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Sample records for range blastp hit

  1. CUDA-BLASTP: accelerating BLASTP on CUDA-enabled graphics hardware.

    Science.gov (United States)

    Liu, Weiguo; Schmidt, Bertil; Müller-Wittig, Wolfgang

    2011-01-01

    Scanning protein sequence database is an often repeated task in computational biology and bioinformatics. However, scanning large protein databases, such as GenBank, with popular tools such as BLASTP requires long runtimes on sequential architectures. Due to the continuing rapid growth of sequence databases, there is a high demand to accelerate this task. In this paper, we demonstrate how GPUs, powered by the Compute Unified Device Architecture (CUDA), can be used as an efficient computational platform to accelerate the BLASTP algorithm. In order to exploit the GPU’s capabilities for accelerating BLASTP, we have used a compressed deterministic finite state automaton for hit detection as well as a hybrid parallelization scheme. Our implementation achieves speedups up to 10.0 on an NVIDIA GeForce GTX 295 GPU compared to the sequential NCBI BLASTP 2.2.22. CUDA-BLASTP source code which is available at https://sites.google.com/site/liuweiguohome/software.

  2. cuBLASTP: Fine-Grained Parallelization of Protein Sequence Search on CPU+GPU.

    Science.gov (United States)

    Zhang, Jing; Wang, Hao; Feng, Wu-Chun

    2017-01-01

    BLAST, short for Basic Local Alignment Search Tool, is a ubiquitous tool used in the life sciences for pairwise sequence search. However, with the advent of next-generation sequencing (NGS), whether at the outset or downstream from NGS, the exponential growth of sequence databases is outstripping our ability to analyze the data. While recent studies have utilized the graphics processing unit (GPU) to speedup the BLAST algorithm for searching protein sequences (i.e., BLASTP), these studies use coarse-grained parallelism, where one sequence alignment is mapped to only one thread. Such an approach does not efficiently utilize the capabilities of a GPU, particularly due to the irregularity of BLASTP in both execution paths and memory-access patterns. To address the above shortcomings, we present a fine-grained approach to parallelize BLASTP, where each individual phase of sequence search is mapped to many threads on a GPU. This approach, which we refer to as cuBLASTP, reorders data-access patterns and reduces divergent branches of the most time-consuming phases (i.e., hit detection and ungapped extension). In addition, cuBLASTP optimizes the remaining phases (i.e., gapped extension and alignment with trace back) on a multicore CPU and overlaps their execution with the phases running on the GPU.

  3. 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.

  4. CBI students: target hit!

    CERN Multimedia

    CERN Bulletin

    2015-01-01

    The students on the third Challenge Based Innovation (CBI) @CERN course have been working on their society-oriented projects since September. Last Thursday, 10 December, they finally presented all their proofs-of-concept and prototypes to a packed audience at IdeaSquare.   CBI students presenting their projects at IdeaSquare (Image: Carlos Yarza/IED Barcelona). Twenty-seven students from four universities and over ten countries have been working on the CERN CBI course since last September. Labour mobility, food safety, literacy and water safety are the four projects that the students have been working on. Thanks to help and inspiration from a wide range of people working at CERN, especially in the Knowledge Transfer group, the students have redefined and focused their original challenges and have developed four concepts to solve societal challenges: * Team Bohr developed a concept for encouraging labour mobility and talent exchange in Europe, combining data analysis and existing online ...

  5. 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

  6. Mixed Hitting-Time Models

    NARCIS (Netherlands)

    Abbring, J.H.

    2007-01-01

    We study a mixed hitting-time (MHT) model that specifies durations as the first time a Lévy process - a continuous-time process with stationary and independent increments� crosses a heterogeneous threshold. Such models are of substantial interest because they can be reduced from optimal-stopping

  7. Mixed hitting-time models

    NARCIS (Netherlands)

    Abbring, J.H.

    2012-01-01

    We study mixed hitting-time models that specify durations as the first time a Lévy process—a continuous-time process with stationary and independent increments—crosses a heterogeneous threshold. Such models are of substantial interest because they can be deduced from optimal-stopping models with

  8. When science hits the headlines...

    Directory of Open Access Journals (Sweden)

    Greco Pietro

    2002-09-01

    Full Text Available A survey has been recently carried out for the first time in Italy concerning science communication through the media and the result has been that science hits the headlines. It is often front-page news in the press and it is also often among the main points of the news on TV.

