

  4. Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

    Science.gov (United States)

    Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

    2017-10-05

    One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

  5. Računarska simulacija utroška municije do prvog pogotka u iznenadnom sukobu dva tenka / Computer simulation of ammunition consumption until the first hit in a sudden two-tank conflict

    Directory of Open Access Journals (Sweden)

    Radomir Janković

    2004-05-01

    Full Text Available Predmet ovog rada je računarska simulacija utroška municije do prvog pogotka glavnih oruđa dva tenka u iznenadnom sukobu. Prvi pogodak je bitan, jer često ima presudan uticaj na krajnji ishod sukoba tenkova. Tenkovi su naoružani različitim glavnim oruđima, od kojih je jedno protivoklopna vođena raketa, a drugo top sa brzim potkalibarnim probojnim projektilima. Definisan je iznenadni sukob tenkova, date su polazne pretpostavke i prikazan je simulacioni model pomoću grafičke predstave kretanja platformi, matematičkih transformacija i algoritamskog opisa. Model je implementiran pomoću simulacionog jezika GPSS World. Analizirani su rezultati 10 eksperimenata pri različitim vrednostima početnog rastojanja tenkova u iznenadnom sukobu. / The subject of the paper is computer simulation of ammunition consumption until the first hit in a sudden two-tank conflict. The first hit is important because it is often decisive in a two-tank conflict issue. The tanks are armed with different main weapons, one of which is a guided antiarmour missile, and the other is a classic gun which fires armour piercing rounds. The sudden conflict of tanks has been defined, starting assumptions have been given and the simulation model has been presented by means of the graphic representation of the platforms moving, mathematical transforms and algorithmic description. The model has been implemented by means of the GPSS World simulation language. The results of 10 experiments have been analyzed with various initial distances of the tanks in conflict.

  6. Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

    Science.gov (United States)

    Sanders, John M; Beshore, Douglas C; Culberson, J Christopher; Fells, James I; Imbriglio, Jason E; Gunaydin, Hakan; Haidle, Andrew M; Labroli, Marc; Mattioni, Brian E; Sciammetta, Nunzio; Shipe, William D; Sheridan, Robert P; Suen, Linda M; Verras, Andreas; Walji, Abbas; Joshi, Elizabeth M; Bueters, Tjerk

    2017-08-24

    High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter. These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected liabilities that may require significant optimization. Accordingly, these in silico data can direct ADMET experimentation and profoundly impact the progression of hit series. Several prospective examples are presented to substantiate the value of this approach.

  7. Synthetic Medicinal Chemistry in Chagas' Disease: Compounds at The Final Stage of "Hit-To-Lead" Phase.

    Science.gov (United States)

    Cerecetto, Hugo; González, Mercedes

    2010-03-25

    Chagas' disease, or American trypanosomosiasis, has been the most relevant illness produced by protozoa in Latin America. Synthetic medicinal chemistry efforts have provided an extensive number of chemodiverse hits at the "active-to-hit" stage. However, only a more limited number of these have been studied in vivo in models of Chagas' disease. Herein, we survey some of the cantidates able to surpass the "hit-to-lead" stage discussing their limitations or merit to enter in clinical trials in the short term.

  8. Health information technology knowledge and skills needed by HIT employers.

    Science.gov (United States)

    Fenton, S H; Gongora-Ferraez, M J; Joost, E

    2012-01-01

    To evaluate the health information technology (HIT) workforce knowledge and skills needed by HIT employers. Statewide face-to-face and online focus groups of identified HIT employer groups in Austin, Brownsville, College Station, Dallas, El Paso, Houston, Lubbock, San Antonio, and webinars for rural health and nursing informatics. HIT employers reported needing an HIT workforce with diverse knowledge and skills ranging from basic to advanced, while covering information technology, privacy and security, clinical practice, needs assessment, contract negotiation, and many other areas. Consistent themes were that employees needed to be able to learn on the job and must possess the ability to think critically and problem solve. Many employers wanted persons with technical skills, yet also the knowledge and understanding of healthcare operations. The HIT employer focus groups provided valuable insight into employee skills needed in this fast-growing field. Additionally, this information will be utilized to develop a statewide HIT workforce needs assessment survey.

  9. Reconstruction of hit time and hit position of annihilation quanta in the J-PET detector using the Mahalanobis distance

    Directory of Open Access Journals (Sweden)

    Sharma Neha Gupta

    2015-12-01

    Full Text Available The J-PET detector being developed at the Jagiellonian University is a positron emission tomograph composed of the long strips of polymer scintillators. At the same time, it is a detector system that will be used for studies of the decays of positronium atoms. The shape of photomultiplier signals depends on the hit time and hit position of the gamma quantum. In order to take advantage of this fact, a dedicated sampling front-end electronics that enables to sample signals in voltage domain with the time precision of about 20 ps and novel reconstruction method based on the comparison of examined signal with the model signals stored in the library has been developed. As a measure of the similarity, we use the Mahalanobis distance. The achievable position and time resolution depend on the number and values of the threshold levels at which the signal is sampled. A reconstruction method as well as preliminary results are presented and discussed.

  10. Improvements to the ion Doppler spectrometer diagnostic on the HIT-SI experiments

    Science.gov (United States)

    Hossack, Aaron; Chandra, Rian; Everson, Chris; Jarboe, Tom

    2018-03-01

    An ion Doppler spectrometer diagnostic system measuring impurity ion temperature and velocity on the HIT-SI and HIT-SI3 spheromak devices has been improved with higher spatiotemporal resolution and lower error than previously described devices. Hardware and software improvements to the established technique have resulted in a record of 6.9 μs temporal and ≤2.8 cm spatial resolution in the midplane of each device. These allow Ciii and Oii flow, displacement, and temperature profiles to be observed simultaneously. With 72 fused-silica fiber channels in two independent bundles, and an f/8.5 Czerny-Turner spectrometer coupled to a video camera, frame rates of up to ten times the imposed magnetic perturbation frequency of 14.5 kHz were achieved in HIT-SI, viewing the upper half of the midplane. In HIT-SI3, frame rates of up to eight times the perturbation frequency were achieved viewing both halves of the midplane. Biorthogonal decomposition is used as a novel filtering tool, reducing uncertainty in ion temperature from ≲13 to ≲5 eV (with an instrument temperature of 8-16 eV) and uncertainty in velocity from ≲2 to ≲1 km/s. Doppler shift and broadening are calculated via the Levenberg-Marquardt algorithm, after which the errors in velocity and temperature are uniquely specified. Axisymmetric temperature profiles on HIT-SI3 for Ciii peaked near the inboard current separatrix at ≈40 eV are observed. Axisymmetric plasma displacement profiles have been measured on HIT-SI3, peaking at ≈6 cm at the outboard separatrix. Both profiles agree with the upper half of the midplane observable by HIT-SI. With its complete midplane view, HIT-SI3 has unambiguously extracted axisymmetric, toroidal current dependent rotation of up to 3 km/s. Analysis of the temporal phase of the displacement uncovers a coherent structure, locked to the applied perturbation. Previously described diagnostic systems could not achieve such results.

  11. 75 FR 21629 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2010-04-26

    ... Technology; HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Standards Committee's Workgroups: Clinical Operations Vocabulary... developed by the HIT Policy Committee. Date and Time: The HIT Standards Committee Workgroups will hold the...

  12. 77 FR 66617 - HIT Policy and Standards Committees; Workgroup Application Database

    Science.gov (United States)

    2012-11-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy and Standards Committees; Workgroup Application... of New ONC HIT FACA Workgroup Application Database. The Office of the National Coordinator (ONC) has.... Name of Committees: HIT Standards Committee and HIT Policy Committee. General Function of the...

  13. Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi.

    Science.gov (United States)

    Keenan, Martine; Alexander, Paul W; Chaplin, Jason H; Abbott, Michael J; Diao, Hugo; Wang, Zhisen; Best, Wayne M; Perez, Catherine J; Cornwall, Scott M J; Keatley, Sarah K; Thompson, R C Andrew; Charman, Susan A; White, Karen L; Ryan, Eileen; Chen, Gong; Ioset, Jean-Robert; von Geldern, Thomas W; Chatelain, Eric

    2013-10-01

    Inhibitors of Trypanosoma cruzi with novel mechanisms of action are urgently required to diversify the current clinical and preclinical pipelines. Increasing the number and diversity of hits available for assessment at the beginning of the discovery process will help to achieve this aim. We report the evaluation of multiple hits generated from a high-throughput screen to identify inhibitors of T. cruzi and from these studies the discovery of two novel series currently in lead optimization. Lead compounds from these series potently and selectively inhibit growth of T. cruzi in vitro and the most advanced compound is orally active in a subchronic mouse model of T. cruzi infection. High-throughput screening of novel compound collections has an important role to play in diversifying the trypanosomatid drug discovery portfolio. A new T. cruzi inhibitor series with good drug-like properties and promising in vivo efficacy has been identified through this process.

  14. 76 FR 46297 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... developed by the HIT Policy Committee. Date and Time: The HIT Standards Committee Workgroups will hold the...

  15. Neurodevelopmental Animal Models Reveal the Convergent Role of Neurotransmitter Systems, Inflammation, and Oxidative Stress as Biomarkers of Schizophrenia: Implications for Novel Drug Development.

    Science.gov (United States)

    Möller, M; Swanepoel, T; Harvey, B H

    2015-07-15

    Schizophrenia is a life altering disease with a complex etiology and pathophysiology, and although antipsychotics are valuable in treating the disorder, certain symptoms and/or sufferers remain resistant to treatment. Our poor understanding of the underlying neuropathological mechanisms of schizophrenia hinders the discovery and development of improved pharmacological treatment, so that filling these gaps is of utmost importance for an improved outcome. A vast amount of clinical data has strongly implicated the role of inflammation and oxidative insults in the pathophysiology of schizophrenia. Preclinical studies using animal models are fundamental in our understanding of disease development and pathology as well as the discovery and development of novel treatment options. In particular, social isolation rearing (SIR) and pre- or postnatal inflammation (PPNI) have shown great promise in mimicking the biobehavioral manifestations of schizophrenia. Furthermore, the "dual-hit" hypothesis of schizophrenia states that a first adverse event such as genetic predisposition or a prenatal insult renders an individual susceptible to develop the disease, while a second insult (e.g., postnatal inflammation, environmental adversity, or drug abuse) may be necessary to precipitate the full-blown syndrome. Animal models that emphasize the "dual-hit" hypothesis therefore provide valuable insight into understanding disease progression. In this Review, we will discuss SIR, PPNI, as well as possible "dual-hit" animal models within the context of the redox-immune-inflammatory hypothesis of schizophrenia, correlating such changes with the recognized monoamine and behavioral alterations of schizophrenia. Finally, based on these models, we will review new therapeutic options, especially those targeting immune-inflammatory and redox pathways.

  16. Numerical modelling of local deposition patients, activity distributions and cellular hit probabilities of inhaled radon progenies in human airways

    International Nuclear Information System (INIS)

    Farkas, A.; Balashazy, I.; Szoeke, I.

    2003-01-01

    The general objective of our research is modelling the biophysical processes of the effects of inhaled radon progenies. This effort is related to the rejection or support of the linear no threshold (LNT) dose-effect hypothesis, which seems to be one of the most challenging tasks of current radiation protection. Our approximation and results may also serve as a useful tool for lung cancer models. In this study, deposition patterns, activity distributions and alpha-hit probabilities of inhaled radon progenies in the large airways of the human tracheobronchial tree are computed. The airflow fields and related particle deposition patterns strongly depend on the shape of airway geometry and breathing pattern. Computed deposition patterns of attached an unattached radon progenies are strongly inhomogeneous creating hot spots at the carinal regions and downstream of the inner sides of the daughter airways. The results suggest that in the vicinity of the carinal regions the multiple hit probabilities are quite high even at low average doses and increase exponentially in the low-dose range. Thus, even the so-called low doses may present high doses for large clusters of cells. The cell transformation probabilities are much higher in these regions and this phenomenon cannot be modeled with average burdens. (authors)

  17. Near-optimal alternative generation using modified hit-and-run sampling for non-linear, non-convex problems

    Science.gov (United States)

    Rosenberg, D. E.; Alafifi, A.

    2016-12-01

    Water resources systems analysis often focuses on finding optimal solutions. Yet an optimal solution is optimal only for the modelled issues and managers often seek near-optimal alternatives that address un-modelled objectives, preferences, limits, uncertainties, and other issues. Early on, Modelling to Generate Alternatives (MGA) formalized near-optimal as the region comprising the original problem constraints plus a new constraint that allowed performance within a specified tolerance of the optimal objective function value. MGA identified a few maximally-different alternatives from the near-optimal region. Subsequent work applied Markov Chain Monte Carlo (MCMC) sampling to generate a larger number of alternatives that span the near-optimal region of linear problems or select portions for non-linear problems. We extend the MCMC Hit-And-Run method to generate alternatives that span the full extent of the near-optimal region for non-linear, non-convex problems. First, start at a feasible hit point within the near-optimal region, then run a random distance in a random direction to a new hit point. Next, repeat until generating the desired number of alternatives. The key step at each iterate is to run a random distance along the line in the specified direction to a new hit point. If linear equity constraints exist, we construct an orthogonal basis and use a null space transformation to confine hits and runs to a lower-dimensional space. Linear inequity constraints define the convex bounds on the line that runs through the current hit point in the specified direction. We then use slice sampling to identify a new hit point along the line within bounds defined by the non-linear inequity constraints. This technique is computationally efficient compared to prior near-optimal alternative generation techniques such MGA, MCMC Metropolis-Hastings, evolutionary, or firefly algorithms because search at each iteration is confined to the hit line, the algorithm can move in one

  18. Hit-and-run, hit-and-stay, and commensal bacteria present different peptide content when viewed from the perspective of the T cell.

    Science.gov (United States)

    He, Lu; De Groot, Anne S; Bailey-Kellogg, Chris

    2015-11-27

    Different types of bacteria face different pressures from the immune system, with those that persist ("hit-and-stay") potentially having to adapt more in order to escape than those prone to short-lived infection ("hit-and-run"), and with commensal bacteria potentially different from both due to additional physical mechanisms for avoiding immune detection. The Janus Immunogenicity Score (JIS) was recently developed to assess the likelihood of T cell recognition of an antigen, using an analysis that considers both binding of a peptide within the antigen by major histocompatability complex (MHC) and recognition of the peptide:MHC complex by cognate T cell receptor (TCR). This score was shown to be predictive of T effector vs. T regulatory or null responses in experimental data, as well as to distinguish viruses representative of the hit-and-stay vs. hit-and-run phenotypes. Here, JIS-based analyses were conducted in order to characterize the extent to which the pressure to avoid T cell recognition is manifested in genomic differences among representative hit-and-run, hit-and-stay, and commensal bacteria. Overall, extracellular proteins were found to have different JIS profiles from cytoplasmic ones. Contrasting the bacterial groups, extracellular proteins were shown to be quite different across the groups, much more so than intracellular proteins. The differences were evident even at the level of corresponding peptides in homologous protein pairs from hit-and-run and hit-and-stay bacteria. The multi-level analysis of patterns of immunogenicity across different groups of bacteria provides a new way to approach questions of bacterial immune camouflage or escape, as well as to approach the selection and optimization of candidates for vaccine design. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

    Science.gov (United States)

    Klinkhammer, Brent; Gruchalla, Michael

    2018-03-01

    Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P HIT were significantly older than controls ( P HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

  20. Do pigeons prefer alternatives that include near-hit outcomes?

    Science.gov (United States)

    Stagner, Jessica P; Case, Jacob P; Sticklen, Mary F; Duncan, Amanda K; Zentall, Thomas R

    2015-07-01

    Pigeons show suboptimal choice on a gambling-like task similar to that shown by humans. Humans also show a preference for gambles in which there are near hits (losses that come close to winning). In the present research, we asked if pigeons would show a preference for alternatives with near-hit-like trials. In Experiment 1, we included an alternative that presented a near hit, in which a stimulus associated with reinforcement (a presumed conditioned reinforcer) changed to a stimulus associated with the absence of reinforcement (a presumed conditioned inhibitor). The pigeons tended to avoid this alternative. In Experiment 2, we varied the duration of the presumed conditioned reinforcer (2 vs. 8 s) that changed to a presumed conditioned inhibitor (8 vs. 2 s) and found that the longer the conditioned reinforcer was presented, the more the pigeons avoided it. In Experiment 3, the near-hit alternative involved an ambiguous stimulus for 8 s that changed to a presumed conditioned reinforcer (or a presumed conditioned inhibitor) for 2 s, but the pigeons still avoided it. In Experiment 4, we controlled for the duration of the conditioned reinforcer by presenting it first for 2 s followed by the ambiguous stimulus for 8 s. Once again, the pigeons avoided the alternative with the near-hit trials. In all 4 experiments, the pigeons tended to avoid alternatives that provided near-hit-like trials. We concluded that humans may be attracted to near-hit trials because near-hit trials give them the illusion of control, whereas this does not appear to be a factor for pigeons. (c) 2015 APA, all rights reserved).

  1. Combined hit theory-microdosimetric explanation of cellular radiobiological action

    International Nuclear Information System (INIS)

    Bond, V.P.; Varma, M.N.

    1983-01-01

    Hit theory is combined with microdosimetry in a stochastic approach that explains the observed responses of cell populations exposed in radiation fields of different qualities. The central thesis is that to expose a population of cells in a low-level radiation field is to subject the cells to the potential for interaction with charged particles in the vicinity of the cells, quantifiable in terms of the charged particle fluence theta. When such an interaction occurs there is a resulting stochastic transfer of energy to a critical volume (CV) of cross section sigma, within the cell(s). The severity of cell injury is dependent on the amount of energy thus imparted, or the hit size. If the severity is above some minimal level, there is a non-zero probability that the injury will result in a quantal effect (e.g., a mutational or carcinogenic initial event, cell transformation). A microdosimetric proportional counter, viewed here as a phantom cell CV that permits measurements not possible in the living cell, is used to determine the incidence of hit cells and the spectrum of hit sizes. Each hit is then weighted on the basis of an empirically-determined function that provides the fraction of cells responding quantally, as a function of hit size. The sum of the hits so weighted provides the incidence of quantally-responding cells, for any amount of exposure theta in a radiation field of any quality or mixture qualities. The hit size weighting function for pink mutations in Tradescantia is discussed, as are its implications in terms of a replacement for RBE and dose equivalent. 14 references, 9 figures

  2. Rare transformation to double hit lymphoma in Waldenstrom's macroglobulinemia.

    Science.gov (United States)

    Okolo, Onyemaechi N; Johnson, Ariel C; Yun, Seongseok; Arnold, Stacy J; Anwer, Faiz

    2017-08-01

    Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL. The paper also broadens to include discussions on current topics in the classification, diagnosis, possible causes of transformation, and treatment of WM, including transformation to double hit lymphoma. The significance of this case lies in that the presence of double hit lymphoma-like genetic mutations in WM have not been previously described in the literature and potentially such changes are harbinger of extra-nodal presentation, aggressive growth, and possibly poor prognosis, if data from other double-hit lymphoma are extrapolated.

  3. Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.

    Directory of Open Access Journals (Sweden)

    Maha-Hamadien Abdulla

    2009-07-01

    Full Text Available Praziquantel (PZQ is the only widely available drug to treat schistosomiasis. Given the potential for drug resistance, it is prudent to search for novel therapeutics. Identification of anti-schistosomal chemicals has traditionally relied on phenotypic (whole organism screening with adult worms in vitro and/or animal models of disease-tools that limit automation and throughput with modern microtiter plate-formatted compound libraries.A partially automated, three-component phenotypic screen workflow is presented that utilizes at its apex the schistosomular stage of the parasite adapted to a 96-well plate format with a throughput of 640 compounds per month. Hits that arise are subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease. Two GO/NO GO criteria filters in the workflow prioritize hit compounds for tests in the animal disease model in accordance with a target drug profile that demands short-course oral therapy. The screen workflow was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of which 821 are drugs already approved for human use. This affords a unique starting point to 'reposition' (re-profile drugs as anti-schistosomals with potential savings in development timelines and costs.Multiple and dynamic phenotypes could be categorized for schistosomula and adults in vitro, and a diverse set of 'hit' drugs and chemistries were identified, including anti-schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits prioritized for tests in the animal disease model, a number of leads were identified, one of which compares reasonably well with PZQ in significantly decreasing worm and egg burdens, and disease-associated pathology. Data arising from the three components of the screen are posted online as a community resource.To accelerate the identification of novel anti-schistosomals, we have developed a partially automated screen workflow that

  4. Overview of the HIT-SI3 spheromak experiment

    Science.gov (United States)

    Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Everson, C. J.; Penna, J. M.; Nelson, B. A.

    2017-10-01

    The HIT-SI and HIT-SI3 spheromak experiments (a = 23 cm) study efficient, steady-state current drive for magnetic confinement plasmas using a novel method which is ideal for low aspect ratio, toroidal geometries. Sustained spheromaks show coherent, imposed plasma motion and low plasma-generated mode activity, indicating stability. Analysis of surface magnetic fields in HIT-SI indicates large n = 0 and 1 mode amplitudes and little energy in higher modes. Within measurement uncertainties all the n = 1 energy is imposed by the injectors, rather than being plasma-generated. The fluctuating field imposed by the injectors is sufficient to sustain the toroidal current through dynamo action whereas the plasma-generated field is not (Hossack et al., Phys. Plasmas, 2017). Ion Doppler spectroscopy shows coherent, imposed plasma motion inside r 10 cm in HIT-SI and a smaller volume of coherent motion in HIT-SI3. Coherent motion indicates the spheromak is stable and a lack of plasma-generated n = 1 energy indicates the maximum q is maintained below 1 for stability during sustainment. In HIT-SI3, the imposed mode structure is varied to test the plasma response (Hossack et al., Nucl. Fusion, 2017). Imposing n = 2, n = 3, or large, rotating n = 1 perturbations is correlated with transient plasma-generated activity. Work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences, under Award Number DE-FG02-96ER54361.

  5. Computing Principal Eigenvectors of Large Web Graphs: Algorithms and Accelerations Related to PageRank and HITS

    Science.gov (United States)

    Nagasinghe, Iranga

    2010-01-01

    This thesis investigates and develops a few acceleration techniques for the search engine algorithms used in PageRank and HITS computations. PageRank and HITS methods are two highly successful applications of modern Linear Algebra in computer science and engineering. They constitute the essential technologies accounted for the immense growth and…

  6. Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.

    Science.gov (United States)

    Prusator, D K; Greenwood-Van Meerveld, B

    2016-12-01

    Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific. Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS). Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups. This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats. © 2016 John Wiley & Sons Ltd.

  7. The effect of road and environmental characteristics on pedestrian hit-and-run accidents in Ghana.

    Science.gov (United States)

    Aidoo, Eric Nimako; Amoh-Gyimah, Richard; Ackaah, Williams

    2013-04-01

    The number of pedestrians who have died as a result of being hit by vehicles has increased in recent years, in addition to vehicle passenger deaths. Many pedestrians who were involved in road traffic accident died as a result of the driver leaving the pedestrian who was struck unattended at the scene of the accident. This paper seeks to determine the effect of road and environmental characteristics on pedestrian hit-and-run accidents in Ghana. Using pedestrian accident data extracted from the National Road Traffic Accident Database at the Building and Road Research Institute (BRRI) of the Council for Scientific and Industrial Research (CSIR), Ghana, a binary logit model was employed in the analysis. The results from the estimated model indicate that fatal accidents, unclear weather, nighttime conditions, and straight and flat road sections without medians and junctions significantly increase the likelihood that the vehicle driver will leave the scene after hitting a pedestrian. Thus, integrating median separation and speed humps into road design and construction and installing street lights will help to curb the problem of pedestrian hit-and-run accidents in Ghana. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Comparison of validity and reliability of the Migraine disability assessment (MIDAS) versus headache impact test (HIT) in an Iranian population.

    Science.gov (United States)

    Ghorbani, Abbas; Chitsaz, Ahmad

    2011-01-01

    Migraine is one of the most common headaches that affect 11% or more adult population. Recently, researchers have designed two questionnaires, namely Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS), with the aim of improving migraine care. These two tests provide a standard measurement about migraine's effects on people's life style that divide patients into 4 groups (grades) based on headaches intensity. The aim of this study was to compare the validity and reliability of these two tests. This study was designed as a multicenter, descriptive study to compare validity and reliability of Persian version of MIDAS and HIT questionnaires in 240 males and females with a migraine diagnosis according to criteria for headache and facial pain of the International Headache Society (IHS). The patients were enrolled in the study from 3 neurology clinics in Isfahan, Iran, between July 2004 and January 2005 and were evaluated at baseline (visit 1) and 4 weeks later (visit 2). According to our study, there was a high correlation between two tests (r = 0.94). This decreased their MIDAS grade in comparison to their grade HIT questionnaire. These findings demonstrated that Persian version of HIT have the same validity and reliability as MIDAS. Replying to HIT questionnaire was easier than MIDAS for Iranian patients. Physicians can reliably use the Persian translation of both MIDAS and HIT questionnaires to define the severity of illness and its treatment strategy as a self-administered report by migraine patients. However, we recommend HIT for its simplicity in headache clinics.

  9. Two-photon LIF on the HIT-SI3 experiment: Absolute density and temperature measurements of deuterium neutrals

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Drew, E-mail: dbelliott@mix.wvu.edu; Siddiqui, Umair; Scime, Earl [Department of Physics and Astronomy, West Virginia University, Morgantown, West Virginia 26056 (United States); Sutherland, Derek; Everson, Chris; Morgan, Kyle; Hossack, Aaron; Nelson, Brian; Jarboe, Tom [Department of Aerospace Engineering, University of Washington, Seattle, Washington 98105 (United States)

    2016-11-15

    Two-photon laser-induced fluorescence measurements were performed on the helicity injected torus (HIT-SI3) device to determine the density and temperature of the background neutral deuterium population. Measurements were taken in 2 ms long pulsed plasmas after the inductive helicity injectors were turned off. Attempts to measure neutrals during the main phase of the plasma were unsuccessful, likely due to the density of neutrals being below the detection threshold of the diagnostic. An unexpectedly low density of atomic deuterium was measured in the afterglow; roughly 100 times lower than the theoretical prediction of 10{sup 17} m{sup −3}. The neutral temperatures measured were on the order of 1 eV. Temporally and spatially resolved neutral density and temperature data are presented.

  10. Evaluation of flow cytometric HIT assays in relation to an IgG-Specific immunoassay and clinical outcome.

    Science.gov (United States)

    Kerényi, Adrienne; Beke Debreceni, Ildikó; Oláh, Zsolt; Ilonczai, Péter; Bereczky, Zsuzsanna; Nagy, Béla; Muszbek, László; Kappelmayer, János

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment caused by platelet activating IgG antibodies generated against the platelet factor 4 (PF4)-heparin complex. Thrombocytopenia and thrombosis are the leading clinical symptoms of HIT. The clinical pretest probability of HIT was evaluated by the 4T score system. Laboratory testing of HIT was performed by immunological detection of antibodies against PF4-heparin complex (EIA) and two functional assays. Heparin-dependent activation of donor platelets by patient plasma was detected by flow cytometry. Increased binding of Annexin-V to platelets and elevated number of platelet-derived microparticles (PMP) were the indicators of platelet activation. EIA for IgG isotype HIT antibodies was performed in 405 suspected HIT patients. Based on negative EIA results, HIT was excluded in 365 (90%) of cases. In 40 patients with positive EIA test result functional tests were performed. Platelet activating antibodies were detected in 17 cases by Annexin V binding. PMP count analysis provided nearly identical results. The probability of a positive flow cytometric assay result was higher in patients with elevated antibody titer. 71% of patients with positive EIA and functional assay had thrombosis. EIA is an important first line laboratory test in the diagnosis of HIT; however, HIT must be confirmed by a functional test. Annexin V binding and PMP assays using flow cytometry are functional HIT tests convenient in a clinical diagnostic laboratory. The positive results of functional assays may predict the onset of thrombosis. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

  11. Creating a safe place for pediatric care: A no hit zone.

    Science.gov (United States)

    Frazier, Erin R; Liu, Gilbert C; Dauk, Kelly L

    2014-07-01

    Our goal was to create and implement a program, Kosair Children's Hospital's No Hit Zone, which trains health care workers in de-escalation techniques to address parental disruptive behaviors and physical discipline of children commonly encountered in the hospital environment. The Child Abuse Task Force, a multidisciplinary group, along with key hospital administrators developed specific content for the policy, as well as marketing and educational materials. The No Hit Zone policy designates Kosair Children's Hospital as "an environment in which no adult shall hit a child, no adult shall hit another adult, no child shall hit an adult, and no child shall hit another child. When hitting is observed, it is everyone's responsibility to interrupt the behavior as well as communicate system policy to those present." Via a multidisciplinary, collaborative approach, the No Hit Zone was successfully implemented at Kosair Children's Hospital in 2012. Cost was nominal, and the support of key hospital administrators was critical to the program's success. Education of health professionals on de-escalation techniques and intervention with families at the early signs of parental stress occurred via live sessions and online training via case-based scenarios. The No Hit Zone is an important program used to provide a safe and caring environment for all families and staff of Kosair Children's Hospital. Demand for the program continues, demonstrated by the establishment of No Hit Zones at other local hospitals and multiple outpatient clinics. This article offers information for other organizations planning to conduct similar initiatives. Copyright © 2014 by the American Academy of Pediatrics.

  12. Validation of single-fluid and two-fluid magnetohydrodynamic models of the helicity injected torus spheromak experiment with the NIMROD code

    International Nuclear Information System (INIS)

    Akcay, Cihan; Victor, Brian S.; Jarboe, Thomas R.; Kim, Charlson C.

    2013-01-01

    We present a comparison study of 3-D pressureless resistive MHD (rMHD) and 3-D presureless two-fluid MHD models of the Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI). HIT-SI is a current drive experiment that uses two geometrically asymmetric helicity injectors to generate and sustain toroidal plasmas. The comparable size of the collisionless ion skin depth d i to the resistive skin depth predicates the importance of the Hall term for HIT-SI. The simulations are run with NIMROD, an initial-value, 3-D extended MHD code. The modeled plasma density and temperature are assumed uniform and constant. The helicity injectors are modeled as oscillating normal magnetic and parallel electric field boundary conditions. The simulations use parameters that closely match those of the experiment. The simulation output is compared to the formation time, plasma current, and internal and surface magnetic fields. Results of the study indicate 2fl-MHD shows quantitative agreement with the experiment while rMHD only captures the qualitative features. The validity of each model is assessed based on how accurately it reproduces the global quantities as well as the temporal and spatial dependence of the measured magnetic fields. 2fl-MHD produces the current amplification (I tor /I inj ) and formation time τ f demonstrated by HIT-SI with similar internal magnetic fields. rMHD underestimates (I tor /I inj ) and exhibits much a longer τ f . Biorthogonal decomposition (BD), a powerful mathematical tool for reducing large data sets, is employed to quantify how well the simulations reproduce the measured surface magnetic fields without resorting to a probe-by-probe comparison. BD shows that 2fl-MHD captures the dominant surface magnetic structures and the temporal behavior of these features better than rMHD

  13. The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Larsen, Steen; Danielsen, J H; Søndergård, Stine Dam

    2015-01-01

    High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60-90% of maximal oxygen uptake (VO2peak )]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT...... of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. Km (app) for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal...... muscle and adipose tissue. Maximal OXPHOS capacity with complex I- and II-linked substrates was increased after training in skeletal muscle but not in adipose tissue. In conclusion, 6 weeks of HIT increased VO2peak . Mitochondrial content and mitochondrial OXPHOS capacity were increased in skeletal...

  14. Fundamental Studies of Butane Oxidation over Model-Supported Vanadium Oxide Catalysts: Molecular Structure-Reactivity Relationships

    NARCIS (Netherlands)

    Wachs, I.E.; Jehng, J.M.; Deo, G.; Weckhuysen, B.M.; Guliants, V.V.; Benziger, J.B.; Sundaresan, S.

    1997-01-01

    The oxidation of n-butane to maleic anhydride was investigated over a series of model-supported vanadia catalysts where the vanadia phase was present as a two-dimensional metal oxide overlayer on the different oxide supports (TiO2, ZrO2, CeO2, Nb2O5, Al2O3, and SiO2). No correlation was found

  15. A combined hit theory-microdosimetric explanation of cellular radiobiological action

    International Nuclear Information System (INIS)

    Bond, V.P.; Varma, M.N.

    1983-01-01

    Hit theory is combined with microdosimetry in a stochastic approach that explains the observed responses of cell populations exposed in radiation fields of different qualities. The central thesis is that to expose a population of cells in a low-level radiation field is to subject the cells to the potential for interaction with charged particles, quantifiable in terms of the charged particle fluence PHI. When such an interaction occurs there is resulting stochastic transfer of energy to a critical volume (CV) of cross-section σ within the cell(s). The severity of cell injury is dependent on the amount of energy thus imparted, or the hit size. If the severity is above some minimal level, there is a non-zero probability that the injury will result in a quantal effect (e.g., a mutational or carcinogenic initial event, cell transformation). A microdosimetric proportional counter, viewed here as a phantom cell CV that permits measurements not possible in the living cell, is used to determine the incidence of hit cells and the spectrum of hit sizes. Each hit is then weighted on the basis of an empirically determined function that provides the fraction of cells responding quantally, as a function of hit size. The sum of the hits so weighted provides the incidence of quantally responding cells, for any amount of exposure PHI in a radiation field of any quality or mixture of qualities. The hit size weighting function for pink mutations in Tradescantia is discussed, as are its implications in terms of a replacement for relative biological effectiveness and dose equivalent. (author)

  16. 76 FR 55914 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-09-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  17. 76 FR 46297 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  18. 76 FR 22399 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  19. 76 FR 28784 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  20. 75 FR 29762 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2010-05-27

    ... Technology HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Policy Committee's Workgroups: Meaningful Use, Privacy & Security Policy... specifications, and certification criteria are needed. Date and Time: The HIT Policy Committee Workgroups will...

  1. 76 FR 14974 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  2. 76 FR 50735 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... standards, implementation specifications, and certification criteria are needed. Date and Time: The HIT...

  3. Modeling of nitrous oxide production by autotrophic ammonia-oxidizing bacteria with multiple production pathways.

    Science.gov (United States)

    Ni, Bing-Jie; Peng, Lai; Law, Yingyu; Guo, Jianhua; Yuan, Zhiguo

    2014-04-01

    Autotrophic ammonia oxidizing bacteria (AOB) have been recognized as a major contributor to N2O production in wastewater treatment systems. However, so far N2O models have been proposed based on a single N2O production pathway by AOB, and there is still a lack of effective approach for the integration of these models. In this work, an integrated mathematical model that considers multiple production pathways is developed to describe N2O production by AOB. The pathways considered include the nitrifier denitrification pathway (N2O as the final product of AOB denitrification with NO2(-) as the terminal electron acceptor) and the hydroxylamine (NH2OH) pathway (N2O as a byproduct of incomplete oxidation of NH2OH to NO2(-)). In this model, the oxidation and reduction processes are modeled separately, with intracellular electron carriers introduced to link the two types of processes. The model is calibrated and validated using experimental data obtained with two independent nitrifying cultures. The model satisfactorily describes the N2O data from both systems. The model also predicts shifts of the dominating pathway at various dissolved oxygen (DO) and nitrite levels, consistent with previous hypotheses. This unified model is expected to enhance our ability to predict N2O production by AOB in wastewater treatment systems under varying operational conditions.

  4. Finite element modelling of the oxidation kinetics of Zircaloy-4 with a controlled metal-oxide interface and the influence of growth stress

    International Nuclear Information System (INIS)

    Zumpicchiat, Guillaume; Pascal, Serge; Tupin, Marc; Berdin-Méric, Clotilde

    2015-01-01

    Highlights: We developed two finite element models of zirconium-based alloy oxidation using the CEA Cast3M code to simulate the oxidation kinetics of Zircaloy-4: the diffuse interface model and the sharp interface model. We also studied the effect of stresses on the oxidation kinetics. The main results are: • Both models lead to parabolic oxidation kinetics in agreement with the Wagner’s theory. • The modellings enable to calculate the stress distribution in the oxide as well as in the metal. • A strong effect of the hydrostatic stress on the oxidation kinetics has been evidenced. • The stress gradient effect changes the parabolic kinetics into a sub-parabolic law closer to the experimental kinetics because of the stress gradient itself, but also because of the growth stress increase with the oxide thickness. - Abstract: Experimentally, zirconium-based alloys oxidation kinetics is sub-parabolic, by contrast with the Wagner theory which predicts a parabolic kinetics. Two finite element models have been developed to simulate this phenomenon: the diffuse interface model and the sharp interface model. Both simulate parabolic oxidation kinetics. The growth stress effects on oxygen diffusion are studied to try to explain the gap between theory and experience. Taking into account the influence of the hydrostatic stress and its gradient into the oxygen flux expression, sub-parabolic oxidation kinetics have been simulated. The sub-parabolic behaviour of the oxidation kinetics can be explained by a non-uniform compressive stress level into the oxide layer.

  5. 76 FR 46298 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held virtually on August 17, 2011...

  6. 76 FR 50734 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on September 28, 2011, from 9...

  7. 77 FR 2727 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-01-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on February 29, 2012, from 9...

  8. 76 FR 70455 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 14, 2011, from 9...

  9. 75 FR 5595 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2010-02-03

    ... Technology HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Health Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy Committee...

  10. 77 FR 73661 - HIT Standards Committee Advisory Meetings; Notice of Meetings

    Science.gov (United States)

    2012-12-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meetings; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: These meetings will be held on the following dates and...

  11. 76 FR 70454 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Policy Committee's Workgroups... certification criteria are needed. Date and Time: The HIT Policy Committee Workgroups will hold the following...

  12. 76 FR 28784 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... implementation of the Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT...

  13. 76 FR 50736 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... implementation of the Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT...

  14. 76 FR 14975 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of... be open to the public via dial-in access only. Name of Committees: HIT Standards Committee's... implementation of the Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT...

  15. 77 FR 65691 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on November 13, 2012, from 9...

  16. 77 FR 50690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-08-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on September 19, 2012, from 9...

  17. 75 FR 21628 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2010-04-26

    ... Technology HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  18. 76 FR 55913 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-09-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held virtually on October 21, 2011...

  19. 77 FR 65690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 19, 2012, from 9...

  20. Assessing the lipophilicity of fragments and early hits

    Science.gov (United States)

    Mortenson, Paul N.; Murray, Christopher W.

    2011-07-01

    A key challenge in many drug discovery programs is to accurately assess the potential value of screening hits. This is particularly true in fragment-based drug design (FBDD), where the hits often bind relatively weakly, but are correspondingly small. Ligand efficiency (LE) considers both the potency and the size of the molecule, and enables us to estimate whether or not an initial hit is likely to be optimisable to a potent, druglike lead. While size is a key property that needs to be controlled in a small molecule drug, there are a number of additional properties that should also be considered. Lipophilicity is amongst the most important of these additional properties, and here we present a new efficiency index (LLEAT) that combines lipophilicity, size and potency. The index is intuitively defined, and has been designed to have the same target value and dynamic range as LE, making it easily interpretable by medicinal chemists. Monitoring both LE and LLEAT should help both in the selection of more promising fragment hits, and controlling molecular weight and lipophilicity during optimisation.

  1. A recalculation of the dose-effect-relationship of the ''life span study'' of Hiroshima and Nagasaki with the ''single-hit model''

    International Nuclear Information System (INIS)

    Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

    1996-01-01

    The basis of this new model is the multistage process of carcinogeneses. The Single-Hit Model is a further development of the Armitage-Doll Model [1] for the special case of a short exposure. It provides simultaneously the age-dependent mortality-rate (incidence-rate) of the spontaneous and radiation induced solid tumors and dose-effect relationships at any age after exposure. The model results in a biologically based dose-effect relationship, which is similar to the Relativ-Risk-Model suggested by the ICRP 60 [2]. The present model is able to describe the increased mortality rate of the bomb survivors more accurate than the Relativ-Risk-Model. (orig.) [de

  2. Plasma response to sustainment with imposed-dynamo current drive in HIT-SI and HIT-SI3

    Science.gov (United States)

    Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Penna, J. M.; Everson, C. J.; Nelson, B. A.

    2017-07-01

    The helicity injected torus—steady inductive (HIT-SI) program studies efficient, steady-state current drive for magnetic confinement plasmas using a novel experimental method. Stable, high-beta spheromaks have been sustained using steady, inductive current drive. Externally induced loop voltage and magnetic flux are oscillated together so that helicity and power injection are always positive, sustaining the edge plasma current indefinitely. Imposed-dynamo current drive (IDCD) theory further shows that the entire plasma current is sustained. The method is ideal for low aspect ratio, toroidal geometries with closed flux surfaces. Experimental studies of spheromak plasmas sustained with IDCD have shown stable magnetic profiles with evidence of pressure confinement. New measurements show coherent motion of a stable spheromak in response to the imposed perturbations. On the original device two helicity injectors were mounted on either side of the spheromak and the injected mode spectrum was predominantly n  =  1. Coherent, rigid motion indicates that the spheromak is stable and a lack of plasma-generated n  =  1 energy indicates that the maximum q is maintained below 1 during sustainment. Results from the HIT-SI3 device are also presented. Three inductive helicity injectors are mounted on one side of the spheromak flux conserver. Varying the relative injector phasing changes the injected mode spectrum which includes n  =  2, 3, and higher modes.

  3. 77 FR 16035 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-03-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on March 27, 2012, from 9 a.m...

  4. 76 FR 79684 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-12-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on January 25, 2012, from 9 a...

  5. 77 FR 15760 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-03-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on April 18, 2012, from 9 a.m...

  6. 76 FR 14976 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on April 20, 2011, from 9 a.m...

  7. 76 FR 39109 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-07-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on July 20, 2011, from 9 a.m...

  8. 76 FR 28782 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on June 22, 2011, from 9 a.m...

  9. 77 FR 27459 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-05-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on June 20, 2012, from 9 a.m...

  10. 77 FR 37408 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-06-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... be open to the public. Name of Committee: HIT Standards Committee. General Function of the Committee... with policies developed by the HIT Policy Committee. Date and Time: The meeting will be held on July 19...

  11. 77 FR 22787 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-04-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on May 24, 2012, from 9 a.m...

  12. 76 FR 22396 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on May 18, 2011, from 9 a.m...

  13. 77 FR 60438 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-03

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on October 17, 2012, from 9 a...

  14. 76 FR 9783 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-02-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on March 29, 2011, from 9 a.m...

  15. 77 FR 45353 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-07-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on August 15, 2012, from 9:00...

  16. Hitting the nail on the head: Force vectors in verb semantics

    NARCIS (Netherlands)

    Goldschmidt, A.; Zwarts, J.

    2016-01-01

    We present an analysis of force verbs, like hit, as involving paths with force-dynamic properties, modelled through force vectors. This allows us to explain a number of observations about the lexical meaning and composition of these verbs. For instance, force adverbs such as hard specify the

  17. Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

    Science.gov (United States)

    Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

    2017-01-01

    Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

  18. High energy ion hit technique to local area using microbeam

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Ryuichi; Kamiya, Tomihiro; Suda, Tamotsu; Sakai, Takuro; Hirao, Toshio; Kobayashi, Yasuhiko; Watanabe, Hiroshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1997-03-01

    Single energetic ion hit technique has been developed as an application of ion microbeam technique, in order to study the effect of local damage or injury to materials and living organisms. The overall performance is basically defined by those of separate techniques: microbeam formation, microbeam positioning, single ion detection, detection signal processing, hit timing control, and hit verification. Recent progress on the developments of these techniques at JAERI-TIARA facility are reviewed. (author)

  19. Database for High Throughput Screening Hits (dHITS): a simple tool to retrieve gene specific phenotypes from systematic screens done in yeast.