  9. Formulation of the multi-hit model with a non-Poisson distribution of hits.

    Science.gov (United States)

    Vassiliev, Oleg N

    2012-07-15

    We proposed a formulation of the multi-hit single-target model in which the Poisson distribution of hits was replaced by a combination of two distributions: one for the number of particles entering the target and one for the number of hits a particle entering the target produces. Such an approach reflects the fact that radiation damage is a result of two different random processes: particle emission by a radiation source and interaction of particles with matter inside the target. Poisson distribution is well justified for the first of the two processes. The second distribution depends on how a hit is defined. To test our approach, we assumed that the second distribution was also a Poisson distribution. The two distributions combined resulted in a non-Poisson distribution. We tested the proposed model by comparing it with previously reported data for DNA single- and double-strand breaks induced by protons and electrons, for survival of a range of cell lines, and variation of the initial slopes of survival curves with radiation quality for heavy-ion beams. Analysis of cell survival equations for this new model showed that they had realistic properties overall, such as the initial and high-dose slopes of survival curves, the shoulder, and relative biological effectiveness (RBE) In most cases tested, a better fit of survival curves was achieved with the new model than with the linear-quadratic model. The results also suggested that the proposed approach may extend the multi-hit model beyond its traditional role in analysis of survival curves to predicting effects of radiation quality and analysis of DNA strand breaks. Our model, although conceptually simple, performed well in all tests. The model was able to consistently fit data for both cell survival and DNA single- and double-strand breaks. It correctly predicted the dependence of radiation effects on parameters of radiation quality. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Hitting is contagious in baseball: evidence from long hitting streaks.

    Directory of Open Access Journals (Sweden)

    Joel R Bock

    Full Text Available Data analysis is used to test the hypothesis that "hitting is contagious". A statistical model is described to study the effect of a hot hitter upon his teammates' batting during a consecutive game hitting streak. Box score data for entire seasons comprising [Formula: see text] streaks of length [Formula: see text] games, including a total [Formula: see text] observations were compiled. Treatment and control sample groups ([Formula: see text] were constructed from core lineups of players on the streaking batter's team. The percentile method bootstrap was used to calculate [Formula: see text] confidence intervals for statistics representing differences in the mean distributions of two batting statistics between groups. Batters in the treatment group (hot streak active showed statistically significant improvements in hitting performance, as compared against the control. Mean [Formula: see text] for the treatment group was found to be [Formula: see text] to [Formula: see text] percentage points higher during hot streaks (mean difference increased [Formula: see text] points, while the batting heat index [Formula: see text] introduced here was observed to increase by [Formula: see text] points. For each performance statistic, the null hypothesis was rejected at the [Formula: see text] significance level. We conclude that the evidence suggests the potential existence of a "statistical contagion effect". Psychological mechanisms essential to the empirical results are suggested, as several studies from the scientific literature lend credence to contagious phenomena in sports. Causal inference from these results is difficult, but we suggest and discuss several latent variables that may contribute to the observed results, and offer possible directions for future research.

  11. 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…

  12. Hitting Is Contagious: Experience and Action Induction

    Science.gov (United States)

    Gray, Rob; Beilock, Sian L.

    2011-01-01

    In baseball, it is believed that "hitting is contagious," that is, probability of success increases if the previous few batters get a hit. Could this effect be partially explained by action induction--that is, the tendency to perform an action related to one that has just been observed? A simulation was used to investigate the effect of inducing…

  13. 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 factor......-users. The CTA methodology is based on a Socio-technical understanding of technological development as an open ended, emergent process. The CTA was used during the EHR development process in the Region of North Jutland where it proved successful inproviding learning and feedback between all relevant groups...... in HIT development. A new evaluation methodology, including an analytical framework, has been developed specifically for HIT development: Constructive Technology Assessment (CTA) for HIT. It offers solutions to both the problems associated with summative technology evaluation and a way to involve end...

  14. 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.