    Science.gov (United States)

    Chuartzman, Silvia G; Schuldiner, Maya

    2018-03-25

    In the last decade several collections of Saccharomyces cerevisiae yeast strains have been created. In these collections every gene is modified in a similar manner such as by a deletion or the addition of a protein tag. Such libraries have enabled a diversity of systematic screens, giving rise to large amounts of information regarding gene functions. However, often papers describing such screens focus on a single gene or a small set of genes and all other loci affecting the phenotype of choice ('hits') are only mentioned in tables that are provided as supplementary material and are often hard to retrieve or search. To help unify and make such data accessible, we have created a Database of High Throughput Screening Hits (dHITS). The dHITS database enables information to be obtained about screens in which genes of interest were found as well as the other genes that came up in that screen - all in a readily accessible and downloadable format. The ability to query large lists of genes at the same time provides a platform to easily analyse hits obtained from transcriptional analyses or other screens. We hope that this platform will serve as a tool to facilitate investigation of protein functions to the yeast community. © 2018 The Authors Yeast Published by John Wiley & Sons Ltd.

  20. All hypertopologies are hit-and-miss

    Directory of Open Access Journals (Sweden)

    Somshekhar Naimpally

    2002-04-01

    Full Text Available We solve a long standing problem by showing that all known hypertopologies are hit-and-miss. Our solution is not merely of theoretical importance. This representation is useful in the study of comparison of the Hausdorff-Bourbaki or H-B uniform topologies and the Wijsman topologies among themselves and with others. Up to now some of these comparisons needed intricate manipulations. The H-B uniform topologies were the subject of intense activity in the 1960's in connection with the Isbell-Smith problem. We show that they are proximally locally finite topologies from which the solution to the above problem follows easily. It is known that the Wijsman topology on the hyperspace is the proximal ball (hit-and-miss topology in”nice” metric spaces including the normed linear spaces. With the introduction of a new far-miss topology we show that the Wijsman topology is hit-and-miss for all metric spaces. From this follows a natural generalization of the Wijsman topology to the hyperspace of any T1 space. Several existing results in the literature are easy consequences of our work.

  1. Transfer, loss and physical processing of water in hit-and-run collisions of planetary embryos

    Science.gov (United States)

    Burger, C.; Maindl, T. I.; Schäfer, C. M.

    2018-01-01

    Collisions between large, similar-sized bodies are believed to shape the final characteristics and composition of terrestrial planets. Their inventories of volatiles such as water are either delivered or at least significantly modified by such events. Besides the transition from accretion to erosion with increasing impact velocity, similar-sized collisions can also result in hit-and-run outcomes for sufficiently oblique impact angles and large enough projectile-to-target mass ratios. We study volatile transfer and loss focusing on hit-and-run encounters by means of smooth particle hydrodynamics simulations, including all main parameters: impact velocity, impact angle, mass ratio and also the total colliding mass. We find a broad range of overall water losses, up to 75% in the most energetic hit-and-run events, and confirm the much more severe consequences for the smaller body also for stripping of volatile layers. Transfer of water between projectile and target inventories is found to be mostly rather inefficient, and final water contents are dominated by pre-collision inventories reduced by impact losses, for similar pre-collision water mass fractions. Comparison with our numerical results shows that current collision outcome models are not accurate enough to reliably predict these composition changes in hit-and-run events. To also account for non-mechanical losses, we estimate the amount of collisionally vaporized water over a broad range of masses and find that these contributions are particularly important in collisions of ˜ Mars-sized bodies, with sufficiently high impact energies, but still relatively low gravity. Our results clearly indicate that the cumulative effect of several (hit-and-run) collisions can efficiently strip protoplanets of their volatile layers, especially the smaller body, as it might be common, e.g., for Earth-mass planets in systems with Super-Earths. An accurate model for stripping of volatiles that can be included in future planet

  2. Cosmic Ray Hit Detection with Homogenous Structures

    Science.gov (United States)

    Smirnov, O. M.

    Cosmic ray (CR) hits can affect a significant number of pixels both on long-exposure ground-based CCD observations and on the Space Telescope frames. Thus, methods of identifying the damaged pixels are an important part of the data preprocessing for practically any application. The paper presents an implementation of a CR hit detection algorithm based on a homogenous structure (also called cellular automata ), a concept originating in artificial intelligence and dicrete mathematics. Each pixel of the image is represented by a small automaton, which interacts with its neighbors and assumes a distinct state if it ``decides'' that a CR hit is present. On test data, the algorithm has shown a high detection rate (~0.7 ) and a low false alarm rate (frame. A homogenous structure is extremely trainable, which can be very important for processing large batches of data obtained under similar conditions. Training and optimizing issues are discussed, as well as possible other applications of this concept to image processing.

  3. The Rock that Hit New York

    Energy Technology Data Exchange (ETDEWEB)

    Meade, Roger Allen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Keksis, August Lawrence [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-03

    On January 12, 1975, a rock seemed to fall from the sky over New York State’s Schoharie County hitting the tractor of a local farmer, who was “preparing his fields for spring planting.” As the farmer later described the event to a reporter from the UFO INVESTIGATOR, the object glanced off the tractor, fell to the ground, and melted its way through a patch of ice that was two and one half inches thick. The farmer, Leonard Tillapaugh, called the county sheriff, Harvey Stoddard, who recovered the rock, noting that it “was still warm.” Why and how a sample of the rock came to Los Alamos is not known. However, it captivated a wide Laboratory audience, was subjected to rigorous testing and evaluation. Los Alamos used the scientific method in the manner promoted by Hynek. Did Los Alamos solve the mystery of the rock’s origin? Not definitively. Although the exact origin could not be determined, it was shown conclusively that the rock was not from outer space. With that said, the saga of Rock that hit New York came to an end. Nothing more was said or written about it. The principals involved have long since passed from the scene. The NICAP ceased operations in 1980. And, the rock, itself, has disappeared.

  4. Promiscuous 2-aminothiazoles (PrATs): a frequent hitting scaffold.

    Science.gov (United States)

    Devine, Shane M; Mulcair, Mark D; Debono, Cael O; Leung, Eleanor W W; Nissink, J Willem M; Lim, San Sui; Chandrashekaran, Indu R; Vazirani, Mansha; Mohanty, Biswaranjan; Simpson, Jamie S; Baell, Jonathan B; Scammells, Peter J; Norton, Raymond S; Scanlon, Martin J

    2015-02-12

    We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), as frequent-hitting fragments in biophysical binding assays. This was exemplified by 4-phenylthiazol-2-amine being identified as a hit in 14/14 screens against a diverse range of protein targets, suggesting that this scaffold is a poor starting point for fragment-based drug discovery. This prompted us to analyze this scaffold in the context of an academic fragment library used for fragment-based drug discovery (FBDD) and two larger compound libraries used for high-throughput screening (HTS). This analysis revealed that such "promiscuous 2-aminothiazoles" (PrATs) behaved as frequent hitters under both FBDD and HTS settings, although the problem was more pronounced in the fragment-based studies. As 2-ATs are present in known drugs, they cannot necessarily be deemed undesirable, but the combination of their promiscuity and difficulties associated with optimizing them into a lead compound makes them, in our opinion, poor scaffolds for fragment libraries.

  5. A fast DSP-based calorimeter hit scanning system

    International Nuclear Information System (INIS)

    Sekikawa, S.; Arai, I.; Suzuki, A.; Watanabe, A.; Marlow, D.R.; Mindas, C.R.; Wixted, R.L.

    1997-01-01

    A custom made digital signal processor (DSP) based system has been developed to scan calorimeter hits read by a 32-channel FASTBUS waveform recorder board. The scanner system identifies hit calorimeter elements by surveying their discriminated outputs. This information is used to generate a list of addresses, which guides the read-out process. The system is described and measurements of the scan times are given. (orig.)

  6. Pattern recognition with vector hits

    International Nuclear Information System (INIS)

    Frühwirth, R

    2012-01-01

    Trackers at the future high-luminosity LHC, designed to have triggering capability, will feature layers of stacked modules with a small stack separation. This will allow the reconstruction of track stubs or vector hits with position and direction information, but lacking precise curvature information. This opens up new possibilities for track finding, online and offline. Two track finding methods, the Kalman filter and the convergent Hough transform are studied in this context. Results from a simplified fast simulation are presented. It is shown that the performance of the methods depends to a large extent on the size of the stack separation. We conclude that the detector design and the choice of the track finding algorithm(s) are strongly coupled and should proceed conjointly.

  7. Effects of Experimental Volleyball Rules Quantified by Type and Number of Jumps, Hits and Contacts

    Directory of Open Access Journals (Sweden)

    Mladen Stankovic

    2017-10-01

    Full Text Available The purpose of this study was to determine the influence of the two new rules tested at the inaugural U23 Men’s Volleyball World Championship (21-point set excluding the fifth set, and 15 seconds between rallies–10 seconds from the finished point until the referee’s whistle for serve and five seconds for performing the serve on number and types of jumps and number of contacts and hits. The analysis comprised 25,930 jumps (an essential physical activity for volleyball, 15,706 contacts and 10,224 hits during 36 matches played by 144 males aged under 23 at the first Under 23 Men’s World Championships organized in Uberlandia, Brazil, in 2013. Two investigations were conducted: 1 Analysis of jumps by Jump type, In-game role and Level of set win; 2 Analysis of contacts (reception, setting, block, defense and hits (serve and attack by Type, In-game role and Set outcome. Significant differences (p=0.000 were found between in-game role and jump type, as Middle blocker performed the most (34.7%, followed by Outside hitter (24.9%, Setter (24.6% and Opposite (15.8%. Significant differences were found for number and types of Hits between set Winner and Loser teams only for serves by Setter (p<0.001 and Middle blocker (p<0.05. The results showed major differences in jumps, hits and contacts between in-game roles: Middle blocker was the most frequent jumping position, followed by Outside hitter and Setter. The Libero showed a new tendency of being Setter with a jump after the initial Setter defense.

  8. Lessons learnt from the Wenchuan earthquake: performance evaluation of treatment of critical injuries in hardest-hit areas.

    Science.gov (United States)

    Jiang, Jie; Li, Youping; Huang, Xiaolin; Li, Bing; Su, Lin; Zhong, Dake; Shi, Chenghu; Li, Mingxu; Shan, Juan; Chen, Yin

    2012-08-01

    Critical injury treatment in the hardest-hit areas after a great earthquake was retrospectively analyzed to determine how best to reduce mortality and disability and increase the rehabilitation rate through postquake medical relief. Retrospective analysis, primary sources, and secondary sources were comprehensively retrieved and analyzed. According to incomplete data, 30,620 injured were rescued by themselves among the hardest-hit areas in the 72 hours immediately following the earthquake. Critically injured patients accounted for 22% of total inpatients. Mortality rates declined with greater distance from the epicenter: rates were 12.21% for municipal healthcare centers in the hardest-hit areas, 4.50% for municipal medical units in peripheral quake-hit areas, 2.50% for provincial medical units in peripheral quake-hit areas, and 2.17% for Ministry of Health-affiliated hospitals in peripheral quake-hit areas. The number of injured with fractures on body, limbs or unknown-parts, severe conditions as well as other kinds of non-traumatic diseases received in second-line hospitals was much more than those treated in first-line hospitals with more severe injuries. Among 10,373 injured in stable condition transferred to third-line hospitals, 99.07% were discharged from hospitals within four months, while the mortality rate was 0.017%. The medical relief model of "supervising body helping subordinate unit, severely stricken areas assisting hardest-hit areas, least-hit areas supporting both hardest-hit and severely stricken areas, and self help and mutual assistance applied between hardest-hit areas" was roughly established for injured from severely stricken areas after the Wenchuan Earthquake. The "four-centralization" treatment principle, which referred to concentrating patients, experts, resources and treatment for those injured in critical condition effectively reduced the mortality from 15.06% to 2.9%. Timely, scientific, and standard on-site triage and postmedical

  9. Kinetic modeling of antimony(III) oxidation and sorption in soils.

    Science.gov (United States)

    Cai, Yongbing; Mi, Yuting; Zhang, Hua

    2016-10-05

    Kinetic batch and saturated column experiments were performed to study the oxidation, adsorption and transport of Sb(III) in two soils with contrasting properties. Kinetic and column experiment results clearly demonstrated the extensive oxidation of Sb(III) in soils, and this can in return influence the adsorption and transport of Sb. Both sorption capacity and kinetic oxidation rate were much higher in calcareous Huanjiang soil than in acid red Yingtan soil. The results indicate that soil serve as a catalyst in promoting oxidation of Sb(III) even under anaerobic conditions. A PHREEQC model with kinetic formulations was developed to simulate the oxidation, sorption and transport of Sb(III) in soils. The model successfully described Sb(III) oxidation and sorption data in kinetic batch experiment. It was less successful in simulating the reactive transport of Sb(III) in soil columns. Additional processes such as colloid facilitated transport need to be quantified and considered in the model. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The average number of alpha-particle hits to the cell nucleus required to eradicate a tumour cell population

    International Nuclear Information System (INIS)

    Roeske, John C; Stinchcomb, Thomas G

    2006-01-01

    Alpha-particle emitters are currently being considered for the treatment of micrometastatic disease. Based on in vitro studies, it has been speculated that only a few alpha-particle hits to the cell nucleus are considered lethal. However, such estimates do not consider the stochastic variations in the number of alpha-particle hits, energy deposited, or in the cell survival process itself. Using a tumour control probability (TCP) model for alpha-particle emitters, we derive an estimate of the average number of hits to the cell nucleus required to provide a high probability of eradicating a tumour cell population. In simulation studies, our results demonstrate that the average number of hits required to achieve a 90% TCP for 10 4 clonogenic cells ranges from 18 to 108. Those cells that have large cell nuclei, high radiosensitivities and alpha-particle emissions occurring primarily in the nuclei tended to require more hits. As the clinical implementation of alpha-particle emitters is considered, this type of analysis may be useful in interpreting clinical results and in designing treatment strategies to achieve a favourable therapeutic outcome. (note)

  11. Syntrophic acetate oxidation in two-phase (acid-methane) anaerobic digesters.

    Science.gov (United States)

    Shimada, T; Morgenroth, E; Tandukar, M; Pavlostathis, S G; Smith, A; Raskin, L; Kilian, R E

    2011-01-01

    The microbial processes involved in two-phase anaerobic digestion were investigated by operating a laboratory-scale acid-phase (AP) reactor and analyzing two full-scale, two-phase anaerobic digesters operated under mesophilic (35 °C) conditions. The digesters received a blend of primary sludge and waste activated sludge (WAS). Methane levels of 20% in the laboratory-scale reactor indicated the presence of methanogenic activity in the AP. A phylogenetic analysis of an archaeal 16S rRNA gene clone library of one of the full-scale AP digesters showed that 82% and 5% of the clones were affiliated with the orders Methanobacteriales and Methanosarcinales, respectively. These results indicate that substantial levels of aceticlastic methanogens (order Methanosarcinales) were not maintained at the low solids retention times and acidic conditions (pH 5.2-5.5) of the AP, and that methanogenesis was carried out by hydrogen-utilizing methanogens of the order Methanobacteriales. Approximately 43, 31, and 9% of the archaeal clones from the methanogenic phase (MP) digester were affiliated with the orders Methanosarcinales, Methanomicrobiales, and Methanobacteriales, respectively. A phylogenetic analysis of a bacterial 16S rRNA gene clone library suggested the presence of acetate-oxidizing bacteria (close relatives of Thermacetogenium phaeum, 'Syntrophaceticus schinkii,' and Clostridium ultunense). The high abundance of hydrogen consuming methanogens and the presence of known acetate-oxidizing bacteria suggest that acetate utilization by acetate oxidizing bacteria in syntrophic interaction with hydrogen-utilizing methanogens was an important pathway in the second-stage of the two-phase digestion, which was operated at high ammonium-N concentrations (1.0 and 1.4 g/L). A modified version of the IWA Anaerobic Digestion Model No. 1 (ADM1) with extensions for syntrophic acetate oxidation and weak-acid inhibition adequately described the dynamic profiles of volatile acid production

  12. Potential Impacts of two SO2 oxidation pathways on regional sulfate concentrations: acqueous-hase oxidation by NO2 and gas-phase oxidation by Stabilized Criegee Intermediates

    Science.gov (United States)

    We examine the potential impacts of two additional sulfate production pathways using the Community Multiscale Air Quality modeling system. First we evaluate the impact of the aqueous-phase oxidation of S(IV) by nitrogen dioxide using two published rate constants, differing by 1-2...

  13. Selective Oxidation of Lignin Model Compounds.

    Science.gov (United States)

    Gao, Ruili; Li, Yanding; Kim, Hoon; Mobley, Justin K; Ralph, John

    2018-05-02

    Lignin, the planet's most abundant renewable source of aromatic compounds, is difficult to degrade efficiently to welldefined aromatics. We developed a microwave-assisted catalytic Swern oxidation system using an easily prepared catalyst, MoO 2 Cl 2 (DMSO) 2 , and DMSO as the solvent and oxidant. It demonstrated high efficiency in transforming lignin model compounds containing the units and functional groups found in native lignins. The aromatic ring substituents strongly influenced the selectivity of β-ether phenolic dimer cleavage to generate sinapaldehyde and coniferaldehyde, monomers not usually produced by oxidative methods. Time-course studies on two key intermediates provided insight into the reaction pathway. Owing to the broad scope of this oxidation system and the insight gleaned with regard to its mechanism, this strategy could be adapted and applied in a general sense to the production of useful aromatic chemicals from phenolics and lignin. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Hit Identification and Optimization in Virtual Screening: Practical Recommendations Based Upon a Critical Literature Analysis

    Science.gov (United States)

    Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B.; Szukala, Richard; Johnson, Michael E.; Hevener, Kirk E.

    2013-01-01

    A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, drug-like, and ADMET filters were applied to the reported hits to assess the quality of compounds reported and a careful analysis of a subset of the studies which presented hit optimization was performed. This data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, defining hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria. PMID:23688234

  15. Hit identification and optimization in virtual screening: practical recommendations based on a critical literature analysis.

    Science.gov (United States)

    Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B; Szukala, Richard; Johnson, Michael E; Hevener, Kirk E

    2013-09-12

    A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses, and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, druglike, and ADMET filters were applied to the reported hits to assess the quality of compounds reported, and a careful analysis of a subset of the studies that presented hit optimization was performed. These data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, definition of hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria.

  16. Sun exposure causes somatic second-hit mutations and angiofibroma development in tuberous sclerosis complex

    Science.gov (United States)

    Tyburczy, Magdalena E.; Wang, Ji-an; Li, Shaowei; Thangapazham, Rajesh; Chekaluk, Yvonne; Moss, Joel; Kwiatkowski, David J.; Darling, Thomas N.

    2014-01-01

    Tuberous sclerosis complex (TSC) is characterized by the formation of tumors in multiple organs and is caused by germline mutation in one of two tumor suppressor genes, TSC1 and TSC2. As for other tumor suppressor gene syndromes, the mechanism of somatic second-hit events in TSC tumors is unknown. We grew fibroblast-like cells from 29 TSC skin tumors from 22 TSC subjects and identified germline and second-hit mutations in TSC1/TSC2 using next-generation sequencing. Eighteen of 22 (82%) subjects had a mutation identified, and 8 of the 18 (44%) subjects were mosaic with mutant allele frequencies of 0 to 19% in normal tissue DNA. Multiple tumors were available from four patients, and in each case, second-hit mutations in TSC2 were distinct indicating they arose independently. Most remarkably, 7 (50%) of the 14 somatic point mutations were CC>TT ultraviolet ‘signature’ mutations, never seen as a TSC germline mutation. These occurred exclusively in facial angiofibroma tumors from sun-exposed sites. These results implicate UV-induced DNA damage as a cause of second-hit mutations and development of TSC facial angiofibromas and suggest that measures to limit UV exposure in TSC children and adults should reduce the frequency and severity of these lesions. PMID:24271014

  17. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

    Science.gov (United States)

    Warkentin, Theodore E; Pai, Menaka; Linkins, Lori-Ann

    2017-08-31

    Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban. © 2017 by The American Society of Hematology.

  18. Efficiency Improvement of HIT Solar Cells on p-Type Si Wafers.

    Science.gov (United States)

    Wei, Chun-You; Lin, Chu-Hsuan; Hsiao, Hao-Tse; Yang, Po-Chuan; Wang, Chih-Ming; Pan, Yen-Chih

    2013-11-22

    Single crystal silicon solar cells are still predominant in the market due to the abundance of silicon on earth and their acceptable efficiency. Different solar-cell structures of single crystalline Si have been investigated to boost efficiency; the heterojunction with intrinsic thin layer (HIT) structure is currently the leading technology. The record efficiency values of state-of-the art HIT solar cells have always been based on n-type single-crystalline Si wafers. Improving the efficiency of cells based on p-type single-crystalline Si wafers could provide broader options for the development of HIT solar cells. In this study, we varied the thickness of intrinsic hydrogenated amorphous Si layer to improve the efficiency of HIT solar cells on p-type Si wafers.

  19. Straightforward hit identification approach in fragment-based discovery of bromodomain-containing protein 4 (BRD4) inhibitors.

    Science.gov (United States)

    Borysko, Petro; Moroz, Yurii S; Vasylchenko, Oleksandr V; Hurmach, Vasyl V; Starodubtseva, Anastasia; Stefanishena, Natalia; Nesteruk, Kateryna; Zozulya, Sergey; Kondratov, Ivan S; Grygorenko, Oleksandr O

    2018-05-09

    A combination approach of a fragment screening and "SAR by catalog" was used for the discovery of bromodomain-containing protein 4 (BRD4) inhibitors. Initial screening of 3695-fragment library against bromodomain 1 of BRD4 using thermal shift assay (TSA), followed by initial hit validation, resulted in 73 fragment hits, which were used to construct a follow-up library selected from available screening collection. Additionally, analogs of inactive fragments, as well as a set of randomly selected compounds were also prepared (3 × 3200 compounds in total). Screening of the resulting sets using TSA, followed by re-testing at several concentrations, counter-screen, and TR-FRET assay resulted in 18 confirmed hits. Compounds derived from the initial fragment set showed better hit rate as compared to the other two sets. Finally, building dose-response curves revealed three compounds with IC 50  = 1.9-7.4 μM. For these compounds, binding sites and conformations in the BRD4 (4UYD) have been determined by docking. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. COPD: A stepwise or a hit hard approach?

    Directory of Open Access Journals (Sweden)

    A.J. Ferreira

    2016-07-01

    Full Text Available Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or “hit hard” approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS are recommended, a step-up or “hit hard” approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications.This paper discusses and proposes stepwise, “hit hard”, step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach. Keywords: COPD, Stepwise, Hit hard, Step-up, ICS withdrawal, Bronchodilators, ICS

  1. Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery.

    Science.gov (United States)

    Heifetz, Alexander; Southey, Michelle; Morao, Inaki; Townsend-Nicholson, Andrea; Bodkin, Mike J

    2018-01-01

    GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.

  2. Double-hit B-cell lymphomas

    NARCIS (Netherlands)

    Aukema, Sietse M.; Siebert, Reiner; Schuuring, Ed; van Imhoff, Gustaaf W.; Kluin-Nelemans, Hanneke C.; Boerma, Evert-Jan; Kluin, Philip M.

    2011-01-01

    In many B-cell lymphomas, chromosomal translocations are biologic and diagnostic hallmarks of disease. An intriguing subset is formed by the so-called double-hit (DH) lymphomas that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint,

  3. Are stripes beneficial? Dazzle camouflage influences perceived speed and hit rates.

    Directory of Open Access Journals (Sweden)

    Bettina von Helversen

    Full Text Available In the animal kingdom, camouflage refers to patterns that help potential prey avoid detection. Mostly camouflage is thought of as helping prey blend in with their background. In contrast, disruptive or dazzle patterns protect moving targets and have been suggested as an evolutionary force in shaping the dorsal patterns of animals. Dazzle patterns, such as stripes and zigzags, are thought to reduce the probability with which moving prey will be captured by impairing predators' perception of speed. We investigated how different patterns of stripes (longitudinal-i.e., parallel to movement direction-and vertical-i.e., perpendicular to movement direction affect the probability with which humans can hit moving objects and if differences in hitting probability are caused by a misperception of speed. A first experiment showed that longitudinally striped objects were hit more often than unicolored objects. However, vertically striped objects did not differ from unicolored objects. A second study examining the link between perceived speed and hitting probability showed that longitudinally and vertically striped objects were both perceived as moving faster and were hit more often than unicolored objects. In sum, our results provide evidence that striped patterns disrupt the perception of speed, which in turn influences how often objects are hit. However, the magnitude and the direction of the effects depend on additional factors such as speed and the task setup.

  4. Variation in number of hits for complex searches in Google Scholar

    Directory of Open Access Journals (Sweden)

    Wichor Matthijs Bramer, BSc

    2016-11-01

    Full Text Available Objective: Google Scholar is often used to search for medical literature. Numbers of results reported by Google Scholar outperform the numbers reported by traditional databases. How reliable are these numbers? Why are often not all available 1,000 references shown? Methods: For several complex search strategies used in systematic review projects, the number of citations and the total number of versions were calculated. Several search strategies were followed over a two-year period, registering fluctuations in reported search results. Results: Changes in numbers of reported search results varied enormously between search strategies and dates. Theories for calculations of the reported and shown number of hits were not proved. Conclusions: The number of hits reported in Google Scholar is an unreliable measure. Therefore, its repeatability is problematic, at least when equal results are needed.

  5. Influence of Running on Pistol Shot Hit Patterns.

    Science.gov (United States)

    Kerkhoff, Wim; Bolck, Annabel; Mattijssen, Erwin J A T

    2016-01-01

    In shooting scene reconstructions, risk assessment of the situation can be important for the legal system. Shooting accuracy and precision, and thus risk assessment, might be correlated with the shooter's physical movement and experience. The hit patterns of inexperienced and experienced shooters, while shooting stationary (10 shots) and in running motion (10 shots) with a semi-automatic pistol, were compared visually (with confidence ellipses) and statistically. The results show a significant difference in precision (circumference of the hit patterns) between stationary shots and shots fired in motion for both inexperienced and experienced shooters. The decrease in precision for all shooters was significantly larger in the y-direction than in the x-direction. The precision of the experienced shooters is overall better than that of the inexperienced shooters. No significant change in accuracy (shift in the hit pattern center) between stationary shots and shots fired in motion can be seen for all shooters. © 2015 American Academy of Forensic Sciences.

  6. The impact of Health Information Technology (I-HIT) Scale: the Australian results.

    Science.gov (United States)

    Cook, Robyn; Foster, Joanne

    2009-01-01

    One of role of the nurse in the clinical setting is that of co-ordinating communication across the healthcare team. On a daily basis nurses interact with the person receiving care, their family members, and multiple care providers thus placing the nurse in the central position with access to a vast array of information on the person. Through this nurses have historically functioned as "information repositories". With the advent of Health Information Technology (HIT) tools there is a potential that HIT could impact interdisciplinary communication, practice efficiency and effectiveness, relationships and workflow in acute care settings [1][3]. In 2005, the HIMSS Nursing Informatics Community developed the I-HIT Scale to measure the impact of HIT on the nursing role and interdisciplinary communication in USA hospitals. In 2007, nursing informatics colleagues from Australia, Finland, Ireland, New Zealand, Scotland and the USA formed a research collaborative to validate the I-HIT in six additional countries. This paper will discuss the background, methodology, results and implications from the Australian I-HIT survey of over 1,100 nurses. The results are currently being analyzed and will be presented at the conference.

  7. Tolosa-Hunt Syndrome in Double-Hit Lymphoma

    Directory of Open Access Journals (Sweden)

    Prakash Peddi

    2015-01-01

    Full Text Available Tolosa-Hunt syndrome (THS is a painful condition characterized by hemicranial pain, retroorbital pain, loss of vision, oculomotor nerve paralysis, and sensory loss in distribution of ophthalmic and maxillary division of trigeminal nerve. Lymphomas rarely involve cavernous sinus and simulate Tolosa-Hunt syndrome. Here we present a first case of double-hit B cell lymphoma (DHL relapsing and masquerading as Tolosa-Hunt syndrome. The neurological findings were explained by a lymphomatous infiltration of the right Gasserian ganglion which preceded systemic relapse. As part of this report, the diagnostic criteria for Tolosa-Hunt syndrome and double-hit lymphoma are reviewed and updated treatment recommendations are presented.

  8. 75 FR 62399 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-10-08

    ... Technology; HIT Standards Committee Schedule for the Assessment of HIT Policy Committee Recommendations.... SUMMARY: Section 3003(b)(3) of the American Recovery and Reinvestment Act of 2009 mandates that the HIT Standards Committee develop a schedule for the assessment of policy recommendations developed by the HIT...

  9. HIT-6 and MIDAS as measures of headache disability in a headache referral population.

    Science.gov (United States)

    Sauro, Khara M; Rose, Marianne S; Becker, Werner J; Christie, Suzanne N; Giammarco, Rose; Mackie, Gordon F; Eloff, Arnoldas G; Gawel, Marek J

    2010-03-01

    The objective of this study was to compare the headache impact test (HIT-6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache-related disability. The degree of headache-related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. We compared HIT-6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT-6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI-II) scores. A positive correlation was found between HIT-6 and MIDAS scores (r = 0.52). The BDI-II scores correlated equally with the HIT-6 and the MIDAS (r = 0.42). There was a non-monotonic relationship between headache frequency and the MIDAS, and a non-linear monotonic relationship between headache frequency and the HIT-6 (r = 0.24). The correlation was higher between the intensity and the HIT-6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy-nine percent of patients fell into the most severe HIT-6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT-6 than with the MIDAS (McNemar chi-square = 191 on 6 d.f., P MIDAS appear to measure headache-related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT-6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT-6 and MIDAS together may give a more accurate assessment of a patient's headache-related disability.

  10. Development and formative evaluation of the e-Health Implementation Toolkit (e-HIT

    Directory of Open Access Journals (Sweden)

    Mair Frances

    2010-10-01

    Full Text Available Abstract Background The use of Information and Communication Technology (ICT or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice. This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format. Results The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience. Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls Conclusions The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations.

  11. #MaybeHeDoesntHitYou: Social Media Underscore the Realities of Intimate Partner Violence.

    Science.gov (United States)

    McCauley, Heather L; Bonomi, Amy E; Maas, Megan K; Bogen, Katherine W; O'Malley, Teagen L

    2018-03-22

    Public intimate partner violence (IPV) discourse emphasizes physical violence. In May 2016, the Twitter hashtag #MaybeHeDoesntHitYou generated a public conversation about abuse beyond physical IPV. Because of the often-disconnect between IPV research and what survivors struggle to name as abuse in their daily lives, we sought to understand how IPV discourse was unfolding as a result of the #MaybeHeDoesntHitYou hashtag. NCapture was used to collect publically available Twitter data containing the hashtag "#MaybeHeDoesntHitYou" from May 10, 2016 to May 17, 2016. Using the Duluth Power and Control Wheel (a range of tactics used by abusers to control and harm their partners) and the Women's Experience with Battering (WEB) framework (emotional and behavioral responses to being abused), we analyzed 1,229 original content tweets using qualitative content analysis. All dimensions of the Power and Control Wheel and five of six dimensions of the WEB framework were expressed via #MaybeHeDoesntHitYou; users did not express yearning for intimacy with their abusive partners. Users described one form of IPV not currently represented within the Power and Control Wheel-reproductive coercion (e.g., "#MaybeHeDoesntHitYou but he refuses to use condoms and forces you not to use contraception so you try to do it behind his back"). Two additional themes emerged; users challenged the gender pronoun of the hashtag, highlighting that abuse may happen with partners of all genders, and users provided social support for others (e.g., "#MaybeHeDoesntHitYou is real. Bruises and scars aren't the only measure of abuse! If this is you, help is there…"). Results from our study underscore the potential for social media platforms to be powerful agents for engaging public dialogue about the realities of IPV, as well as a space for seeking and providing social support about this critical women's health issue.

  12. Does ′heparin-induced thrombocytopenia′ hit our minds?

    Directory of Open Access Journals (Sweden)

    Arun R Thangavel

    2016-01-01

    Full Text Available Unfractionated heparin is a widely used drug to prevent deep vein thrombosis and pulmonary emboli in patients at risk. With the advent of newer anticoagulants having lesser side effects, its use has diminished but not out of service. Here, we report a case of deep venous thrombosis, in a patient on prophylactic dose of heparin, which was later found to be a manifestation of heparin-induced thrombocytopenia (HIT. Thrombosis in the presence of heparin prophylaxis should be considered as HIT rather than a failure of anticoagulation.

  13. Nedley Depression Hit Hypothesis: Identifying Depression and Its Causes.

    Science.gov (United States)

    Nedley, Neil; Ramirez, Francisco E

    2016-11-01

    Depression is often diagnosed using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. We propose how certain lifestyle choices and non-modifiable factors can predict the development of depression. We identified 10 cause categories (hits or "blows" to the brain) and theorize that four or more active hits could trigger a depression episode. Methods. A sample of 4271 participants from our community-based program (70% female; ages 17-94 years) was assessed at baseline and at the eighth week of the program using a custom test. Ten cause categories were examined as predictors of depression are (1) Genetic, (2)Developmental, (3)Lifestyle, (4)Circadian Rhythm, (5)Addiction, (6)Nutrition, (7)Toxic, (8)Social/Complicated Grief, (9)Medical Condition, and (10)Frontal Lobe. Results. The relationship between the DSM-5 score and a person having four hits categories in the first program week showed a sensitivity of 89.98 % (95% CI: 89.20 % - 90.73%), specificity 48.84% (CI 45.94-51.75) and Matthew Correlation Coefficient (MCC) .41 . For the eight-week test, the results showed a sensitivity 83.6% (CI 81.9-85.5), specificity 53.7% (CI 51.7-55.6) and MCC .38. Overall, the hits that improved the most from baseline after the eighth week were: Nutrition (47%), Frontal lobe (36%), Addiction (24%), Circadian rhythm (24%), Lifestyle (20%), Social (12%) and Medical (10%). Conclusions. The Nedley four-hit hypothesis seems to predict a depressive episode and correlates well with the DSM-5 criteria with good sensitivity and MCC but less specificity. Identifying these factors and applying lifestyle therapies could play an important role in the treatment of depressed individuals.

  14. Ultrathin Oxide Passivation Layer by Rapid Thermal Oxidation for the Silicon Heterojunction Solar Cell Applications

    OpenAIRE

    Lee, Youngseok; Oh, Woongkyo; Dao, Vinh Ai; Hussain, Shahzada Qamar; Yi, Junsin

    2012-01-01

    It is difficult to deposit extremely thin a-Si:H layer in heterojunction with intrinsic thin layer (HIT) solar cell due to thermal damage and tough process control. This study aims to understand oxide passivation mechanism of silicon surface using rapid thermal oxidation (RTO) process by examining surface effective lifetime and surface recombination velocity. The presence of thin insulating a-Si:H layer is the key to get high Voc by lowering the leakage current (I0) which improves the efficie...

  15. Thermal oxidative degradation kinetics of agricultural residues using distributed activation energy model and global kinetic model.

    Science.gov (United States)

    Ren, Xiu'e; Chen, Jianbiao; Li, Gang; Wang, Yanhong; Lang, Xuemei; Fan, Shuanshi

    2018-08-01

    The study concerned the thermal oxidative degradation kinetics of agricultural residues, peanut shell (PS) and sunflower shell (SS). The thermal behaviors were evaluated via thermogravimetric analysis and the kinetic parameters were determined by using distributed activation energy model (DAEM) and global kinetic model (GKM). Results showed that thermal oxidative decomposition of two samples processed in three zones; the ignition, burnout, and comprehensive combustibility between two agricultural residues were of great difference; and the combustion performance could be improved by boosting heating rate. The activation energy ranges calculated by the DAEM for the thermal oxidative degradation of PS and SS were 88.94-145.30 kJ mol -1 and 94.86-169.18 kJ mol -1 , respectively. The activation energy obtained by the GKM for the oxidative decomposition of hemicellulose and cellulose was obviously lower than that for the lignin oxidation at identical heating rate. To some degree, the determined kinetic parameters could acceptably simulate experimental data. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Current drive experiments in the HIT-II spherical tokamak

    International Nuclear Information System (INIS)

    Jarboe, T.R.; Gu, P.; Isso, V.A.; Jewell, P.E.; McCollam, K.J.; Nelson, B.A.; Ramon, R.; Redd, A.J.; Sieck, P.E.; Smith, R.J.; Nagata, M.; Uyama, T.

    2001-01-01

    The Helicity Injected Torus (Hit) program has made progress in understanding relaxation and helicity injection current drive. Helicity-conserving MHD activity during the inductive (Ohmic) current ramp demonstrates the profile flattening needed for coaxial helicity injection (CHI). Results from cathode and anode central column (CC) CHI pulses are consistent with the electron locking model of current drive from a pure n=1 mode. Finally, low density CHI, compatible with Ohmic operation, has been achieved. Some enhancement of CHI discharges with the application of Ohmic is shown. (author)

  17. 77 FR 57567 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-09-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  18. 77 FR 50690 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-08-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  19. 77 FR 15760 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-03-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  20. 76 FR 39108 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-07-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS ACTION: Notice of... the public. Name of Committee: HIT Policy Committee. General Function of the Committee: to provide...

  1. 77 FR 37407 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-06-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  2. 76 FR 22397 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  3. 77 FR 22787 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-04-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  4. 77 FR 27459 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-05-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  5. 76 FR 28783 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  6. 76 FR 79684 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-12-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  7. 77 FR 73660 - HIT Policy Committee Advisory Meetings; Notice of Meetings

    Science.gov (United States)

    2012-12-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  8. 77 FR 28881 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-05-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  9. 76 FR 46298 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  10. 77 FR 65691 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-10-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  11. 76 FR 70455 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  12. 77 FR 2727 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-01-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  13. 76 FR 14975 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-03-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  14. 76 FR 50734 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  15. 76 FR 55912 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2011-09-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... the public. Name of Committee: HIT Policy Committee. General Function of the Committee: To provide...

  16. 77 FR 41788 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2012-07-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  17. SHIELD-HIT12A - a Monte Carlo particle transport program for ion therapy research

    DEFF Research Database (Denmark)

    Bassler, Niels; Hansen, David Christoffer; Lühr, Armin

    2014-01-01

    . We experienced that new users quickly learn to use SHIELD-HIT12A and setup new geometries. Contrary to previous versions of SHIELD-HIT, the 12A distribution comes along with easy-to-use example files and an English manual. A new implementation of Vavilov straggling resulted in a massive reduction......Abstract. Purpose: The Monte Carlo (MC) code SHIELD-HIT simulates the transport of ions through matter. Since SHIELD-HIT08 we added numerous features that improves speed, usability and underlying physics and thereby the user experience. The “-A” fork of SHIELD-HIT also aims to attach SHIELD....... It supports native formats compatible with the heavy ion treatment planning system TRiP. Stopping power files follow ICRU standard and are generated using the libdEdx library, which allows the user to choose from a multitude of stopping power tables. Results: SHIELD-HIT12A runs on Linux and Windows platforms...

  18. Increase in peripheral oxidative stress during hypercholesterolemia is not reflected in the central nervous system: evidence from two mouse models.

    Science.gov (United States)

    Ding, Tao; Yao, Yeumang; Praticò, Domenico

    2005-05-01

    In recent years oxidative stress has been widely implicated as a pathogenetic mechanism of several diseases, and a variety of indices and assays have been developed to assess this phenomenon in complex biological systems. Most of these biomarkers can be measured virtually in every biological fluid and tissue, providing us with the opportunity to assess their formation at local site of oxidative injury. However, despite their widespread use, it is still not completely clear how their peripheral formation correlates with the levels measured in the central nervous system. For this reason, we utilized two well-characterized animal models of chronic peripheral oxidative stress, low-density lipoprotein receptor (LDLR)-deficient and C57BL/6 mice on a high fat diet. After 8 weeks on the diet, we assessed isoprostane, marker of lipid peroxidation, and carbonyls, marker of protein oxidation, in several organs of these animals. Compared with animals on chow, mice on the high fat diet showed a significant increase in both biomarkers in plasma, heart, aorta and liver but not in brain tissues. This observation was confirmed by the selective accumulation of radioactivity in the peripheral organs but not in the brains of mice injected with tritiated isoprostane. Our findings indicate that in hypercholesterolemia the peripheral formation of oxidative products does not contribute to their levels found in the central nervous system.

  19. Heparin- induced thrombocytopenia (HIT: a case report of CABG patient

    Directory of Open Access Journals (Sweden)

    Alireza Jahangirifard

    2016-08-01

    Full Text Available Heparin- induced thrombocytopenia (HIT is an antibody mediated adverse effect of heparin therapy which is classified into two subtypes, HITI which is non-immune, spontaneously reversible thrombocytopenia and; HITII which is an autoimmune-mediated adverse effect of heparin therapy. In this case report, we described a 65-year old male patient with HITII after coronary artery bypass grafting.Key words: Heparin- induced thrombocytopenia, Heparin- induced thrombosis, coronary artery bypass grafting.

  20. 75 FR 21629 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Science.gov (United States)

    2010-04-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee...

  1. A new model for extinction and recolonization in two dimensions: quantifying phylogeography.

    Science.gov (United States)

    Barton, Nicholas H; Kelleher, Jerome; Etheridge, Alison M

    2010-09-01

    Classical models of gene flow fail in three ways: they cannot explain large-scale patterns; they predict much more genetic diversity than is observed; and they assume that loosely linked genetic loci evolve independently. We propose a new model that deals with these problems. Extinction events kill some fraction of individuals in a region. These are replaced by offspring from a small number of parents, drawn from the preexisting population. This model of evolution forwards in time corresponds to a backwards model, in which ancestral lineages jump to a new location if they are hit by an event, and may coalesce with other lineages that are hit by the same event. We derive an expression for the identity in allelic state, and show that, over scales much larger than the largest event, this converges to the classical value derived by Wright and Malécot. However, rare events that cover large areas cause low genetic diversity, large-scale patterns, and correlations in ancestry between unlinked loci. © 2010 The Author(s). Journal compilation © 2010 The Society for the Study of Evolution.

  2. Shock waves in binary oxides memristors

    Science.gov (United States)

    Tesler, Federico; Tang, Shao; Dobrosavljević, Vladimir; Rozenberg, Marcelo

    2017-09-01

    Progress of silicon based technology is nearing its physical limit, as minimum feature size of components is reaching a mere 5 nm. The resistive switching behavior of transition metal oxides and the associated memristor device is emerging as a competitive technology for next generation electronics. Significant progress has already been made in the past decade and devices are beginning to hit the market; however, it has been mainly the result of empirical trial and error. Hence, gaining theoretical insight is of essence. In the present work we report a new connection between the resistive switching and shock wave formation, a classic topic of non-linear dynamics. We argue that the profile of oxygen ions that migrate during the commutation in insulating binary oxides may form a shock wave, which propagates through a poorly conductive region of the device. We validate the scenario by means of model simulations.

  3. Multi-hit time-to-amplitude CAMAC module (MTAC)

    International Nuclear Information System (INIS)

    Kang, H.