  15. Optical spectrosopy of HiTS supernovae

    Science.gov (United States)

    Anderson, J.; Forster, F.; Smith, C.; Vivas, K.; Pignata, G.; Olivares, F.; Hamuy, M.; Martin, J. San; Maureira, J. C.; Cabrera, G.; Gonzalez-Gaitan, S.; Galbany, L.; Bufano, F.; de Jaeger, T.; Hsiao, E.; Munoz, R.; Vera, E.

    2015-04-01

    We report optical wavelength spectroscopy obtained using the Goodman instrument mounted on the SOAR at CTIO on UT 2015-03-30, for two supernovae discovered by HiTS, the High Cadence Transient Survey (see ATELs #7289, #7290).

  16. Optical Diagnostics on HIT-SI3

    Science.gov (United States)

    Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

    2016-10-01

    Interferometry and Thomson Scattering are implemented on the HIT-SI3 (Helicity Injected Torus - Steady Inductive 3) device to provide time resolved measurements of electron density and spatially resolved measurements of electron temperature, respectively. HIT-SI3 is a modification of the original HIT-SI apparatus that uses three injectors instead of two. The scientific aim of HIT-SI3 is to develop a deeper understanding of how injector behavior and interactions influence current drive and spheromak stability. The interferometer system makes use of an intermediate frequency between two parallel 184.3 μm Far-Infrared (FIR) laser cavities which are optically pumped by a CO2 laser. The phase shift in this beat frequency due to the plasma index of refraction is used to calculate the line-integrated electron density. To measure the electron temperature, Thomson Scattered light from a 20 J (1 GW pulse) Ruby laser off of free electrons in the HIT-SI3 plasma is measured simultaneously at four locations across the spheromak (nominally 23 cm minor radius). Polychromators bin the collected light into 3 spectral bands to detect the relative level of scattering. Work supported by the D.O.E.

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

    Science.gov (United States)

    2012-04-18

    ..., and privacy and security. Other groups are convened to address specific issues as needed, such as the... Vocabulary Task Force. HIT Standards Committee's Schedule for the Assessment of HIT Policy Committee... those priority areas, it will: (A) Direct the appropriate workgroup or other special group to develop a...

  18. A hemispherical imaging and tracking (HIT) system

    Science.gov (United States)

    Gilbert, John A.; Fair, Sara B.; Caldwell, Scott E.; Gronner, Sally J.

    1992-05-01

    A hemispherical imaging and tracking (HIT) system is described which is used for an interceptor designed to acquire, select, home, and hit-to-kill reentry vehicle targets from intercontinental ballistic missiles. The system provides a sizable field of view, over which a target may be tracked and yields a unique and distinctive optical signal when the system is 'on target'. The system has an infinite depth of focus and no moving parts are required for imaging within a hemisphere. Critical alignment of the HIT system is based on the comparison of signals captured through different points on an annular window. Assuming that the perturbations are radially symmetric, errors may be eliminated during the subtraction.

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

    Directory of Open Access Journals (Sweden)

    Yu-Lei Wan

    Full Text Available 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.

  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. Epigenetic reprogramming: Prdm14 hits the accelerator

    NARCIS (Netherlands)

    Geijsen, N.|info:eu-repo/dai/nl/194303403

    2012-01-01

    The EMBO Journal (2012) 31, 2247 - 2248 doi:10.1038/emboj.2012.117 Published online: 20 April 2012 There is an Article (May 2012) associated with this Have you seen?. Epigenetic reprogramming: Prdm14 hits the accelerator Niels Geijsen1 Hubrecht Institute KNAW, School of Veterinary Medicine, Utrecht

  3. 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.

  4. 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

  5. The Separation Measurement of P -Hit and N -Hit Charge Sharing With an ``S-Like'' Inverter Chains Test Structure

    Science.gov (United States)

    Huang, Pengcheng; Chen, Shuming; Chen, Jianjun; Liang, Bin; Song, Ruiqiang

    2017-04-01

    In this paper, an “S-like” inverter chains (SLIC) test structure is designed for the separation measurement of N-hit and P-hit charge sharing. The heavy-ion experiments were performed in 65-nm bulk dual-well and triple-well technology, and the N-hit and P-hit pulse quenching (PQ) span is attained. The results has verified the ability of the “SLIC” test structure to characterize P-hit and N-hit PQ, and the results also indicate that the N+ deep well can enhance the action extent of N-hit charge sharing greatly though it will reduce the action extent P-hit charge sharing.