    1980-10-01

    A Multi-Hit Time-to-Amplitude Module (MTAC) for the SLAC Mark III drift chamber system has been designed to measure drift time by converting time-proportional chamber signals into analog levels, and converting the analog data by slow readout via a semi-autonomous controller in a CAMAC crate. The single width CAMAC module has 16 wire channels, each with a 4-hit capacity. An externally generated common start initiates an internal precision ramp voltage which is then sampled using a novel shift register gating scheme and CMOS sampling switches. The detailed design and performance specifications are described

  4. Simulating secondary organic aerosol in a regional air quality model using the statistical oxidation model - Part 1: Assessing the influence of constrained multi-generational ageing

    Science.gov (United States)

    Jathar, S. H.; Cappa, C. D.; Wexler, A. S.; Seinfeld, J. H.; Kleeman, M. J.

    2016-02-01

    Multi-generational oxidation of volatile organic compound (VOC) oxidation products can significantly alter the mass, chemical composition and properties of secondary organic aerosol (SOA) compared to calculations that consider only the first few generations of oxidation reactions. However, the most commonly used state-of-the-science schemes in 3-D regional or global models that account for multi-generational oxidation (1) consider only functionalization reactions but do not consider fragmentation reactions, (2) have not been constrained to experimental data and (3) are added on top of existing parameterizations. The incomplete description of multi-generational oxidation in these models has the potential to bias source apportionment and control calculations for SOA. In this work, we used the statistical oxidation model (SOM) of Cappa and Wilson (2012), constrained by experimental laboratory chamber data, to evaluate the regional implications of multi-generational oxidation considering both functionalization and fragmentation reactions. SOM was implemented into the regional University of California at Davis / California Institute of Technology (UCD/CIT) air quality model and applied to air quality episodes in California and the eastern USA. The mass, composition and properties of SOA predicted using SOM were compared to SOA predictions generated by a traditional two-product model to fully investigate the impact of explicit and self-consistent accounting of multi-generational oxidation.Results show that SOA mass concentrations predicted by the UCD/CIT-SOM model are very similar to those predicted by a two-product model when both models use parameters that are derived from the same chamber data. Since the two-product model does not explicitly resolve multi-generational oxidation reactions, this finding suggests that the chamber data used to parameterize the models captures the majority of the SOA mass formation from multi-generational oxidation under the conditions

  5. Hypertrophic Cardiomyopathy: A Vicious Cycle Triggered by Sarcomere Mutations and Secondary Disease Hits.

    Science.gov (United States)

    Wijnker, Paul J M; Sequeira, Vasco; Kuster, Diederik W D; Velden, Jolanda van der

    2018-04-11

    Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by left ventricular hypertrophy, diastolic dysfunction, and myocardial disarray. Disease onset occurs between 20 and 50 years of age, thus affecting patients in the prime of their life. HCM is caused by mutations in sarcomere proteins, the contractile building blocks of the heart. Despite increased knowledge of causal mutations, the exact path from genetic defect leading to cardiomyopathy is complex and involves additional disease hits. Recent Advances: Laboratory-based studies indicate that HCM development not only depends on the primary sarcomere impairment caused by the mutation but also on secondary disease-related alterations in the heart. Here we propose a vicious mutation-induced disease cycle, in which a mutation-induced energy depletion alters cellular metabolism with increased mitochondrial work, which triggers secondary disease modifiers that will worsen disease and ultimately lead to end-stage HCM. Evidence shows excessive cellular reactive oxygen species (ROS) in HCM patients and HCM animal models. Oxidative stress markers are increased in the heart (oxidized proteins, DNA, and lipids) and serum of HCM patients. In addition, increased mitochondrial ROS production and changes in endogenous antioxidants are reported in HCM. Mutant sarcomeric protein may drive excessive levels of cardiac ROS via changes in cardiac efficiency and metabolism, mitochondrial activation and/or dysfunction, impaired protein quality control, and microvascular dysfunction. Interventions restoring metabolism, mitochondrial function, and improved ROS balance may be promising therapeutic approaches. We discuss the effects of current HCM pharmacological therapies and potential future therapies to prevent and reverse HCM. Antioxid. Redox Signal. 00, 000-000.

  6. A New Track Reconstruction Algorithm suitable for Parallel Processing based on Hit Triplets and Broken Lines

    Directory of Open Access Journals (Sweden)

    Schöning André

    2016-01-01

    Full Text Available Track reconstruction in high track multiplicity environments at current and future high rate particle physics experiments is a big challenge and very time consuming. The search for track seeds and the fitting of track candidates are usually the most time consuming steps in the track reconstruction. Here, a new and fast track reconstruction method based on hit triplets is proposed which exploits a three-dimensional fit model including multiple scattering and hit uncertainties from the very start, including the search for track seeds. The hit triplet based reconstruction method assumes a homogeneous magnetic field which allows to give an analytical solutions for the triplet fit result. This method is highly parallelizable, needs fewer operations than other standard track reconstruction methods and is therefore ideal for the implementation on parallel computing architectures. The proposed track reconstruction algorithm has been studied in the context of the Mu3e-experiment and a typical LHC experiment.

  7. NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

    Science.gov (United States)

    Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

    2017-01-01

    The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity.

    Science.gov (United States)

    Sarvagalla, Sailu; Singh, Vivek Kumar; Ke, Yi-Yu; Shiao, Hui-Yi; Lin, Wen-Hsing; Hsieh, Hsing-Pang; Hsu, John T A; Coumar, Mohane Selvaraj

    2015-01-01

    Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as molecular weight (MW) and lipophilicity occurs. This could be effectively tackled by the right choice of hit compounds for optimization. In this regard, ligand efficiency (LE) and ligand efficiency dependent lipophilicity (LELP) indices are more often used to choose fragment-like hits for optimization. To identify hits with appropriate LE, we used a MW cut-off library. Next, structure-based virtual screening using software (Libdock and Glide) in the Aurora A crystal structure (PDB ID: 3E5A) was carried out, and the top scoring 18 compounds tested for Aurora A enzyme inhibition. This resulted in the identification of a novel tetrahydro-pyrazolo-isoquinoline hit 7 (IC50 = 852 nM, LE = 0.44, LELP = 8.36) with fragment-like properties suitable for further hit optimization. Moreover, hit 7 was found to be selective for Aurora A (Aurora B IC50 = 35,150 nM) and the possible reasons for selectivity investigated by docking two tautomeric forms (2H- and 3H-pyrazole) of 7 in Auroras A and B (PDB ID: 4AF3) crystal structures. This docking study shows that the major 3H-pyrazole tautomer of 7 binds in Aurora A stronger than in Aurora B.

  9. Charge deposition model for investigating SE-microdose effect in trench power MOSFETs

    Science.gov (United States)

    Xin, Wan; Weisong, Zhou; Daoguang, Liu; Hanliang, Bo; Jun, Xu

    2015-05-01

    It was demonstrated that heavy ions can induce large current—voltage (I-V) characteristics shift in commercial trench power MOSFETs, named single event microdose effect (SE-microdose effect). A model is presented to describe this effect. This model calculates the charge deposition by a single heavy ion hitting oxide and the subsequent charge transport under an electric field. Holes deposited at the SiO2/Si interface by a Xe ion are calculated by using this model. The calculated results were then used in Sentaurus TCAD software to simulate a trench power MOSFET's I-V curve shift after a Xe ion has hit it. The simulation results are consistent with the related experiment's data. In the end, several factors which affect the SE-microdose effect in trench power MOSFETs are investigated by using this model.

  10. Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities.

    Science.gov (United States)

    Warkentin, Theodore E; Sheppard, Jo-Ann I; Chu, F Victor; Kapoor, Anil; Crowther, Mark A; Gangji, Azim

    2015-01-01

    Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (eg, platelet serotonin-release assay [SRA]) has been recommended as the target serological end point to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive. © 2015 by The American Society of Hematology.

  11. Progress on FIR interferometry and Thomson Scattering measurements on HIT-SI3

    Science.gov (United States)

    Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

    2017-10-01

    Spatially resolved measurements of the electron temperature (Te) and density (ne) will be fundamental in assessing the degree to which HIT-SI3 demonstrates closed magnetic flux and energy confinement. Further, electron temperature measurements have not yet been made on an inductively-driven spheromak. Far infrared (FIR) interferometer and Thomson Scattering (TS) systems have been installed on the HIT-SI3 spheromak. The TS system currently implemented on HIT-SI3 was originally designed for other magnetic confinement experiments, and progress continues toward modifying and optimizing for HIT-SI3 plasmas. Initial results suggest that the electron temperature is of order 10 eV. Plans to modify the TS system to provide more sensitivity and accuracy at low temperatures are presented. The line-integrated ne is measured on one chord by the FIR interferometer, with densities near 5x1019 m-3. Four cylindrical volumes have been added to the HIT-SI3 apparatus to enhance passive pumping. It is hoped that this will allow for more control of the density during the 2 ms discharges. Density measurements from before and after the installation of the passive pumping volumes are presented for comparison.

  12. A mathematical model of bacteria capable of complete oxidation of ammonium predicts improved nitrogen removal and reduced production of nitrous oxide

    OpenAIRE

    Pokhilko, Alexandra; Ebenhöh, Oliver

    2017-01-01

    The removal of excess nutrients\\ud from water ecosystems requires oxidation of toxic\\ud ammonium by two types of bacteria; one oxidizes\\ud ammonium to nitrite and the other oxidizes nitrite\\ud to nitrate. The oxidation of ammonium is often\\ud incomplete and nitrite accumulates. Nitrite is also\\ud toxic, and is converted by the ammoniumoxidizing\\ud bacteria to nitrous oxide, a powerful\\ud greenhouse gas. Here we use mathematical\\ud modeling to analyze a potential solution to the\\ud problems re...

  13. 76 FR 4352 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2011-01-25

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Policy Committee's Workgroups: Meaningful Use, Privacy & Security Tiger..., implementation specifications, and certification criteria are needed. Date and Time: The HIT Policy Committee...

  14. The T10 beam produces a few hits per event. In ALICE the SSD will have to cope with many hits per strip. In the three centimeters of aluminium the beam will produce many secondary particles. This increases the chance of multiple hits per strip, although not to the level in ALICE.

    CERN Multimedia

    Nooren, G.

    2004-01-01

    The T10 beam produces a few hits per event. In ALICE the SSD will have to cope with many hits per strip. In the three centimeters of aluminium the beam will produce many secondary particles. This increases the chance of multiple hits per strip, although not to the level in ALICE.

  15. Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology: description and application to clinical feedback systems.

    Science.gov (United States)

    Lyon, Aaron R; Lewis, Cara C; Melvin, Abigail; Boyd, Meredith; Nicodimos, Semret; Liu, Freda F; Jungbluth, Nathaniel

    2016-09-22

    Health information technologies (HIT) have become nearly ubiquitous in the contemporary healthcare landscape, but information about HIT development, functionality, and implementation readiness is frequently siloed. Theory-driven methods of compiling, evaluating, and integrating information from the academic and commercial sectors are necessary to guide stakeholder decision-making surrounding HIT adoption and to develop pragmatic HIT research agendas. This article presents the Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology, a structured, theory-driven method for compiling and evaluating information from multiple sectors. As an example demonstration of the methodology, we apply HIT-ACE to mental and behavioral health measurement feedback systems (MFS). MFS are a specific class of HIT that support the implementation of routine outcome monitoring, an evidence-based practice. HIT-ACE is guided by theories and frameworks related to user-centered design and implementation science. The methodology involves four phases: (1) coding academic and commercial materials, (2) developer/purveyor interviews, (3) linking putative implementation mechanisms to hit capabilities, and (4) experimental testing of capabilities and mechanisms. In the current demonstration, phase 1 included a systematic process to identify MFS in mental and behavioral health using academic literature and commercial websites. Using user-centered design, implementation science, and feedback frameworks, the HIT-ACE coding system was developed, piloted, and used to review each identified system for the presence of 38 capabilities and 18 additional characteristics via a consensus coding process. Bibliometic data were also collected to examine the representation of the systems in the scientific literature. As an example, results are presented for the application of HIT-ACE phase 1 to MFS wherein 49 separate MFS were identified, reflecting a diverse array of characteristics

  16. 75 FR 3906 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-01-25

    ... Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National... only. Name of Committees: HIT Policy Committee's Workgroups: Meaningful Use, Privacy & Security Policy... specifications, and certification criteria are needed. Date and Time: The HIT Policy Committee Workgroups will...

  17. Mechanistic models for cancer development after short time radiation exposure

    International Nuclear Information System (INIS)

    Kottbauer, M. M.

    1997-12-01

    In this work two biological based models were developed. First the single-hit model for solid tumors (SHM-S) and second the single-hit model for leukemia (SHM-L). These models are a further development of the Armitage-Doll model for the special case of a short time radiation exposure. The basis of the models is the multistage process of carcinogeneses. The single-hit models provide simultaneously the age-dependent cancer-rate of spontaneous and radiation induced tumors as well as the dose-effect relationships at any age after exposure. The SHM-S leads to a biological based dose-effect relationship, which is similar to the relative risk model suggested by the ICRP 60. The SHM-S describes the increased mortality rate of the bomb survivors more accurate than the relative risk model. The SHM-L results in an additive dose-effect relationship. It is shown that only small differences in the derivation of the two models lead to the two dose-effect relationships. Beside the radiation exposure the new models consider the decrease of the cancer mortality rate at higher ages (age>75) which can be traced back mainly to three causes: competitive causes of death, reduction of cell proliferation and reduction of risk groups. The single-hit models also consider children cancer, the different rates of incidence and mortality, influence of the immune system and the cell-killing effect. (author)

  18. 75 FR 65636 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-10-26

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  19. 75 FR 57027 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-09-17

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  20. 75 FR 42090 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-07-20

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards... Strategic Plan, and in accordance with policies developed by the HIT Policy Committee. Date and Time: The...

  1. Laboratory tests for identification or exclusion of heparin induced thrombocytopenia: HIT or miss?

    Science.gov (United States)

    Favaloro, Emmanuel J

    2018-02-01

    Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin ("anti-PF4-heparin"). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay ("screening"), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed. The most common contemporary immunological assays comprise enzyme-linked immunosorbent assay [ELISA], chemiluminescence, lateral flow, and particle gel techniques. The most common functional assays measure platelet aggregation or platelet activation events (e.g., serotonin release assay; heparin-induced platelet activation (HIPA); flow cytometry). All assays have some sensitivity and specificity to HIT antibodies, but differ in terms of relative sensitivity and specificity for pathological HIT, as well as false negative and false positive error rate. This brief article overviews the different available laboratory methods, as well as providing a suggested approach to diagnosis or exclusion of HIT. © 2017 Wiley Periodicals, Inc.

  2. A Simplified Model for Volatile-N Oxidation

    DEFF Research Database (Denmark)

    Hansen, Stine; Glarborg, Peter

    2010-01-01

    In solid fuel flames, NO is largely formed from the oxidation of volatile nitrogen compounds such as HCN and NH3. To be able to model the nitrogen chemistry in these flames, it is necessary to have an adequate model for volatile-N oxidation. Simple global models for oxidation of HCN and NH3 from...... the literature should be used cautiously, since their predictive capabilities are limited, particularly under reducing conditions. Models for HCN/NH3/NO conversion based on the systematic reduction of a detailed chemical kinetic model offer high accuracy but rely on input estimates of combustion intermediates...... for the sub-bituminous and bituminous coals, especially at lower temperatures. The semiempirical correlations for estimating radical concentrations may also be useful in combination with models for other trace species, such as sulfur oxides, organic species, etc....

  3. HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.

    Science.gov (United States)

    Favaloro, Emmanuel J; McCaughan, Georgia; Mohammed, Soma; Lau, Kun Kan Edwin; Gemmell, Rosalie; Cavanaugh, Lauren; Donikian, Dea; Kondo, Mayuko; Brighton, Timothy; Pasalic, Leonardo

    2018-04-17

    Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG (PF4-H) ), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]. We observed both false positive and false negative test findings with most assays. Overall, the whole blood aggregation method provided a reasonable alternative to SRA for identifying functional HIT. STiC, AcuStar and ELISA procedures were fairly comparable in terms of screening for HIT, although STiC and AcuStar both yielded false negatives, albeit also resulting in fewer false positives than ELISA. The 4T score had less utility in our patient cohort than we were expecting, although there was an association with the likelihood of HIT. Nevertheless, we accept that our observations are based on limited test numbers. In conclusion, no single approach (clinical or laboratory) was associated with optimal sensitivity or specificity of HIT exclusion or identification, and thus, a combination of clinical evaluation and laboratory testing will best ensure the accuracy of diagnosis. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  4. Paraquat: model for oxidant-initiated toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Bus, J.S.; Gibson, J.E.

    1984-04-01

    Paraquat, a quaternary ammonium bipyridyl herbicide, produces degenerative lesions in the lung after systemic administration to man and animals. The pulmonary toxicity of paraquat resembles in several ways the toxicity of several other lung toxins, including oxygen, nitrofurantoin and bleomycin. Although a definitive mechanism of toxicity of parquat has not been delineated, a cyclic single electron reduction/oxidation of the parent molecule is a critical mechanistic event. The redox cycling of paraquat has two potentially important consequences relevant to the development of toxicity: generation of activated oxygen (e.g., superoxide anion, hydrogen perioxide, hydroxyl radical) which is highly reactive to cellular macromolecules; and/or oxidation of reducing equivalents (e.g., NADPH, reduced glutathione) necessary for normal cell function. Paraquat-induced pulmonary toxicity, therefore, is a potentially useful model for evaluation of oxidant mechanisms of toxicity. Furthermore, characterization of the consequences of intracellular redox cycling of xenobiotics will no doubt provide basic information regarding the role of this phenomena in the development of chemical toxicity. 105 references, 2 figures.

  5. Validation of the Impact of Health Information Technology (I-HIT) Scale: an international collaborative.

    Science.gov (United States)

    Dykes, Patricia C; Hurley, Ann C; Brown, Suzanne; Carr, Robyn; Cashen, Margaret; Collins, Rita; Cook, Robyn; Currie, Leanne; Docherty, Charles; Ensio, Anneli; Foster, Joanne; Hardiker, Nicholas R; Honey, Michelle L L; Killalea, Rosaleen; Murphy, Judy; Saranto, Kaija; Sensmeier, Joyce; Weaver, Charlotte

    2009-01-01

    In 2005, the Healthcare Information Management Systems Society (HIMSS) Nursing Informatics Community developed a survey to measure the impact of health information technology (HIT), the I-HIT Scale, on the role of nurses and interdisciplinary communication in hospital settings. In 2007, nursing informatics colleagues from Australia, England, Finland, Ireland, New Zealand, Scotland and the United States formed a research collaborative to validate the I-HIT across countries. All teams have completed construct and face validation in their countries. Five out of six teams have initiated reliability testing by practicing nurses. This paper reports the international collaborative's validation of the I-HIT Scale completed to date.

  6. Simulating secondary organic aerosol in a regional air quality model using the statistical oxidation model – Part 1: Assessing the influence of constrained multi-generational ageing

    Directory of Open Access Journals (Sweden)

    S. H. Jathar

    2016-02-01

    Full Text Available Multi-generational oxidation of volatile organic compound (VOC oxidation products can significantly alter the mass, chemical composition and properties of secondary organic aerosol (SOA compared to calculations that consider only the first few generations of oxidation reactions. However, the most commonly used state-of-the-science schemes in 3-D regional or global models that account for multi-generational oxidation (1 consider only functionalization reactions but do not consider fragmentation reactions, (2 have not been constrained to experimental data and (3 are added on top of existing parameterizations. The incomplete description of multi-generational oxidation in these models has the potential to bias source apportionment and control calculations for SOA. In this work, we used the statistical oxidation model (SOM of Cappa and Wilson (2012, constrained by experimental laboratory chamber data, to evaluate the regional implications of multi-generational oxidation considering both functionalization and fragmentation reactions. SOM was implemented into the regional University of California at Davis / California Institute of Technology (UCD/CIT air quality model and applied to air quality episodes in California and the eastern USA. The mass, composition and properties of SOA predicted using SOM were compared to SOA predictions generated by a traditional two-product model to fully investigate the impact of explicit and self-consistent accounting of multi-generational oxidation.Results show that SOA mass concentrations predicted by the UCD/CIT-SOM model are very similar to those predicted by a two-product model when both models use parameters that are derived from the same chamber data. Since the two-product model does not explicitly resolve multi-generational oxidation reactions, this finding suggests that the chamber data used to parameterize the models captures the majority of the SOA mass formation from multi-generational oxidation under

  7. Effective progression of nuclear magnetic resonance-detected fragment hits.

    Science.gov (United States)

    Eaton, Hugh L; Wyss, Daniel F

    2011-01-01

    Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Concurrent inhibition of MYC and BCL2 is a potentially effective treatment strategy for double hit and triple hit B-cell lymphomas.

    Science.gov (United States)

    Cinar, Munevver; Rosenfelt, Fred; Rokhsar, Sepehr; Lopategui, Jean; Pillai, Raju; Cervania, Melissa; Pao, Andy; Cinar, Bekir; Alkan, Serhan

    2015-07-01

    Double hit lymphoma or triple hit lymphoma (DHL/THL) is a rare form of aggressive B-Cell Lymphoma. Overexpression of MYC, BCL2 or/and BCL6 due to genomic rearrangements are the key molecular features of DHL/THL. Patients with DHL/THL show very aggressive disease course and poor survival due to the lack of effective treatment modalities. Here, we established new THL cell model and assessed its in vitro growth characteristics along with the DHL cell line in response to potent MYC inhibitors, 10058-F4 and JQ-1, and a BCL2 inhibitor, ABT-199, with or without chemotherapeutic agent vincristine or doxorubicin. We found that 10058-F4, JQ-1 or ABT-199 exposure as a single agent inhibited the growth of DHL/THL cells in a dose-dependent manner. Combined exposure of 10058-F4 or JQ-1 and ABT-199 as well as vincristine or doxorubicin markedly suppressed the growth of DHL/THL cells compared with the single treatment. As assessed by multiple approaches, apoptosis induced by ABT-199, 10058-F4 or JQ-1 was underlying cause of the observed growth suppression. These findings suggest that co-inhibition of MYC and BCL2 signaling is a promising therapeutic strategy for patients with DHL/THL lymphomas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. HIT Solar Cells with N-Type Low-Cost Metallurgical Si

    Directory of Open Access Journals (Sweden)

    Xing Yang

    2018-01-01

    Full Text Available A conversion efficiency of 20.23% of heterojunction with intrinsic thin layer (HIT solar cell on 156 mm × 156 mm metallurgical Si wafer has been obtained. Applying AFORS-HET software simulation, HIT solar cell with metallurgical Si was investigated with regard to impurity concentration, compensation level, and their impacts on cell performance. It is known that a small amount of impurity in metallurgical Si materials is not harmful to solar cell properties.

  10. Reliability and comparison of gain values with occurrence of saccades in the EyeSeeCam video head impulse test (vHIT)

    DEFF Research Database (Denmark)

    Hviid Korsager, Leise Elisabeth; Schmidt, Jesper Hvass; Faber, Christian

    2016-01-01

    . There is a lack of knowledge regarding the reliability of the two parameters. The objective was to investigate the reliability of vHIT by comparing gain values between examiners on the same subjects, and to see how differences affected the occurrence of saccades. SUBJECTS: 25 subjects who had undergone cochlear...... coefficient (ICC) of the gain values between examiners ranged from 0.62 to 0.70. Differences in gain values amongst examiners did not seem to affect the occurrence of saccades in the same patient. The occurrence of saccades, therefore, seems to be more reliable than the gain value in the evaluation......The vHIT (video head impulse test) investigates the vestibular function in two ways: a VOR (vestibulo-ocular reflex) gain value and a head impulse diagram. From the diagram covert and overt saccades can be detected. Evaluation of the vestibular function based on vHIT depends on both parameters...

  11. A business case for HIT adoption: effects of "meaningful use" EHR financial incentives on clinic revenue.

    Science.gov (United States)

    Behkami, Nima A; Dorr, David A; Morrice, Stuart

    2010-01-01

    The goal of this study is to describe a framework that allows decision makers to efficiently evaluate factors that affect Electronic Health Record (EHR) adoption and test suitable interventions; specifically financial incentives. The United States healthcare delivery system is experiencing a transformation to improve population health. There is strong agreement that "meaningful use" of Health Information Technology (HIT) is a major enabler in this effort. However it's also understood that the high cost of implementing an EHR is an obstacle for adoption. To help understand these complexities we developed a simulation model designed to capture the dynamic nature of policy interventions that affect the adoption of EHR. We found that "Effective" use of HIT approaches break-even-point and larger clinic revenue many times faster that "average" or "poor" use of HIT. This study uses a systems perspective to the evaluate EHR adoption process through the "meaningful use" redesign as proposed in the American Reinvestment and Recovery Act 2009 in the United States healthcare industry by utilizing the System Dynamics methodology and Scenario Analysis.

  12. Charge deposition model for investigating SE-microdose effect in trench power MOSFETs

    International Nuclear Information System (INIS)

    Wan Xin; Zhou Weisong; Liu Daoguang; Bo Hanliang; Xu Jun

    2015-01-01

    It was demonstrated that heavy ions can induce large current—voltage (I–V) characteristics shift in commercial trench power MOSFETs, named single event microdose effect (SE-microdose effect). A model is presented to describe this effect. This model calculates the charge deposition by a single heavy ion hitting oxide and the subsequent charge transport under an electric field. Holes deposited at the SiO 2 /Si interface by a Xe ion are calculated by using this model. The calculated results were then used in Sentaurus TCAD software to simulate a trench power MOSFET's I–V curve shift after a Xe ion has hit it. The simulation results are consistent with the related experiment's data. In the end, several factors which affect the SE-microdose effect in trench power MOSFETs are investigated by using this model. (paper)

  13. Two-Step Oxidation of Refractory Gold Concentrates with Different Microbial Communities.

    Science.gov (United States)

    Wang, Guo-Hua; Xie, Jian-Ping; Li, Shou-Peng; Guo, Yu-Jie; Pan, Ying; Wu, Haiyan; Liu, Xin-Xing

    2016-11-28

    Bio-oxidation is an effective technology for treatment of refractory gold concentrates. However, the unsatisfactory oxidation rate and long residence time, which cause a lower cyanide leaching rate and gold recovery, are key factors that restrict the application of traditional bio-oxidation technology. In this study, the oxidation rate of refractory gold concentrates and the adaption of microorganisms were analyzed to evaluate a newly developed two-step pretreatment process, which includes a high temperature chemical oxidation step and a subsequent bio-oxidation step. The oxidation rate and recovery rate of gold were improved significantly after the two-step process. The results showed that the highest oxidation rate of sulfide sulfur could reach to 99.01 % with an extreme thermophile microbial community when the pulp density was 5%. Accordingly, the recovery rate of gold was elevated to 92.51%. Meanwhile, the results revealed that moderate thermophiles performed better than acidophilic mesophiles and extreme thermophiles, whose oxidation rates declined drastically when the pulp density was increased to 10% and 15%. The oxidation rates of sulfide sulfur with moderate thermophiles were 93.94% and 65.73% when the pulp density was increased to 10% and 15%, respectively. All these results indicated that the two-step pretreatment increased the oxidation rate of refractory gold concentrates and is a potential technology to pretreat the refractory sample. Meanwhile, owing to the sensitivity of the microbial community under different pulp density levels, the optimization of microbial community in bio-oxidation is necessary in industry.

  14. Investigation of Zircaloy-2 oxidation model for SFP accident analysis

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, Yoshiyuki, E-mail: nemoto.yoshiyuki@jaea.go.jp [Japan Atomic Energy Agency, 2-4 Shirakata, Ohaza, Tokai-mura, Naka-gun, Ibaraki, 319-1195 (Japan); Kaji, Yoshiyuki; Ogawa, Chihiro; Kondo, Keietsu [Japan Atomic Energy Agency, 2-4 Shirakata, Ohaza, Tokai-mura, Naka-gun, Ibaraki, 319-1195 (Japan); Nakashima, Kazuo; Kanazawa, Toru; Tojo, Masayuki [Global Nuclear Fuel – Japan Co., Ltd., 2-3-1, Uchikawa, Yokosuka-shi, Kanagawa, 239-0836 (Japan)

    2017-05-15

    The authors previously conducted thermogravimetric analyses on Zircaloy-2 in air. By using the thermogravimetric data, an oxidation model was constructed in this study so that it can be applied for the modeling of cladding degradation in spent fuel pool (SFP) severe accident condition. For its validation, oxidation tests of long cladding tube were conducted, and computational fluid dynamics analyses using the constructed oxidation model were proceeded to simulate the experiments. In the oxidation tests, high temperature thermal gradient along the cladding axis was applied and air flow rates in testing chamber were controlled to simulate hypothetical SFP accidents. The analytical outputs successfully reproduced the growth of oxide film and porous oxide layer on the claddings in oxidation tests, and validity of the oxidation model was proved. Influence of air flow rate for the oxidation behavior was thought negligible in the conditions investigated in this study. - Highlights: •An oxidation model of Zircaloy-2 in air environment was developed. •The oxidation model was validated by the comparison with oxidation tests using long cladding tubes in hypothetical spent fuel pool accident condition. •The oxidation model successfully reproduced the typical oxidation behavior in air.

  15. Biophysics: for HTS hit validation, chemical lead optimization, and beyond.

    Science.gov (United States)

    Genick, Christine C; Wright, S Kirk

    2017-09-01

    There are many challenges to the drug discovery process, including the complexity of the target, its interactions, and how these factors play a role in causing the disease. Traditionally, biophysics has been used for hit validation and chemical lead optimization. With its increased throughput and sensitivity, biophysics is now being applied earlier in this process to empower target characterization and hit finding. Areas covered: In this article, the authors provide an overview of how biophysics can be utilized to assess the quality of the reagents used in screening assays, to validate potential tool compounds, to test the integrity of screening assays, and to create follow-up strategies for compound characterization. They also briefly discuss the utilization of different biophysical methods in hit validation to help avoid the resource consuming pitfalls caused by the lack of hit overlap between biophysical methods. Expert opinion: The use of biophysics early on in the drug discovery process has proven crucial to identifying and characterizing targets of complex nature. It also has enabled the identification and classification of small molecules which interact in an allosteric or covalent manner with the target. By applying biophysics in this manner and at the early stages of this process, the chances of finding chemical leads with novel mechanisms of action are increased. In the future, focused screens with biophysics as a primary readout will become increasingly common.

  16. High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors.

    Science.gov (United States)

    Myers, Stephanie M; Bawn, Ruth H; Bisset, Louise C; Blackburn, Timothy J; Cottyn, Betty; Molyneux, Lauren; Wong, Ai-Ching; Cano, Celine; Clegg, William; Harrington, Ross W; Leung, Hing; Rigoreau, Laurent; Vidot, Sandrine; Golding, Bernard T; Griffin, Roger J; Hammonds, Tim; Newell, David R; Hardcastle, Ian R

    2016-08-08

    The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase.

  17. Two-Step Electrochemical Intercalation and Oxidation of Graphite for the Mass Production of Graphene Oxide.

    Science.gov (United States)

    Cao, Jianyun; He, Pei; Mohammed, Mahdi A; Zhao, Xin; Young, Robert J; Derby, Brian; Kinloch, Ian A; Dryfe, Robert A W

    2017-12-06

    Conventional chemical oxidation routes for the production of graphene oxide (GO), such as the Hummers' method, suffer from environmental and safety issues due to their use of hazardous and explosive chemicals. These issues are addressed by electrochemical oxidation methods, but such approaches typically have a low yield due to inhomogeneous oxidation. Herein we report a two-step electrochemical intercalation and oxidation approach to produce GO on the large laboratory scale (tens of grams) comprising (1) forming a stage 1 graphite intercalation compound (GIC) in concentrated sulfuric acid and (2) oxidizing and exfoliating the stage 1 GIC in an aqueous solution of 0.1 M ammonium sulfate. This two-step approach leads to GO with a high yield (>70 wt %), good quality (>90%, monolayer), and reasonable oxygen content (17.7 at. %). Moreover, the as-produced GO can be subsequently deeply reduced (3.2 at. % oxygen; C/O ratio 30.2) to yield highly conductive (54 600 S m -1 ) reduced GO. Electrochemical capacitors based on the reduced GO showed an ultrahigh rate capability of up to 10 V s -1 due to this high conductivity.

  18. Mathematical modeling of nitrous oxide production in an anaerobic/oxic/anoxic process.

    Science.gov (United States)

    Ding, Xiaoqian; Zhao, Jianqiang; Hu, Bo; Chen, Ying; Ge, Guanghuan; Li, Xiaoling; Wang, Sha; Gao, Kun; Tian, Xiaolei

    2016-12-01

    This study incorporates three currently known nitrous oxide (N 2 O) production pathways: ammonium-oxidizing bacteria (AOB) denitrification, incomplete hydroxylamine (NH 2 OH) oxidation, and heterotrophic denitrification on intracellular polymers, into a mathematical model to describe N 2 O production in an anaerobic/oxic/anoxic (AOA) process for the first time. The developed model was calibrated and validated by four experimental cases, then evaluated by two independent anaerobic/aerobic (AO) studies from literature. The modeling results displayed good agreement with the measured data. N 2 O was primarily generated in the aerobic stage by AOB denitrification (67.84-81.64%) in the AOA system. Smaller amounts of N 2 O were produced via incomplete NH 2 OH oxidation (15.61-32.17%) and heterotrophic denitrification on intracellular polymers (0-12.47%). The high nitrite inhibition on N 2 O reductase led to the increased N 2 O accumulation in heterotrophic denitrification on intracellular polymers. The new model was capable of modeling nitrification-denitrification dynamics and heterotrophic denitrification on intracellular polymers in the AOA system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Upgrade tracking with the UT Hits

    CERN Document Server

    Gandini, P; Wang, J

    2014-01-01

    The performance of the LHCb tracking system for the upgrade on long tracks is evaluated in terms of efficiency and ghost rate reduction for several different sets of requirements. We find that the efficiency is quite high and that the ghost rate reduction is substantial. We also describe the current algorithm for adding UT hits to the tracks.

  20. LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes.

    Science.gov (United States)

    Carlson, Hanqian L; Quinn, Jeffrey J; Yang, Yul W; Thornburg, Chelsea K; Chang, Howard Y; Stadler, H Scott

    2015-12-01

    Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage.

  1. EASY-HIT: HIV full-replication technology for broad discovery of multiple classes of HIV inhibitors.

    Science.gov (United States)

    Kremb, Stephan; Helfer, Markus; Heller, Werner; Hoffmann, Dieter; Wolff, Horst; Kleinschmidt, Andrea; Cepok, Sabine; Hemmer, Bernhard; Durner, Jörg; Brack-Werner, Ruth

    2010-12-01

    HIV replication assays are important tools for HIV drug discovery efforts. Here, we present a full HIV replication system (EASY-HIT) for the identification and analysis of HIV inhibitors. This technology is based on adherently growing HIV-susceptible cells, with a stable fluorescent reporter gene activated by HIV Tat and Rev. A fluorescence-based assay was designed that measures HIV infection by two parameters relating to the early and the late phases of HIV replication, respectively. Validation of the assay with a panel of nine reference inhibitors yielded effective inhibitory concentrations consistent with published data and allowed discrimination between inhibitors of early and late phases of HIV replication. Finer resolution of the effects of reference drugs on different steps of HIV replication was achieved in secondary time-of-addition assays. The EASY-HIT assay yielded high Z' scores (>0.9) and signal stabilities, confirming its robustness. Screening of the LOPAC(1280) library identified 10 compounds (0.8%), of which eight were known to inhibit HIV, validating the suitability of this assay for screening applications. Studies evaluating anti-HIV activities of natural products with the EASY-HIT technology led to the identification of three novel inhibitory compounds that apparently act at different steps of HIV-1 replication. Furthermore, we demonstrate successful evaluation of plant extracts for HIV-inhibitory activities, suggesting application of this technology for the surveillance of biological extracts with anti-HIV activities. We conclude that the EASY-HIT technology is a versatile tool for the discovery and characterization of HIV inhibitors.

  2. Oxide behaviour modelling progress in COMETHE

    International Nuclear Information System (INIS)

    Vliet, J. van; Hoppe, N.

    1983-01-01

    An attempt has been made to develop a global model which simultaneously describes many important aspects of uranium oxide under irradiation. The individual models describing fuel structural changes, swelling and gas release, which were earlier separate from one another, are now part of a more realistic integral fuel model. Fission gas release depends now on an explicitely calculated open porosity, which is generated by fuel swelling; the latter is in turn connected to fission gas release. The paper describes the individual oxide models and how they are linked together. (author)

  3. Visual Illusions and the Control of Ball Placement in Goal-Directed Hitting

    Science.gov (United States)

    Caljouw, Simone R.; Van der Kamp, John; Savelsbergh, Geert J. P.

    2010-01-01

    When hitting, kicking, or throwing balls at targets, online control in the target area is impossible. We assumed this lack of late corrections in the target area would induce an effect of a single-winged Muller-Lyer illusion on ball placement. After extensive practice in hitting balls to different landing locations, participants (N = 9) had to hit…

  4. Spontaneous HIT syndrome post-knee replacement surgery with delayed recovery of thrombocytopenia: a case report and literature review.

    Science.gov (United States)

    Poudel, Dilli Ram; Ghimire, Sushil; Dhital, Rashmi; Forman, Daniel A; Warkentin, Theodore E

    2017-09-01

    Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 10 9 /L. Prior to diagnostic consideration of spontaneous HIT syndrome, the patient briefly received unfractionated heparin (UFH) and one dose of enoxaparin. The patient's serum tested strongly positive for anti-PF4/heparin antibodies by two different PF4-dependent enzyme-linked immunosorbent assays (ELISAs) and by serotonin release assay (SRA). Failure of fondaparinux anticoagulation (persisting HIT-associated disseminated intravascular coagulation) prompted switching to argatroban. Severe thrombocytopenia persisted (platelet count nadir, 12 × 10 9 /L, on POD21), and 9 days after starting argatroban symptomatic right leg deep-vein thrombosis (DVT) occurred, prompting switch to rivaroxaban. Thereafter, her course was uneventful, although platelet count recovery was prolonged, reaching 99 × 10 9 /L by POD45 and 199 × 10 9 /L by POD79. The patient's serum elicited strong serotonin release in the absence of heparin (seen even with 1/32 serum dilution) that was enhanced by pharmacological concentrations of UFH (0.1 and 0.3 IU/mL) and fondaparinux (0.1-1.2 μg/mL, i.e., in vitro fondaparinux "cross-reactivity"). Ultimately, platelet count recovery was

  5. Modelling of multicomponent diffusion in a two-phase oxide-metal corium pool by a diffuse interface method

    International Nuclear Information System (INIS)

    Cardon, Clement

    2016-01-01

    This Ph.D. topic is focused on the modelling of stratification kinetics for an oxide-metal corium pool (U-O-Zr-steel system) in terms of multicomponent and multiphase diffusion. This work is part of a larger research effort for the development of a detailed corium pool modelling based on a CFD approach for thermal hydraulics. The overall goal is to improve the understanding of the involved phenomena and obtain closure laws for integral macroscopic models. The phase-field method coupled with an energy functional using the CALPHAD method appears to be relevant for this purpose. In a first part, we have developed a diffuse interface model in order to describe the diffusion process in the U-O system. This model has been coupled with a CALPHAD thermodynamic database and its parameterization has been developed with, in particular, an up-scaling procedure related to the interface thickness. Then, within the framework of a modelling for the U-O-Zr ternary system, we have proposed a generalization of the diffuse interface model through an assumption of local equilibrium for redox mechanisms. A particular attention was paid to the model analysis by 1D numerical simulations with a special focus on the steady state composition profiles. Finally we have applied this model to the U-O-Zr-Fe system. For that purpose, we have considered a configuration close to small-scale experimental tests of oxide-metal corium pool stratification. (author) [fr

  6. Matching Diabetes and Alcoholism: Oxidative Stress, Inflammation, and Neurogenesis Are Commonly Involved

    Directory of Open Access Journals (Sweden)

    Jorge M. Barcia

    2015-01-01

    Full Text Available Diabetes and alcohol misuse are two of the major challenges in health systems worldwide. These two diseases finally affect several organs and systems including the central nervous system. Hippocampus is one of the most relevant structures due to neurogenesis and memory-related processing among other functions. The present review focuses on the common profile of diabetes and ethanol exposure in terms of oxidative stress and proinflammatory and prosurvival recruiting transcription factors affecting hippocampal neurogenesis. Some aspects around antioxidant strategies are also included. As a global conclusion, the present review points out some common hits on both diseases giving support to the relations between alcohol intake and diabetes.

  7. Aggressive B cell Lymphoma: Optimal Therapy for MYC-positive, Double-Hit, and Triple-Hit DLBCL.

    Science.gov (United States)

    Dunleavy, Kieron

    2015-12-01

    Approximately 10% of cases of diffuse large B cell lymphoma (DLBCL) harbor a MYC rearrangement and this has been associated with an inferior outcome following standard therapy across many different studies. Double-hit and triple-hit lymphomas harbor concurrent rearrangements of MYC and BCL2 and/or BCL6 and are also associated with a very aggressive course and poor clinical outcome. It is unclear and there is lack of consensus on how these diseases should be approached therapeutically. They are characterized typically by high tumor proliferation and likely require Burkitt lymphoma-type strategies and several retrospective studies suggest that more intensive approaches than rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) may be beneficial. One challenge in this respect is that most patients with these diseases are older than 60 years and generally have poor tolerability of regimens typically used in Burkitt lymphoma. Dose-adjusted EPOCH-R is an alternative effective immunochemotherapy platform for DLBCL and is effective in Burkitt lymphoma, and retrospective studies suggest that it is effective and feasible in patients with DLBCL that harbors a MYC rearrangement with or without a BCL-2 translocation (double-hit). A multicenter study of this approach in MYC-rearranged DLBCL is ongoing and preliminary results are very encouraging. There is a lack of consensus on the role of consolidation stem cell transplantation in patients who achieve a good response to initial therapy but at this point in time, no (retrospective) studies have demonstrated any benefit. These diseases are also associated with a high rate of CNS involvement and progression and checking for cerebrospinal fluid by cytology and flow cytometry at initial diagnosis should be considered. In summary, based on retrospective data and preliminary prospective data (as more mature data is awaited), while Burkitt-type regimens may be feasible in young patients, DA-EPOCH-R is a

  8. Simulation optimizing of n-type HIT solar cells with AFORS-HET

    Science.gov (United States)

    Yao, Yao; Xiao, Shaoqing; Zhang, Xiumei; Gu, Xiaofeng

    2017-07-01

    This paper presents a study of heterojunction with intrinsic thin layer (HIT) solar cells based on n-type silicon substrates by a simulation software AFORS-HET. We have studied the influence of thickness, band gap of intrinsic layer and defect densities of every interface. Details in mechanisms are elaborated as well. The results show that the optimized efficiency reaches more than 23% which may give proper suggestions to practical preparation for HIT solar cells industry.

  9. Modeling SOA formation from the oxidation of intermediate volatility n-alkanes

    Directory of Open Access Journals (Sweden)

    J. Lee-Taylor

    2012-08-01

    Full Text Available The chemical mechanism leading to SOA formation and ageing is expected to be a multigenerational process, i.e. a successive formation of organic compounds with higher oxidation degree and lower vapor pressure. This process is here investigated with the explicit oxidation model GECKO-A (Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere. Gas phase oxidation schemes are generated for the C8–C24 series of n-alkanes. Simulations are conducted to explore the time evolution of organic compounds and the behavior of secondary organic aerosol (SOA formation for various preexisting organic aerosol concentration (COA. As expected, simulation results show that (i SOA yield increases with the carbon chain length of the parent hydrocarbon, (ii SOA yield decreases with decreasing COA, (iii SOA production rates increase with increasing COA and (iv the number of oxidation steps (i.e. generations needed to describe SOA formation and evolution grows when COA decreases. The simulated oxidative trajectories are examined in a two dimensional space defined by the mean carbon oxidation state and the volatility. Most SOA contributors are not oxidized enough to be categorized as highly oxygenated organic aerosols (OOA but reduced enough to be categorized as hydrocarbon like organic aerosols (HOA, suggesting that OOA may underestimate SOA. Results show that the model is unable to produce highly oxygenated aerosols (OOA with large yields. The limitations of the model are discussed.

  10. Oxidation of methionine in PrP is dependent upon the oxidant and the amino acid two positions removed

    Science.gov (United States)

    Background/Introduction. Methionine oxidation has been shown both to be associated with prion formation and implicated in the inhibition of amyloid formation in model systems. This work is based on model systems where hydrogen peroxide was used as an oxidant. Materials and Methods. We developed...

  11. Effect of morphology and solvent on two-photon absorption of nano zinc oxide

    Energy Technology Data Exchange (ETDEWEB)

    Kavitha, M.K. [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram 695547, Kerala (India); Haripadmam, P.C.; Gopinath, Pramod; Krishnan, Bindu [Department of Physics, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram 695547, Kerala (India); John, Honey, E-mail: honey@iist.ac.in [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram 695547, Kerala (India)

    2013-05-15

    Highlights: ► ZnO nanospheres and triangular structures synthesis by novel precipitation technique. ► The effect of precursor concentration on the size and shape of nano ZnO. ► Open aperture Z-scan measurements of the ZnO nanoparticle dispersions. ► Nanospheres exhibit higher two photon absorption coefficient than triangular nanostructures. ► Nanospheres dispersed in water exhibit higher two photon absorption coefficient than its dispersion in 2-propanol. - Abstract: In this paper, we report the effect of morphology and solvent on the two-photon absorption of nano zinc oxide. Zinc oxide nanoparticles in two different morphologies like nanospheres and triangular nanostructures are synthesized by novel precipitation technique and their two-photon absorption coefficient is measured using open aperture Z-scan technique. Experimental results show that the zinc oxide nanospheres exhibit higher two-photon absorption coefficient than the zinc oxide triangular nanostructures. The zinc oxide nanospheres dispersed in water exhibit higher two-photon absorption coefficient than that of its dispersion in 2-propanol. The zinc oxide nanospheres dispersed in water shows a decrease in two-photon absorption coefficient with an increase in on-axis irradiance. The result confirms the dependence of shape and solvent on the two-photon absorption of nano zinc oxide.

  12. Assessment of the performances of AcuStar HIT and the combination with heparin-induced multiple electrode aggregometry: a retrospective study.

    Science.gov (United States)

    Minet, V; Bailly, N; Douxfils, J; Osselaer, J C; Laloy, J; Chatelain, C; Elalamy, I; Chatelain, B; Dogné, J M; Mullier, F

    2013-09-01

    Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods. We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis. Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n=81). The clinical diagnosis was established by analysing in a standardized manner the patient's medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference. Using the recommended thresholds (1.00AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89AU, HIT-Ab: 9.41AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed. Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Modelling of Zircaloy-steam-oxidation under severe fuel damage conditions

    International Nuclear Information System (INIS)

    Malang, S.; Neitzel, H.J.

    1983-01-01

    Small break loss-of-coolant accidents and special transients in an LWR, in combination with loss of required safety systems, may lead to an uncovered core for an extended period of time. As a consequence, the cladding temperature could rise up to the melting point due to the decay heat, resulting in severely damaged fuel rods. During heat-up the claddings oxidize due to oxygen uptake from the steam atmosphere in the core. The modeling and assessment of the Zircaloy-steam oxidation under such conditions is important, mainly for two reasons: The oxidation of the cladding influences the temperature transients due to the exothermic heat of reaction; the amount of liquified fuel depends on the oxide layer thickness and the oxygen content of the remaining Zircaloy metal when the melting point is reached. (author)

  14. Two oxidation pathways of bioactive flavonol rhamnazin under ambient conditions

    International Nuclear Information System (INIS)

    Ramešová, Šárka; Degano, Ilaria; Sokolová, Romana

    2014-01-01

    Graphical abstract: - Highlights: • The oxidation mechanism of rhamnazin has not been solved yet. • Rhamnazin decomposes in solution during minutes handled in the presence of air. • The main oxidation product of rhamnazin was identified even if it is not stable. • Two parallel oxidation mechanisms of rhamnazin in air were determined. - Abstract: Two pathways of the oxidation mechanism of rhamnazin under ambient conditions are proposed. The redox potential of rhamnazin strongly depends on the presence of dissociation forms in solution. In situ spectroelectrochemistry and identification of degradation products by HPLC-DAD and HPLC–ESI-MS/MS confirmed the presence of fast subsequent chemical reactions following the electron transfer. As demonstrated, strict anaerobic conditions have to be preserved in studies of antioxidant properties and of its pharmacological efficiency. In the absence of oxygen, 2,4-dihydroxy-2-(4′-hydroxy-3′-methoxybenzoyl) -6-methoxy-benzofuran-3(2H)-one was identified as the only oxidation product

  15. USER FRUSTRATION IN HIT INTERFACES: EXPLORING PAST HCI RESEARCH FOR A BETTER UNDERSTANDING OF CLINICIANS' EXPERIENCES.

    Science.gov (United States)

    Opoku-Boateng, Gloria A

    2015-01-01

    User frustration research has been one way of looking into clinicians' experience with health information technology use and interaction. In order to understand how clinician frustration with Health Information Technology (HIT) use occurs, there is the need to explore Human-Computer Interaction (HCI) literature that addresses both frustration and HIT use. In the past three decades, HCI frustration research has increased and expanded. Researchers have done a lot of work to understand emotions, end-user frustration and affect. This paper uses a historical literature review approach to review the origins of emotion and frustration research and explore the research question; Does HCI research on frustration provide insights on clinicians' frustration with HIT interfaces? From the literature review HCI research on emotion and frustration provides additional insights that can indeed help explain user frustration in HIT. Different approaches and HCI perspectives also help frame HIT user frustration research as well as inform HIT system design. The paper concludes with a suggested directions on how future design and research may take.

  16. A Model Based on Cocitation for Web Information Retrieval

    Directory of Open Access Journals (Sweden)

    Yue Xie

    2014-01-01

    Full Text Available According to the relationship between authority and cocitation in HITS, we propose a new hyperlink weighting scheme to describe the strength of the relevancy between any two webpages. Then we combine hyperlink weight normalization and random surfing schemes as used in PageRank to justify the new model. In the new model based on cocitation (MBCC, the pages with stronger relevancy are assigned higher values, not just depending on the outlinks. This model combines both features of HITS and PageRank. Finally, we present the results of some numerical experiments, showing that the MBCC ranking agrees with the HITS ranking, especially in top 10. Meanwhile, MBCC keeps the superiority of PageRank, that is, existence and uniqueness of ranking vectors.

  17. HitRECord: Cultura remix y copyright. Una experiencia en primera persona en el interior de la Compañía de Producción hitRECord.

    OpenAIRE

    Sabater Planelles, Pablo

    2016-01-01

    El Proyecto que hemos desarrollado, mezcla investigación y experiencia en primera persona entorno a dos temas principales con la finalidad de abordarlos, experimentarlos y comprenderlos de la mejor manera en el contexto actual. Mantienen una estrecha confrontación entre ellos y gran relación con la comunidad online hitRECord. Éstos son el copyright y la cultura remix. HitRECord es una plataforma online impulsada en el 2010 por el actor y artista Joseph Gordon-Levitt, convertida en una ...

  18. Development of pulsation technique for single ion hit system

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Takuro; Hamano, Tsuyoshi; Hirao, Toshio; Kamiya, Tomihiro [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1996-12-01

    When a high energy heavy ion enters into a substance, high density of ionization and excitement occurrs along its flying trace. Especially, when such an ion enters into a semiconductor cell, a bit inversion called single event is occurred or a phenomenon destroyed element itself on case of the worst is formed. The present semiconductor cell is made in a size of some micron square, as different from its accumulated degree. In order to analyze the single event phenomenon formed by entering ion into such fine region in detail, a technique possible enter heavy ion beam with space resolution under 1 micron to each sample is necessary. In order to develop this technique, a static type high speed beam switch for control of entering a beam into a sample and a single ion detector for detecting entrance of ion into the sample were installed to heavy ion microbeam forming apparatus. The single ion hit system in Takasaki Radiation Chemistry Research Establishment, JAERI succeeded in detection and control technique of the single ion and control of noise due to pulsization and finished development of basic technique of the single ion hit, since now. After today, it is planned to hit actually the single ion onto the sample and evaluate its accuracy. (G.K.)

  19. Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis.

    Science.gov (United States)

    Suzuki, Hitoshi

    2018-05-08

    IgA nephropathy (IgAN) is the most prevalent glomerular disease worldwide and is associated with a poor prognosis. Development of curative treatment strategies and approaches for early diagnosis is necessary. Renal biopsy is the gold standard for the diagnosis and assessment of disease activity. However, reliable biomarkers are needed for the noninvasive diagnosis of this disease and to more fully delineate the risk of progression. With regard to the pathogenesis of IgAN, the multi-hit hypothesis, including production of galactose-deficient IgA1 (Gd-IgA1; Hit 1), IgG or IgA autoantibodies that recognize Gd-IgA1 (Hit 2), and their subsequent immune complexes formation (Hit 3) and glomerular deposition (Hit 4), has been widely supported by many studies. Although the prognostic values of several biomarkers have been discussed, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of Gd-IgA1 and Gd-IgA1-containing immune complexes. In addition, urinary Gd-IgA1 may represent a disease-specific biomarker for IgAN. We also confirmed that there is a significant correlation between serum levels of these effector molecules and disease activity, suggesting that each can be considered a practical surrogate marker of therapeutic response. Thus, these disease-oriented specific serum and urine biomarkers may be useful for screening of potential IgAN with isolated hematuria, earlier diagnosis, disease activity, and eventually, response to treatment. In this review, we discuss these concepts, with a focus on potential clinical applications of these biomarkers.

  20. Developments in kinetic modelling of chalcocite particle oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Jaervi, J; Ahokainen, T; Jokilaakso, A [Helsinki Univ. of Technology, Otaniemi (Finland). Lab. of Materials Processing and Powder Metallurgy

    1998-12-31

    A mathematical model for simulating chalcocite particle oxidation is presented. Combustion of pure chalcocite with oxygen is coded as a kinetic module which can be connected as a separate part of commercial CFD-package, PHOENICS. Heat transfer, fluid flow and combustion phenomena can be simulated using CFD-calculation together with the kinetic model. Interaction between gas phase and particles are taken into account by source terms. The aim of the kinetic model is to calculate the particle temperature, contents of species inside the particle, oxygen consumption and formation of sulphur dioxide. Four oxidation reactions are considered and the shrinking core model is used to describe the rate of the oxidation reactions. The model is verified by simulating the particle oxidation reactions in a laboratory scale laminar-flow furnace under different conditions and the model predicts the effects of charges correctly. In the future, the model validation will be done after experimental studies in the laminar flow-furnace. (author) 18 refs.

  1. Developments in kinetic modelling of chalcocite particle oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Jaervi, J.; Ahokainen, T.; Jokilaakso, A. [Helsinki Univ. of Technology, Otaniemi (Finland). Lab. of Materials Processing and Powder Metallurgy

    1997-12-31

    A mathematical model for simulating chalcocite particle oxidation is presented. Combustion of pure chalcocite with oxygen is coded as a kinetic module which can be connected as a separate part of commercial CFD-package, PHOENICS. Heat transfer, fluid flow and combustion phenomena can be simulated using CFD-calculation together with the kinetic model. Interaction between gas phase and particles are taken into account by source terms. The aim of the kinetic model is to calculate the particle temperature, contents of species inside the particle, oxygen consumption and formation of sulphur dioxide. Four oxidation reactions are considered and the shrinking core model is used to describe the rate of the oxidation reactions. The model is verified by simulating the particle oxidation reactions in a laboratory scale laminar-flow furnace under different conditions and the model predicts the effects of charges correctly. In the future, the model validation will be done after experimental studies in the laminar flow-furnace. (author) 18 refs.

  2. Hit-size effectiveness theory applied to high doses of low LET radiation for pink mutations in Tradescantia

    International Nuclear Information System (INIS)

    Varma, M.N.; Bond, V.P.; Matthews, G.

    1985-01-01

    A hit-size effectiveness function which represents the probability of inducing a pink mutation in Tradescantia as a function of lineal energy density has been obtained (1) using observed pink mutation data for seven different radiation qualities and their respective single event microdosimetric spectra. In obtaining this function only the linear portions of dose-response curves were used. A significant improvement of the concepts embodied in the proposed hit-size effectiveness theory would be the demonstration of its applicability at high doses (where multiple hits are produced) and high dose rates (at which no significant biological repair takes place). In this article details are given on preliminary calculations of the pink mutation frequency in Tradescantia at 1, 5, 10, 20, and 60 rads for 250 kVp x rays, using the multi-hit spectra and the hit-size effectiveness function obtained on the basis of single hit microdosimetric spectra as outline in (1). A comparison of the calculated and observed pink mutation frequencies indicate excellent agreement and suggests the possibility of obtaining the hit-size effectiveness function from high dose biological-effect data obtained using low-LET radiations. 6 refs., 3 figs., 3 tabs

  3. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Claire S Leblond

    2012-02-01

    Full Text Available Autism spectrum disorders (ASD are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls. We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4% patients and in 16 of 1,090 (1.5% controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70. In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013. Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

  4. Application of Two Cobalt-Based Metal-Organic Frameworks as Oxidative Desulfurization Catalysts.

    Science.gov (United States)

    Masoomi, Mohammad Yaser; Bagheri, Minoo; Morsali, Ali

    2015-12-07

    Two new porous cobalt-based metal-organic frameworks, [Co6(oba)5(OH)2(H2O)2(DMF)4]n · 5DMF (TMU-10) and [Co3(oba)3(O) (Py)0.5] n · 4DMF · Py (TMU-12) have been synthesized by solvothermal method using a nonlinear dicarboxylate ligand. Under mild reaction conditions, these compounds exhibited good catalytic activity and reusability in oxidative desulfurization (ODS) reaction of model oil which was prepared by dissolving dibenzothiophene (DBT) in n-hexane. FT-IR and Mass analysis showed that the main product of DBT oxidation is its corresponding sulfone, which was adsorbed on the surfaces of catalysts. The activation energy was obtained as 13.4 kJ/mol.

  5. Contribution of Visual Information about Ball Trajectory to Baseball Hitting Accuracy.

    Directory of Open Access Journals (Sweden)

    Takatoshi Higuchi

    Full Text Available The contribution of visual information about a pitched ball to the accuracy of baseball-bat contact may vary depending on the part of trajectory seen. The purpose of the present study was to examine the relationship between hitting accuracy and the segment of the trajectory of the flying ball that can be seen by the batter. Ten college baseball field players participated in the study. The systematic error and standardized variability of ball-bat contact on the bat coordinate system and pitcher-to-catcher direction when hitting a ball launched from a pitching machine were measured with or without visual occlusion and analyzed using analysis of variance. The visual occlusion timing included occlusion from 150 milliseconds (ms after the ball release (R+150, occlusion from 150 ms before the expected arrival of the launched ball at the home plate (A-150, and a condition with no occlusion (NO. Twelve trials in each condition were performed using two ball speeds (31.9 m·s-1 and 40.3 m·s-1. Visual occlusion did not affect the mean location of ball-bat contact in the bat's long axis, short axis, and pitcher-to-catcher directions. Although the magnitude of standardized variability was significantly smaller in the bat's short axis direction than in the bat's long axis and pitcher-to-catcher directions (p < 0.001, additional visible time from the R+150 condition to the A-150 and NO conditions resulted in a further decrease in standardized variability only in the bat's short axis direction (p < 0.05. The results suggested that there is directional specificity in the magnitude of standardized variability with different visible time. The present study also confirmed the limitation to visual information is the later part of the ball trajectory for improving hitting accuracy, which is likely due to visuo-motor delay.

  6. Complementation of biotransformations with chemical C-H oxidation: copper-catalyzed oxidation of tertiary amines in complex pharmaceuticals.

    Science.gov (United States)

    Genovino, Julien; Lütz, Stephan; Sames, Dalibor; Touré, B Barry

    2013-08-21

    The isolation, quantitation, and characterization of drug metabolites in biological fluids remain challenging. Rapid access to oxidized drugs could facilitate metabolite identification and enable early pharmacology and toxicity studies. Herein, we compared biotransformations to classical and new chemical C-H oxidation methods using oxcarbazepine, naproxen, and an early compound hit (phthalazine 1). These studies illustrated the low preparative efficacy of biotransformations and the inability of chemical methods to oxidize complex pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a broad range of functionalities and displays a high level of chemoselectivity, which is not generally explained by the strength of the C-H bonds but by the individual structural chemotype. This study represents a first step toward establishing a chemical toolkit (chemotransformations) that can selectively oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug metabolites.

  7. Phase-field modeling of corrosion kinetics under dual-oxidants

    Science.gov (United States)

    Wen, You-Hai; Chen, Long-Qing; Hawk, Jeffrey A.

    2012-04-01

    A phase-field model is proposed to simulate corrosion kinetics under a dual-oxidant atmosphere. It will be demonstrated that the model can be applied to simulate corrosion kinetics under oxidation, sulfidation and simultaneous oxidation/sulfidation processes. Phase-dependent diffusivities are incorporated in a natural manner and allow more realistic modeling as the diffusivities usually differ by many orders of magnitude in different phases. Simple free energy models are then used for testing the model while calibrated free energy models can be implemented for quantitative modeling.

  8. Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

    Science.gov (United States)

    Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

    2012-11-01

    The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

  9. PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

    Science.gov (United States)

    Haile, Lydia A; Rao, Roshni; Polumuri, Swamy K; Arepally, Gowthami M; Keire, David A; Verthelyi, Daniela; Sommers, Cynthia D

    2017-11-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies developed in response to multi-molecular complexes formed by platelet factor 4 (PF4) bound to heparin or cell surface glycosaminoglycans. These antibody complexes activate platelets and monocytes typically through FcγRIIA receptors increasing the production of PF4, inflammatory mediators, tissue factor and thrombin. The influence of underlying events in HIT including complex-induced pro-inflammatory cell activation and structural determinants leading to local inflammatory responses are not fully understood. The stoichiometry and complex component requirements were determined by incubating fresh peripheral blood mononuclear cells (PBMC) with different concentrations of unfractionated heparin (H), low molecular weight heparin (LMWH), PF4- and anti-PF4-H complex antibodies (KKO). Cytokine mRNA or protein were measured by qRT-PCR or Meso Scale Discovery technology, respectively. Gene expression profile analysis for 594 genes was performed using Nanostring technology and analyzed using Ingenuity Pathway Analysis software. The data show that antibodies magnify immune responses induced in PBMCs by PF4 alone or in complex with heparin or LMWH. We propose that following induction of HIT antibodies by heparin-PF4 complexes, binding of the antibodies to PF4 is sufficient to induce a local pro-inflammatory response which may play a role in the progression of HIT. In vitro assays using PBMCs may be useful in characterizing local inflammatory and innate immune responses induced by HIT antibodies in the presence of PF4 and different sources of heparins. The findings and conclusions in this article are solely the responsibility of the authors and are not being formally disseminated by the Food and Drug Administration. Thus, they should not be

  10. Reaction modelling of Iron Oxide Bromination in the UT-3 thermochemical cycle for Hydrogen production from water

    International Nuclear Information System (INIS)

    Amir-Rusli

    1996-01-01

    Analysis modelling of the iron oxide bromination had been carried out using experiment data from the iron oxide bromination in the UT-3 thermochemical cycle. Iron oxide in the form of pellets were made of the calcination of the mixture of iron oxide, silica, graphite and cellulose at 1473 K. Thermobalance reactor was used to study the kinetic reactions of the iron oxide bromination at a temperature of 473 K for 2 - 6 hours. The data collected from the experiments were used as input for the common models. However, none of these models could not explain the result of the experiments. A new model, a combination of two kinetic reactions : exposed particle and coated particle was created and worked successfully

  11. Measurements and Simulations on the Mechanisms of Efficiency Losses in HIT Solar Cells

    Directory of Open Access Journals (Sweden)

    Silvio Pierro

    2015-01-01

    Full Text Available We study the electrical and the optical behavior of HIT solar cell by means of measurements and optoelectrical simulations by TCAD simulations. We compare the HIT solar cell with a conventional crystalline silicon solar cell to identify the strengths and weaknesses of the HIT technology. Results highlight different mechanisms of electrical and optical efficiency losses caused by the presence of the amorphous silicon layer. The higher resistivity of the a-Si layers implies a smaller distance between the metal lines that causes a higher shadowing. The worst optical coupling between the amorphous silicon and the antireflective coating implies a slight increase of reflectivity around the 600 nm wavelength.

  12. The Holistic Integrity Test (HIT - quantified resilience analysis

    Directory of Open Access Journals (Sweden)

    Dobson Mike

    2016-01-01

    Full Text Available The Holistic Integrity Test (HIT - Quantified Resilience Analysis. Rising sea levels and wider climate change mean we face an increasing risk from flooding and other natural hazards. Tough economic times make it difficult to economically justify or afford the desired level of engineered risk reduction. Add to this significant uncertainty from a range of future predictions, constantly updated with new science. We therefore need to understand not just how to reduce the risk, but what could happen should above design standard events occur. In flood terms this includes not only the direct impacts (damage and loss of life, but the wider cascade impacts to infrastructure systems and the longer term impacts on the economy and society. However, understanding the “what if” is only the first part of the equation; a range of improvement measures to mitigate such effects need to be identified and implemented. These measures should consider reducing the risk, lessening the consequences, aiding the response, and speeding up the recovery. However, they need to be objectively assessed through quantitative analysis, which underpins them technically and economically. Without such analysis, it cannot be predicted how measures will perform if the extreme events occur. It is also vital to consider all possible hazards as measures for one hazard may hinder the response to another. The Holistic Integrity Test (HIT, uses quantitative system analysis and “HITs” the site, its infrastructure, contained dangers and wider regional system to determine how it copes with a range of severe shock events, Before, During and After the event, whilst also accounting for uncertainty (as illustrated in figure 1. First explained at the TINCE 2014 Nuclear Conference in Paris, it was explained in terms of a Nuclear Facility needing to analyse the site in response to post Fukushima needs; the hit is however universally applicable. The HIT has three key risk reduction goals: The

  13. Two Catalysts for Selective Oxidation of Contaminant Gases

    Science.gov (United States)

    Wright, John D.

    2011-01-01

    Two catalysts for the selective oxidation of trace amounts of contaminant gases in air have been developed for use aboard the International Space Station. These catalysts might also be useful for reducing concentrations of fumes in terrestrial industrial facilities especially facilities that use halocarbons as solvents, refrigerant liquids, and foaming agents, as well as facilities that generate or utilize ammonia. The first catalyst is of the supported-precious-metal type. This catalyst is highly active for the oxidation of halocarbons, hydrocarbons, and oxygenates at low concentrations in air. This catalyst is more active for the oxidation of hydrocarbons and halocarbons than are competing catalysts developed in recent years. This catalyst completely converts these airborne contaminant gases to carbon dioxide, water, and mineral acids that can be easily removed from the air, and does not make any chlorine gas in the process. The catalyst is thermally stable and is not poisoned by chlorine or fluorine atoms produced on its surface during the destruction of a halocarbon. In addition, the catalyst can selectively oxidize ammonia to nitrogen at a temperature between 200 and 260 C, without making nitrogen oxides, which are toxic. The temperature of 260 C is higher than the operational temperature of any other precious-metal catalyst that can selectively oxidize ammonia. The purpose of the platinum in this catalyst is to oxidize hydrocarbons and to ensure that the oxidation of halocarbons goes to completion. However, the platinum exhibits little or no activity for initiating the destruction of halocarbons. Instead, the attack on the halocarbons is initiated by the support. The support also provides a high surface area for exposure of the platinum. Moreover, the support resists deactivation or destruction by halogens released during the destruction of halocarbons. The second catalyst is of the supported- metal-oxide type. This catalyst can selectively oxidize ammonia to

  14. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

    Science.gov (United States)

    Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

    2015-07-01

    A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

  15. Direct determination of the hit locations from experimental HPGe pulses

    Energy Technology Data Exchange (ETDEWEB)

    Désesquelles, P., E-mail: Pierre.Desesquelles@in2p3.fr [Univ. Paris-Sud, CSNSM CNRS/IN2P3, 15 rue G. Clémenceau, 91405 Orsay (France); Boston, A.J.; Boston, H.C.; Cresswell, J.R.; Dimmock, M.R. [Oliver Lodge Laboratory, The University of Liverpool, Oxford Street, Liverpool L69 7ZE (United Kingdom); Lazarus, I.H. [STFC Daresbury Laboratory, Daresbury, Warrington WA4 4AD (United Kingdom); Ljungvall, J. [Univ. Paris-Sud, CSNSM CNRS/IN2P3, 15 rue G. Clémenceau, 91405 Orsay (France); Nelson, L. [Oliver Lodge Laboratory, The University of Liverpool, Oxford Street, Liverpool L69 7ZE (United Kingdom); Nga, D.-T. [Univ. Paris-Sud, CSNSM CNRS/IN2P3, 15 rue G. Clémenceau, 91405 Orsay (France); Nolan, P.J.; Rigby, S.V. [Oliver Lodge Laboratory, The University of Liverpool, Oxford Street, Liverpool L69 7ZE (United Kingdom); Simpson, J. [STFC Daresbury Laboratory, Daresbury, Warrington WA4 4AD (United Kingdom); Van-Oanh, N.-T. [Univ. Paris-Sud, LCP UMR8000 CNRS, 15 rue G. Clémenceau, 91405 Orsay (France)

    2013-11-21

    The gamma-tracking technique optimises the determination of the energy and emission angle of gamma-rays detected by modern segmented HPGe detectors. This entails the determination, using the delivered pulse shapes, of the interaction points of the gamma-ray within the crystal. The direct method presented here allows the localisation of the hits using only a large sample of pulses detected in the actual operating conditions. No external crystal scanning system or pulse shape simulation code is needed. In order to validate this method, it is applied to sets of pulses obtained using the University of Liverpool scanning system. The hit locations are determined by the method with good precision.

  16. Modeling of thermal expansion coefficient of perovskite oxide for solid oxide fuel cell cathode

    Science.gov (United States)

    Heydari, F.; Maghsoudipour, A.; Alizadeh, M.; Khakpour, Z.; Javaheri, M.

    2015-09-01

    Artificial intelligence models have the capacity to eliminate the need for expensive experimental investigation in various areas of manufacturing processes, including the material science. This study investigates the applicability of adaptive neuro-fuzzy inference system (ANFIS) approach for modeling the performance parameters of thermal expansion coefficient (TEC) of perovskite oxide for solid oxide fuel cell cathode. Oxides (Ln = La, Nd, Sm and M = Fe, Ni, Mn) have been prepared and characterized to study the influence of the different cations on TEC. Experimental results have shown TEC decreases favorably with substitution of Nd3+ and Mn3+ ions in the lattice. Structural parameters of compounds have been determined by X-ray diffraction, and field emission scanning electron microscopy has been used for the morphological study. Comparison results indicated that the ANFIS technique could be employed successfully in modeling thermal expansion coefficient of perovskite oxide for solid oxide fuel cell cathode, and considerable savings in terms of cost and time could be obtained by using ANFIS technique.

  17. The immune imbalance in the second hit of pancreatitis is independent of IL-17A.

    Science.gov (United States)

    Thomson, John-Edwin; Brand, Martin; Fonteh, Pascaline

    2018-04-01

    Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP. Thirty-six patients with mild (n = 16), moderate (n = 10) and severe (n = 10) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for analysis of routine clinical markers as well as cytokine analysis. Flow cytometry and a IL-17A ELISA was performed to determine cytokine concentrations. There were no significant differences between days 7, 9, 11 and 13 for either the mild/moderate or SAP groups for IL-17A (CBA assay or ELISA), IFN-γ, TNF-α, IL-2 or IL-4. For each of the study days, the mean IL-6 and IL-10 concentrations were significantly higher in the SAP group compared to the mild/moderate group. WCC, CRP and PCT were all significantly higher in severe acute pancreatitis over the study days. An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  18. A physiologically based kinetic model for bacterial sulfide oxidation.

    Science.gov (United States)

    Klok, Johannes B M; de Graaff, Marco; van den Bosch, Pim L F; Boelee, Nadine C; Keesman, Karel J; Janssen, Albert J H

    2013-02-01

    In the biotechnological process for hydrogen sulfide removal from gas streams, a variety of oxidation products can be formed. Under natron-alkaline conditions, sulfide is oxidized by haloalkaliphilic sulfide oxidizing bacteria via flavocytochrome c oxidoreductase. From previous studies, it was concluded that the oxidation-reduction state of cytochrome c is a direct measure for the bacterial end-product formation. Given this physiological feature, incorporation of the oxidation state of cytochrome c in a mathematical model for the bacterial oxidation kinetics will yield a physiologically based model structure. This paper presents a physiologically based model, describing the dynamic formation of the various end-products in the biodesulfurization process. It consists of three elements: 1) Michaelis-Menten kinetics combined with 2) a cytochrome c driven mechanism describing 3) the rate determining enzymes of the respiratory system of haloalkaliphilic sulfide oxidizing bacteria. The proposed model is successfully validated against independent data obtained from biological respiration tests and bench scale gas-lift reactor experiments. The results demonstrate that the model is a powerful tool to describe product formation for haloalkaliphilic biomass under dynamic conditions. The model predicts a maximum S⁰ formation of about 98 mol%. A future challenge is the optimization of this bioprocess by improving the dissolved oxygen control strategy and reactor design. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Effects on ontogenesis of Carausius morosus hit by cosmic heavy ions

    International Nuclear Information System (INIS)

    Reitz, G.; Buecker, H.; Ruether, W.

    1990-01-01

    Among the biological problems that arise in long duration spaceflights, the effects of weightlessness and ionizing radiation appear to be the two main risk factors. Eggs of the stick insect Carausius morosus were exposed to spaceflight conditions during the 12.56 day Biosatellite mission Cosmos 1887. Five different ages were used, representing different sensitivities to radiation and different capacities for regeneration. During spaceflight the eggs continued their development. Already, in the Spacelab D1 mission in 1985, it has been shown that microgravity leads to a reduced hatching rate of eggs exposed during the early steps of development. When the eggs were hit by a heavy ion, a further but not significant reduction of the hatching rate was observed. Hatching was normal for eggs which were exposed on a 1 g reference centrifuge in space. Heavy ion hits caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high rate of anomalies. In the experiment on Cosmos 1887 these results were confirmed. Studies on the embryonic development before hatching showed no major difference between flight and ground control specimen, neither in speed of development nor in morphological anomalies. Hatching therefore seems to be the critical point in insect ontogenesis. (author)

  20. Two-stage unified stretched-exponential model for time-dependence of threshold voltage shift under positive-bias-stresses in amorphous indium-gallium-zinc oxide thin-film transistors

    Science.gov (United States)

    Jeong, Chan-Yong; Kim, Hee-Joong; Hong, Sae-Young; Song, Sang-Hun; Kwon, Hyuck-In

    2017-08-01

    In this study, we show that the two-stage unified stretched-exponential model can more exactly describe the time-dependence of threshold voltage shift (ΔV TH) under long-term positive-bias-stresses compared to the traditional stretched-exponential model in amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). ΔV TH is mainly dominated by electron trapping at short stress times, and the contribution of trap state generation becomes significant with an increase in the stress time. The two-stage unified stretched-exponential model can provide useful information not only for evaluating the long-term electrical stability and lifetime of the a-IGZO TFT but also for understanding the stress-induced degradation mechanism in a-IGZO TFTs.

  1. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma

    Directory of Open Access Journals (Sweden)

    Xiao Yi Zhou

    2018-06-01

    Full Text Available Purpose: Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. Observations: A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Conclusions and importance: Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy. Keywords: Lymphoma, Triple-hit lymphoma, Orbital mass

  2. Lower bounds on the periodic Hamming correlations of frequency hopping sequences with low hit zone

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this paper, several periodic Hamming correlation lower bounds for frequency hopping sequences with low hit zone, with respect to the size p of the frequency slot set, the sequence length L, the family size M, low hit zone LH ( or no hit zone NH ), the maximum periodic Hamming autocorrelation sidelobe Ha and the maximum periodic Hamming crosscorrelation Hc, are established. It is shown that the new bounds include the known Lempel-Greenberger bounds, T.S. Seay bounds and Peng-Fan bounds for the conventional frequency hopping sequences as special cases.

  3. 75 FR 6398 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-02-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Adoption/Certification Workgroup Meeting; Notice of Meeting AGENCY: Office... of Committee: HIT Policy Committee's Adoption/Certification Workgroup. General Function of the...

  4. Do repeated rumble strip hits improve driver alertness?

    NARCIS (Netherlands)

    Watling, C.N.; Akerstedt, T.; Kecklund, L.G.; Anund, A.

    2016-01-01

    Driving while sleepy is associated with increased crash risk. Rumble strips are designed to alert a sleepy or inattentive driver when they deviate outside their driving lane. The current study sought to examine the effects of repeated rumble strip hits on levels of physiological and subjective

  5. Genome-Scale, Constraint-Based Modeling of Nitrogen Oxide Fluxes during Coculture of Nitrosomonas europaea and Nitrobacter winogradskyi

    Science.gov (United States)

    Giguere, Andrew T.; Murthy, Ganti S.; Bottomley, Peter J.; Sayavedra-Soto, Luis A.

    2018-01-01

    ABSTRACT Nitrification, the aerobic oxidation of ammonia to nitrate via nitrite, emits nitrogen (N) oxide gases (NO, NO2, and N2O), which are potentially hazardous compounds that contribute to global warming. To better understand the dynamics of nitrification-derived N oxide production, we conducted culturing experiments and used an integrative genome-scale, constraint-based approach to model N oxide gas sources and sinks during complete nitrification in an aerobic coculture of two model nitrifying bacteria, the ammonia-oxidizing bacterium Nitrosomonas europaea and the nitrite-oxidizing bacterium Nitrobacter winogradskyi. The model includes biotic genome-scale metabolic models (iFC578 and iFC579) for each nitrifier and abiotic N oxide reactions. Modeling suggested both biotic and abiotic reactions are important sources and sinks of N oxides, particularly under microaerobic conditions predicted to occur in coculture. In particular, integrative modeling suggested that previous models might have underestimated gross NO production during nitrification due to not taking into account its rapid oxidation in both aqueous and gas phases. The integrative model may be found at https://github.com/chaplenf/microBiome-v2.1. IMPORTANCE Modern agriculture is sustained by application of inorganic nitrogen (N) fertilizer in the form of ammonium (NH4+). Up to 60% of NH4+-based fertilizer can be lost through leaching of nitrifier-derived nitrate (NO3−), and through the emission of N oxide gases (i.e., nitric oxide [NO], N dioxide [NO2], and nitrous oxide [N2O] gases), the latter being a potent greenhouse gas. Our approach to modeling of nitrification suggests that both biotic and abiotic mechanisms function as important sources and sinks of N oxides during microaerobic conditions and that previous models might have underestimated gross NO production during nitrification. PMID:29577088

  6. Genome-Scale, Constraint-Based Modeling of Nitrogen Oxide Fluxes during Coculture of Nitrosomonas europaea and Nitrobacter winogradskyi.

    Science.gov (United States)

    Mellbye, Brett L; Giguere, Andrew T; Murthy, Ganti S; Bottomley, Peter J; Sayavedra-Soto, Luis A; Chaplen, Frank W R

    2018-01-01

    Nitrification, the aerobic oxidation of ammonia to nitrate via nitrite, emits nitrogen (N) oxide gases (NO, NO 2 , and N 2 O), which are potentially hazardous compounds that contribute to global warming. To better understand the dynamics of nitrification-derived N oxide production, we conducted culturing experiments and used an integrative genome-scale, constraint-based approach to model N oxide gas sources and sinks during complete nitrification in an aerobic coculture of two model nitrifying bacteria, the ammonia-oxidizing bacterium Nitrosomonas europaea and the nitrite-oxidizing bacterium Nitrobacter winogradskyi . The model includes biotic genome-scale metabolic models (iFC578 and iFC579) for each nitrifier and abiotic N oxide reactions. Modeling suggested both biotic and abiotic reactions are important sources and sinks of N oxides, particularly under microaerobic conditions predicted to occur in coculture. In particular, integrative modeling suggested that previous models might have underestimated gross NO production during nitrification due to not taking into account its rapid oxidation in both aqueous and gas phases. The integrative model may be found at https://github.com/chaplenf/microBiome-v2.1. IMPORTANCE Modern agriculture is sustained by application of inorganic nitrogen (N) fertilizer in the form of ammonium (NH 4 + ). Up to 60% of NH 4 + -based fertilizer can be lost through leaching of nitrifier-derived nitrate (NO 3 - ), and through the emission of N oxide gases (i.e., nitric oxide [NO], N dioxide [NO 2 ], and nitrous oxide [N 2 O] gases), the latter being a potent greenhouse gas. Our approach to modeling of nitrification suggests that both biotic and abiotic mechanisms function as important sources and sinks of N oxides during microaerobic conditions and that previous models might have underestimated gross NO production during nitrification.

  7. Integral transforms of the quantum mechanical path integral: Hit function and path-averaged potential

    Science.gov (United States)

    Edwards, James P.; Gerber, Urs; Schubert, Christian; Trejo, Maria Anabel; Weber, Axel

    2018-04-01

    We introduce two integral transforms of the quantum mechanical transition kernel that represent physical information about the path integral. These transforms can be interpreted as probability distributions on particle trajectories measuring respectively the relative contribution to the path integral from paths crossing a given spatial point (the hit function) and the likelihood of values of the line integral of the potential along a path in the ensemble (the path-averaged potential).

  8. Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum.

    Science.gov (United States)

    Avery, Vicky M; Bashyam, Sridevi; Burrows, Jeremy N; Duffy, Sandra; Papadatos, George; Puthukkuti, Shyni; Sambandan, Yuvaraj; Singh, Shivendra; Spangenberg, Thomas; Waterson, David; Willis, Paul

    2014-05-27

    In view of the need to continuously feed the pipeline with new anti-malarial agents adapted to differentiated and more stringent target product profiles (e.g., new modes of action, transmission-blocking activity or long-duration chemo-protection), a chemical library consisting of more than 250,000 compounds has been evaluated in a blood-stage Plasmodium falciparum growth inhibition assay and further assessed for chemical diversity and novelty. The selection cascade used for the triaging of hits from the chemical library started with a robust three-step in vitro assay followed by an in silico analysis of the resulting confirmed hits. Upon reaching the predefined requirements for selectivity and potency, the set of hits was subjected to computational analysis to assess chemical properties and diversity. Furthermore, known marketed anti-malarial drugs were co-clustered acting as 'signposts' in the chemical space defined by the hits. Then, in cerebro evaluation of the chemical structures was performed to identify scaffolds that currently are or have been the focus of anti-malarial medicinal chemistry programmes. Next, prioritization according to relaxed physicochemical parameters took place, along with the search for structural analogues. Ultimately, synthesis of novel chemotypes with desired properties was performed and the resulting compounds were subsequently retested in a P. falciparum growth inhibition assay. This screening campaign led to a 1.25% primary hit rate, which decreased to 0.77% upon confirmatory repeat screening. With the predefined potency (EC₅₀  10) criteria, 178 compounds progressed to the next steps where chemical diversity, physicochemical properties and novelty assessment were taken into account. This resulted in the selection of 15 distinct chemical series. A selection cascade was applied to prioritize hits resulting from the screening of a medium-sized chemical library against blood-stage P. falciparum. Emphasis was placed on chemical

  9. Hit size effectiveness in relation to the microdosimetric site size

    International Nuclear Information System (INIS)

    Varma, M.N.; Wuu, C.S.; Zaider, M.

    1994-01-01

    This paper examines the effect of site size (that is, the diameter of the microdosimetric volume) on the hit size effectiveness function (HSEF), q(y), for several endpoints relevant in radiation protection. A Bayesian and maximum entropy approach is used to solve the integral equations that determine, given microdosimetric spectra and measured initial slopes, the function q(y). All microdosimetric spectra have been calculated de novo. The somewhat surprising conclusion of this analysis is that site size plays only a minor role in selecting the hit size effectiveness function q(y). It thus appears that practical means (e.g. conventional proportional counters) are already at hand to actually implement the HSEF as a radiation protection tool. (Author)

  10. Nitrous Oxide Production in a Granule-based Partial Nitritation Reactor: A Model-based Evaluation.

    Science.gov (United States)

    Peng, Lai; Sun, Jing; Liu, Yiwen; Dai, Xiaohu; Ni, Bing-Jie

    2017-04-03

    Sustainable wastewater treatment has been attracting increasing attentions over the past decades. However, the production of nitrous oxide (N 2 O), a potent GHG, from the energy-efficient granule-based autotrophic nitrogen removal is largely unknown. This study applied a previously established N 2 O model, which incorporated two N 2 O production pathways by ammonia-oxidizing bacteria (AOB) (AOB denitrification and the hydroxylamine (NH 2 OH) oxidation). The two-pathway model was used to describe N 2 O production from a granule-based partial nitritation (PN) reactor and provide insights into the N 2 O distribution inside granules. The model was evaluated by comparing simulation results with N 2 O monitoring profiles as well as isotopic measurement data from the PN reactor. The model demonstrated its good predictive ability against N 2 O dynamics and provided useful information about the shift of N 2 O production pathways inside granules for the first time. The simulation results indicated that the increase of oxygen concentration and granule size would significantly enhance N 2 O production. The results further revealed a linear relationship between N 2 O production and ammonia oxidation rate (AOR) (R 2  = 0.99) under the conditions of varying oxygen levels and granule diameters, suggesting that bulk oxygen and granule size may exert an indirect effect on N 2 O production by causing a change in AOR.

  11. Modelling the Krebs cycle and oxidative phosphorylation.

    Science.gov (United States)

    Korla, Kalyani; Mitra, Chanchal K

    2014-01-01

    The Krebs cycle and oxidative phosphorylation are the two most important sets of reactions in a eukaryotic cell that meet the major part of the total energy demands of a cell. In this paper, we present a computer simulation of the coupled reactions using open source tools for simulation. We also show that it is possible to model the Krebs cycle with a simple black box with a few inputs and outputs. However, the kinetics of the internal processes has been modelled using numerical tools. We also show that the Krebs cycle and oxidative phosphorylation together can be combined in a similar fashion - a black box with a few inputs and outputs. The Octave script is flexible and customisable for any chosen set-up for this model. In several cases, we had no explicit idea of the underlying reaction mechanism and the rate determining steps involved, and we have used the stoichiometric equations that can be easily changed as and when more detailed information is obtained. The script includes the feedback regulation of the various enzymes of the Krebs cycle. For the electron transport chain, the pH gradient across the membrane is an essential regulator of the kinetics and this has been modelled empirically but fully consistent with experimental results. The initial conditions can be very easily changed and the simulation is potentially very useful in a number of cases of clinical importance.

  12. Modelling of UO2 oxidation in steam

    International Nuclear Information System (INIS)

    Brito, A.C.; Iglesias, F.C.; Liu, Y.