  6. Schizophrenia two-hit hypothesis in velo-cardio facial syndrome.

    Science.gov (United States)

    Williams, Hywel J; Monks, Stephen; Murphy, Kieran C; Kirov, George; O'Donovan, Michael C; Owen, Michael J

    2013-03-01

    Deletion of chr22q11 gives rise to velo-cardio facial syndrome (VCFS) and increases schizophrenia risk. The source of this elevated risk although unknown could result from stochastic, environmental, or genetic factors, the latter encompassing a range of complexity from polygenic mechanisms to "second-hit" mutations. For this study we tested the two-hit hypothesis where additional risk is conferred through a second CNV. We identified large (>100 kb) CNVs in 48 VCFS cases (23 with psychosis--25 without) and show in the psychotic VCFS group there is a significant (P = 0.02) increase in the average size of CNVs (354-227 kb). To identify second-hit loci we focused on individuals possessing gene-centric CNVs and through literature mining identified 4 (31%) psychotic VCFS individuals (n = 13) that overlapped loci previously implicated in neuropsychiatric disorders compared to 1 (10%) from the non-psychotic VCFS individuals (n = 10). For replication 17 VCFS patients with schizophrenia from the molecular genetics of schizophrenia dataset were used to identify further CNVs. Thirteen individuals possessing gene-centric CNVs were identified including 3 (23%) individuals possessing a potential second-hit, taking the overall total in the psychotic VCFS group (n = 26) to 7 (27%) potential second-hit loci. Notably a deletion in a psychotic VCFS patient at 2q23.1 hit the gene MBD5 which when deleted gives rise to intellectual disability, epilepsy, and autistic features. Through this study we potentially extend this phenotypic spectrum to include schizophrenia. Our results suggest the two-hit hypothesis may be relevant to a proportion of VCFS patients with psychosis but sample sizes are small and further studies warranted. Copyright © 2013 Wiley Periodicals, Inc.

  7. Cutaneous presentation of Double Hit Lymphoma

    Directory of Open Access Journals (Sweden)

    Yousef Khelfa MD, FACP

    2016-04-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin lymphoma (NHL, representing approximately 25% of diagnosed NHL. DLBCL is heterogeneous disease both clinically and genetically. The 3 most common chromosomal translocations in DLBCL involve the oncogenes BCL2, BCL6, and MYC. Double hit (DH DLBCL is an aggressive form in which MYC rearrangement is associated with either BCL2 or BCL6 rearrangement. Patients typically present with a rapidly growing mass, often with B symptoms. Extranodal disease is often present. Though there is a paucity of prospective trials in this subtype, double hit lymphoma (DHL has been linked to very poor outcomes when patients are treated with standard R-CHOP. There is, therefore, a lack of consensus regarding the standard treatment for DHL. Several retrospective analyses have been conducted to help guide treatment of this disease. These suggest that DA EPOCH-R may be the most promising regimen and that achievement of complete resolution predicts better long-term outcomes.

  8. 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.

  9. Towards multi-hit readout of TPCs for exotic beam tracking

    Energy Technology Data Exchange (ETDEWEB)

    Allred, Timothy; Enders, Joachim; Hucka, Jan-Paul; Schlemme, Steffen [Institut fuer Kernphysik, TU Darmstadt (Germany); Nociforo, Chiara; Pietri, Stephane; Prochazka, Andrej [GSI Helmholtzzentrum fuer Schwerionenforschung (Germany)

    2015-07-01

    The Super-FRS beam diagnostics system supports the set up and adjustment of the separator and provides tracking and event-by-event particle identification. A TPC-type detector with GEM amplification and with multi-hit single-strip readout is proposed to be used as a tracking detector. The main challenges for such a detector are position resolution below 1 mm, high dynamic range (1000) and high-efficiency tracking up to 10 MHz ion rate. One of the planned improvements towards a high-rate capability of single-ion tracking is the multi-hit readout of the TPC detectors. Present TPC detectors with delay-line readout were tested with multihit electronics at the GSI fragment separator FRS with Au beam at 1 GeV/nucl. up to 150 kHz. Results are presented in comparison to single-hit readout.