    1996-01-01

    A computer model has been developed for calculating oxidation of UO 2 at high temperatures in steam oxidising conditions. Several methods to calculate the partial pressure of oxygen in the fuel and in the environment surrounding the fuel are available. The various methodologies have been compared and the best models have been compiled into a computer model which will be implemented into fuel thermal/mechanical behaviour codes such as FACTAR 2.0 (LOECI) and ELESIM/ELOCA. Calculations from the computer model have been compared to experimental results. The calculated oxidation reaction kinetics are in good agreement with the experimental data. (author)

  13. Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase Omega-1 as an Example.

    Science.gov (United States)

    Xie, Yiyue; Dahlin, Jayme L; Oakley, Aaron J; Casarotto, Marco G; Board, Philip G; Baell, Jonathan B

    2018-05-10

    Early stage drug discovery reporting on relatively new or difficult targets is often associated with insufficient hit triage. Literature reviews of such targets seldom delve into the detail required to critically analyze the associated screening hits reported. Here we take the enzyme glutathione transferase omega-1 (GSTO1-1) as an example of a relatively difficult target and review the associated literature involving small-molecule inhibitors. As part of this process we deliberately pay closer-than-usual attention to assay interference and hit quality aspects. We believe this Perspective will be a useful guide for future development of GSTO1-1 inhibitors, as well serving as a template for future review formats of new or difficult targets.

  14. Optimization of a model of red blood cells for the study of anti-oxidant drugs, in terms of concentration of oxidant and phosphate buffer.

    Science.gov (United States)

    Bureau, A; Lahet, J-J; Lenfant, F; Bouyer, F; Petitjean, M; Chaillot, B; Freysz, M

    2005-08-01

    The aggression of erythrocytes by an oxidative stress induces hemolysis. This paper aims to valid a model of erythrocytes in terms of composition of the phosphate buffer solution and of concentration of a well-known oxidant, AAPH. Three compositions of phosphate buffer solution are mixed with three concentrations of oxidant. The influence of these two parameters on hemolysis is independently studied by a variance analysis and a Kruskal-Wallis test when ANOVA is not available. The hemolysis rate increases with time at fixed oxidant concentration, but is not influenced by the composition of the buffer solution. The highest hemolysis rate, 90%, was only measured within 2 h with the highest oxidant concentration. If we retain this concentration of oxidant, the lower concentration of the buffer can by eliminated by a significant less hemolysis and the highest concentration of the buffer can by chosen in regard of the better precision for a similar hemolysis compared to the mean buffer. We hope to study the effect of anti-oxidant agent with such a model of erythrocytes.

  15. Model for low temperature oxidation during long term interim storage

    Energy Technology Data Exchange (ETDEWEB)

    Desgranges, Clara; Bertrand, Nathalie; Gauvain, Danielle; Terlain, Anne [Service de la Corrosion et du Comportement des Materiaux dans leur Environnement, CEA/Saclay - 91191 Gif-sur-Yvette Cedex (France); Poquillon, Dominique; Monceau, Daniel [CIRIMAT UMR 5085, ENSIACET-INPT, 31077 Toulouse Cedex 4 (France)

    2004-07-01

    For high-level nuclear waste containers in long-term interim storage, dry oxidation will be the first and the main degradation mode during about one century. The metal lost by dry oxidation over such a long period must be evaluated with a good reliability. To achieve this goal, modelling of the oxide scale growth is necessary and this is the aim of the dry oxidation studies performed in the frame of the COCON program. An advanced model based on the description of elementary mechanisms involved in scale growth at low temperatures, like partial interfacial control of the oxidation kinetics and/or grain boundary diffusion, is developed in order to increase the reliability of the long term extrapolations deduced from basic models developed from short time experiments. Since only few experimental data on dry oxidation are available in the temperature range of interest, experiments have also been performed to evaluate the relevant input parameters for models like grain size of oxide scale, considering iron as simplified material. (authors)

  16. Model for low temperature oxidation during long term interim storage

    International Nuclear Information System (INIS)

    Desgranges, Clara; Bertrand, Nathalie; Gauvain, Danielle; Terlain, Anne; Poquillon, Dominique; Monceau, Daniel

    2004-01-01

    For high-level nuclear waste containers in long-term interim storage, dry oxidation will be the first and the main degradation mode during about one century. The metal lost by dry oxidation over such a long period must be evaluated with a good reliability. To achieve this goal, modelling of the oxide scale growth is necessary and this is the aim of the dry oxidation studies performed in the frame of the COCON program. An advanced model based on the description of elementary mechanisms involved in scale growth at low temperatures, like partial interfacial control of the oxidation kinetics and/or grain boundary diffusion, is developed in order to increase the reliability of the long term extrapolations deduced from basic models developed from short time experiments. Since only few experimental data on dry oxidation are available in the temperature range of interest, experiments have also been performed to evaluate the relevant input parameters for models like grain size of oxide scale, considering iron as simplified material. (authors)

  17. 76 FR 1432 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2011-01-10

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of Meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  18. 75 FR 8954 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-02-26

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  19. 75 FR 70923 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-11-19

    ... Technology; HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee...

  20. 75 FR 70923 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2010-11-19

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  1. 75 FR 29761 - Office of the National Coordinator for Health Information Technology: HIT Standards Committee...

    Science.gov (United States)

    2010-05-27

    ... Technology: HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  2. 76 FR 4354 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

    Science.gov (United States)

    2011-01-25

    ... Technology; HIT Standards Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Standards...

  3. New methods for the characterization of pyrocarbon; The two component model of pyrocarbon

    Energy Technology Data Exchange (ETDEWEB)

    Luhleich, H.; Sutterlin, L.; Hoven, H.; Nickel, H.

    1972-04-19

    In the first part, new experiments to clarify the origin of different pyrocarbon components are described. Three new methods (plasma-oxidation, wet-oxidation, ultrasonic method) are presented to expose the carbon black like component in the pyrocarbon deposited in fluidized beds. In the second part, a two component model of pyrocarbon is proposed and illustrated by examples.

  4. Asymptotically exact solution of a local copper-oxide model

    International Nuclear Information System (INIS)

    Zhang Guangming; Yu Lu.

    1994-03-01

    We present an asymptotically exact solution of a local copper-oxide model abstracted from the multi-band models. The phase diagram is obtained through the renormalization-group analysis of the partition function. In the strong coupling regime, we find an exactly solved line, which crosses the quantum critical point of the mixed valence regime separating two different Fermi-liquid (FL) phases. At this critical point, a many-particle resonance is formed near the chemical potential, and a marginal-FL spectrum can be derived for the spin and charge susceptibilities. (author). 15 refs, 1 fig

  5. Development of evaluation method on flow-induced vibration and corrosion of components in two-phase flow by coupled analysis. 5. Evaluation of wall thinning rate with the coupled model of static electrochemical analysis and dynamic double oxide layer analysis

    International Nuclear Information System (INIS)

    Uchida, Shunsuke; Naitoh, Masanori; Okada, Hidetoshi; Uehara, Yasushi

    2008-01-01

    Wall thinning rates due to FAC were calculated with the coupled model of static electrochemical analysis and dynamic double oxide layer analysis at the identified danger zone. Anodic and cathodic current densities and ECPs were calculated with the static electrochemistry model and ferrous ion release rate determined by the anodic current density was used as input for the dynamic double oxide layer model. Thickness of oxide film and its characteristics determined by the dynamic double oxide layer model were used for the electrochemistry model to determine the resistances of cathodic current from the bulk to the surface and anodic current from the surface to the bulk. Two models were coupled to determine local corrosion rate and ECP for various corrosive conditions. The calculated results of the coupled models had good agreement with the measured ones. (author)

  6. Experimental and modeling study of the oxidation of n- and iso-butanal

    KAUST Repository

    Veloo, Peter S.; Dagaut, P.; Togbé , Casimir; Dayma, Guillaume; Sarathy, Mani; Westbrook, Charles K.; Egolfopoulos, Fokion N.

    2013-01-01

    Understanding the kinetics of large molecular weight aldehydes is essential in the context of both conventional and alternative fuels. For example, they are key intermediates formed during the low-temperature oxidation of hydrocarbons as well as during the high-temperature oxidation of oxygenated fuels such as alcohols. In this study, an experimental and kinetic modeling investigation of n-butanal (. n-butyraldehyde) and iso-butanal (. iso-butyraldehyde or 2-methylpropanal) oxidation kinetics was performed. Experiments were performed in a jet stirred reactor and in counterflow flames over a wide range of equivalence ratios, temperatures, and pressures. The jet stirred reactor was utilized to observe the evolution of stable intermediates and products for the oxidation of n- and iso-butanal at elevated pressures and low to intermediate temperatures. The counterflow configuration was utilized for the determination of laminar flame speeds. A detailed chemical kinetic interpretative model was developed and validated consisting of 244 species and 1198 reactions derived from a previous study of the oxidation of propanal (propionaldehyde). Extensive reaction pathway and sensitivity analysis was performed to provide detailed insight into the mechanisms governing low-, intermediate-, and high-temperature reactivity. The simulation results using the present model are in good agreement with the experimental laminar flame speeds and well within a factor of two of the speciation data obtained in the jet stirred reactor. © 2013 The Combustion Institute.

  7. Experimental and modeling study of the oxidation of n- and iso-butanal

    KAUST Repository

    Veloo, Peter S.

    2013-09-01

    Understanding the kinetics of large molecular weight aldehydes is essential in the context of both conventional and alternative fuels. For example, they are key intermediates formed during the low-temperature oxidation of hydrocarbons as well as during the high-temperature oxidation of oxygenated fuels such as alcohols. In this study, an experimental and kinetic modeling investigation of n-butanal (. n-butyraldehyde) and iso-butanal (. iso-butyraldehyde or 2-methylpropanal) oxidation kinetics was performed. Experiments were performed in a jet stirred reactor and in counterflow flames over a wide range of equivalence ratios, temperatures, and pressures. The jet stirred reactor was utilized to observe the evolution of stable intermediates and products for the oxidation of n- and iso-butanal at elevated pressures and low to intermediate temperatures. The counterflow configuration was utilized for the determination of laminar flame speeds. A detailed chemical kinetic interpretative model was developed and validated consisting of 244 species and 1198 reactions derived from a previous study of the oxidation of propanal (propionaldehyde). Extensive reaction pathway and sensitivity analysis was performed to provide detailed insight into the mechanisms governing low-, intermediate-, and high-temperature reactivity. The simulation results using the present model are in good agreement with the experimental laminar flame speeds and well within a factor of two of the speciation data obtained in the jet stirred reactor. © 2013 The Combustion Institute.

  8. Short-stack modeling of degradation in solid oxide fuel cells. Part I. Contact degradation

    Energy Technology Data Exchange (ETDEWEB)

    Gazzarri, J.I. [Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC V6T 1Z4 (Canada); Kesler, O. [Department of Mechanical and Industrial Engineering, University of Toronto, 5 King' s College Road, Toronto, ON M5S 3G8 (Canada)

    2008-01-21

    As the first part of a two paper series, we present a two-dimensional impedance model of a working solid oxide fuel cell (SOFC) to study the effect of contact degradation on the impedance spectrum for the purpose of non-invasive diagnosis. The two dimensional modeled geometry includes the ribbed interconnect, and is adequate to represent co- and counter-flow configurations. Simulated degradation modes include: cathode delamination, interconnect oxidation, and interconnect-cathode detachment. The simulations show differences in the way each degradation mode impacts the impedance spectrum shape, suggesting that identification is possible. In Part II, we present a sensitivity analysis of the results to input parameter variability that reveals strengths and limitations of the method, as well as describing possible interactions between input parameters and concurrent degradation modes. (author)

  9. Short-stack modeling of degradation in solid oxide fuel cells. Part I. Contact degradation

    Science.gov (United States)

    Gazzarri, J. I.; Kesler, O.

    As the first part of a two paper series, we present a two-dimensional impedance model of a working solid oxide fuel cell (SOFC) to study the effect of contact degradation on the impedance spectrum for the purpose of non-invasive diagnosis. The two dimensional modeled geometry includes the ribbed interconnect, and is adequate to represent co- and counter-flow configurations. Simulated degradation modes include: cathode delamination, interconnect oxidation, and interconnect-cathode detachment. The simulations show differences in the way each degradation mode impacts the impedance spectrum shape, suggesting that identification is possible. In Part II, we present a sensitivity analysis of the results to input parameter variability that reveals strengths and limitations of the method, as well as describing possible interactions between input parameters and concurrent degradation modes.

  10. Oxidative DNA as related to cancer and aging

    International Nuclear Information System (INIS)

    Ames, B.N.

    1987-01-01

    DNA damage in man can result from a variety of endogenous processes. Of particular importance as endogenous processes may be metabolic pathways that generate oxygen radicals and other reactive oxygen species. Oxygen radicals have been shown to produce DNA base damage and strand breaks. Two products that are formed in DNA in vitro by chemical oxidation or ionizing radiation (and oxidative mutagen) are thymine glycol and hydroxymethyl-uracil, both oxidation products of thymine. Specific mammalian DNA repair systems are known to excise these lesions from DNA in vitro. The authors' laboratory has recently reported the identification, in both human and rat urine, of thymine glycol, thymidine glycol, and hydroxymethyluracil. They now have considerable evidence that these products are derived from the repair of oxidized DNA. The total output of these three compounds represents the formation of about 1,000 oxidized thymine residues per cell per day in man. Since these products are only three of a considerable number of types of oxidative DNA damage products described by radiobiologists, there are likely to be several thousand oxidative DNA hits per cell per day in man. Rats, which have a higher specific metabolic rate and a shorter life span, excrete about 15 times more thymine glycol, thymidine glycol, and hydroxymethyluracil per kilogram body weight. The authors also describe new methods for measuring the levels, which are considerable, of hydrogen peroxide and lipid hydroperoxides in normal plasma and tissues. These non-invasive assays of DNA and other oxidation products may allow the direct testing of current theories that relate oxidative metabolism to the processes of cancer and aging in man

  11. Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials hit 88/89 and hit 91

    International Nuclear Information System (INIS)

    Timmermann, Beate; Kortmann, Rolf-Dieter; Kuehl, Joachim; Meisner, Christoph; Slavc, Irene; Pietsch, Thorsten; Bamberg, Michael

    2000-01-01

    Purpose: To evaluate the outcome in children with anaplastic ependymomas after surgery, irradiation, and chemotherapy; and to identify prognostic factors for survival. Methods and Materials: Fifty-five children (n = 27 girls, 28 boys; median age at diagnosis, 6.2 years) with newly diagnosed anaplastic ependymomas were treated in the multicenter, prospective trials HIT 88/89 and HIT 91. Macroscopic complete resection was achieved in 28 patients; 27 patients underwent incomplete resection. All patients received chemotherapy before (n = 40) or after irradiation (n = 15). The irradiation volume encompassed either the neuraxis followed by a boost to the primary tumor site (n = 40) or the tumor region only (n = 13). No radiotherapy was administered in two patients. Results: Median follow-up was 38 months. The overall survival rate at 3 years after surgery was 75.6%. Disease progression occurred in 25 children with local progression occurring in 20. The median time to disease progression was 45 months. The only significant prognostic factor was the extent of resection (estimated progression-free survival [EPFS] after 3 years was 83.3% after complete resection and 38.5% after incomplete resection) and the presence of metastases at the time of diagnosis (0% vs. 65.8% 3-year EPFS in localized tumors). Age, sex, tumor site, mode of chemotherapy, and irradiation volume did not influence survival. Conclusions: Treatment centers should be meticulous about surgery and diagnostic workup. Because the primary tumor region is the predominant site of failure it is important to intensify local treatment. Dose escalation by hyperfractionation or stereotactic radiotherapy might be a promising approach in macroscopically residual disease. The role of adjuvant chemotherapy requires further study

  12. Evaluating four mathematical models for nitrous oxide production by autotrophic ammonia-oxidizing bacteria.

    Science.gov (United States)

    Ni, Bing-Jie; Yuan, Zhiguo; Chandran, Kartik; Vanrolleghem, Peter A; Murthy, Sudhir

    2013-01-01

    There is increasing evidence showing that ammonia-oxidizing bacteria (AOB) are major contributors to N(2)O emissions from wastewater treatment plants (WWTPs). Although the fundamental metabolic pathways for N(2)O production by AOB are now coming to light, the mechanisms responsible for N(2)O production by AOB in WWTP are not fully understood. Mathematical modeling provides a means for testing hypotheses related to mechanisms and triggers for N(2)O emissions in WWTP, and can then also become a tool to support the development of mitigation strategies. This study examined the ability of four mathematical model structures to describe two distinct mechanisms of N(2)O production by AOB. The production mechanisms evaluated are (1) N(2)O as the final product of nitrifier denitrification with NO(2)- as the terminal electron acceptor and (2) N(2)O as a byproduct of incomplete oxidation of hydroxylamine (NH(2)OH) to NO(2)-. The four models were compared based on their ability to predict N(2)O dynamics observed in three mixed culture studies. Short-term batch experimental data were employed to examine model assumptions related to the effects of (1) NH4+ concentration variations, (2) dissolved oxygen (DO) variations, (3) NO(2)- accumulations and (4) NH(2OH as an externally provided substrate. The modeling results demonstrate that all these models can generally describe the NH4+, NO(2)-, and NO(3)- data. However, none of these models were able to reproduce all measured N(2)O data. The results suggest that both the denitrification and NH(2)OH pathways may be involved in N(2)O production and could be kinetically linked by a competition for intracellular reducing equivalents. A unified model capturing both mechanisms and their potential interactions needs to be developed with consideration of physiological complexity. Copyright © 2012 Wiley Periodicals, Inc.

  13. Unchanged content of oxidative enzymes in fast-twitch muscle fibers and V˙O2 kinetics after intensified training in trained cyclists

    DEFF Research Database (Denmark)

    Christensen, Peter Møller; Gunnarsson, Thomas Gunnar Petursson; Thomassen, Martin

    2015-01-01

    perturbation during INT. Pulmonary V˙O2 kinetics was determined in eight trained male cyclists (V˙O2-max: 59 ± 4 (means ± SD) mL min(-1) kg(-1)) during MOD (205 ± 12 W ~65% V˙O2-max) and INT (286 ± 17 W ~85% V˙O2-max) exercise before and after a 7-week HIT period (30-sec sprints and 4-min intervals) with a 50...... DW(-1) min(-1)) of CS (56 ± 8 post-HIT vs. 59 ± 10 pre-HIT), HAD (27 ± 6 vs. 29 ± 3) and PFK (340 ± 69 vs. 318 ± 105) and the capillary to fiber ratio (2.30 ± 0.16 vs. 2.38 ± 0.20) was unaltered following HIT. V˙O2 kinetics was unchanged with HIT and the speed of the primary response did not differ...... of oxidative enzymes in fast-twitch fibers, and did not change V˙O2 kinetics....

  14. Role of Health Information Technology (HIT) in disability determinations: when medical records become medical evidence.

    Science.gov (United States)

    Tulu, Bengisu; Daniels, Susan; Feldman, Sue; Horan, Thomas A

    2008-11-06

    This exploratory study investigated the impact of incomplete medical evidence on the SSA disability determination process and the role of HIT as a solution. We collected qualitative data from nineteen expert-interviews. Findings indicate that HIT can lead to innovative solutions that can significantly improve the determination process.

  15. Influence of The Difference of Perception and Kinesthetic Exercise Methods Against Precision Hit The Ball Softball

    Directory of Open Access Journals (Sweden)

    Fajar Rokhayah

    2017-06-01

    Full Text Available The purpose of this study was to determine: 1 The difference between the effects of training methods and the gradual striking distance striking distance remains as to the accuracy of hitting the ball Softball. 2 The difference in accuracy influence Softball hitting the ball between the athletes who have a good kinesthetic perception, kinesthetic perception was, and kinesthetic perception less. 3 The effect of interaction between training methods with kinesthetic perception as to the accuracy of hitting the ball Softball. This study used an experimental method with 2x3 factorial design. The results of this study were: 1 There is a significant difference between the gradual striking distance training methods and training methods remain striking distance of the ability to hit a softball with the result of the acquisition value p-value = 0.027 smaller than 0.05. 2 There is a significant difference between athletes who have a kinesthetic perception of good, moderate, lacking the ability to hit a softball with the result of the acquisition value p-value = 0.000, which is smaller than 0.05. 3 There is an interaction between striking distance training methods and kinesthetic perception of the ability to hit a softball with the result of the acquisition value p-value = 0.000, which is smaller than 0.05 The conclusion of this study were: 1 Gradually striking distance training methods have a better effect than the fixed striking distance training methods. 2 Athletes who have less kinesthetic perception has better results than the athletes who have good kinesthetic perception and being. 3 There is an interaction between striking distance training methods and kinesthetic perception of the ability to hit a softball.

  16. More epigenetic hits than meets the eye: microRNAs and genes associated with the tumorigenesis of retinoblastoma

    Directory of Open Access Journals (Sweden)

    Adriana H.O. Reis

    2012-12-01

    Full Text Available Retinoblastoma (RB, a childhood neoplasia of the retinoblasts, can occur unilaterally or bilaterally, with one or multiple foci per eye. RB is associated with somatic loss-of-function of both alleles of the tumor suppressor gene RB1. Hereditary forms emerge due to germline loss-of-function mutations in RB1 alleles. RB has long been the prototypic ‘‘model’’ cancer ever since Knudson’s ‘‘two-hit’’ hypothesis. However, a simple two-hit model for RB is challenged by an increasing number of studies documenting additional hits that contribute to RB development. Here we review the genetics and epigenetics of RB with a focus on the role of small noncoding RNAs (microRNAs and on novel findings indicating the relevance of DNA methylation in the development and prognosis of this neoplasia. Studies point to an elaborated landscape of genetic and epigenetic complexity, in which a number of events and pahtways play crucial roles in the origin and prognosis of RB. These include roles for microRNAs, inprinted loci, and parent-of-origin contributions to RB1 regulation and RB progression. This complexity is also manifested in the structure of the RB1 locus itself: it includes numerous repetitive DNA segments and retrotransposon insertion elements, some of which are actively transcribed from the RB1 locus. Altogether, we conclude that RB1 loss of function represents the tip of an iceberg of events that determine RB development, progression, severity, and disease risk. Comprehensive assessment of personalized RB risk will require genetic and epigenetic evaluations beyond RB1 protein coding sequences.

  17. SPH based modelling of oxide and oxide film formation in gravity die castings

    International Nuclear Information System (INIS)

    Ellingsen, K; M'Hamdi, M; Coudert, T

    2015-01-01

    Gravity die casting is an important casting process which has the capability of making complicated, high-integrity components for e.g. the automotive industry. Oxides and oxide films formed during filling affect the cast product quality. The Smoothed particle hydrodynamics (SPH) method is particularly suited to follow complex flows. The SPH method has been used to study filling of a gravity die including the formation and transport of oxides and oxide films for two different filling velocities. A low inlet velocity leads to a higher amount of oxides and oxide films in the casting. The study demonstrates the usefulness of the SPH method for an increased understanding of the effect of different filling procedures on the cast quality. (paper)

  18. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    International Nuclear Information System (INIS)

    Puddu, A.; Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L.

    2010-01-01

    Research highlights: → GLP-1 prevents AGEs-induced cell death. → GLP-1 prevents AGEs-induced oxidative stress. → GLP-1 ameliorated AGEs-induced cell dysfunction. → GLP-1 attenuates AGEs-induced RAGE increment. → GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  19. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

    Science.gov (United States)

    Zhou, Xiao Yi; Lu, Xinyan; Raparia, Kirtee; Chen, Yi-Hua

    2018-06-01

    Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy.

  20. Windows(Registered Trademark)-Based Software Models Cyclic Oxidation Behavior

    Science.gov (United States)

    Smialek, J. L.; Auping, J. V.

    2004-01-01

    Oxidation of high-temperature aerospace materials is a universal issue for combustion-path components in turbine or rocket engines. In addition to the question of the consumption of material due to growth of protective scale at use temperatures, there is also the question of cyclic effects and spallation of scale on cooldown. The spallation results in the removal of part of the protective oxide in a discontinuous step and thereby opens the way for more rapid oxidation upon reheating. In experiments, cyclic oxidation behavior is most commonly characterized by measuring changes in weight during extended time intervals that include hundreds or thousands of heating and cooling cycles. Weight gains occurring during isothermal scale-growth processes have been well characterized as being parabolic or nearly parabolic functions of time because diffusion controls reaction rates. In contrast, the net weight change in cyclic oxidation is the sum of the effects of the growth and spallation of scale. Typically, the net weight gain in cyclic oxidation is determined only empirically (that is, by measurement), with no unique or straightforward mathematical connection to either the rate of growth or the amount of metal consumed. Thus, there is a need for mathematical modeling to infer spallation mechanisms. COSP is a computer program that models the growth and spallation processes of cyclic oxidation on the basis of a few elementary assumptions that were discussed in COSP: A Computer Model of Cyclic Oxidation, Oxidation of Metals, vol. 36, numbers 1 and 2, 1991, pages 81-112. Inputs to the model include the selection of an oxidation-growth law and a spalling geometry, plus oxide-phase, growth-rate, cycle-duration, and spall-constant parameters. (The spalling fraction is often shown to be a constant factor times the existing amount of scale.) The output of COSP includes the net change in weight, the amounts of retained and spalled oxide, the total amounts of oxygen and metal

  1. Pelvic rotation torque during fast-pitch softball hitting under three ball height conditions.

    Science.gov (United States)

    Iino, Yoichi; Fukushima, Atsushi; Kojima, Takeji

    2014-08-01

    The purpose of this study was to investigate the relevance of hip joint angles to the production of the pelvic rotation torque in fast-pitch softball hitting and to examine the effect of ball height on this production. Thirteen advanced female softball players hit stationary balls at three different heights: high, middle, and low. The pelvic rotation torque, defined as the torque acting on the pelvis through the hip joints about the pelvic superior-inferior axis, was determined from the kinematic and force plate data using inverse dynamics. Irrespective of the ball heights, the rear hip extension, rear hip external rotation, front hip adduction, and front hip flexion torques contributed to the production of pelvic rotation torque. Although the contributions of the adduction and external rotation torques at each hip joint were significantly different among the ball heights, the contributions of the front and rear hip joint torques were similar among the three ball heights owing to cancelation of the two torque components. The timings of the peaks of the hip joint torque components were significantly different, suggesting that softball hitters may need to adjust the timings of the torque exertions fairly precisely to rotate the upper body effectively.

  2. Advanced methods of solid oxide fuel cell modeling

    CERN Document Server

    Milewski, Jaroslaw; Santarelli, Massimo; Leone, Pierluigi

    2011-01-01

    Fuel cells are widely regarded as the future of the power and transportation industries. Intensive research in this area now requires new methods of fuel cell operation modeling and cell design. Typical mathematical models are based on the physical process description of fuel cells and require a detailed knowledge of the microscopic properties that govern both chemical and electrochemical reactions. ""Advanced Methods of Solid Oxide Fuel Cell Modeling"" proposes the alternative methodology of generalized artificial neural networks (ANN) solid oxide fuel cell (SOFC) modeling. ""Advanced Methods

  3. Markov chains with quasitoeplitz transition matrix: first zero hitting

    Directory of Open Access Journals (Sweden)

    Alexander M. Dukhovny

    1989-01-01

    Full Text Available This paper continues the investigation of Markov Chains with a quasitoeplitz transition matrix. Generating functions of first zero hitting probabilities and mean times are found by the solution of special Riemann boundary value problems on the unit circle. Duality is discussed.

  4. Comparison of Ductile-to-Brittle Transition Behavior in Two Similar Ferritic Oxide Dispersion Strengthened Alloys

    Science.gov (United States)

    Chao, Jesus; Rementeria, Rosalia; Aranda, Maria; Capdevila, Carlos; Gonzalez-Carrasco, Jose Luis

    2016-01-01

    The ductile-to-brittle transition (DBT) behavior of two similar Fe-Cr-Al oxide dispersion strengthened (ODS) stainless steels was analyzed following the Cottrell–Petch model. Both alloys were manufactured by mechanical alloying (MA) but by different forming routes. One was manufactured as hot rolled tube, and the other in the form of hot extruded bar. The two hot forming routes considered do not significantly influence the microstructure, but cause differences in the texture and the distribution of oxide particles. These have little influence on tensile properties; however, the DBT temperature and the upper shelf energy (USE) are significantly affected because of delamination orientation with regard to the notch plane. Whereas in hot rolled material the delaminations are parallel to the rolling surface, in the hot extruded material, they are randomly oriented because the material is transversally isotropic. PMID:28773764

  5. Comparison of Ductile-to-Brittle Transition Behavior in Two Similar Ferritic Oxide Dispersion Strengthened Alloys.

    Science.gov (United States)

    Chao, Jesus; Rementeria, Rosalia; Aranda, Maria; Capdevila, Carlos; Gonzalez-Carrasco, Jose Luis

    2016-07-29

    The ductile-to-brittle transition (DBT) behavior of two similar Fe-Cr-Al oxide dispersion strengthened (ODS) stainless steels was analyzed following the Cottrell-Petch model. Both alloys were manufactured by mechanical alloying (MA) but by different forming routes. One was manufactured as hot rolled tube, and the other in the form of hot extruded bar. The two hot forming routes considered do not significantly influence the microstructure, but cause differences in the texture and the distribution of oxide particles. These have little influence on tensile properties; however, the DBT temperature and the upper shelf energy (USE) are significantly affected because of delamination orientation with regard to the notch plane. Whereas in hot rolled material the delaminations are parallel to the rolling surface, in the hot extruded material, they are randomly oriented because the material is transversally isotropic.

  6. Hype, Hope, and Hit in Movies

    DEFF Research Database (Denmark)

    Dholakia, Nikhilesh; Turcan, Romeo V.

    2012-01-01

    This paper is part of an ongoing project to develop an interdisciplinary metatheory of bubbles, relevant to the contemporary era of globalization and rapid, technology-aided communication flows. Just in the first few years of the 21st century, several bubbles have appeared – the so-called dotcom ...... cultural field where relatively small bubbles may form. Movies represent a good arena to examine cultural bubbles on a scale that is not daunting, and where the hype-hope-hit dynamics can be observed more frequently than in most other settings....

  7. The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.

    Science.gov (United States)

    Daskalakis, Nikolaos P; Bagot, Rosemary C; Parker, Karen J; Vinkers, Christiaan H; de Kloet, E R

    2013-09-01

    Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. B-HIT - A Tool for Harvesting and Indexing Biodiversity Data.

    Directory of Open Access Journals (Sweden)

    Patricia Kelbert

    Full Text Available With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF implemented a Harvesting and Indexing Toolkit (HIT, which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups.

  9. Comparative kinetic and energetic modelling of phyllosemiquinone oxidation in Photosystem I.

    Science.gov (United States)

    Santabarbara, Stefano; Zucchelli, Giuseppe

    2016-04-14

    The oxidation kinetics of phyllo(semi)quinone (PhQ), which acts as an electron transfer (ET) intermediate in the Photosystem I reaction centre, are described by a minimum of two exponential phases, characterised by lifetimes in the 10-30 ns and 150-300 ns ranges. The fastest phase is considered to be dominated by the oxidation of the PhQ molecule coordinated by the PsaB reaction centre subunit (PhQB), and the slowest phase is dominated by the oxidation of the PsaA coordinated PhQ (PhQA). Testing different energetic schemes within a unified theory-based kinetic modelling approach provides reliable limit-values for some of the physical-chemical parameters controlling these ET reactions: (i) the value of ΔG(0) associated with PhQA oxidation is smaller than ∼+30 meV; (ii) the value of the total reorganisation energy (λt) likely exceeds 0.7 eV; (iii) different mean nuclear modes are coupled to PhQB and PhQA oxidation, the former being larger, and both being ≥100 cm(-1).

  10. Analysis of impact noise induced by hitting of titanium head golf driver.

    Science.gov (United States)

    Kim, Young Ho; Kim, Young Chul; Lee, Jun Hee; An, Yong-Hwi; Park, Kyung Tae; Kang, Kyung Min; Kang, Yeon June

    2014-11-01

    The hitting of titanium head golf driver against golf ball creates a short duration, high frequency impact noise. We analyzed the spectra of these impact noises and evaluated the auditory hazards from exposure to the noises. Noises made by 10 titanium head golf drivers with five maximum hits were collected, and the spectra of the pure impact sounds were studied using a noise analysis program. The noise was measured at 1.7 m (position A) and 3.4 m (position B) from the hitting point in front of the hitter and at 3.4 m (position C) behind the hitting point. Average time duration was measured and auditory risk units (ARUs) at position A were calculated using the Auditory Hazard Assessment Algorithm for Humans. The average peak levels at position A were 119.9 dBA at the sound pressure level (SPL) peak and 100.0 dBA at the overall octave level. The average peak levels (SPL and overall octave level) at position B were 111.6 and 96.5 dBA, respectively, and at position C were 111.5 and 96.7 dBA, respectively. The average time duration and ARUs measured at position A were 120.6 ms and 194.9 units, respectively. Although impact noises made by titanium head golf drivers showed relatively low ARUs, individuals enjoying golf frequently may be susceptible to hearing loss due to the repeated exposure of this intense impact noise with short duration and high frequency. Unprotected exposure to impact noises should be limited to prevent cochleovestibular disorders.

  11. First hitting probabilities for semi markov chains and estimation

    DEFF Research Database (Denmark)

    Georgiadis, Stylianos

    2017-01-01

    We first consider a stochastic system described by an absorbing semi-Markov chain with finite state space and we introduce the absorption probability to a class of recurrent states. Afterwards, we study the first hitting probability to a subset of states for an irreducible semi-Markov chain...

  12. An explanation of closed-flux formation and sustainment using coaxial helicity injection on HIT-II

    International Nuclear Information System (INIS)

    Jarboe, T R

    2010-01-01

    An explanation of the closed-flux operation on HIT-II is given. This method of operation generated flux amplification and closed flux on HIT-II without the presence of n = 1 or any large amplitude mode as measured from the outside shell. The method of operating also prevents hard absorber arcs and maximizes the toroidal current.

  13. On hitting children: a review of corporal punishment in the United States.

    Science.gov (United States)

    Knox, Michele

    2010-01-01

    Research has clearly demonstrated associations between corporal punishment of children and maladaptive behavior patterns such as aggression and delinquency. Hitting children is an act of violence and a clear violation of children's human rights. In this article, the position of the United States on corporal punishment of children is discussed. Professional and international progress on ending corporal punishment is explained, and the relationship between corporal punishment and child abuse is discussed. An appeal is made for prevention efforts such as parent education and removal of social sanctions for hitting children that may hold significant promise for preventing child maltreatment.

  14. The head tracks and gaze predicts: how the world's best batters hit a ball.

    Directory of Open Access Journals (Sweden)

    David L Mann

    Full Text Available Hitters in fast ball-sports do not align their gaze with the ball throughout ball-flight; rather, they use predictive eye movement strategies that contribute towards their level of interceptive skill. Existing studies claim that (i baseball and cricket batters cannot track the ball because it moves too quickly to be tracked by the eyes, and that consequently (ii batters do not - and possibly cannot - watch the ball at the moment they hit it. However, to date no studies have examined the gaze of truly elite batters. We examined the eye and head movements of two of the world's best cricket batters and found both claims do not apply to these batters. Remarkably, the batters coupled the rotation of their head to the movement of the ball, ensuring the ball remained in a consistent direction relative to their head. To this end, the ball could be followed if the batters simply moved their head and kept their eyes still. Instead of doing so, we show the elite batters used distinctive eye movement strategies, usually relying on two predictive saccades to anticipate (i the location of ball-bounce, and (ii the location of bat-ball contact, ensuring they could direct their gaze towards the ball as they hit it. These specific head and eye movement strategies play important functional roles in contributing towards interceptive expertise.

  15. Kinetic models of controllable pore growth of anodic aluminum oxide membrane

    Science.gov (United States)

    Huang, Yan; Zeng, Hong-yan; Zhao, Ce; Qu, Ye-qing; Zhang, Pin

    2012-06-01

    An anodized Al2O3 (AAO) membrane with apertures about 72 nm in diameter was prepared by two-step anodic oxidation. The appearance and pore arrangement of the AAO membrane were characterized by energy dispersive x-ray spectroscopy and scanning electron microscopy. It was confirmed that the pores with high pore aspect ratio were parallel, well-ordered, and uniform. The kinetics of pores growth in the AAO membrane was derived, and the kinetic models showed that pores stopped developing when the pressure ( σ) trended to equal the surface tension at the end of anodic oxidation. During pore expansion, the effects of the oxalic acid concentration and expansion time on the pore size were investigated, and the kinetic behaviors were explained with two kinetic models derived in this study. They showed that the pore size increased with extended time ( r= G· t+ G'), but decreased with increased concentration ( r = - K·ln c- K') through the derived mathematic formula. Also, the values of G, G', K, and K' were derived from our experimental data.

  16. Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

    Science.gov (United States)

    Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

    2015-01-01

    Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.

  17. Effects of Photobiomodulation Therapy on Oxidative Stress in Muscle Injury Animal Models: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Solange Almeida dos Santos

    2017-01-01

    Full Text Available This systematic review was performed to identify the role of photobiomodulation therapy on experimental muscle injury models linked to induce oxidative stress. EMBASE, PubMed, and CINAHL were searched for studies published from January 2006 to January 2016 in the areas of laser and oxidative stress. Any animal model using photobiomodulation therapy to modulate oxidative stress was included in analysis. Eight studies were selected from 68 original articles targeted on laser irradiation and oxidative stress. Articles were critically assessed by two independent raters with a structured tool for rating the research quality. Although the small number of studies limits conclusions, the current literature indicates that photobiomodulation therapy can be an effective short-term approach to reduce oxidative stress markers (e.g., thiobarbituric acid-reactive and to increase antioxidant substances (e.g., catalase, glutathione peroxidase, and superoxide dismutase. However, there is a nonuniformity in the terminology used to describe the parameters and dose for low-level laser treatment.

  18. A two-dimensional analytical subthreshold behavior model for junctionless dual-material cylindrical surrounding-gate MOSFETs

    International Nuclear Information System (INIS)

    Li Cong; Zhuang Yi-Qi; Zhang Li; Jin Gang

    2014-01-01

    A two-dimensional analytical subthreshold behavior model for junctionless dual-material cylindrical surrounding-gate (JLDMCSG) metal-oxide-semiconductor field-effect transistors (MOSFETs) is proposed. It is derived by solving the two-dimensional Poisson's equation in two continuous cylindrical regions with any simplifying assumption. Using this analytical model, the subthreshold characteristics of JLDMCSG MOSFETs are investigated in terms of channel electrostatic potential, horizontal electric field, and subthreshold current. Compared to junctionless single-material cylindrical surrounding-gate MOSFETs, JLDMCSG MOSFETs can effectively suppress short-channel effects and simultaneously improve carrier transport efficiency. It is found that the subthreshold current of JLDMCSG MOSFETs can be significantly reduced by adopting both a thin oxide and thin silicon channel. The accuracy of the analytical model is verified by its good agreement with the three-dimensional numerical simulator ISE TCAD

  19. Mitochondrial Alterations and Oxidative Stress in an Acute Transient Mouse Model of Muscle Degeneration

    Science.gov (United States)

    Ramadasan-Nair, Renjini; Gayathri, Narayanappa; Mishra, Sudha; Sunitha, Balaraju; Mythri, Rajeswara Babu; Nalini, Atchayaram; Subbannayya, Yashwanth; Harsha, Hindalahalli Chandregowda; Kolthur-Seetharam, Ullas; Bharath, Muchukunte Mukunda Srinivas

    2014-01-01

    Muscular dystrophies (MDs) and inflammatory myopathies (IMs) are debilitating skeletal muscle disorders characterized by common pathological events including myodegeneration and inflammation. However, an experimental model representing both muscle pathologies and displaying most of the distinctive markers has not been characterized. We investigated the cardiotoxin (CTX)-mediated transient acute mouse model of muscle degeneration and compared the cardinal features with human MDs and IMs. The CTX model displayed degeneration, apoptosis, inflammation, loss of sarcolemmal complexes, sarcolemmal disruption, and ultrastructural changes characteristic of human MDs and IMs. Cell death caused by CTX involved calcium influx and mitochondrial damage both in murine C2C12 muscle cells and in mice. Mitochondrial proteomic analysis at the initial phase of degeneration in the model detected lowered expression of 80 mitochondrial proteins including subunits of respiratory complexes, ATP machinery, fatty acid metabolism, and Krebs cycle, which further decreased in expression during the peak degenerative phase. The mass spectrometry (MS) data were supported by enzyme assays, Western blot, and histochemistry. The CTX model also displayed markers of oxidative stress and a lowered glutathione reduced/oxidized ratio (GSH/GSSG) similar to MDs, human myopathies, and neurogenic atrophies. MS analysis identified 6 unique oxidized proteins from Duchenne muscular dystrophy samples (n = 6) (versus controls; n = 6), including two mitochondrial proteins. Interestingly, these mitochondrial proteins were down-regulated in the CTX model thereby linking oxidative stress and mitochondrial dysfunction. We conclude that mitochondrial alterations and oxidative damage significantly contribute to CTX-mediated muscle pathology with implications for human muscle diseases. PMID:24220031

  20. Modelling of the partial oxidation of {alpha}, {beta}-unsaturated aldehydes on Mo-V-oxides based catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Boehnke, H.; Petzoldt, J.C.; Stein, B.; Weimer, C.; Gaube, J.W. [Technische Univ. Darmstadt (Germany). Inst. fuer Chemische Technologie

    1998-12-31

    A kinetic model based on the Mars-van Krevelen mechanism that allows to describe the microkinetics of the heterogeneously catalysed partial oxidation of {alpha}, {beta}-unsaturated aldehydes is presented. This conversion is represented by a network, composed of the oxidation of the {alpha}, {beta}-unsaturated aldehyde towards the {alpha}, {beta}-unsaturated carboxylic acid and the consecutive oxidation of the acid as well as the parallel reaction of the aldehyde to products of deeper oxidation. The reaction steps of aldehyde respectively acid oxidation and catalyst reoxidation have been investigated separately in transient experiments. The combination of steady state and transient experiments has led to an improved understanding of the interaction of the catalyst with the aldehyde and the carboxylic acids as well as to a support of the kinetic model assumptions. (orig.)

  1. The role of lager beer yeast in oxidative stability of model beer

    DEFF Research Database (Denmark)

    Berner, Torben Sune; Arneborg, Nils

    2012-01-01

    that the oxidative stress resistance was strain dependent. Fermentation of model wort in European Brewing Convention tubes using three yeast strains with varying oxidative stress resistances resulted in three model beers with different rates of radical formation as measured by electron spin resonance in forced......AIMS: In this study, we investigated the relationship between the ability of lager brewing yeast strains to tolerate oxidative stress and their ability to produce oxidative stable model beer. METHODS AND RESULTS: Screening of 21 lager brewing yeast strains against diamide and paraquat showed...... in the model beers. CONCLUSIONS: A more oxidative stable beer is not obtained by a more-oxidative-stress-tolerant lager brewing yeast strain, exhibiting a higher secretion of thioredoxin, but rather by a less-oxidative-stress-tolerant strain, exhibiting a higher iron uptake. SIGNIFICANCE AND IMPACT...

  2. Oxidation flow reactors (OFRs): overview of recent field and modeling studies

    Science.gov (United States)

    Jimenez, Jose-Luis; Palm, Brett B.; Peng, Zhe; Hu, Weiwei; Ortega, Amber M.; Li, Rui; Campuzano-Jost, Pedro; Day, Douglas A.; Stark, Harald; Brune, William H.; de Gouw, Joost; Schroder, Jason

    2016-04-01

    Oxidation flow reactors (OFRs) are popular tools for studying SOA formation and aging in both laboratory and field experiments. In an OFR, the concentration of an oxidant (OH, O3, or NO3) can be increased, leading to hours-months of equivalent atmospheric oxidation during the several-minute OFR residence time. Using gas- and particle-phase measurements from several recent field campaigns, we demonstrate SOA formation after oxidation of ambient air in an OFR. Typically, more SOA formation is observed from nighttime air than daytime air. This indicates that the concentration of SOA-forming gases in ambient air is relatively higher at night. Measured ambient VOCs are not able to explain the magnitude of SOA formation in the OFR, suggesting that typically unmeasured S/IVOCs (possibly VOC oxidation products or direct emissions) play a substantial intermediary role in ambient SOA formation. We also present highlights from recent OFR oxidant chemistry modeling studies. HOx, Ox, and photolysis chemistry was modeled for two common OH production methods (utilizing 185+254 nm UV light, or 254 nm only). OH exposure (OHexp) can be estimated within a factor of ~2 using model-derived equations, and can be verified in situ using VOC decay measurements. OHexp is strongly dependent on external OH reactivity, which may cause significant OH suppression in some circumstances (e.g., lab/source studies with high precursor concentrations). UV light photolysis and reaction with oxygen atoms are typically not major reaction pathways. Modeling the fate of condensable low-volatility organic gases (LVOCs) formed in an OFR suggests that LVOC fate is dependent on particle condensational sink. E.g., for the range of particle condensational sink at a remote pine forest, anywhere from 20-80% of produced LVOCs were predicted to condense onto aerosols for an OHexp of ~1 day, with the remainder lost to OFR or sampling line walls. Similar to large chamber wall loss corrections, a correction is needed

  3. Model of dopant action in oxide cathodes

    International Nuclear Information System (INIS)

    Engelsen, Daniel den; Gaertner, Georg

    2005-01-01

    The paper describes an electrochemical model, which largely explains the formation of Ba in the oxide cathode at activation and normal operation. In a non-doped oxide cathode electrolysis of BaO is, besides the exchange reaction from the activators in the cathode nickel, an important source of Ba. By doping with rare earth oxides the conductivity of the oxide layer increases, which implies that the potential difference during current drawing over the oxide layer becomes lower and electrolysis of BaO is suppressed. This implies that the part of the electronic conductivity of the (Ba,Sr)O layer induced by the dopants also controls the sensitivity for poisoning: the higher the dopant level, the larger the sensitivity for poisoning. Furthermore, the suppression of electrolysis during normal operation largely explains why doped oxide cathodes have a better life performance than non-doped cathodes. Finally a hypothesis on the enhancement of sintering upon doping is presented

  4. Comparative supercapacitive properties of asymmetry two electrode coin type supercapacitor cells made from MWCNTs/cobalt oxide and MWCNTs/iron oxide nanocomposite

    CSIR Research Space (South Africa)

    Adekunle, AS

    2015-04-01

    Full Text Available Supercapacitive properties of synthesized metal oxide nanoparticles (MO) vis a vis iron oxides (Fe(sub2)O(sub3)) and cobalt oxide (Co(sub3)O(sub4)) nanoparticles integrated with multi-walled carbon nanotubes (MWCNT) in a two-electrode coin cell type...

  5. Multi-arm multilateral haptics-based immersive tele-robotic system (HITS) for improvised explosive device disposal

    Science.gov (United States)

    Erickson, David; Lacheray, Hervé; Lai, Gilbert; Haddadi, Amir

    2014-06-01

    This paper presents the latest advancements of the Haptics-based Immersive Tele-robotic System (HITS) project, a next generation Improvised Explosive Device (IED) disposal (IEDD) robotic interface containing an immersive telepresence environment for a remotely-controlled three-articulated-robotic-arm system. While the haptic feedback enhances the operator's perception of the remote environment, a third teleoperated dexterous arm, equipped with multiple vision sensors and cameras, provides stereo vision with proper visual cues, and a 3D photo-realistic model of the potential IED. This decentralized system combines various capabilities including stable and scaled motion, singularity avoidance, cross-coupled hybrid control, active collision detection and avoidance, compliance control and constrained motion to provide a safe and intuitive control environment for the operators. Experimental results and validation of the current system are presented through various essential IEDD tasks. This project demonstrates that a two-armed anthropomorphic Explosive Ordnance Disposal (EOD) robot interface can achieve complex neutralization techniques against realistic IEDs without the operator approaching at any time.

  6. Modeling on oxide dependent 2DEG sheet charge density and threshold voltage in AlGaN/GaN MOSHEMT

    Science.gov (United States)

    Panda, J.; Jena, K.; Swain, R.; Lenka, T. R.

    2016-04-01

    We have developed a physics based analytical model for the calculation of threshold voltage, two dimensional electron gas (2DEG) density and surface potential for AlGaN/GaN metal oxide semiconductor high electron mobility transistors (MOSHEMT). The developed model includes important parameters like polarization charge density at oxide/AlGaN and AlGaN/GaN interfaces, interfacial defect oxide charges and donor charges at the surface of the AlGaN barrier. The effects of two different gate oxides (Al2O3 and HfO2) are compared for the performance evaluation of the proposed MOSHEMT. The MOSHEMTs with Al2O3 dielectric have an advantage of significant increase in 2DEG up to 1.2 × 1013 cm-2 with an increase in oxide thickness up to 10 nm as compared to HfO2 dielectric MOSHEMT. The surface potential for HfO2 based device decreases from 2 to -1.6 eV within 10 nm of oxide thickness whereas for the Al2O3 based device a sharp transition of surface potential occurs from 2.8 to -8.3 eV. The variation in oxide thickness and gate metal work function of the proposed MOSHEMT shifts the threshold voltage from negative to positive realizing the enhanced mode operation. Further to validate the model, the device is simulated in Silvaco Technology Computer Aided Design (TCAD) showing good agreement with the proposed model results. The accuracy of the developed calculations of the proposed model can be used to develop a complete physics based 2DEG sheet charge density and threshold voltage model for GaN MOSHEMT devices for performance analysis.

  7. Numerical simulations for the coal/oxidant distribution effects between two-stages for multi opposite burners (MOB) gasifier

    International Nuclear Information System (INIS)

    Unar, Imran Nazir; Wang, Lijun; Pathan, Abdul Ghani; Mahar, Rasool Bux; Li, Rundong; Uqaili, M. Aslam

    2014-01-01

    Highlights: • We simulated a double stage 3D entrained flow coal gasifier with multi-opposite burners. • The various reaction mechanisms have evaluated with experimental results. • The effects of coal and oxygen distribution between two stages on the performance of gasifier have investigated. • The local coal to oxygen ratio is affecting the overall efficiency of gasifier. - Abstract: A 3D CFD model for two-stage entrained flow dry feed coal gasifier with multi opposite burners (MOB) has been developed in this paper. At each stage two opposite nozzles are impinging whereas the two other opposite nozzles are slightly tangential. Various numerical simulations were carried out in standard CFD software to investigate the impacts of coal and oxidant distributions between the two stages of the gasifier. Chemical process was described by Finite Rate/Eddy Dissipation model. Heterogeneous and homogeneous reactions were defined using the published kinetic data and realizable k–ε turbulent model was used to solve the turbulence equations. Gas–solid interaction was defined by Euler–Lagrangian frame work. Different reaction mechanism were investigated first for the validation of the model from published experimental results. Then further investigations were made through the validated model for important parameters like species concentrations in syngas, char conversion, maximum inside temperature and syngas exit temperature. The analysis of the results from various simulated cases shows that coal/oxidant distribution between the stages has great influence on the overall performance of gasifier. The maximum char conversion was found 99.79% with coal 60% and oxygen 50% of upper level of injection. The minimum char conversion was observed 95.45% at 30% coal with 40% oxygen at same level. In general with oxygen and coal above or equal to 50% of total at upper injection level has shown an optimized performance

  8. Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

    2008-02-10

    The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

  9. Influence of multi-hit capability on quantitative measurement of NiPtSi thin film with laser-assisted atom probe tomography

    International Nuclear Information System (INIS)

    Kinno, T.; Akutsu, H.; Tomita, M.; Kawanaka, S.; Sonehara, T.; Hokazono, A.; Renaud, L.; Martin, I.; Benbalagh, R.; Sallé, B.; Takeno, S.

    2012-01-01

    Highlights: ► Laser-assisted atom probe tomography was applied to NiPtSi films on Si substrates. ► Comparison of depth profiles of single-hit events and those of multi-hit events. ► ∼80% of Pt atoms were detected in multi-hit events. ► Multiple-ion detection is important for Laser-assisted atom probe tomography. - Abstract: Laser-assisted atom probe tomography (LA-APT) was applied to NiPtSi (0, 30, and 50% Pt contents) thin films on Si substrates. Consistent results with those of high-resolution Rutherford backscattering spectrometry (HR-RBS) were obtained. Based on the obtained data sets, the composition profiles from only the signals of single-hit events, meaning detection of one ion by one laser pulse, were compiled. The profiles from only the signals of multi-hit events, meaning detection of multiple ions by one laser pulse, were also compiled. There were large discrepancies with respect to Ni and Pt concentrations among the compiled profiles and the original profiles including the signals of both types of detection events. Additionally, the profiles compiled from single-hit events showed that Si concentration in NiPtSi layer became smaller toward the surface, differing from the original profiles and the multi-hit profiles. These results suggest that capability of simultaneous multiple-ion detection is important for appropriate LA-APT analyses.

  10. Hit discovery of Mycobacterium tuberculosis inosine 5'-monophosphate dehydrogenase, GuaB2, inhibitors.

    Science.gov (United States)

    Sahu, Niteshkumar U; Singh, Vinayak; Ferraris, Davide M; Rizzi, Menico; Kharkar, Prashant S

    2018-04-18

    Tuberculosis remains a global concern. There is an urgent need of newer antitubercular drugs due to the development of resistant forms of Mycobacterium tuberculosis (Mtb). Inosine 5'-monophosphate dehydrogenase (IMPDH), guaB2, of Mtb, required for guanine nucleotide biosynthesis, is an attractive target for drug development. In this study, we screened a focused library of 73 drug-like molecules with desirable calculated/predicted physicochemical properties, for growth inhibitory activity against drug-sensitive MtbH37Rv. The eight hits and mycophenolic acid, a prototype IMPDH inhibitor, were further evaluated for activity on purified Mtb-GuaB2 enzyme, target selectivity using a conditional knockdown mutant of guaB2 in Mtb, followed by cross-resistance to IMPDH inhibitor-resistant SRMV2.6 strain of Mtb, and activity on human IMPDH2 isoform. One of the hits, 13, a 5-amidophthalide derivative, has shown growth inhibitory potential and target specificity against the Mtb-GuaB2 enzyme. The hit, 13, is a promising molecule with potential for further development as an antitubercular agent. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Modeling and parametric simulations of solid oxide fuel cells with methane carbon dioxide reforming

    International Nuclear Information System (INIS)

    Ni, Meng

    2013-01-01

    Highlights: ► A 2D model is developed for solid oxide fuel cells (SOFCs). ► CH 4 reforming by CO 2 (MCDR) is included. ► SOFC with MCDR shows comparable performance with methane steam reforming SOFC. ► Increasing CO electrochemical oxidation greatly enhances the SOFC performance. ► Effects of potential and temperature on SOFC performance are also discussed. - Abstract: A two-dimensional model is developed to simulate the performance of solid oxide fuel cells (SOFCs) fed with CO 2 and CH 4 mixture. The electrochemical oxidations of both CO and H 2 are included. Important chemical reactions are considered in the model, including methane carbon dioxide reforming (MCDR), reversible water gas shift reaction (WGSR), and methane steam reforming (MSR). It’s found that at a CH 4 /CO 2 molar ratio of 50/50, MCDR and reversible WGSR significantly influence the cell performance while MSR is negligibly small. The performance of SOFC fed with CO 2 /CH 4 mixture is comparable to SOFC running on CH 4 /H 2 O mixtures. The electric output of SOFC can be enhanced by operating the cell at a low operating potential or at a high temperature. In addition, the development of anode catalyst with high activity towards CO electrochemical oxidation is important for SOFC performance enhancement. The model can serve as a useful tool for optimization of the SOFC system running on CH 4 /CO 2 mixtures

  12. Emissivity model of steel 430 during the growth of oxide layer at 800-1100 K and 1.5 μm

    Science.gov (United States)

    Xing, Wei; Shi, Deheng; Sun, Jinfeng; Zhu, Zunlue

    2018-01-01

    This work studied the variation in spectral emissivity with growth of oxide layer at the different temperatures. For this reason, we measured the normal spectral emissivity during the growth of oxide layer on the sample surface at a wavelength of 1.5 μm over a temperature range 800-1100 K. In the experiment, the temperature was measured by the two thermocouples, which were symmetrically welded onto the front surface of specimens. The average of their readings was regarded as the true temperature. The detector should be perpendicular to the specimen surface as accurately as possible. The variation in spectral emissivity with growth of oxide layer was evaluated at a certain temperature. Altogether 11 emissivity models were evaluated. The conclusion was gained that the more the number of parameters used in the models was, the better the fitting accuracy became. On the whole, all the PEE models, the four-parameter LEE model and the five-parameter PFE, PLE and LEE models could be employed to well fit this kind of variation. The variation in spectral emissivity with temperature was determined at a certain thickness of oxide film. Almost all the models studied in this paper could be used to accurately evaluate this variation. The approximate models of spectral emissivity as a function of temperature and oxide-layer thickness were proposed. The strong oscillations of spectral emissivity were observed, which were affirmed to arise from the interference effect between the two radiations stemming from the oxide layer and from the substrate. The uncertainties in the temperature of steel 430 generated only by the surface oxidization were approximately 4.1-10.7 K in this experiment.

  13. Multiscale model of metal alloy oxidation at grain boundaries

    International Nuclear Information System (INIS)

    Sushko, Maria L.; Alexandrov, Vitaly; Schreiber, Daniel K.; Rosso, Kevin M.; Bruemmer, Stephen M.

    2015-01-01

    High temperature intergranular oxidation and corrosion of metal alloys is one of the primary causes of materials degradation in nuclear systems. In order to gain insights into grain boundary oxidation processes, a mesoscale metal alloy oxidation model is established by combining quantum Density Functional Theory (DFT) and mesoscopic Poisson-Nernst-Planck/classical DFT with predictions focused on Ni alloyed with either Cr or Al. Analysis of species and fluxes at steady-state conditions indicates that the oxidation process involves vacancy-mediated transport of Ni and the minor alloying element to the oxidation front and the formation of stable metal oxides. The simulations further demonstrate that the mechanism of oxidation for Ni-5Cr and Ni-4Al is qualitatively different. Intergranular oxidation of Ni-5Cr involves the selective oxidation of the minor element and not matrix Ni, due to slower diffusion of Ni relative to Cr in the alloy and due to the significantly smaller energy gain upon the formation of nickel oxide compared to that of Cr 2 O 3 . This essentially one-component oxidation process results in continuous oxide formation and a monotonic Cr vacancy distribution ahead of the oxidation front, peaking at alloy/oxide interface. In contrast, Ni and Al are both oxidized in Ni-4Al forming a mixed spinel NiAl 2 O 4 . Different diffusivities of Ni and Al give rise to a complex elemental distribution in the vicinity of the oxidation front. Slower diffusing Ni accumulates in the oxide and metal within 3 nm of the interface, while Al penetrates deeper into the oxide phase. Ni and Al are both depleted from the region 3–10 nm ahead of the oxidation front creating voids. The oxide microstructure is also different. Cr 2 O 3 has a plate-like structure with 1.2–1.7 nm wide pores running along the grain boundary, while NiAl 2 O 4 has 1.5 nm wide pores in the direction parallel to the grain boundary and 0.6 nm pores in the perpendicular direction providing an additional

  14. The probability of a tornado missile hitting a target

    International Nuclear Information System (INIS)

    Goodman, J.; Koch, J.E.

    1983-01-01

    It is shown that tornado missile transportation is a diffusion Markovian process. Therefore, the Green's function method is applied for the estimation of the probability of hitting a unit target area. This propability is expressed through a joint density of tornado intensity and path area, a probability of tornado missile injection and a tornado missile height distribution. (orig.)

  15. Three job stress models/concepts and oxidative DNA damage in a sample of workers in Japan.

    Science.gov (United States)

    Inoue, Akiomi; Kawakami, Norito; Ishizaki, Masao; Tabata, Masaji; Tsuchiya, Masao; Akiyama, Miki; Kitazume, Akiko; Kuroda, Mitsuyo; Shimazu, Akihito

    2009-04-01

    Three job stress models/concepts (the job demands-control [DC] model, the effort-reward imbalance [ERI] model, and organizational justice) have been linked to coronary heart disease (CHD) at work. In recent years, oxidative DNA damage has been identified as a new risk factor for CHD. However, evidence for the association between these job stressors and oxidative DNA damage is limited. The present cross-sectional study investigated the association between these job stress models/concepts and oxidative DNA damage as a possible mediator of the adverse health effects of job stress. A total of 166 male and 51 female workers of a manufacturing factory in Japan were surveyed using a mailed questionnaire regarding job stressors and demographic, occupational, and lifestyle variables. Urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were also measured. In male subjects, the urinary concentrations of 8-OHdG were significantly higher among the group with lower interactional justice, one of the two components of organizational justice; however, no association was observed with the DC model or the ERI model. In female subjects, high job demands/control ratio was significantly and positively associated with the urinary concentrations of 8-OHdG. Interactional justice among male workers and the DC model-based strain among female workers may be associated with increased urinary concentrations of 8-OHdG which possibly reflects oxidative DNA damage.

  16. High-intensity exercise training does not influence body weight but improves lipid oxidation in obese adults: a 6-week RCT.

    Science.gov (United States)

    Jabbour, Georges; Iancu, Horia-Daniel

    2017-01-01

    This study examined the effects of 6 weeks of high-intensity training (HIT) on lipid oxidation (LO) rates during incremental exercises in obese adults. Twenty-four obese adults were randomised into a no-exercise control group (n=12; body mass index=33.3 (4.8) kg.m -2 ) and a HIT group (18 sessions of 6×6 s of supramaximal cycling and 2 min passive intervals; n=12; body mass index=33.2 (2.8)kg.m -2 ). The percentage of LO contribution was computed at rest and for all workloads (25, 50, 75, 100 and 125 W) in both groups before and after training via a graded maximal cycling test. After training, the HIT group showed significantly higher LO at rest and at 25, 50 and 75 W compared with baseline (ptraining group, the homoeostasis model assessment of insulin resistance (HOMA-IR) index decreased significantly from the baseline value (p<0.01) and the control group value (p<0.01). The increases in LO observed at rest and stages 25, 50 and 75 W were positively correlated with the declines in the HOMA-IR index (r=0.87, r=0.83, r=0.91 and r=0.88; p<0.01). In obese adults, HIT increased lipid contributions to energy release at rest and in response to incremental exercise, while there were no changes in participants' aerobic capacity. This supports the hypothesis that metabolic changes rather than improved aerobic capacity are important to improve LO. ISRCTN66508384. Stage: post-results.

  17. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    Science.gov (United States)

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qHIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

  18. A biomechanical comparison in the lower limb and lumbar spine between a hit and drag flick in field hockey.

    Science.gov (United States)

    Ng, Leo; Rosalie, Simon M; Sherry, Dorianne; Loh, Wei Bing; Sjurseth, Andreas M; Iyengar, Shrikant; Wild, Catherine Y

    2018-03-01

    Research has revealed that field hockey drag flickers have greater odds of hip and lumbar injuries compared to non-drag flickers (DF). This study aimed to compare the biomechanics of a field hockey hit and a specialised field hockey drag flick. Eighteen male and seven female specialised hockey DF performed a hit and a drag flick in a motion analysis laboratory with an 18-camera three-dimensional motion analysis system and a calibrated multichannel force platform to examine differences in lower limb and lumbar kinematics and kinetics. Results revealed that drag flicks were performed with more of a forward lunge on the left lower limb resulting in significantly greater left ankle dorsiflexion, knee, hip and lumbar flexion (Pshit. Drag flicks were also performed with significantly greater lateral flexion (P hit. Differences in kinematics lead to greater shear, compression and tensile forces in multiple left lower limb and lumbar joints in the drag flick compared to the hit (P hit may have ramifications with respect to injury in field hockey drag flickers.

  19. Modeling of simultaneous anaerobic methane and ammonium oxidation in a membrane biofilm reactor.

    Science.gov (United States)

    Chen, Xueming; Guo, Jianhua; Shi, Ying; Hu, Shihu; Yuan, Zhiguo; Ni, Bing-Jie

    2014-08-19

    Nitrogen removal by using the synergy of denitrifying anaerobic methane oxidation (DAMO) and anaerobic ammonium oxidation (Anammox) microorganisms in a membrane biofilm reactor (MBfR) has previously been demonstrated experimentally. In this work, a mathematical model is developed to describe the simultaneous anaerobic methane and ammonium oxidation by DAMO and Anammox microorganisms in an MBfR for the first time. In this model, DAMO archaea convert nitrate, both externally fed and/or produced by Anammox, to nitrite, with methane as the electron donor. Anammox and DAMO bacteria jointly remove the nitrite fed/produced, with ammonium and methane as the electron donor, respectively. The model is successfully calibrated and validated using the long-term (over 400 days) dynamic experimental data from the MBfR, as well as two independent batch tests at different operational stages of the MBfR. The model satisfactorily describes the methane oxidation and nitrogen conversion data from the system. Modeling results show the concentration gradients of methane and nitrogen would cause stratification of the biofilm, where Anammox bacteria mainly grow in the biofilm layer close to the bulk liquid and DAMO organisms attach close to the membrane surface. The low surface methane loadings result in a low fraction of DAMO microorganisms, but the high surface methane loadings would lead to overgrowth of DAMO bacteria, which would compete with Anammox for nitrite and decrease the fraction of Anammox bacteria. The results suggest an optimal methane supply under the given condition should be applied not only to benefit the nitrogen removal but also to avoid potential methane emissions.

  20. Oxidation of organics in water in microfluidic electrochemical reactors: Theoretical model and experiments

    International Nuclear Information System (INIS)

    Scialdone, Onofrio; Guarisco, Chiara; Galia, Alessandro

    2011-01-01

    The electrochemical oxidation of organics in water performed in micro reactors on boron doped diamond (BDD) anode was investigated both theoretically and experimentally in order to find the influence of various operative parameters on the conversion and the current efficiency CE of the process. The electrochemical oxidation of formic acid (FA) was selected as a model case. High conversions for a single passage of the electrolytic solution inside the cell were obtained by operating with proper residence times and low distances between cathode and anode. The effect of initial concentration, flow rate and current density was investigated in detail. Theoretical predictions were in very good agreement with experimental results for both mass transfer control, oxidation reaction control and mixed kinetic regimes in spite of the fact that no adjustable parameters was used. Mass transfer process was successfully modelled by considering for simplicity a constant Sh number (e.g., a constant mass transfer coefficient k m ) for a process performed with no high values of the current intensity to minimize the effect of the gas bubbling on the flowdynamic pattern. For mixed kinetic regimes, two different modelling approaches were used. In the first one, the oxidation of organics at BDD was assumed to be mass transfer controlled and to occur with an intrinsic 100% CE when applied current density is higher than the limiting current density. In the second case, the CE of the process was modelled assuming that the competition between organic and water oxidation depends only on the electrodic material and on the nature and the concentration of the organic. In the latter case a better agreement between experimental data and theoretical predictions was observed.

  1. Profiling the biological activity of oxide nanomaterials with mechanistic models

    NARCIS (Netherlands)

    Burello, E.

    2013-01-01

    In this study we present three mechanistic models for profiling the potential biological and toxicological effects of oxide nanomaterials. The models attempt to describe the reactivity, protein adsorption and membrane adhesion processes of a large range of oxide materials and are based on properties

  2. Prediction of Potential Hit Song and Musical Genre Using Artificial Neural Networks

    Science.gov (United States)

    Monterola, Christopher; Abundo, Cheryl; Tugaff, Jeric; Venturina, Lorcel Ericka

    Accurately quantifying the goodness of music based on the seemingly subjective taste of the public is a multi-million industry. Recording companies can make sound decisions on which songs or artists to prioritize if accurate forecasting is achieved. We extract 56 single-valued musical features (e.g. pitch and tempo) from 380 Original Pilipino Music (OPM) songs (190 are hit songs) released from 2004 to 2006. Based on an effect size criterion which measures a variable's discriminating power, the 20 highest ranked features are fed to a classifier tasked to predict hit songs. We show that regardless of musical genre, a trained feed-forward neural network (NN) can predict potential hit songs with an average accuracy of ΦNN = 81%. The accuracy is about +20% higher than those of standard classifiers such as linear discriminant analysis (LDA, ΦLDA = 61%) and classification and regression trees (CART, ΦCART = 57%). Both LDA and CART are above the proportional chance criterion (PCC, ΦPCC = 50%) but are slightly below the suggested acceptable classifier requirement of 1.25*ΦPCC = 63%. Utilizing a similar procedure, we demonstrate that different genres (ballad, alternative rock or rock) of OPM songs can be automatically classified with near perfect accuracy using LDA or NN but only around 77% using CART.

  3. Degradation of lithium ion batteries employing graphite negatives and nickel-cobalt-manganese oxide + spinel manganese oxide positives: Part 2, chemical-mechanical degradation model

    Science.gov (United States)

    Purewal, Justin; Wang, John; Graetz, Jason; Soukiazian, Souren; Tataria, Harshad; Verbrugge, Mark W.

    2014-12-01

    Capacity fade is reported for 1.5 Ah Li-ion batteries containing a mixture of Li-Ni-Co-Mn oxide (NCM) + Li-Mn oxide spinel (LMO) as positive electrode material and a graphite negative electrode. The batteries were cycled at a wide range of temperatures (10 °C-46 °C) and discharge currents (0.5C-6.5C). The measured capacity losses were fit to a simple physics-based model which calculates lithium inventory loss from two related mechanisms: (1) mechanical degradation at the graphite anode particle surface caused by diffusion-induced stresses (DIS) and (2) chemical degradation caused by lithium loss to continued growth of the solid-electrolyte interphase (SEI). These two mechanisms are coupled because lithium is consumed through SEI formation on newly exposed crack surfaces. The growth of crack surface area is modeled as a fatigue phenomenon due to the cyclic stresses generated by repeated lithium insertion and de-insertion of graphite particles. This coupled chemical-mechanical degradation model is consistent with the observed capacity loss features for the NCM + LMO/graphite cells.

  4. European scale modeling of sulfur, oxidized nitrogen and photochemical oxidants. Model development and evaluation for the 1994 growing season

    Energy Technology Data Exchange (ETDEWEB)

    Langner, J.; Bergstroem, R. [Swedish Meteorological and Hydrological Inst., Norrkoeping (Sweden); Pleijel, K. [Swedish Environmental Research Inst., Goeteborg (Sweden)

    1998-09-01

    A chemical mechanism, including the relevant reactions leading to the production of ozone and other photochemical oxidants, has been implemented in the MATCH regional tracer transport/chemistry/deposition model. The aim has been to develop a model platform that can be used as a basis for a range of regional scale studies involving atmospheric chemistry, including assessment of the importance of different sources of pollutants to the levels of photochemical oxidants and air pollutant forecasting. Meteorological input data to the model were taken from archived output from the operational version of HIRLAM at SMHI. Evaluation of model calculations over Europe for a six month period in 1994 for a range of chemical components show good results considering known sources of error and uncertainties in input data and model formulation. With limited further work the system is sufficiently good to be applied for scenario studies and for regional scale air pollutant forecasts 42 refs, 24 figs, 17 tabs

  5. Modelling of nitrogen oxides distribution in the hearth of gas-fired industrial furnace

    Science.gov (United States)

    Zhubrin, S.; Glazov, V.; Guzhov, S.

    2017-11-01

    A model is proposed for calculating the formation and transportation of nitrogen oxides in the combustion chamber of an industrial furnace heated by gaseous fuels burning. The calculations use a three-dimensional stationary description of turbulent flow and mixing of fuel and oxidizer flows in the presence of heat transfer, mass transfer, and momentum between them transfer. Simulation of the spatial pattern of nitrogen oxides formation in the working space of the furnace is performed in the programming and computing suite SCAN. It is shown that the temperature non-uniformity over the hearth surface is not too pronounced due to the organization of the inclined flow inlet in the direction of the hearth, which is a desirable feature of the furnace operation. The highest concentration of combustion products is observed in the zone of maximum temperatures. In addition, the existence of two zones of the highest generation of oxides has been determined. The first zone is located approximately in the center of the hearth, and the second is located on the far external surface of the furnace. The possibility of using the developed model in the SCAN complex for carrying out parametric studies and engineering calculations, as well as for modification in the direction of adjusting and adapting the model to the regime-constructive features of specific energy technological devices, is noted.

  6. Magnetism-tuning strategies for graphene oxide based on magnetic oligoacene oxide patches model.

    Science.gov (United States)

    Wen, Yanjie; Yen, Chia-Liang; Yan, Linyin; Kono, Hirohiko; Lin, Sheng-Hsien; Ling, Yong-Chien

    2018-01-31

    Graphene oxide (GO) has wide application potential owing to its 2D structure and diverse modification sites for various targeted uses. The introduction of magnetism into GO structures has further advanced the controllability of the application of GO materials. Herein, the concept of modular design and modeling was applied to tune the magnetism of GO. To obtain desirable magnetic properties, diradical-structured GO patches were formed by the introduction of two functional groups to break the Kekule structure of the benzene ring. In these diradical GO patches, the energy of the triplet state was lower than those of the open-shell broken-symmetry singlet state and closed-shell singlet state. To create such multi-radical patches, a practical approach is to determine a substantial spatial separation of the α and β spin densities in the molecule. Thus, systematic design strategies and tests were evaluated. The first strategy was extending the distance between the distribution center of the α and β spin densities; the second was controlling the delocalization directions of the α and β electrons; the third was controlling the delocalization extension of the α and β electrons by oxidative modification, and finally introducing multi-radical structures into the molecular system and controlling the position of each radical. Herein, successful molecular models with a large magnetic coupling constant (∼3600 cm -1 ) were obtained. This study paves the way to explore ferromagnetic MGO guided by theoretical study, which may become reality soon.

  7. Concentrated Hitting Times of Randomized Search Heuristics with Variable Drift

    DEFF Research Database (Denmark)

    Lehre, Per Kristian; Witt, Carsten

    2014-01-01

    Drift analysis is one of the state-of-the-art techniques for the runtime analysis of randomized search heuristics (RSHs) such as evolutionary algorithms (EAs), simulated annealing etc. The vast majority of existing drift theorems yield bounds on the expected value of the hitting time for a target...

  8. Modeling Manganese Sorption and Surface Oxidation During Filtration

    OpenAIRE

    Bierlein, Kevin Andrew

    2012-01-01

    Soluble manganese (Mn) is a common contaminant in drinking water sources. High levels of Mn can lead to aesthetic water quality problems, necessitating removal of Mn during treatment to minimize consumer complaints. Mn may be removed during granular media filtration by the â natural greensand effect,â in which soluble Mn adsorbs to manganese oxide-coated (MnOx(s)) media and is then oxidized by chlorine, forming more manganese oxide. This research builds on a previous model developed by Mer...

  9. Improved stratospheric atmosphere forecasts in the general circulation model through a methane oxidation parametrization

    Science.gov (United States)

    Wang, S.; Jun, Z.

    2017-12-01

    Climatic characteristics of tropical stratospheric methane have been well researched using various satellite data, and numerical simulations have furtherly conducted using chemical climatic models, while the impact of stratospheric methane oxidation on distribution of water vapor is not paid enough attention in general circulation models. Simulated values of water vapour in the tropical upper stratosphere, and throughout much of the extratropical stratosphere, were too low. Something must be done to remedy this deficiency in order to producing realistic stratospheric water vapor using a general circulation model including the whole stratosphere. Introduction of a simple parametrization of the upper-stratospheric moisture source due to methane oxidation and a sink due to photolysis in the mesosphere was conducted. Numerical simulations and analysis of the influence of stratospheric methane on the prediction of tropical stratospheric moisture and temperature fields were carried out. This study presents the advantages of methane oxidation parametrization in producing a realistic distribution of water vapour in the tropical stratosphere and analyzes the impact of methane chemical process on the general circulation model using two storm cases including a heavy rain in South China and a typhoon caused tropical storm.It is obvious that general circulation model with methane oxidation parametrization succeeds in simulating the water vapor and temperature in stratosphere. The simulating rain center value of contrast experiment is increased up to 10% than that of the control experiment. Introduction of methane oxidation parametrization has modified the distribution of water vapour and then producing a broadly realistic distribution of temperature. Objective weather forecast verifications have been performed using simulating results of one month, which demonstrate somewhat positive effects on the model skill. There is a certain extent impact of methane oxidation

  10. An automated single ion hit at JAERI heavy ion microbeam to observe individual radiation damage

    International Nuclear Information System (INIS)

    Kamiya, Tomihiro; Sakai, Takuro; Naitoh, Yutaka; Hamano, Tsuyoshi; Hirao, Toshio

    1999-01-01

    Microbeam scanning and a single ion hit technique have been combined to establish an automated beam positioning and single ion hit system at the JAERI Takasaki heavy ion microbeam system. Single ion irradiation on preset points of a sample in various patterns can be performed automatically in a short period. The reliability of the system was demonstrated using CR-39 nuclear track detectors. Single ion hit patterns were achieved with a positioning accuracy of 2 μm or less. In measurement of single event transient current using this system, the reduction of the pulse height by accumulation of radiation damages was observed by single ion injection to the same local areas. This technique showed a possibility to get some quantitative information about the lateral displacement of an individual radiation effect in silicon PIN photodiodes. This paper will give details of the irradiation system and present results from several experiments

  11. Volcano Relations for Oxidation of Hydrogen Halides over Rutile Oxide Surfaces

    DEFF Research Database (Denmark)

    Toftelund, Anja; Man, Isabela C.; Hansen, Heine A.

    2012-01-01

    over a range of different rutile oxide surfaces. Based on the scaling relations, two descriptors are identified that describe the reactions uniquely. By combining scaling with the micro-kinetic model, activity volcanoes for the three different oxidation reactions are derived. It is found...

  12. Duas classes de mutação na evolução de policitemia vera para leucemia mielóide aguda Two-hit model of leukemogenesis in the evolution of polycythemia vera to acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Juliana C. C. Ribeiro

    2009-04-01

    case of PV with evolution to AML in which it was possible to demonstrate the two-hit model of leukemogenesis: one mutation confers proliferative advantage and another interferes with differentiation. Case: A 55-year-old female patient was diagnosed with PV in 2002 and treated with phlebotomies and hydroxyurea. In 2006, there was progression topost-polycythemic fibrosis with AML one year later. She presented the JAK2V617F mutation. The result of karyotyping performed at diagnosis was normal and at transformation, 46,XX,del(20(q13.1 was detected in 4/20 metaphases. FISH analysis of a stored sample for 20q13 showed the deletion in 20% of interphases confirming the earlier presence of a clonal abnormality that was not detected by karyotyping. The JAK2V617F mutation is sufficient to cause proliferation of hematopoietic cells and has been established as a primary pathogenetic mechanism in PV. However, the evolution of the disease is heterogeneous, suggesting the occurrence of additional phenomena contributing to leukemogenesis. This case demonstrates the two-hit model in the progression of PV to LMA, in which a class of mutation induces proliferative advantage and another blocks differentiation. Two events which contribute to proliferation and to maturation blockade were detected in this patient. Other mechanisms may be implicated and prospective studies should be encouraged in an attempt to elucidate the different steps involved in leukemogenesis.

  13. Patterns of Hits to the Nearshore from a Major Fairway in the Gulf of Finland

    Science.gov (United States)

    Viikmae, B.; Soomere, T.

    2012-04-01

    The Baltic Sea hosts one of the heaviest ship traffic in the world. Although relatively small in size, still up to 15% of the world's cargo is transported along its numerous fairways. The largest threat to the environment is oil transportation that has increased more than by a factor of two in 2000-2008 and a 40% increase is expected by the year 2015. One of the major marine highways in the European waters enters the Baltic Sea through the Danish Straits, crosses the Baltic Proper and stretches through the Gulf of Finland to Saint Petersburg. An area that is highly vulnerable to ship pollution is the nearshore that usually has the largest ecological value. While the probability of coastal pollution for open ocean coasts can be reduced by shifting ship routes farther offshore, the problem for narrow bays, like the Gulf of Finland, is how to minimize the probability of hitting any of the coasts. To a certain extent, light can be shed to this problem by means of quantification of the offshore areas in terms of their ability to serve a danger to coastal environment if pollution would happen in these areas. A convenient way to address this problem is to use statistical analysis of a large number of Lagrangian trajectories of test particles representing the potential pollution and passively carried by surface currents. In this paper, we make and attempt to quantify the link between potential sources of pollution along an existing fairway and the sections of the coast reached by current-driven pollution. The problem is analysed by means of considering hits to the nearshore from a major fairway in the Gulf of Finland and by making sure whether certain parts of the coast are hit by pollution particles most frequently and whether or not these pollution particles stem from certain specific parts of the fairway. Trajectories are simulated in the Gulf of Finland by placing tracers among a line that follows one of the major fairways from the Baltic Proper to Saint Petersburg

  14. Modified Wagner model for the active-to-passive transition in the oxidation of Si3N4

    International Nuclear Information System (INIS)

    Wang Junjie; Zhang Litong; Zeng Qingfeng; Cheng Laifei; Xu Yongdong

    2008-01-01

    Si 3 N 4 is used as the coating material of space shuttle structures which receive very high thermal fluxes during the atmospheric re-entry phase. Two main regimes govern the oxidation of Si 3 N 4 : the passive oxidation, with the formation of a protective silica layer leading generally to a mass gain, and the active oxidation, with vaporization of SiO leading to a mass loss of the sample. To ensure that silicon nitride will efficiently protect a material in given oxidizing environments, its own oxidation behaviour must be previously known. Therefore, the active-to-passive transition of Si 3 N 4 oxidation is a problem of deep scientific importance and of wide technological relevance. In this paper, a modified Wager model for the active-to-passive transition in the oxidation of Si 3 N 4 is presented, which includes the non-equilibrium effects caused by the mass transfer. The present theoretical calculations satisfactorily explained the reported experimental and theoretical data. The influence of flow rate on the active-to-passive transition boundary has been explained using our model. The rate controlling mechanism of the oxidation at the active-to-passive transition point is proposed

  15. Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas.

    Science.gov (United States)

    He, Miaoxia; Chen, Keting; Li, Suhong; Zhang, Shimin; Zheng, Jianming; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin

    2016-01-01

    Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better

  16. Computational Breakthrough of Natural Lead Hits from the Genus of Arisaema against Human Respiratory Syncytial Virus.

    Science.gov (United States)

    Kant, Kamal; Lal, Uma Ranjan; Ghosh, Manik

    2018-01-01

    To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV. Selected 60 phytochemical entities were evaluated on the docking behavior of human RSV receptor (PDB: 4UCC) using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). Furthermore, kinetic properties and toxicity nature of top graded ligands were analyzed through QikProp and ProTox tools. Notably, rutin (glide score: -8.49), schaftoside (glide score: -8.18) and apigenin-6,8-di-C-β-D-galactoside (glide score - 7.29) have resulted in hopeful natural lead hits with an ideal range of kinetic descriptors values. ProTox tool (oral rodent toxicity) has resulted in likely toxicity targets of apex-graded tested ligands. Finally, the whole efforts can be explored further as a model to confirm its anti-human RSV potential with wet laboratory experiments. Rutin, schaftoside, and apigenin-6,8-di-C-β-D-galactoside showed promising top hits docking profile against human respiratory syncytial virusMoreover, absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptorsProTox tool highlighted toxicity class ranges, LD 50 values, and possible toxicity targets of apex-graded tested ligands. Abbreviations used: RSV: Respiratory syncytial virus, PRRSV: Porcine respiratory and reproductive syndrome virus, ADME-T: Absorption, distribution, metabolism, excretion, and toxicity.

  17. Validation of extended magnetohydrodynamic simulations of the HIT-SI3 experiment using the NIMROD code

    Science.gov (United States)

    Morgan, K. D.; Jarboe, T. R.; Hossack, A. C.; Chandra, R. N.; Everson, C. J.

    2017-12-01

    The HIT-SI3 experiment uses a set of inductively driven helicity injectors to apply a non-axisymmetric current drive on the edge of the plasma, driving an axisymmetric spheromak equilibrium in a central confinement volume. These helicity injectors drive a non-axisymmetric perturbation that oscillates in time, with relative temporal phasing of the injectors modifying the mode structure of the applied perturbation. A set of three experimental discharges with different perturbation spectra are modelled using the NIMROD extended magnetohydrodynamics code, and comparisons are made to both magnetic and fluid measurements. These models successfully capture the bulk dynamics of both the perturbation and the equilibrium, though disagreements related to the pressure gradients experimentally measured exist.

  18. Immature oxidative stress management as a unifying principle in the pathogenesis of necrotizing enterocolitis: insights from an agent-based model.

    Science.gov (United States)

    Kim, Moses; Christley, Scott; Alverdy, John C; Liu, Donald; An, Gary

    2012-02-01

    Necrotizing enterocolitis (NEC) is a complex disease involving prematurity, enteral feeding, and bacterial effects. We propose that the underlying initial condition in its pathogenesis is reduced ability of the neonatal gut epithelial cells (NGECs) to clear oxidative stress (OS), and that when such a NGEC population is exposed to enteral feeding, the increased metabolic OS tips the population toward apoptosis, inflammation, bacterial activation, and eventual necrosis. The multi-factorial complexity of NEC requires characterization with computational modeling, and herein, we used an agent-based model (ABM) to instantiate and examine our unifying hypothesis of the pathogenesis of NEC. An ABM of the neonatal gut was created with NGEC computational agents incorporating rules for pathways for OS, p53, tight junctions, Toll-like receptor (TLR)-4, nitric oxide, and nuclear factor-kappa beta (NF-κB). The modeled bacteria activated TLR-4 on contact with NGECs. Simulations included parameter sweeps of OS response, response to feeding, addition of bacteria, and alterations in gut mucus production. The ABM reproduced baseline cellular respiration and clearance of OS. Reduction in OS clearance consistent with clinical NEC led to senescence, apoptosis, or inflammation, with disruption of tight junctions, but rarely to NGEC necrosis. An additional "hit" of bacteria activating TLR-4 potentiated a shift to NGEC necrosis across the entire population. The mucus layer was modeled to limit bacterial-NGEC interactions and reduce this effect, but concomitant apoptosis in the goblet cell population reduced the efficacy of the mucus layer and limited its protective effect in simulated experiments. This finding suggests a means by which increased apoptosis at the cellular population level can lead to a transition to the necrosis outcome. Our ABM incorporates known components of NEC and demonstrates that impaired OS management can lead to apoptosis and inflammation of NGECs, rendering the

  19. Multistage model for the action of cytotoxic T lymphocytes in multicellular conjugates

    International Nuclear Information System (INIS)

    Macken, C.A.; Perelson, A.S.