  10. Arabidopsis CDS blastp result - KOME | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us KOME Ar...0.18908/lsdba.nbdc00120-017 Description of data contents Results of blastp searches against Arabidopsis thal...on method Predicted CDSs of Arabidopsis thaliana used for the searches were obtained from the TIGR Arabidops...the full-length cDNA sequences against predicted CDSs of Arabidopsis thaliana. The results are filtered with...[ Credits ] English ]; } else if ( url.search(//en//) != -1 ) { url = url.replace(/

  11. Permanent Ocular Injury Following Paintball Pellet Hit: A Medicolegal Case.

    Science.gov (United States)

    Ghazanfari-Nasrabad, Mahdi; Amrollahi-Sharifabadi, Mohammad; Kargar-Bideh, Omidreza; Azizi-Sharifabad, Saeed

    2016-01-01

    Paintball is a ubiquitous recreation, with severe and occasionally irreversible injuries. In this study, a rare medicolegal case of paintball-related closed globe blunt ocular injury was described. An 18-year-old boy who was hit in his right eye by a paintball pellet presented with severe eye pain and blurred vision. Ophthalmologic examinations showed lid edema, conjunctival hyperemia, conjunctival laceration, subconjunctival hemorrhage, corneal edema, anterior vitreous hemorrhage, congested sclera, commotio retinae, vitreous hemorrhage, retinal hemorrhage, macular edema, and macular hole. After maximum medical improvement, the patient who sustained incurable maculopathy and decreased visual acuity was referred to the legal medicine center for appraisal of the impairment. AMA Guides was used to assess the impairment of the functional vision. Despite his monocular visual defect, the patient was rated in the range of mild vision loss namely AMA class 1 with 22 percentage visual system impairment. © 2015 American Academy of Forensic Sciences.

  12. One-hit wonders of genomic instability

    Directory of Open Access Journals (Sweden)

    Strunnikov Alexander V

    2010-05-01

    Full Text Available Abstract Recent data show that cells from many cancers exhibit massive chromosome instability. The traditional view is that the gradual accumulation of mutations in genes involved in transcriptional regulation and cell cycle controls results in tumor development. This, however, does not exclude the possibility that some mutations could be more potent than others in destabilizing the genome by targeting both chromosomal integrity and corresponding checkpoint mechanisms simultaneously. Three such examples of "single-hit" lesions potentially leading to heritable genome destabilization are discussed. They include: failure to release sister chromatid cohesion due to the incomplete proteolytic cleavage of cohesin; massive merotelic kinetochore misattachments upon condensin depletion; and chromosome under-replication. In all three cases, cells fail to detect potential chromosomal bridges before anaphase entry, indicating that there is a basic cell cycle requirement to maintain a degree of sister chromatid bridging that is not recognizable as chromosomal damage.

  13. Screening of TB Actives for Activity against Nontuberculous Mycobacteria Delivers High Hit Rates

    Directory of Open Access Journals (Sweden)

    Jian Liang Low

    2017-08-01

    Full Text Available The prevalence of lung disease due to infections with nontuberculous mycobacteria (NTM has been increasing and surpassed tuberculosis (TB in some countries. Treatment outcomes are often unsatisfactory, highlighting an urgent need for new anti-NTM medications. Although NTM in general do not respond well to TB specific drugs, the similarities between NTM and Mycobacterium tuberculosis at the molecular and cell structural level suggest that compound libraries active against TB could be leveraged for NTM drug discovery. Here we tested this hypothesis. The Pathogen Box from the Medicines for Malaria Venture (MMV is a collection of 400 diverse drug-like compounds, among which 129 are known to be active against M. tuberculosis. By screening this compound collection against two NTM species, Mycobacterium abscessus and Mycobacterium avium, we showed that indeed the hit rates for NTM among TB active compounds is significantly higher compared to compounds that are not active against TB. MIC/dose response confirmation identified 10 top hits. Bactericidal activity determination demonstrated attractive potency for a subset of the confirmed hits. In vivo pharmacokinetic profiling showed that some of the compounds present reasonable starting points for medicinal chemistry programs. Three of the top hits were oxazolidinones, suggesting the potential for repositioning this class of protein synthesis inhibitors to replace linezolid which suffers from low potency. Two hits were inhibitors of the trehalose monomycolate transporter MmpL3, suggesting that this transmembrane protein may be an attractive target for NTM. Other hits are predicted to target a range of functions, including cell division (FtsZ, DNA gyrase (GyrB, dihydrofolate reductase, RNA polymerase and ABC transporters. In conclusion, our study showed that screening TB active compounds for activity against NTM resulted in high hit rates, suggesting that this may be an attractive approach to kick start NTM