    1984-01-01

    The authors propose a multistage stochastic model to explain data on the kinetics of target cell lysis by cytotoxic T lymphocytes in multicellular conjugates. A novel feature of this model is that the authors explicitly consider both the lethal hitting stage and the target cell disintegration stage of the cytolytic process. Further, the authors allow for the possibility that target cell disintegration is itself a complex process composed of many events. The comparison of this model with the data of other investigators suggests that cytotoxic T cells deliver lethal hits at random to undamage target cells. Having received a lethal hit, the target cell disintegrates over a variable length of time. The disintegration times of target cells from different conjugates appear to be randomly distributed and to be consistent with a model in which disintegration occurs by at least two major, sequential, rate-limiting events. For conjugates containing one lymphocyte and multiple target cells, the mean rate at which a lethally hit target cell disintegrates is found to be independent of the total number of target cells in the conjugate. This model predicts that in such multicellular conjugates, individual target cells lyse one by one, on average at approximately 30-min intervals, thus agreeing closely with previously reported experimental observations. 35 references, 3 figures, 2 tables

  20. X-hitting: A new algorithm for novelty detection and dereplication by UV spectra of complex mixtures of natural products

    DEFF Research Database (Denmark)

    Hansen, Michael Edberg; Smedsgaard, Jørn; Larsen, Thomas Ostenfeld

    2005-01-01

    A major challenge in lead discovery is to detect well-known and trivial compounds rapidly, a process known as dereplication, so that isolation, structure elucidation, and pharmacological investigations can be focused on novel compounds. In this paper, we present a new algorithm, X-hitting, based...... on cross sample comparison of full UV spectra from HPLC analysis of highly complex natural product extracts/samples. X-Hitting allows automatic identification of known compounds but more important also allows finding of potentially new or similar compounds. We demonstrate this new algorithm by automatic...... identification of known structures, a task we call cross-hitting, and tentative identification of potentially new bioactive compounds, a task we call new-hitting, in HPLC data from analysis of fungal extracts. Both tasks are illustrated using 18 important reference compounds and complex fungal extracts obtained...

  1. The detector response simulation for the CBM silicon tracking system as a tool for hit error estimation

    Energy Technology Data Exchange (ETDEWEB)

    Malygina, Hanna [Goethe Universitaet Frankfurt (Germany); KINR, Kyiv (Ukraine); GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Friese, Volker; Zyzak, Maksym [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Collaboration: CBM-Collaboration

    2016-07-01

    The Compressed Baryonic Matter experiment(CBM) at FAIR is designed to explore the QCD phase diagram in the region of high net-baryon densities. As the central detector component, the Silicon Tracking System (STS) is based on double-sided micro-strip sensors. To achieve realistic modelling, the response of the silicon strip sensors should be precisely included in the digitizer which simulates a complete chain of physical processes caused by charged particles traversing the detector, from charge creation in silicon to a digital output signal. The current implementation of the STS digitizer comprises non-uniform energy loss distributions (according to the Urban theory), thermal diffusion and charge redistribution over the read-out channels due to interstrip capacitances. Using the digitizer, one can test an influence of each physical processes on hit error separately. We have developed a new cluster position finding algorithm and a hit error estimation method for it. Estimated errors were verified by the width of pull distribution (expected to be about unity) and its shape.

  2. Compositional evolution of particle-phase reaction products and water in the heterogeneous OH oxidation of model aqueous organic aerosols

    Directory of Open Access Journals (Sweden)

    M. M. Chim

    2017-12-01

    Full Text Available Organic compounds present at or near the surface of aqueous droplets can be efficiently oxidized by gas-phase OH radicals, which alter the molecular distribution of the reaction products within the droplet. A change in aerosol composition affects the hygroscopicity and leads to a concomitant response in the equilibrium amount of particle-phase water. The variation in the aerosol water content affects the aerosol size and physicochemical properties, which in turn governs the oxidation kinetics and chemistry. To attain better knowledge of the compositional evolution of aqueous organic droplets during oxidation, this work investigates the heterogeneous OH-radical-initiated oxidation of aqueous methylsuccinic acid (C5H8O4 droplets, a model compound for small branched dicarboxylic acids found in atmospheric aerosols, at a high relative humidity of 85 % through experimental and modeling approaches. Aerosol mass spectra measured by a soft atmospheric pressure ionization source (Direct Analysis in Real Time, DART coupled with a high-resolution mass spectrometer reveal two major products: a five carbon atom (C5 hydroxyl functionalization product (C5H8O5 and a C4 fragmentation product (C4H6O3. These two products likely originate from the formation and subsequent reactions (intermolecular hydrogen abstraction and carbon–carbon bond scission of tertiary alkoxy radicals resulting from the OH abstraction occurring at the methyl-substituted carbon site. Based on the identification of the reaction products, a kinetic model of oxidation (a two-product model coupled with the Aerosol Inorganic–Organic Mixtures Functional groups Activity Coefficients (AIOMFAC model is built to simulate the size and compositional changes of aqueous methylsuccinic acid droplets during oxidation. Model results show that at the maximum OH exposure, the droplets become slightly more hygroscopic after oxidation, as the mass fraction of water is predicted to increase from

  3. Two-electron electrochemical oxidation of quercetin and kaempferol changes only the flavonoid C-ring

    DEFF Research Database (Denmark)

    Jørgensen, Lars; Cornett, Claus; Justesen, Ulla

    1998-01-01

    Bulk electrolysis of the antioxidant flavonoids quercetin and kaempferol in acetonitrile both yield a single oxidation product in two-electron processes. The oxidation products are more polar than their parent compounds, with an increased molecular weight of 16g/mol, and were identified as 2......-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3 (2H)-benzofuranone and 2-(4-hydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone for quercetin and kaempferol, respectively. Two-electron oxidation of the parent flavonoid is suggested to yield a 3,4-flavandione with unchanged substitution pattern in the A- and B-ring, which...... may rearrange to form the substituted 3(2H)-benzofuranone through the chalcan-trione ring-chain tautomer. The acidity of the 3-OH group is suggested to determine the fate of the flavonoid phenoxyl radical originally formed by one-electron oxidation, as no well-defined oxidation product of luteolin...

  4. In vitro radiosensitivity of six human cell lines. A comparative study with different statistical models

    International Nuclear Information System (INIS)

    Fertil, B.; Deschavanne, P.J.; Lachet, B.; Malaise, E.P.

    1980-01-01

    The intrinsic radiosensitivity of human cell lines (five tumor and one nontransformed fibroblastic) was studied in vitro. The survival curves were fitted by the single-hit multitarget, the two-hit multitarget, the single-hit multitarget with initial slope, and the quadratic models. The accuracy of the experimental results permitted evaluation of the various fittings. Both a statistical test (comparison of variances left unexplained by the four models) and a biological consideration (check for independence of the fitted parameters vis-a-vis the portion of the survival curve in question) were carried out. The quadratic model came out best with each of them. It described the low-dose effects satisfactorily, revealing a single-hit lethal component. This finding and the fact that the six survival curves displayed a continuous curvature ruled out the adoption of the target models as well as the widely used linear regression. As calculated by the quadratic model, the parameters of the six cell lines lead to the following conclusions: (a) the intrinsic radiosensitivity varies greatly among the different cell lines; (b) the interpretation of the fibroblast survival curve is not basically different from that of the tumor cell lines; and (c) the radiosensitivity of these human cell lines is comparable to that of other mammalian cell lines

  5. The accelerator facility of the Heidelberg Ion-Beam Therapy Centre (HIT)

    Science.gov (United States)

    Peters, Andreas

    The following sections are included: * Introduction * Beam parameters * General layout of the HIT facility * The accelerator chain in detail * Operational aspects of a particle therapy facility * 24/7 accelerator operation at 335 days per year * Safety and regulatory aspects * Status and perspectives * References

  6. 76 FR 39107 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Science.gov (United States)

    2011-07-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice... of the Office of the National Coordinator for Health Information Technology (ONC). The [[Page 39108...

  7. Optimal Fixed-Interval Integrated Guidance-Control Laws for Hit-to-Kill Missiles

    National Research Council Canada - National Science Library

    Menon, P. K; Sweriduk, G. D; Ohlmeyer, E. J

    2003-01-01

    Due to their potential for reducing the weapon size and efficiency, design methods for realizing hit-to- kill capabilities in missile systems are of significant research interest in the missile flight control community...

  8. Cellular Automata Modelling of Photo-Induced Oxidation Processes in Molecularly Doped Polymers

    Directory of Open Access Journals (Sweden)

    David M. Goldie

    2016-11-01

    Full Text Available The possibility of employing cellular automata (CA to model photo-induced oxidation processes in molecularly doped polymers is explored. It is demonstrated that the oxidation dynamics generated using CA models exhibit stretched-exponential behavior. This dynamical characteristic is in general agreement with an alternative analysis conducted using standard rate equations provided the molecular doping levels are sufficiently low to prohibit the presence of safe-sites which are impenetrable to dissolved oxygen. The CA models therefore offer the advantage of exploring the effect of dopant agglomeration which is difficult to assess from standard rate equation solutions. The influence of UV-induced bleaching or darkening upon the resulting oxidation dynamics may also be easily incorporated into the CA models and these optical effects are investigated for various photo-oxidation product scenarios. Output from the CA models is evaluated for experimental photo-oxidation data obtained from a series of hydrazone-doped polymers.

  9. Unified computational model of transport in metal-insulating oxide-metal systems

    Science.gov (United States)

    Tierney, B. D.; Hjalmarson, H. P.; Jacobs-Gedrim, R. B.; Agarwal, Sapan; James, C. D.; Marinella, M. J.

    2018-04-01

    A unified physics-based model of electron transport in metal-insulator-metal (MIM) systems is presented. In this model, transport through metal-oxide interfaces occurs by electron tunneling between the metal electrodes and oxide defect states. Transport in the oxide bulk is dominated by hopping, modeled as a series of tunneling events that alter the electron occupancy of defect states. Electron transport in the oxide conduction band is treated by the drift-diffusion formalism and defect chemistry reactions link all the various transport mechanisms. It is shown that the current-limiting effect of the interface band offsets is a function of the defect vacancy concentration. These results provide insight into the underlying physical mechanisms of leakage currents in oxide-based capacitors and steady-state electron transport in resistive random access memory (ReRAM) MIM devices. Finally, an explanation of ReRAM bipolar switching behavior based on these results is proposed.

  10. Flooding Simulation of Extreme Event on Barnegat Bay by High-Resolution Two Dimensional Hydrodynamic Model

    Science.gov (United States)

    Wang, Y.; Ramaswamy, V.; Saleh, F.

    2017-12-01

    Barnegat Bay located on the east coast of New Jersey, United States and is separated from the Atlantic Ocean by the narrow Barnegat Peninsula which acts as a barrier island. The bay is fed by several rivers which empty through small estuaries along the inner shore. In terms of vulnerability from flooding, the Barnegat Peninsula is under the influence of both coastal storm surge and riverine flooding. Barnegat Bay was hit by Hurricane Sandy causing flood damages with extensive cross-island flow at many streets perpendicular to the shoreline. The objective of this work is to identify and quantify the sources of flooding using a two dimensional inland hydrodynamic model. The hydrodynamic model was forced by three observed coastal boundary conditions, and one hydrologic boundary condition from United States Geological Survey (USGS). The model reliability was evaluated with both FEMA spatial flooding extend and USGS High water marks. Simulated flooding extent showed good agreement with the reanalysis spatial inundation extents. Results offered important perspectives on the flow of the water into the bay, the velocity and the depth of the inundated areas. Using such information can enable emergency managers and decision makers identify evacuation and deploy flood defenses.

  11. Cladding oxidation during air ingress. Part II: Synthesis of modelling results

    International Nuclear Information System (INIS)

    Beuzet, E.; Haurais, F.; Bals, C.; Coindreau, O.; Fernandez-Moguel, L.; Vasiliev, A.; Park, S.

    2016-01-01

    Highlights: • A state-of-the-art for air oxidation modelling in the frame of severe accident is done. • Air oxidation models from main severe accident codes are detailed. • Simulations from main severe accident codes are compared against experimental results. • Perspectives in terms of need for further model development and experiments are given. - Abstract: Air ingress is a potential risk in some low probable situations of severe accidents in a nuclear power plant. Air is a highly oxidizing atmosphere that can lead to an enhanced Zr-based cladding oxidation and core degradation affecting the release of fission products. This is particularly true speaking about ruthenium release, due to its high radiotoxicity and its ability to form highly volatile oxides in a significant manner in presence of air. The oxygen affinity is decreasing from the Zircaloy cladding, fuel and ruthenium inclusions. It is consequently of great need to understand the phenomena governing cladding oxidation by air as a prerequisite for the source term issues in such scenarios. In the past years, many works have been done on cladding oxidation by air under severe accident conditions. This paper with in addition the paper “Cladding oxidation during air ingress – Part I: Synthesis of experimental results” of this journal issue aim at assessing the state of the art on this phenomenon. In this paper, the modelling of air ingress phenomena in the main severe accident codes (ASTEC, ATHLET-CD, MAAP, MELCOR, RELAP/SCDAPSIM, SOCRAT) is described in details, as well as the validation against the integral experiments QUENCH-10, QUENCH-16 and PARAMETER-SF4. A full review of cladding oxidation by air is thus established.

  12. Modelling of oxidation and hydriding behaviour of Zircaloy-2 pressure tubes in PHWR

    International Nuclear Information System (INIS)

    Sah, D.N.; Sunil Kumar; Khan, K.B.

    2002-01-01

    A computer model named DOCTOR (Deuteriding of Coolant Tubes during Operation of Reactor) has been developed for predicting the axial profile of oxide thickness and hydrogen (Deuterium) concentration in PHWR pressure tubes. This model is applicable to single channel or full core analysis. The main source of hydrogen is considered to be oxidation of pressure tube on the i.d. surface by high temperature coolant water. Three stages of oxidation is considered namely, pre- transition, post transition and accelerated. Oxidation rate is considered to be dependent on channel power, axial power/flux distribution, coolant temperature and pre-existing oxide thickness at the location. The kinetics parameters for oxidation model are derived from the actual measurement of oxide thickness on a number of pressure tubes examined in PIE Division. The input data required for the model are: channel power, channel power factor, axial flux distribution, coolant inlet temperature, critical oxide thickness, hydrogen pick up fraction, initial hydrogen in the material and time of operation (efpy). The model calculates the oxide layer thickness on the inside surface of the pressure tube along the length. The amount of hydrogen picked up by the pressure tube is calculated from the oxide thickness using hydrogen pick up fraction determined from the PIE data. The pressure tube length is divided into a number of axial segments for calculation. The temperature and fast neutron flux assumed to be constant in a given segment. The axial temperature profile calculated from the axial power profile in the channel is used for calculating the oxidation rate at various locations in the pressure tube. The model has been validated with PIE data of hydrogen equivalent measurement on a number of irradiated Zircaloy-2 pressure tubes of various PHWRs. The performance of the model in predicting the axial profile of hydrogen in the pressure tubes has been found to be good. (author)

  13. Experimental Study and Mathematical Modeling of Self-Sustained Kinetic Oscillations in Catalytic Oxidation of Methane over Nickel.

    Science.gov (United States)

    Lashina, Elena A; Kaichev, Vasily V; Saraev, Andrey A; Vinokurov, Zakhar S; Chumakova, Nataliya A; Chumakov, Gennadii A; Bukhtiyarov, Valerii I

    2017-09-21

    The self-sustained kinetic oscillations in the oxidation of CH 4 over Ni foil have been studied at atmospheric pressure using an X-ray diffraction technique and mass spectrometry. It has been shown that the regular oscillations appear under oxygen-deficient conditions; CO, CO 2 , H 2 , and H 2 O are detected as the products. According to in situ X-ray diffraction measurements, nickel periodically oxidizes to NiO initiating the reaction-rate oscillations. To describe the oscillations, we have proposed a five-stage mechanism of the partial oxidation of methane over Ni and a corresponding three-variable kinetic model. The mechanism considers catalytic methane decomposition, dissociative adsorption of oxygen, transformation of chemisorbed oxygen to surface nickel oxide, and reaction of adsorbed carbon and oxygen species to form CO. Analysis of the kinetic model indicates that the competition of two processes, i.e., the oxidation and the carbonization of the catalyst surface, is the driving force of the self-sustained oscillations in the oxidation of methane. We have compared this mechanism with the detailed 18-stage mechanism described previously by Lashina et al. (Kinetics and Catalysis 2012, 53, 374-383). It has been shown that both kinetic mechanisms coupled with a continuous stirred-tank reactor model describe well the oscillatory behavior in the oxidation of methane under non-isothermal conditions.

  14. Interactive football training based on rebounders with hit position sensing and audio/light feedback

    DEFF Research Database (Denmark)

    Jensen, Mads Møller; Grønbæk, Kaj; Rasmussen, Majken Kirkegård

    A Danish football club has established a (24/7/365) football training facility, where the authors developed an interactive training installation (http://vimeo.com/28446312). The training installation consist of a 12*12 m square with 4 M­Station Pro rebounders equipped with sensors that enable hit...... position sensing. The rebounders are equipped with loudspeakers and lights being used to call for the ball. Here we discuss one game “Pass ­and ­Turn”, which is meant to train speed in controlling a returned ball, reaction to a call for the ball and turning to hit rebounders to the left, right, behind...

  15. Madoff Debacle Hits Colleges and Raises Questions about Trustee Conflicts

    Science.gov (United States)

    Fain, Paul

    2009-01-01

    Several colleges and universities lost millions in the alleged $50-billion Ponzi scheme run by the Wall Street trader Bernard L. Madoff. The losses include institutions' endowment holdings in hedge funds that were invested with Madoff as well as hits taken by supporting foundations and donors. Several foundations that have been active in higher…

  16. Recent results from the HIT-II and HIT-SI helicity injection current drive experiments

    International Nuclear Information System (INIS)

    Jarboe, T.R.; Hamp, W.T.; Izzo, V.A.; Nelson, B.A.; O'Neill, R.G.; Raman, R.; Redd, A.J.; Sieck, P.E.; Smith, R.J.

    2005-01-01

    Three important results are reported. 1) CHI startup has produced 100 kA of closed current without using poloidal field (PF) coils or any transformer action. The initial equilibrium is then driven to 240 kA with a 3 V transformer loop voltage, indicating high quality plasma. 2) For the first time CHI alone has produced toroidal currents (350 kA) that far exceed q a I inj , and with I p /I tf as high as 1.2. The key to these new results appears to be having the toroidal field small enough that relaxation will occur. 3) The steady inductive helicity injection spheromak experiment has operated at 5 kHz for 6 ms with current amplitudes up to 11 kA in each injector. The helicity injection rate is nearly constant with the ExB flow always into the plasma and not into the walls. NIMROD simulations of HIT-SI show a buildup of spheromak fields. (author)

  17. From Two-Phase to Three-Phase: The New Electrochemical Interface by Oxide Electrocatalysts

    Science.gov (United States)

    Xu, Zhichuan J.

    2018-03-01

    Electrochemical reactions typically occur at the interface between a solid electrode and a liquid electrolyte. The charge exchange behaviour between these two phases determines the kinetics of electrochemical reactions. In the past few years, significant advances have been made in the development of metal oxide electrocatalysts for fuel cell and electrolyser reactions. However, considerable gaps remain in the fundamental understanding of the charge transfer pathways and the interaction between the metal oxides and the conducting substrate on which they are located. In particular, the electrochemical interfaces of metal oxides are significantly different from the traditional (metal) ones, where only a conductive solid electrode and a liquid electrolyte are considered. Oxides are insulating and have to be combined with carbon as a conductive mediator. This electrode configuration results in a three-phase electrochemical interface, consisting of the insulating oxide, the conductive carbon, and the liquid electrolyte. To date, the mechanistic insights into this kind of non-traditional electrochemical interface remain unclear. Consequently conventional electrochemistry concepts, established on classical electrode materials and their two-phase interfaces, are facing challenges when employed for explaining these new electrode materials. [Figure not available: see fulltext.

  18. Oxide-supported metal clusters: models for heterogeneous catalysts

    International Nuclear Information System (INIS)

    Santra, A K; Goodman, D W

    2003-01-01

    Understanding the size-dependent electronic, structural and chemical properties of metal clusters on oxide supports is an important aspect of heterogeneous catalysis. Recently model oxide-supported metal catalysts have been prepared by vapour deposition of catalytically relevant metals onto ultra-thin oxide films grown on a refractory metal substrate. Reactivity and spectroscopic/microscopic studies have shown that these ultra-thin oxide films are excellent models for the corresponding bulk oxides, yet are sufficiently electrically conductive for use with various modern surface probes including scanning tunnelling microscopy (STM). Measurements on metal clusters have revealed a metal to nonmetal transition as well as changes in the crystal and electronic structures (including lattice parameters, band width, band splitting and core-level binding energy shifts) as a function of cluster size. Size-dependent catalytic reactivity studies have been carried out for several important reactions, and time-dependent catalytic deactivation has been shown to arise from sintering of metal particles under elevated gas pressures and/or reactor temperatures. In situ STM methodologies have been developed to follow the growth and sintering kinetics on a cluster-by-cluster basis. Although several critical issues have been addressed by several groups worldwide, much more remains to be done. This article highlights some of these accomplishments and summarizes the challenges that lie ahead. (topical review)

  19. Two Balls' Collision of Mass Ratio 3:1

    Science.gov (United States)

    Ogawara, Yasuo; Hull, Michael M.

    2018-04-01

    Students will sometimes ask why momentum and kinetic energy concepts are both necessary. When physics teachers demonstrate situations that require both an understanding of kinetic energy and momentum, a favorite is Newton's cradle, or a comparable demonstration of two balls of equal mass hitting each other. However, in addition to the case of two balls of equal mass, if a ball hits another ball of three times the mass with equal speed, the results are also interesting, and, like the equal-mass demonstration, both kinetic energy and momentum are critical for understanding the motion.

  20. Numerical modelling of emissions of nitrogen oxides in solid fuel combustion.

    Science.gov (United States)

    Bešenić, Tibor; Mikulčić, Hrvoje; Vujanović, Milan; Duić, Neven

    2018-06-01

    Among the combustion products, nitrogen oxides are one of the main contributors to a negative impact on the environment, participating in harmful processes such as tropospheric ozone and acid rains production. The main source of emissions of nitrogen oxides is the human combustion of fossil fuels. Their formation models are investigated and implemented with the goal of obtaining a tool for studying the nitrogen-containing pollutant production. In this work, numerical simulation of solid fuel combustion was carried out on a three-dimensional model of a drop tube furnace by using the commercial software FIRE. It was used for simulating turbulent fluid flow and temperature field, concentrations of the reactants and products, as well as the fluid-particles interaction by numerically solving the integro-differential equations describing these processes. Chemical reactions mechanisms for the formation of nitrogen oxides were implemented by the user functions. To achieve reasonable calculation times for running the simulations, as well as efficient coupling with the turbulent mixing process, the nitrogen scheme is limited to sufficiently few homogeneous reactions and species. Turbulent fluctuations that affect the reaction rates of nitrogen oxides' concentration are modelled by probability density function approach. Results of the implemented model for nitrogen oxides' formation from coal and biomass are compared to the experimental data. Temperature, burnout and nitrogen oxides' concentration profiles are compared, showing satisfactory agreement. The new model allows the simulation of pollutant formation in the real-world applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. A kinetic model of municipal sludge degradation during non-catalytic wet oxidation.

    Science.gov (United States)

    Prince-Pike, Arrian; Wilson, David I; Baroutian, Saeid; Andrews, John; Gapes, Daniel J

    2015-12-15

    Wet oxidation is a successful process for the treatment of municipal sludge. In addition, the resulting effluent from wet oxidation is a useful carbon source for subsequent biological nutrient removal processes in wastewater treatment. Owing to limitations with current kinetic models, this study produced a kinetic model which predicts the concentrations of key intermediate components during wet oxidation. The model was regressed from lab-scale experiments and then subsequently validated using data from a wet oxidation pilot plant. The model was shown to be accurate in predicting the concentrations of each component, and produced good results when applied to a plant 500 times larger in size. A statistical study was undertaken to investigate the validity of the regressed model parameters. Finally the usefulness of the model was demonstrated by suggesting optimum operating conditions such that volatile fatty acids were maximised. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Quantification of oxide particle composition in model oxide dispersion strengthened steel alloys

    Energy Technology Data Exchange (ETDEWEB)

    London, A.J., E-mail: andrew.london@materials.ox.ac.uk [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Lozano-Perez, S.; Moody, M.P. [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Amirthapandian, S.; Panigrahi, B.K.; Sundar, C.S. [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102, TN (India); Grovenor, C.R.M. [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom)

    2015-12-15

    Oxide dispersion strengthened ferritic steels (ODS) are being considered for structural components of future designs of fission and fusion reactors because of their impressive high-temperature mechanical properties and resistance to radiation damage, both of which arise from the nanoscale oxide particles they contain. Because of the critical importance of these nanoscale phases, significant research activity has been dedicated to analysing their precise size, shape and composition (Odette et al., Annu. Rev. Mater. Res. 38 (2008) 471–503 [1]; Miller et al., Mater. Sci. Technol. 29(10) (2013) 1174–1178 [2]). As part of a project to develop new fuel cladding alloys in India, model ODS alloys have been produced with the compositions, Fe–0.3Y{sub 2}O{sub 3}, Fe–0.2Ti–0.3Y{sub 2}O{sub 3} and Fe–14Cr–0.2Ti–0.3Y{sub 2}O{sub 3}. The oxide particles in these three model alloys have been studied by APT in their as-received state and following ion irradiation (as a proxy for neutron irradiation) at various temperatures. In order to adequately quantify the composition of the oxide clusters, several difficulties must be managed, including issues relating to the chemical identification (ranging and variable peak-overlaps); trajectory aberrations and chemical structure; and particle sizing. This paper presents how these issues can be addressed by the application of bespoke data analysis tools and correlative microscopy. A discussion follows concerning the achievable precision in these measurements, with reference to the fundamental limiting factors.

  3. Quantification of oxide particle composition in model oxide dispersion strengthened steel alloys.

    Science.gov (United States)

    London, A J; Lozano-Perez, S; Moody, M P; Amirthapandian, S; Panigrahi, B K; Sundar, C S; Grovenor, C R M

    2015-12-01

    Oxide dispersion strengthened ferritic steels (ODS) are being considered for structural components of future designs of fission and fusion reactors because of their impressive high-temperature mechanical properties and resistance to radiation damage, both of which arise from the nanoscale oxide particles they contain. Because of the critical importance of these nanoscale phases, significant research activity has been dedicated to analysing their precise size, shape and composition (Odette et al., Annu. Rev. Mater. Res. 38 (2008) 471-503 [1]; Miller et al., Mater. Sci. Technol. 29(10) (2013) 1174-1178 [2]). As part of a project to develop new fuel cladding alloys in India, model ODS alloys have been produced with the compositions, Fe-0.3Y2O3, Fe-0.2Ti-0.3Y2O3 and Fe-14Cr-0.2Ti-0.3Y2O3. The oxide particles in these three model alloys have been studied by APT in their as-received state and following ion irradiation (as a proxy for neutron irradiation) at various temperatures. In order to adequately quantify the composition of the oxide clusters, several difficulties must be managed, including issues relating to the chemical identification (ranging and variable peak-overlaps); trajectory aberrations and chemical structure; and particle sizing. This paper presents how these issues can be addressed by the application of bespoke data analysis tools and correlative microscopy. A discussion follows concerning the achievable precision in these measurements, with reference to the fundamental limiting factors. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. THEORY OF ACTIVE HITTINGS IS IN PROCESSES OF ELECTRO-COAGULATION THE ADMIXTURES IN WATER TECHNOLOGICAL ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    В.В. Березуцький

    2012-10-01

    Full Text Available  In the article theoretical bases of electro-coagulation of admixtures are examined in a water technological environment with the use of theory of the active hittings, which are based on the results of the executed researches and analysis of scientific information. Application of theory of the active hittings is in coagulation, provides high efficiency of process of extraction of admixtures from water environments during minimization of energy consumption and expenses of materials.

  5. Simplified modeling of simultaneous reaction kinetics of carbon oxidation and nitrification in biofilm processes

    Energy Technology Data Exchange (ETDEWEB)

    Tsuneda, S.; Auresenia, J.; Hibiya, K.; Hirata, A. [Waseda University, Department of Chemical Engineering, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555 (Japan)

    2004-06-01

    Batch experiments with varying initial substrate concentrations and biomass volumes were performed in a three-phase fluidized bed biofilm reactor treating simulated domestic wastewater to study the simultaneous carbon oxidation and nitrification in the biofilm process. A simplified mass balance equation for the biofilm was proposed and five different kinetic rate equations were used to match the actual data. The kinetic parameters were obtained by nonlinear regression analysis on a set of two differential equations representing the simultaneous carbon oxidation and nitrification. The competitive inhibition model incorporating the effects of total organic carbon (TOC) concentrations on nitrification rates was the best-suited model based on the average r{sup 2}. In this model, oxygen concentration and its affinity constants were not included. Instead, it was assumed that the rate of carbon oxidation is independent of the NH{sub 4}{sup +}-N, while nitrification is affected by TOC. The number of parameters was successfully minimized without reducing its ability to accurately predict the bulk concentration time course, which would reduce computational complexity and possibly enhance the availability for an actual wastewater treatment process. (Abstract Copyright [2004], Wiley Periodicals, Inc.)

  6. Large-scale Modeling of Nitrous Oxide Production: Issues of Representing Spatial Heterogeneity

    Science.gov (United States)

    Morris, C. K.; Knighton, J.

    2017-12-01

    Nitrous oxide is produced from the biological processes of nitrification and denitrification in terrestrial environments and contributes to the greenhouse effect that warms Earth's climate. Large scale modeling can be used to determine how global rate of nitrous oxide production and consumption will shift under future climates. However, accurate modeling of nitrification and denitrification is made difficult by highly parameterized, nonlinear equations. Here we show that the representation of spatial heterogeneity in inputs, specifically soil moisture, causes inaccuracies in estimating the average nitrous oxide production in soils. We demonstrate that when soil moisture is averaged from a spatially heterogeneous surface, net nitrous oxide production is under predicted. We apply this general result in a test of a widely-used global land surface model, the Community Land Model v4.5. The challenges presented by nonlinear controls on nitrous oxide are highlighted here to provide a wider context to the problem of extraordinary denitrification losses in CLM. We hope that these findings will inform future researchers on the possibilities for model improvement of the global nitrogen cycle.

  7. Simplified kinetic models of methanol oxidation on silver

    DEFF Research Database (Denmark)

    Andreasen, A.; Lynggaard, H.; Stegelmann, C.

    2005-01-01

    Recently the authors developed a microkinetic model of methanol oxidation on silver [A. Andreasen, H. Lynggaard, C. Stegelmann, P. Stoltze, Surf. Sci. 544 (2003) 5-23]. The model successfully explains both surface science experiments and kinetic experiments at industrial conditions applying...

  8. Sensitivity analysis of bubble size and probe geometry on the measurements of interfacial area concentration in gas-liquid two-phase flow

    International Nuclear Information System (INIS)

    Kataoka, Isao; Ishii, Mamoru; Serizawa, Akimi

    1994-01-01

    Interfacial area concentration measurement is quite important in gas-liquid two-phase flow. To determine the accuracy of measurement of the interfacial area using electrical resistivity probes, numerical simulations of a passing bubble through sensors are carried out. The two-sensors method, the four-sensors method and the correlative method are tested and the effects of sensor spacing, bubble diameter and hitting angle of the bubbles on the accuracy of each measurement method are investigated. The results indicated that the two-sensors method is insensitive to the ratio between sensor spacing and bubble diameter, and hitting angle. It overestimates the interfacial area for small hitting angles while it gives a reasonable accuracy for smaller bubbles and large hitting angles. The four-sensors method gives accurate interfacial area measurements particularly for the larger bubble diameters and smaller hitting angles, while for smaller bubbles and larger hitting angles, the escape probability of bubbles through the sensors becomes large and the accuracy becomes worse. The correlative method gives an overall accuracy for interfacial area measurement. Particularly, it gives accurate measurements for large bubbles and larger hitting angles while for smaller hitting angles, the spatial dependence of the correlation functions affects the accuracy. (orig.)

  9. Polyaniline: Aniline oxidation with strong and weak oxidants under various acidity

    Energy Technology Data Exchange (ETDEWEB)

    Bláha, Michal, E-mail: blaha@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6 (Czech Republic); Trchová, Miroslava; Bober, Patrycja; Morávková, Zuzana [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6 (Czech Republic); Prokeš, Jan [Charles University, Faculty of Mathematics and Physics, 180 00 Prague 8 (Czech Republic); Stejskal, Jaroslav [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6 (Czech Republic)

    2017-06-15

    Aniline was oxidized with three strong inorganic oxidants (ammonium peroxydisulfate, cerium(IV) sulfate, potassium dichromate), two weak inorganic oxidants (iron(III) chloride, silver nitrate), and one organic oxidant (p-benzoquinone) in aqueous solutions of methanesulfonic acid (MSA) of various concentration. Whereas oxidation of aniline with ammonium peroxydisulfate yielded high-molecular-weight conducting polyaniline (PANI) in the whole acidity range, the oxidation with cerium(IV) sulfate led also to a single product close to PANI with considerably lower molecular weight and lower conductivity. Potassium dichromate gave PANI only at high concentration of MSA. The use of iron(III) chloride yielded composite mixtures of PANI and low-molecular-weight aniline oligomers. The oxidation of aniline with silver nitrate led to composites of silver and an organic part, which was constituted either by aniline oligomers or conducting polyaniline or both. p-Benzoquinone as oxidant produced mainly aniline oligomers with poor conductivity and 2,5-dianilino-p-benzoquinone-like structure detected in FTIR and Raman spectra when oxidation proceeded with weak oxidants. A general model of oxidation with strong and weak oxidants was formulated. - Highlights: • Comparison of aniline oxidation with oxidants of different redox potential. • UV–vis, FTIR and Raman spectroscopies combined with size-exclusion chromatography. • The contents of polymer and oligomers were analyzed and discussed. • General model of aniline oxidation with strong and weak oxidants was formulated.

  10. "Hits" emerge through self-organized coordination in collective response of free agents

    Science.gov (United States)

    Chakrabarti, Anindya S.; Sinha, Sitabhra

    2016-10-01

    Individuals in free societies frequently exhibit striking coordination when making independent decisions en masse. Examples include the regular appearance of hit products or memes with substantially higher popularity compared to their otherwise equivalent competitors or extreme polarization in public opinion. Such segregation of events manifests as bimodality in the distribution of collective choices. Here we quantify how apparently independent choices made by individuals result in a significantly polarized but stable distribution of success in the context of the box-office performance of movies and show that it is an emergent feature of a system of noninteracting agents who respond to sequentially arriving signals. The aggregate response exhibits extreme variability amplifying much smaller differences in individual cost of adoption. Due to self-organization of the competitive landscape, most events elicit only a muted response but a few stimulate widespread adoption, emerging as "hits".

  11. A framework of induced hyperspace dynamical systems equipped with the hit-or-miss topology

    International Nuclear Information System (INIS)

    Wang Yangeng; Wei Guo; Campbell, William H.; Bourquin, Steven

    2009-01-01

    For any dynamical system (E,d,f), where E is Hausdorff locally compact second countable (HLCSC), let F (resp., 2 E ) denote the space of all closed subsets (resp., non-empty closed subsets) of E equipped with the hit-or-miss topology τ f . Both F and 2 E are again HLCSC (F actually compact), thus metrizable. Let ρ be such a metric (three metrics available). The main purpose is to determine the conditions on f that ensure the continuity of the induced hyperspace maps 2 f :F→F and 2 f :2 E →2 E defined by 2 f (F)=f(F). With this setting, the induced hyperspace systems (F,ρ,2 f ) and (2 E ,ρ,2 f ) are compact and locally compact dynamical systems, respectively. Consequently, dynamical properties, particularly metric related dynamical properties, of the given system (E,d,f) can be explored through these hyperspace systems. In contrast, when the Vietoris topology τ v is equipped on 2 E , the space of the induced hyperspace topological dynamical system (2 E ,τ v ,2 f ) is not metrizable if E is not compact metrizable, e.g., E=R n , implying that metric related dynamical concepts cannot be defined for (2 E ,τ v ,2 f ). Moreover, two examples are provided to illustrate the advantages of the hit-or-miss topology as compared to the Vietoris topology.

  12. Sleeping beauties in psychology: comparisons of "hits" and "missed signals" in psychological journals.

    Science.gov (United States)

    Lange, Lydia L

    2005-05-01

    Scientific publications tend to be forgotten quickly. A few works, however, are still cited 100 years and more after their publication. The author used bibliometric methods to compare "hits" (works noticed by the scientific community soon after their publication) with "missed signals" (works that went unnoticed until much later) by investigating 2 psychological journals founded in the 1890s: Zeitschrift für Psychologie and Psychological Review. All articles that were published in either of these journals up to 1920 and cited more than 25 times in the Web of Science up to the year 2000 were considered for inclusion in the analysis. It emerged that hits corresponded more closely to the focus of scientific attention at the time of the publications than missed signals.

  13. Carbon monoxide oxidation over three different states of copper: Development of a model metal oxide catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Jernigan, Glenn Geoffrey [California Univ., Berkeley, CA (United States). Dept. of Chemistry

    1994-10-01

    Carbon monoxide oxidation was performed over the three different oxidation states of copper -- metallic (Cu), copper (I) oxide (Cu2O), and copper (II) oxide (CuO) as a test case for developing a model metal oxide catalyst amenable to study by the methods of modern surface science and catalysis. Copper was deposited and oxidized on oxidized supports of aluminum, silicon, molybdenum, tantalum, stainless steel, and iron as well as on graphite. The catalytic activity was found to decrease with increasing oxidation state (Cu > Cu2O > CuO) and the activation energy increased with increasing oxidation state (Cu, 9 kcal/mol < Cu2O, 14 kcal/mol < CuO, 17 kcal/mol). Reaction mechanisms were determined for the different oxidation states. Lastly, NO reduction by CO was studied. A Cu and CuO catalyst were exposed to an equal mixture of CO and NO at 300--350 C to observe the production of N2 and CO2. At the end of each reaction, the catalyst was found to be Cu2O. There is a need to study the kinetics of this reaction over the different oxidation states of copper.

  14. Oxidative stress contributes to outcome severity in a Drosophila melanogaster model of classic galactosemia

    Directory of Open Access Journals (Sweden)

    Patricia P. Jumbo-Lucioni

    2013-01-01

    Classic galactosemia is a genetic disorder that results from profound loss of galactose-1P-uridylyltransferase (GALT. Affected infants experience a rapid escalation of potentially lethal acute symptoms following exposure to milk. Dietary restriction of galactose prevents or resolves the acute sequelae; however, many patients experience profound long-term complications. Despite decades of research, the mechanisms that underlie pathophysiology in classic galactosemia remain unclear. Recently, we developed a Drosophila melanogaster model of classic galactosemia and demonstrated that, like patients, GALT-null Drosophila succumb in development if exposed to galactose but live if maintained on a galactose-restricted diet. Prior models of experimental galactosemia have implicated a possible association between galactose exposure and oxidative stress. Here we describe application of our fly genetic model of galactosemia to the question of whether oxidative stress contributes to the acute galactose sensitivity of GALT-null animals. Our first approach tested the impact of pro- and antioxidant food supplements on the survival of GALT-null and control larvae. We observed a clear pattern: the oxidants paraquat and DMSO each had a negative impact on the survival of mutant but not control animals exposed to galactose, and the antioxidants vitamin C and α-mangostin each had the opposite effect. Biochemical markers also confirmed that galactose and paraquat synergistically increased oxidative stress on all cohorts tested but, interestingly, the mutant animals showed a decreased response relative to controls. Finally, we tested the expression levels of two transcripts responsive to oxidative stress, GSTD6 and GSTE7, in mutant and control larvae exposed to galactose and found that both genes were induced, one by more than 40-fold. Combined, these results implicate oxidative stress and response as contributing factors in the acute galactose sensitivity of GALT-null Drosophila and, by

  15. The Paippalādasaṁhitā of the Atharvaveda Kāṇḍa 15 : a new edition with translation and commentary

    NARCIS (Netherlands)

    Lelli, Duccio

    2015-01-01

    The aim of the dissertation is to present a critical edition of kāṇḍa 15 of the Paippalādasaṁhitā of the Atharvaveda. The work is divided into two main parts: an Introduction and the critical edition itself. The Introduction deals first with topics related to the transmission of the text. After

  16. Antiproton annihilation physics annihilation physics in the Monte Carlo particle transport code particle transport code SHIELD-HIT12A

    DEFF Research Database (Denmark)

    Taasti, Vicki Trier; Knudsen, Helge; Holzscheiter, Michael

    2015-01-01

    The Monte Carlo particle transport code SHIELD-HIT12A is designed to simulate therapeutic beams for cancer radiotherapy with fast ions. SHIELD-HIT12A allows creation of antiproton beam kernels for the treatment planning system TRiP98, but first it must be benchmarked against experimental data. An...

  17. Effect of poly(ethylene oxide) homopolymer and two different poly(ethylene oxide-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymers on morphological, optical, and mechanical properties of nanostructured unsaturated polyester.

    Science.gov (United States)

    Builes, Daniel H; Hernández-Ortiz, Juan P; Corcuera, Ma Angeles; Mondragon, Iñaki; Tercjak, Agnieszka

    2014-01-22

    Novel nanostructured unsaturated polyester resin-based thermosets, modified with poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO), and two poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) block copolymers (BCP), were developed and analyzed. The effects of molecular weights, blocks ratio, and curing temperatures on the final morphological, optical, and mechanical properties were reported. The block influence on the BCP miscibility was studied through uncured and cured mixtures of unsaturated polyester (UP) resins with PEO and PPO homopolymers having molecular weights similar to molecular weights of the blocks of BCP. The final morphology of the nanostructured thermosetting systems, containing BCP or homopolymers, was investigated, and multiple mechanisms of nanostructuration were listed and explained. By considering the miscibility of each block before and after curing, it was determined that the formation of the nanostructured matrices followed a self-assembly mechanism or a polymerization-induced phase separation mechanism. The miscibility between PEO or PPO blocks with one of two phases of UP matrix was highlighted due to its importance in the final thermoset properties. Relationships between the final morphology and thermoset optical and mechanical properties were examined. The mechanisms and physics behind the morphologies lead toward the design of highly transparent, nanostructured, and toughened thermosetting UP systems.

  18. HitPredict version 4: comprehensive reliability scoring of physical protein-protein interactions from more than 100 species.

    Science.gov (United States)

    López, Yosvany; Nakai, Kenta; Patil, Ashwini

    2015-01-01

    HitPredict is a consolidated resource of experimentally identified, physical protein-protein interactions with confidence scores to indicate their reliability. The study of genes and their inter-relationships using methods such as network and pathway analysis requires high quality protein-protein interaction information. Extracting reliable interactions from most of the existing databases is challenging because they either contain only a subset of the available interactions, or a mixture of physical, genetic and predicted interactions. Automated integration of interactions is further complicated by varying levels of accuracy of database content and lack of adherence to standard formats. To address these issues, the latest version of HitPredict provides a manually curated dataset of 398 696 physical associations between 70 808 proteins from 105 species. Manual confirmation was used to resolve all issues encountered during data integration. For improved reliability assessment, this version combines a new score derived from the experimental information of the interactions with the original score based on the features of the interacting proteins. The combined interaction score performs better than either of the individual scores in HitPredict as well as the reliability score of another similar database. HitPredict provides a web interface to search proteins and visualize their interactions, and the data can be downloaded for offline analysis. Data usability has been enhanced by mapping protein identifiers across multiple reference databases. Thus, the latest version of HitPredict provides a significantly larger, more reliable and usable dataset of protein-protein interactions from several species for the study of gene groups. Database URL: http://hintdb.hgc.jp/htp. © The Author(s) 2015. Published by Oxford University Press.

  19. Efficiency profile method to study the hit efficiency of drift chambers

    International Nuclear Information System (INIS)

    Abyzov, A.; Bel'kov, A.; Lanev, A.; Spiridonov, A.; Walter, M.; Hulsbergen, W.

    2002-01-01

    A method based on the usage of efficiency profile is proposed to estimate the hit efficiency of drift chambers with a large number of channels. The performance of the method under real conditions of the detector operation has been tested analysing the experimental data from the HERA-B drift chambers

  20. Simulation of a Real-Time Brain Computer Interface for Detecting a Self-Paced Hitting Task.

    Science.gov (United States)

    Hammad, Sofyan H; Kamavuako, Ernest N; Farina, Dario; Jensen, Winnie

    2016-12-01

    An invasive brain-computer interface (BCI) is a promising neurorehabilitation device for severely disabled patients. Although some systems have been shown to work well in restricted laboratory settings, their utility must be tested in less controlled, real-time environments. Our objective was to investigate whether a specific motor task could be reliably detected from multiunit intracortical signals from freely moving animals in a simulated, real-time setting. Intracortical signals were first obtained from electrodes placed in the primary motor cortex of four rats that were trained to hit a retractable paddle (defined as a "Hit"). In the simulated real-time setting, the signal-to-noise-ratio was first increased by wavelet denoising. Action potentials were detected, and features were extracted (spike count, mean absolute values, entropy, and combination of these features) within pre-defined time windows (200 ms, 300 ms, and 400 ms) to classify the occurrence of a "Hit." We found higher detection accuracy of a "Hit" (73.1%, 73.4%, and 67.9% for the three window sizes, respectively) when the decision was made based on a combination of features rather than on a single feature. However, the duration of the window length was not statistically significant (p = 0.5). Our results showed the feasibility of detecting a motor task in real time in a less restricted environment compared to environments commonly applied within invasive BCI research, and they showed the feasibility of using information extracted from multiunit recordings, thereby avoiding the time-consuming and complex task of extracting and sorting single units. © 2016 International Neuromodulation Society.

  1. A linear two-layer model for flat-band shift in irradiated MOS devices

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, J N; Holstrom, F E; Collins, T W [International Business Machines Corp., San Jose, Calif. (USA)

    1976-04-01

    A closed-form mathematical expression is derived for the flat-band shift as a function of gate bias during electron irradiation. The model assumes that the charge in the oxide consists of charged layers of variable thickness at each of the two interfaces, depending on voltage polarity and magnitude. The region of extreme linearity which has been observed by numerous investigators and which normally occurs for the relatively small values of gate bias voltages fits this closed-form solution. Analytical results compare favourably with data obtained from 500 to 700 A thick oxides and with other previously published data.

  2. Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1

    DEFF Research Database (Denmark)

    Rist, Oystein; Grimstrup, Marie; Receveur, Jean-Marie

    2009-01-01

    Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists....... Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7nM and functional...

  3. Reactor modeling and process analysis for partial oxidation of natural gas

    NARCIS (Netherlands)

    Albrecht, B.A.

    2004-01-01

    This thesis analyses a novel process of partial oxidation of natural gas and develops a numerical tool for the partial oxidation reactor modeling. The proposed process generates syngas in an integrated plant of a partial oxidation reactor, a syngas turbine and an air separation unit. This is called

  4. A hit and run approach to inducible direct reprogramming of astrocytes to neural stem cells

    Directory of Open Access Journals (Sweden)

    Maria ePoulou

    2016-04-01

    Full Text Available Temporal and spatial control of gene expression can be achieved using an inducible system as a fundamental tool for regulated transcription in basic, applied and eventually in clinical research. We describe a novel hit and run inducible direct reprogramming approach. In a single step, two days post-transfection, transiently transfected Sox2FLAG under the Leu3p-αIPM inducible control (iSox2 triggers the activation of endogenous Sox2, redirecting primary astrocytes into abundant distinct nestin-positive radial glia cells. This technique introduces a unique novel tool for safe, rapid and efficient reprogramming amendable to regenerative medicine.

  5. Adiabatic condition and the quantum hitting time of Markov chains

    International Nuclear Information System (INIS)

    Krovi, Hari; Ozols, Maris; Roland, Jeremie

    2010-01-01

    We present an adiabatic quantum algorithm for the abstract problem of searching marked vertices in a graph, or spatial search. Given a random walk (or Markov chain) P on a graph with a set of unknown marked vertices, one can define a related absorbing walk P ' where outgoing transitions from marked vertices are replaced by self-loops. We build a Hamiltonian H(s) from the interpolated Markov chain P(s)=(1-s)P+sP ' and use it in an adiabatic quantum algorithm to drive an initial superposition over all vertices to a superposition over marked vertices. The adiabatic condition implies that, for any reversible Markov chain and any set of marked vertices, the running time of the adiabatic algorithm is given by the square root of the classical hitting time. This algorithm therefore demonstrates a novel connection between the adiabatic condition and the classical notion of hitting time of a random walk. It also significantly extends the scope of previous quantum algorithms for this problem, which could only obtain a full quadratic speedup for state-transitive reversible Markov chains with a unique marked vertex.

  6. Optical modeling of nickel-base alloys oxidized in pressurized water reactor

    Energy Technology Data Exchange (ETDEWEB)

    Clair, A. [Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR 6303 CNRS, Universite de Bourgogne, 9 avenue Alain Savary, BP 47870, 21078 Dijon cedex (France); Foucault, M.; Calonne, O. [Areva ANP, Centre Technique Departement Corrosion-Chimie, 30 Bd de l' industrie, BP 181, 71205 Le Creusot (France); Finot, E., E-mail: Eric.Finot@u-bourgogne.fr [Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR 6303 CNRS, Universite de Bourgogne, 9 avenue Alain Savary, BP 47870, 21078 Dijon cedex (France)

    2012-10-01

    The knowledge of the aging process involved in the primary water of pressurized water reactor entails investigating a mixed growth mechanism in the corrosion of nickel-base alloys. A mixed growth induces an anionic inner oxide and a cationic diffusion parallel to a dissolution-precipitation process forms the outer zone. The in situ monitoring of the oxidation kinetics requires the modeling of the oxide layer stratification with the full knowledge of the optical constants related to each component. Here, we report the dielectric constants of the alloys 600 and 690 measured by spectroscopic ellipsometry and fitted to a Drude-Lorentz model. A robust optical stratification model was determined using focused ion beam cross-section of thin foils examined by transmission electron microscopy. Dielectric constants of the inner oxide layer depleted in chromium were assimilated to those of the nickel thin film. The optical constants of both the spinels and extern layer were determined. - Highlights: Black-Right-Pointing-Pointer Spectroscopic ellipsometry of Ni-base alloy oxidation in pressurized water reactor Black-Right-Pointing-Pointer Measurements of the dielectric constants of the alloys Black-Right-Pointing-Pointer Optical simulation of the mixed oxidation process using a three stack model Black-Right-Pointing-Pointer Scattered crystallites cationic outer layer; linear Ni-gradient bottom layer Black-Right-Pointing-Pointer Determination of the refractive index of the spinel and the Cr{sub 2}O{sub 3} layers.

  7. Mathematical modeling of synthesis gas fueled electrochemistry and transport including H2/CO co-oxidation and surface diffusion in solid oxide fuel cell

    Science.gov (United States)

    Bao, Cheng; Jiang, Zeyi; Zhang, Xinxin

    2015-10-01

    Fuel flexibility is a significant advantage of solid oxide fuel cell (SOFC). A comprehensive macroscopic framework is proposed for synthesis gas (syngas) fueled electrochemistry and transport in SOFC anode with two main novelties, i.e. analytical H2/CO electrochemical co-oxidation, and correction of gas species concentration at triple phase boundary considering competitive absorption and surface diffusion. Staring from analytical approximation of the decoupled charge and mass transfer, we present analytical solutions of two defined variables, i.e. hydrogen current fraction and enhancement factor. Giving explicit answer (rather than case-by-case numerical calculation) on how many percent of the current output contributed by H2 or CO and on how great the water gas shift reaction plays role on, this approach establishes at the first time an adaptive superposition mechanism of H2-fuel and CO-fuel electrochemistry for syngas fuel. Based on the diffusion equivalent circuit model, assuming series-connected resistances of surface diffusion and bulk diffusion, the model predicts well at high fuel utilization by keeping fixed porosity/tortuosity ratio. The model has been validated by experimental polarization behaviors in a wide range of operation on a button cell for H2-H2O-CO-CO2-N2 fuel systems. The framework could be helpful to narrow the gap between macro-scale and meso-scale SOFC modeling.

  8. Chemical kinetic models for combustion of hydrocarbons and formation of nitric oxide

    Science.gov (United States)

    Jachimowski, C. J.; Wilson, C. H.

    1980-01-01

    The formation of nitrogen oxides NOx during combustion of methane, propane, and a jet fuel, JP-4, was investigated in a jet stirred combustor. The results of the experiments were interpreted using reaction models in which the nitric oxide (NO) forming reactions were coupled to the appropriate hydrocarbon combustion reaction mechanisms. Comparison between the experimental data and the model predictions reveals that the CH + N2 reaction process has a significant effect on NO formation especially in stoichiometric and fuel rich mixtures. Reaction models were assembled that predicted nitric oxide levels that were in reasonable agreement with the jet stirred combustor data and with data obtained from a high pressure (5.9 atm (0.6 MPa)), prevaporized, premixed, flame tube type combustor. The results also suggested that the behavior of hydrocarbon mixtures, like JP-4, may not be significantly different from that of pure hydrocarbons. Application of the propane combustion and nitric oxide formation model to the analysis of NOx emission data reported for various aircraft gas turbines showed the contribution of the various nitric oxide forming processes to the total NOx formed.

  9. Validation and sensitivity analysis of a two zone Diesel engine model for combustion and emissions prediction

    International Nuclear Information System (INIS)

    Rakopoulos, C.D.; Rakopoulos, D.C.; Giakoumis, E.G.; Kyritsis, D.C.

    2004-01-01

    The present two zone model of a direct injection (DI) Diesel engine divides the cylinder contents into a non-burning zone of air and another homogeneous zone in which fuel is continuously supplied from the injector and burned with entrained air from the air zone. The growth of the fuel spray zone, which comprises a number of fuel-air conical jets equal to the injector nozzle holes, is carefully modelled by incorporating jet mixing, thus determining the amount of oxygen available for combustion. The mass, energy and state equations are applied in each of the two zones to yield local temperatures and cylinder pressure histories. The concentration of the various constituents in the exhaust gases are calculated by adopting a chemical equilibrium scheme for the C-H-O system of the 11 species considered, together with chemical rate equations for the calculation of nitric oxide (NO). A model for evaluation of the soot formation and oxidation rates is included. The theoretical results from the relevant computer program are compared very favourably with the measurements from an experimental investigation conducted on a fully automated test bed, standard 'Hydra', DI Diesel engine installed at the authors' laboratory. In-cylinder pressure and temperature histories, nitric oxide concentration and soot density are among the interesting quantities tested for various loads and injection timings. As revealed, the model is sensitive to the selection of the constants of the fuel preparation and reaction sub-models, so that a relevant sensitivity analysis is undertaken. This leads to a better understanding of the physical mechanisms governed by these constants and also paves the way for construction of a reliable and relatively simple multi-zone model, which incorporates in each zone (packet) the philosophy of the present two zone model

  10. Validation and sensitivity analysis of a two zone diesel engine model for combustion and emissions prediction

    Energy Technology Data Exchange (ETDEWEB)

    Rakopoulos, C.D.; Rakopoulos, D.C.; Giakoumis, E.G. [National Technical University of Athens (Greece). Mechanical Engineering Dept.; Kyritsis, D.C. [University of Illinois at Urbana-Champaign, Urbana, IL (United States). Dept. of Mechanical and Industrial Engineering

    2004-06-01

    The present two zone model of a direct injection (DI) diesel engine divides the cylinder contents into a non-burning zone of air and another homogeneous zone in which fuel is continuously supplied from the injector and burned with entrained air from the air zone. The growth of the fuel spray zone, which comprises a number of fuel-air conical jets equal to the injector nozzle holes, is carefully modelled by incorporating jet mixing, thus determining the amount of oxygen available for combustion. The mass, energy and state equations are applied in each of the two zones to yield local temperatures and cylinder pressure histories. The concentration of the various constituents in the exhaust gases are calculated by adopting a chemical equilibrium scheme for the C-H-O system of the 11 species considered, together with chemical rate equations for the calculation of nitric oxide (NO). A model for evaluation of the soot formation and oxidation rates is included. The theoretical results from the relevant computer program are compared very favourably with the measurements from an experimental investigation conducted on a fully automated test bed, standard ''Hydra'', DI diesel engine installed at the authors' laboratory. In-cylinder pressure and temperature histories, nitric oxide concentration and soot density are among the interesting quantities tested for various loads and injection timings. As revealed, the model is sensitive to the selection of the constants of the fuel preparation and reaction sub-models, so that a relevant sensitivity analysis is undertaken. This leads to a better understanding of the physical mechanisms governed by these constants and also paves the way for construction of a reliable and relatively simple multi-zone model, which incorporates in each zone (packet) the philosophy of the present two zone model. (author)

  11. A conceptual model for the fuel oxidation of defective fuel

    International Nuclear Information System (INIS)

    Higgs, J.D.; Lewis, B.J.; Thompson, W.T.; He, Z.

    2007-01-01

    A mechanistic conceptual model has been developed to predict the fuel oxidation behaviour in operating defective fuel elements for water-cooled nuclear reactors. This theoretical work accounts for gas-phase transport and sheath reactions in the fuel-to-sheath gap to determine the local oxygen potential. An improved thermodynamic analysis has also been incorporated into the model to describe the equilibrium state of the oxidized fuel. The fuel oxidation kinetics treatment accounts for multi-phase transport including normal diffusion and thermodiffusion for interstitial oxygen migration in the solid, as well as gas-phase transport in the fuel pellet cracks. The fuel oxidation treatment is further coupled to a heat conduction equation. A numerical solution of the coupled transport equations is obtained by a finite-element technique with the FEMLAB 3.1 software package. The model is able to provide radial-axial profiles of the oxygen-to-uranium ratio and the fuel temperatures as a function of time in the defective element for a wide range of element powers and defect sizes. The model results are assessed against coulometric titration measurements of the oxygen-to-metal profile for pellet samples taken from ten spent defective elements discharged from the National Research Universal Reactor at the Chalk River Laboratories and commercial reactors

  12. Dynamic modelling of nitrous oxide emissions from three Swedish sludge liquor treatment systems

    DEFF Research Database (Denmark)

    Lindblom, E.; Arnell, M.; Flores-Alsina, X.

    2014-01-01

    The objective of this paper is to model the dynamics and validate the results of nitrous oxide (N2O)emissions from three Swedish nitrifying/denitrifying, nitritation and anammox systems treating real anaerobic digester sludge liquor. The Activated Sludge Model No. 1 is extended to describe N2O...... production by both heterotrophic and autotrophic denitrification. In addition, mass transfer equations are implemented to characterize the dynamics of N2O in the water and the gas phases.The biochemical model is simulated and validated for two hydraulic patterns: (1) a sequencing batch reactor; and, (2...

  13. Non-alcoholic steatohepatitis: review of a growing medical problem.

    Science.gov (United States)

    Te Sligte, K.; Bourass, I.; Sels, J.P.; Driessen, A.; Stockbrugger, R.W.; Koek, G.H.

    2004-02-01

    Non-alcoholic steatohepatitis (NASH) is a metabolic liver disorder that is seen in 2-6% of the general population. It manifests itself by elevated liver enzymes, frequently without symptoms. The histological findings include steatosis, inflammation, fibrosis, and cirrhosis. Three case reports are presented to illustrate features of NASH. A two-hit model has been proposed in the pathogenesis of NASH. The first hit is hepatic steatosis. A hypercaloric diet with high levels of carbohydrates and saturated fatty acids results in elevated plasma free fatty acids (FFA) and expands the adipose tissue. Insulin resistance develops and augments steatosis. Oxidation of FFA yields toxic free radicals, resulting in lipid peroxidation. They cause the second hits: increased oxidative stress on hepatocytes and induction of pro-inflammatory cytokines. When the antioxidant capacities of the liver are insufficient, mitochondrial dysfunction and tumor necrosis factor alpha (TNF-alpha) cause inflammation and fibrosis. Treatment consists of life style modifications, particularly weight loss and exercise. Many drugs have been tried in the treatment of NASH. The insulin-sensitizing drugs metformin, rosiglitazone, and pioglitazone, and the antioxidant vitamin E show promising results. Further investigation of therapeutic options is needed to direct the choice of therapy in the future.

  14. Hitting the nail on the head: Force vectors in verb semantics

    NARCIS (Netherlands)

    Goldschmidt, A.; Zwarts, J.

    2016-01-01

    Hitting the nail on the head: Forces in verb meanings Anja Goldschmidt (UU) & Joost Zwarts (UU) There is a growing recognition of the role of forces in verb meanings, starting with the seminal work of Leonard Talmy (Talmy 1985). In one line of research these forces are analyzed in terms of vectors,

  15. Prenatal cannabis exposure - The "first hit" to the endocannabinoid system.

    Science.gov (United States)

    Richardson, Kimberlei A; Hester, Allison K; McLemore, Gabrielle L

    As more states and countries legalize medical and/or adult recreational marijuana use, the incidences of prenatal cannabis exposure (PCE) will likely increase. While young people increasingly view marijuana as innocuous, marijuana preparations have been growing in potency in recent years, potentially creating global clinical, public health, and workforce concerns. Unlike fetal alcohol spectrum disorder, there is no phenotypic syndrome associated with PCE. There is also no preponderance of evidence that PCE causes lifelong cognitive, behavioral, or functional abnormalities, and/or susceptibility to subsequent addiction. However, there is compelling circumstantial evidence, based on the principles of teratology and fetal malprogramming, suggesting that pregnant women should refrain from smoking marijuana. The usage of marijuana during pregnancy perturbs the fetal endogenous cannabinoid signaling system (ECSS), which is present and active from the early embryonic stage, modulating neurodevelopment and continuing this role into adulthood. The ECSS is present in virtually every brain structure and organ system, and there is also evidence that this system is important in the regulation of cardiovascular processes. Endocannabinoids (eCBs) undergird a broad spectrum of processes, including the early stages of fetal neurodevelopment and uterine implantation. Delta-9-tetrahydrocannabinol (THC), the psychoactive chemical in cannabis, enters maternal circulation, and readily crosses the placental membrane. THC binds to CB receptors of the fetal ECSS, altering neurodevelopment and possibly rewiring ECSS circuitry. In this review, we discuss the Double-Hit Hypothesis as it relates to PCE. We contend that PCE, similar to a neurodevelopmental teratogen, delivers the first hit to the ECSS, which is compromised in such a way that a second hit (i.e., postnatal stressors) will precipitate the emergence of a specific phenotype. In summary, we conclude that perturbations of the

  16. Modeling and sensitivity analysis on the transport of aluminum oxide nanoparticles in saturated sand: effects of ionic strength, flow rate, and nanoparticle concentration.

    Science.gov (United States)

    Rahman, Tanzina; Millwater, Harry; Shipley, Heather J

    2014-11-15

    Aluminum oxide nanoparticles have been widely used in various consumer products and there are growing concerns regarding their exposure in the environment. This study deals with the modeling, sensitivity analysis and uncertainty quantification of one-dimensional transport of nano-sized (~82 nm) aluminum oxide particles in saturated sand. The transport of aluminum oxide nanoparticles was modeled using a two-kinetic-site model with a blocking function. The modeling was done at different ionic strengths, flow rates, and nanoparticle concentrations. The two sites representing fast and slow attachments along with a blocking term yielded good agreement with the experimental results from the column studies of aluminum oxide nanoparticles. The same model was used to simulate breakthrough curves under different conditions using experimental data and calculated 95% confidence bounds of the generated breakthroughs. The sensitivity analysis results showed that slow attachment was the most sensitive parameter for high influent concentrations (e.g. 150 mg/L Al2O3) and the maximum solid phase retention capacity (related to blocking function) was the most sensitive parameter for low concentrations (e.g. 50 mg/L Al2O3). Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.

    Science.gov (United States)

    Miyaoka, Masashi; Kikuti, Yara Y; Carreras, Joaquim; Ikoma, Haruka; Hiraiwa, Shinichiro; Ichiki, Akifumi; Kojima, Minoru; Ando, Kiyoshi; Yokose, Tomoyuki; Sakai, Rika; Hoshikawa, Masahiro; Tomita, Naoto; Miura, Ikuo; Takata, Katsuyoshi; Yoshino, Tadashi; Takizawa, Jun; Bea, Silvia; Campo, Elias; Nakamura, Naoya

    2018-02-01

    Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (Phit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular

  18. As the Economic Crisis Hits Home, Colleges Seek Help from Congress

    Science.gov (United States)

    Field, Kelly

    2008-01-01

    Congress is crafting a second economic-stimulus bill, and the nation's colleges, hit by the deepening fiscal crisis, want a share of the money. Over the last few weeks, colleges and their lobbyists have bombarded members of Congress with letters and phone calls seeking money for research, student aid, and infrastructure. However, Congress is…

  19. Two-phase flow models

    International Nuclear Information System (INIS)

    Delaje, Dzh.

    1984-01-01

    General hypothesis used to simplify the equations, describing two-phase flows, are considered. Two-component and one-component models of two-phase flow, as well as Zuber and Findlay model for actual volumetric steam content, and Wallis model, describing the given phase rates, are presented. The conclusion is made, that the two-component model, in which values averaged in time are included, is applicable for the solving of three-dimensional tasks for unsteady two-phase flow. At the same time, using the two-component model, including values, averaged in space only one-dimensional tasks for unsteady two-phase flow can be solved

  20. Patient-centered care requires a patient-oriented workflow model.

    Science.gov (United States)

    Ozkaynak, Mustafa; Brennan, Patricia Flatley; Hanauer, David A; Johnson, Sharon; Aarts, Jos; Zheng, Kai; Haque, Saira N

    2013-06-01

    Effective design of health information technology (HIT) for patient-centered care requires consideration of workflow from the patient's perspective, termed 'patient-oriented workflow.' This approach organizes the building blocks of work around the patients who are moving through the care system. Patient-oriented workflow complements the more familiar clinician-oriented workflow approaches, and offers several advantages, including the ability to capture simultaneous, cooperative work, which is essential in care delivery. Patient-oriented workflow models can also provide an understanding of healthcare work taking place in various formal and informal health settings in an integrated manner. We present two cases demonstrating the potential value of patient-oriented workflow models. Significant theoretical, methodological, and practical challenges must be met to ensure adoption of patient-oriented workflow models. Patient-oriented workflow models define meaningful system boundaries and can lead to HIT implementations that are more consistent with cooperative work and its emergent features.

  1. Non steady-state model for dry oxidation of nuclear wastes metallic containers in long term interim storage conditions

    International Nuclear Information System (INIS)

    Bertrand, Nathalie; Desgranges, Clara; Poquillon, Dominique; Monceau, Daniel

    2006-01-01

    For high-level nuclear waste containers in long-term interim storage, dry oxidation will be the first and the main degradation mode. The reason is that, for this kind of waste, the temperature on the surface of the containers will be high enough to avoid any condensation phenomena for several years. Even if the scale growth kinetics is expected to be very slow since the temperature will be moderate at the beginning of the storage (around 300 deg. C) and will keep on decreasing, the metal thickness lost by dry oxidation over such a long period must be evaluated with a good reliability. To achieve this goal, modelling of the oxide scale growth is necessary and this is the aim of the dry oxidation studies, performed in the frame of the COCON programme. All existing oxidation models are based on the two main oxidation theories developed by Wagner between the 1930's and 1970's on the one hand, and by Cabrera and Mott in the 1960 and next by Fromhold on the other hand. These used to be associated with high temperature behaviour for Wagner's theory and with low temperature for the second one. Indeed it is certainly more relevant to consider their range of application in terms of the oxide scale thickness rather than in terms of temperature. The question is posed about which theory should an appropriate model rely on. It can be expected that the oxide scale could have a thickness ranging from a few tens of nanometers up to several tens of micrometers depending on temperature and class of alloys chosen. At the present time, low-alloyed steels or carbon steels are considered candidate materials for high-level nuclear waste containers in long term interim storage. For this type of alloys, the scale formed during the dry oxidation stage will be 'rapidly' thick enough to neglect the Mott field. Hence, in a first step, some basic models based on a parabolic rate assumption, that is to say Wagner's model, have been derived from experimental data on iron and on low-alloy steel

  2. Modeling Nitrous Oxide Production during Biological Nitrogen Removal via Nitrification and Denitrification: Extensions to the General ASM Models

    DEFF Research Database (Denmark)

    Ni, Bing-Jie; Ruscalleda, Maël; Pellicer i Nàcher, Carles

    2011-01-01

    on N2O production from four different mixed culture nitrification and denitrification reactor study reports. Modeling results confirm that hydroxylamine oxidation by ammonium oxidizers (AOB) occurs 10 times slower when NO2– participates as final electron acceptor compared to the oxic pathway. Among......Nitrous oxide (N2O) can be formed during biological nitrogen (N) removal processes. In this work, a mathematical model is developed that describes N2O production and consumption during activated sludge nitrification and denitrification. The well-known ASM process models are extended to capture N2O...

  3. Two-Dimensional Metal Oxide Nanomaterials for Next-Generation Rechargeable Batteries.

    Science.gov (United States)

    Mei, Jun; Liao, Ting; Kou, Liangzhi; Sun, Ziqi

    2017-12-01

    The exponential increase in research focused on two-dimensional (2D) metal oxides has offered an unprecedented opportunity for their use in energy conversion and storage devices, especially for promising next-generation rechargeable batteries, such as lithium-ion batteries (LIBs) and sodium-ion batteries (NIBs), as well as some post-lithium batteries, including lithium-sulfur batteries, lithium-air batteries, etc. The introduction of well-designed 2D metal oxide nanomaterials into next-generation rechargeable batteries has significantly enhanced the performance of these energy-storage devices by providing higher chemically active interfaces, shortened ion-diffusion lengths, and improved in-plane carrier-/charge-transport kinetics, which have greatly promoted the development of nanotechnology and the practical application of rechargeable batteries. Here, the recent progress in the application of 2D metal oxide nanomaterials in a series of rechargeable LIBs, NIBs, and other post lithium-ion batteries is reviewed relatively comprehensively. Current opportunities and future challenges for the application of 2D nanomaterials in energy-storage devices to achieve high energy density, high power density, stable cyclability, etc. are summarized and outlined. It is believed that the integration of 2D metal oxide nanomaterials in these clean energy devices offers great opportunities to address challenges driven by increasing global energy demands. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Hit discovery of 4-amino-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide: A novel EGFR inhibitor from a designed small library.

    Science.gov (United States)

    Elkamhawy, Ahmed; Paik, Sora; Hassan, Ahmed H E; Lee, Yong Sup; Roh, Eun Joo

    2017-12-01

    Searching for hit compounds within the huge chemical space resembles the attempt to find a needle in a haystack. Cheminformatics-guided selection of few representative molecules of a rationally designed virtual combinatorial library is a powerful tool to confront this challenge, speed up hit identification and cut off costs. Herein, this approach has been applied to identify hit compounds with novel scaffolds able to inhibit EGFR kinase. From a generated virtual library, six 4-aryloxy-5-aminopyrimidine scaffold-derived compounds were selected, synthesized and evaluated as hit EGFR inhibitors. 4-Aryloxy-5-benzamidopyrimidines inhibited EGFR with IC 50 1.05-5.37 μM. Cell-based assay of the most potent EGFR inhibitor hit (10ac) confirmed its cytotoxicity against different cancerous cells. In spite of no EGFR, HER2 or VEGFR1 inhibition was elicited by 4-aryloxy-5-(thio)ureidopyrimidine derivatives, cell-based evaluation suggested them as antiproliferative hits acting by other mechanism(s). Molecular docking study provided a plausible explanation of incapability of 4-aryloxy-5-(thio)ureidopyrimidines to inhibit EGFR and suggested a reasonable binding mode of 4-aryloxy-5-benzamidopyrimidines which provides a basis to develop more optimized ligands. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Current drive experiments on the HIT-II spherical torus

    International Nuclear Information System (INIS)

    Jarboe, T.R.; Raman, R.; Nelson, B.A.; Holcomb, C.T.; McCollam, K.J.; Sieck, P.E.

    1999-01-01

    This paper describes the following new achievements from the Helicity Injected Torus (HIT) program: a) formation and sustainment of a toroidal magnetic equilibrium using coaxial helicity injection (CHI) in a conducting shell that has an L/R time much shorter than the pulse length; b) static formation of a spherical torus with plasma current over 180 kA using a transformer and feedback controlled equilibrium coils; and c) production of a current increase in a transformer produced spherical torus using CHI. (author)

  6. Current drive experiments on the HIT-II spherical torus

    International Nuclear Information System (INIS)

    Jarboe, T.; Raman, R.; Nelson, B.; Holcomb, C.T.; McCollam, K.J.; Sieck, P.E.

    2001-01-01

    This paper describes the following new achievements from the Helicity Injected Torus (HIT) program: a) formation and sustainment of a toroidal magnetic equilibrium using coaxial helicity injection (CHI) in a conducting shell that has an L/R time much shorter than the pulse length; b) static formation of a spherical torus with plasma current over 180 kA using a transformer and feedback controlled equilibrium coils; and c) production of a current increase in a transformer produced spherical torus using CHI. (author)

  7. A comparison of 100 human genes using an alu element-based instability model.

    Science.gov (United States)

    Cook, George W; Konkel, Miriam K; Walker, Jerilyn A; Bourgeois, Matthew G; Fullerton, Mitchell L; Fussell, John T; Herbold, Heath D; Batzer, Mark A

    2013-01-01

    The human retrotransposon with the highest copy number is the Alu element. The human genome contains over one million Alu elements that collectively account for over ten percent of our DNA. Full-length Alu elements are randomly distributed throughout the genome in both forward and reverse orientations. However, full-length widely spaced Alu pairs having two Alus in the same (direct) orientation are statistically more prevalent than Alu pairs having two Alus in the opposite (inverted) orientation. The cause of this phenomenon is unknown. It has been hypothesized that this imbalance is the consequence of anomalous inverted Alu pair interactions. One proposed mechanism suggests that inverted Alu pairs can ectopically interact, exposing both ends of each Alu element making up the pair to a potential double-strand break, or "hit". This hypothesized "two-hit" (two double-strand breaks) potential per Alu element was used to develop a model for comparing the relative instabilities of human genes. The model incorporates both 1) the two-hit double-strand break potential of Alu elements and 2) the probability of exon-damaging deletions extending from these double-strand breaks. This model was used to compare the relative instabilities of 50 deletion-prone cancer genes and 50 randomly selected genes from the human genome. The output of the Alu element-based genomic instability model developed here is shown to coincide with the observed instability of deletion-prone cancer genes. The 50 cancer genes are collectively estimated to be 58% more unstable than the randomly chosen genes using this model. Seven of the deletion-prone cancer genes, ATM, BRCA1, FANCA, FANCD2, MSH2, NCOR1 and PBRM1, were among the most unstable 10% of the 100 genes analyzed. This algorithm may lay the foundation for comparing genetic risks posed by structural variations that are unique to specific individuals, families and people groups.

  8. Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

    Science.gov (United States)

    Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

    2012-01-01

    Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

  9. Evidence for Single Metal Two Electron Oxidative Addition and Reductive Elimination at Uranium

    OpenAIRE

    Gardner, Benedict M; Kefalidis, Christos E; Lu, Erli; Patel, Dipti; Mcinnes, Eric; Tuna, Floriana; Wooles, Ashley; Maron, Laurent; Liddle, Stephen

    2017-01-01

    Reversible single-metal two-electron oxidative addition and reductive elimination are common fundamental reactions for transition metals that underpin major catalytic transformations. However, these reactions have never been observed together in the f-block because these metals exhibit irreversible one- or multi-electron oxidation or reduction reactions. Here, we report that azobenzene oxidises sterically and electronically unsaturated uranium(III) complexes to afford a uranium(V)-imido compl...

  10. A Structural Molar Volume Model for Oxide Melts Part III: Fe Oxide-Containing Melts

    Science.gov (United States)

    Thibodeau, Eric; Gheribi, Aimen E.; Jung, In-Ho

    2016-04-01

    As part III of this series, the model is extended to iron oxide-containing melts. All available experimental data in the FeO-Fe2O3-Na2O-K2O-MgO-CaO-MnO-Al2O3-SiO2 system were critically evaluated based on the experimental condition. The variations of FeO and Fe2O3 in the melts were taken into account by using FactSage to calculate the Fe2+/Fe3+ distribution. The molar volume model with unary and binary model parameters can be used to predict the molar volume of the molten oxide of the Li2O-Na2O-K2O-MgO-CaO-MnO-PbO-FeO-Fe2O3-Al2O3-SiO2 system in the entire range of compositions, temperatures, and oxygen partial pressures from Fe saturation to 1 atm pressure.

  11. Trends for Methane Oxidation at Solid Oxide Fuel Cell Conditions

    DEFF Research Database (Denmark)

    Kleis, Jesper; Jones, Glenn; Abild-Pedersen, Frank

    2009-01-01

    First-principles calculations are used to predict a plausible reaction pathway for the methane oxidation reaction. In turn, this pathway is used to obtain trends in methane oxidation activity at solid oxide fuel cell (SOFC) anode materials. Reaction energetics and barriers for the elementary...... the Ni surfaces to other metals of interest. This allows the reactivity over the different metals to be understood in terms of two reactivity descriptors, namely, the carbon and oxygen adsorption energies. By combining a simple free-energy analysis with microkinetic modeling, activity landscapes of anode...

  12. Demand spillovers of smash-hit papers: evidence from the 'Male Organ Incident'.

    Science.gov (United States)

    Kässi, Otto; Westling, Tatu

    2013-12-01

    This study explores the short-run spillover effects of popular research papers. We consider the publicity of 'Male Organ and Economic Growth: Does Size Matter?' as an exogenous shock to economics discussion paper demand, a natural experiment of a sort. In particular, we analyze how the very substantial visibility influenced the downloads of Helsinki Center of Economic Research discussion papers. Difference in differences and regression discontinuity analysis are conducted to elicit the spillover patterns. This study finds that the spillover effect to average economics paper demand is positive and statistically significant. It seems that hit papers increase the exposure of previously less downloaded papers. We find that part of the spillover effect could be attributable to Internet search engines' influence on browsing behavior. Conforming to expected patterns, papers residing on the same web page as the hit paper evidence very significant increases in downloads which also supports the spillover thesis. A11, C21. 97K80.

  13. Photoelectrolysis at the oxide-electrolyte interface as interpreted through the 'transition' layer model

    Science.gov (United States)

    Kalia, R. K.; Weber, Michael F.; Schumacher, L.; Dignam, M. J.

    1980-12-01

    A transition layer model of the oxide-electrolyte interface, proposed earlier by one of us, is outlined and then examined in the light of experimental data relating primarily to photoelectrolysis of water at semiconducting oxide electrodes. The model provides useful insight into the behaviour of the system and allows a calculation of thc minimum bias potential needed for photoelectrolysis, thus illuminating the origin of the requirement for such an external bias. In order to electrolyse water without a bias, the model requires an n-type oxide to be sufficiently reduced so that it is thermodynamically capable of chemically reducing water to produce hydrogen at 1 atm pressure. Similarly, for bias-free operation, a p-type metal oxide must be thermodynamically unstable with respect to the release of oxygen at 1 atm pressure. In the face of these requirements it is apparent that oxide stability is bound to be in general a serious problem for nonstoichiometric single metal oxides.

  14. Global atmospheric model for mercury including oxidation by bromine atoms

    Directory of Open Access Journals (Sweden)

    C. D. Holmes

    2010-12-01

    Full Text Available Global models of atmospheric mercury generally assume that gas-phase OH and ozone are the main oxidants converting Hg0 to HgII and thus driving mercury deposition to ecosystems. However, thermodynamic considerations argue against the importance of these reactions. We demonstrate here the viability of atomic bromine (Br as an alternative Hg0 oxidant. We conduct a global 3-D simulation with the GEOS-Chem model assuming gas-phase Br to be the sole Hg0 oxidant (Hg + Br model and compare to the previous version of the model with OH and ozone as the sole oxidants (Hg + OH/O3 model. We specify global 3-D Br concentration fields based on our best understanding of tropospheric and stratospheric Br chemistry. In both the Hg + Br and Hg + OH/O3 models, we add an aqueous photochemical reduction of HgII in cloud to impose a tropospheric lifetime for mercury of 6.5 months against deposition, as needed to reconcile observed total gaseous mercury (TGM concentrations with current estimates of anthropogenic emissions. This added reduction would not be necessary in the Hg + Br model if we adjusted the Br oxidation kinetics downward within their range of uncertainty. We find that the Hg + Br and Hg + OH/O3 models are equally capable of reproducing the spatial distribution of TGM and its seasonal cycle at northern mid-latitudes. The Hg + Br model shows a steeper decline of TGM concentrations from the tropics to southern mid-latitudes. Only the Hg + Br model can reproduce the springtime depletion and summer rebound of TGM observed at polar sites; the snowpack component of GEOS-Chem suggests that 40% of HgII deposited to snow in the Arctic is transferred to the ocean and land reservoirs, amounting to a net deposition flux to the Arctic of 60 Mg a−1. Summertime events of depleted Hg0 at Antarctic sites due to subsidence are much better simulated by

  15. Oxidation in air of two refractory alloys (Nicral D and Hastelloy X) at 900 and 1100 deg. C

    International Nuclear Information System (INIS)

    Sannier, J.; Dominget, R.; Darras, R.

    1960-01-01

    The oxidation in air of two refractory alloys (Nicral D and Hastelloy X) has been studied at 900 and 1100 deg. C, by means of recording thermo-balances and microscopic cross section examination. At 900 deg. C, the surface oxidation rates of the two alloys are quite similar, but at 1100 deg. C the alloy Nicral D oxidizes faster than the alloy Hastelloy X. On the other hand, after heating at 1100 deg. C for 150 hours, Nicral D shows both intergranular oxidation and a small amount of internal oxidation, whereas Hastelloy X is especially subject to internal oxidation. In addition, two descaling methods were compared: an electrolytic method, in a sodium hydroxide-sodium carbonate bath, and a chemical method using a sodium nitrate-sodium peroxide bath; the latter appears suitable only for Hastelloy X. Reprint of a paper published in Journal of nuclear materials, 3, p. 213-225, 1959 [fr

  16. Computer modelling of radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Khvostunov, Igor K.; Nikjoo, Hooshang

    2002-01-01

    Radiation-induced genomic instability and bystander effects are now well established consequences of exposure of living cells to ionising radiation. It has been observed that cells not directly hit by radiation tracks may still exhibit radiation effects. We present a quantitative modelling of the radiation-induced bystander effect based on a diffusion model of spreading the bystander signal. The model assumes the bystander factor to be a protein of low molecular weight, given out by the hit cell, diffusing in the medium and reacting with non-hit cells. The model calculations successfully predict the results of cell survival in an irradiated conditioned medium. The model predicts the shape of dose-effect relationship for cell survival and oncogenic transformation induced by broad-beam and micro-beam irradiation by alpha-particles. (author)

  17. Behaviour of defective CANDU fuel: fuel oxidation kinetic and thermodynamic modelling

    International Nuclear Information System (INIS)

    Higgs, J.

    2005-01-01

    The thermal performance of operating CANDU fuel under defect conditions is affected by the ingress of heavy water into the fuel element. A mechanistic model has been developed to predict the extent of fuel oxidation in defective fuel and its affect on fuel thermal performance. A thermodynamic treatment of such oxidized fuel has been performed as a basis for the boundary conditions in the kinetic model. Both the kinetic and thermodynamic models have been benchmarked against recent experimental work. (author)

  18. An in vitro liver model--assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Gaiser, Birgit K; Hutchison, Gary R

    2012-01-01

    Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials (NM) have been shown to translocate to the liver. Since oxidative stress has been implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five...... titanium dioxide (TiO2), two zinc oxide (ZnO), two multi-walled carbon nanotubes (MWCNT) and one silver (Ag) NM) on oxidative responses of C3A cell line as a model for potential detrimental properties of nanomaterials on the liver.......Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials (NM) have been shown to translocate to the liver. Since oxidative stress has been implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five...

  19. Evidence for single metal two electron oxidative addition and reductive elimination at uranium.

    Science.gov (United States)

    Gardner, Benedict M; Kefalidis, Christos E; Lu, Erli; Patel, Dipti; McInnes, Eric J L; Tuna, Floriana; Wooles, Ashley J; Maron, Laurent; Liddle, Stephen T

    2017-12-01

    Reversible single-metal two-electron oxidative addition and reductive elimination are common fundamental reactions for transition metals that underpin major catalytic transformations. However, these reactions have never been observed together in the f-block because these metals exhibit irreversible one- or multi-electron oxidation or reduction reactions. Here we report that azobenzene oxidises sterically and electronically unsaturated uranium(III) complexes to afford a uranium(V)-imido complex in a reaction that satisfies all criteria of a single-metal two-electron oxidative addition. Thermolysis of this complex promotes extrusion of azobenzene, where H-/D-isotopic labelling finds no isotopomer cross-over and the non-reactivity of a nitrene-trap suggests that nitrenes are not generated and thus a reductive elimination has occurred. Though not optimally balanced in this case, this work presents evidence that classical d-block redox chemistry can be performed reversibly by f-block metals, and that uranium can thus mimic elementary transition metal reactivity, which may lead to the discovery of new f-block catalysis.

  20. Efficacy of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinone derivatives against different Trypanosoma cruzi discrete type units: Identification of a promising hit compound.

    Science.gov (United States)

    Lara, L S; Moreira, C S; Calvet, C M; Lechuga, G C; Souza, R S; Bourguignon, S C; Ferreira, V F; Rocha, D; Pereira, M C S

    2018-01-20

    The limited efficacy of benznidazole (Bz) indicated by failures of current Phase II clinical trials emphasizes the urgent need to identify new drugs with improved safety and efficacy for treatment of Chagas disease (CD). Herein, we analyzed the efficacy of a series of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against different Trypanosoma cruzi discrete type units (DTUs) of relevant clinical forms of CD. Cytotoxic and trypanocidal effect of naphthoquinone derivatives were assessed in mammalian cells, trypomastigotes and intracellular amastigotes using, luminescent assays (CellTiter-Glo and T. cruzi Dm28c-luciferase) and/or counting with a light microscope. Reactive oxygen species (ROS) production and intracellular targets of promising compounds were assessed with 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCFDA) probe and ultrastructural analysis, respectively. ADMET properties were analyzed by in silico modeling. Most of the compounds showed low cytotoxic effect. Only two compounds (Compounds 2 and 11) had IC 50 values lower than Bz, showing higher susceptibility of bloodstream trypomastigotes. Compound 2 exhibited greater efficacy against trypomastigotes from different T. cruzi DTUs, even better than Bz against Brazil and CL strains. Ultrastructural analysis revealed changes in intracellular compartments, suggesting autophagy as one possible mechanism of action. Oxidative stress, induced by Compound 2, resulted in elevated level of ROS, leading to parasite death. Compound 2 was also effective against intracellular amastigotes, showing high selectivity index. ADMET analysis predicted good oral bioavailability, reduced drug metabolism and no carcinogenic potential for Compound 2. The data highlight Compound 2 as a hit compound and stimulate further structural and pharmacological optimization to potentiate its trypanocidal activity and selectivity. Copyright © 2017. Published by Elsevier Masson SAS.