  14. 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)

  15. 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

  16. For Some Skin Cancers, Targeted Drug Hits the Mark

    Science.gov (United States)

    ... Cancer Skin Cancer Screening Research For Some Skin Cancers, Targeted Drug Hits the Mark Adapted from the NCI Cancer ... this page included, e.g., “For Some Skin Cancers, Targeted Drug Hits the Mark was originally published by the ...

  17. Recent Improvements in the SHIELD-HIT Code

    DEFF Research Database (Denmark)

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

    2012-01-01

    reproduces experimental measurements with high accuracy. Conclusions: SHIELD-HIT is now faster, more user-friendly and accurate, and has an enhanced functionality with some features being currently unique to SHIELD-HIT. The possibility of data file exchange with existing treatment planning software for heavy...

  18. The first neutron beam hits EAR2

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    On 25 July 2014, about a year after construction work began, the Experimental Area 2 (EAR2) of CERN’s neutron facility n_TOF recorded its first beam. Unique in many aspects, EAR2 will start its rich programme of experimental physics this autumn.   The last part of the EAR2 beamline: the neutrons come from the underground target and reach the top of the beamline, where they hit the samples. Built about 20 metres above the neutron production target, EAR2 is in fact a bunker connected to the n_TOF underground facilities via a duct 80 cm in diameter, where the beamline is installed. The feet of the bunker support pillars are located on the concrete structure of the n_TOF tunnel and part of the structure lies above the old ISR building. A beam dump located on the roof of the building completes the structure. Neutrons are used by physicists to study neutron-induced reactions with applications in a number of fields, including nuclear waste transmutation, nuclear technology, nuclear astrop...

  19. Hits, Fhits and Nits: beyond enzymatic function.

    Science.gov (United States)

    Huebner, Kay; Saldivar, Joshua C; Sun, Jin; Shibata, Hidetaka; Druck, Teresa

    2011-01-01

    We have briefly summarized what is known about these proteins, but in closing wish to feature the outstanding questions. Hint1 was discovered mistakenly as an inhibitor of Protein Kinase C and designated Pkci, a designation that still confuses the literature. The other Hint family members were discovered by homology to Hint1. Aprataxin was discovered as a result of the hunt for a gene responsible for AOA1. Fhit was discovered through cloning of a familial chromosome translocation breakpoint on chromosome 3 that interrupts the large FHIT gene within an intron, in the FRA3B chromosome region (Ohta et al., 1996), now known to be the region of the human genome most susceptible to DNA damage due to replication stress (Durkin et al., 2008). The NitFhit fusion genewas discovered during searches for Fhit homologs in flies and worms because the fly/worm Nit polypeptide is fused to the 5'-end of the Fhit gene; the mammalian Nit gene family was discovered because of the NitFhit fusion gene, in searches for homologs to the Nit polypeptide of the NitFhit gene. Each of the Hit family member proteins is reported to have enzymatic activities toward putative substrates involving nucleosides or dinucleosides. Most surprisingly, each of the Hit family proteins discussed has been implicated in important DNA damage response pathways and/or tumor suppression pathways. And for each of them it has been difficult to assign definite substrates, to know if the substrates and catalytic products have biological functions, to know if that function is related to the DNA damage response and suppressor functions, and to precisely define the pathways through which tumor suppression occurs. When the fly Nit sequence was found at the 5'-end of the fly Fhit gene, this gene was hailed as a Rosetta stone gene/protein that would help in discovery of the function of Fhit, because the Nit protein should be in the same signal pathway (Pace et al., 2000). However, the mammalian Nit family proteins have

  20. The realization of HITS algorithm based on MapReduce

    Directory of Open Access Journals (Sweden)

    YU Hui

    2013-10-01

    Full Text Available In this paper,we use Hadoop to redesign HITS algrothim according to the research of HITS algrothim and the cloud computing framework Hadoop which base on MapReduce progaming model.Meanwhile,we analysize the effect of diffenent blocksize and cluster scale in influent on the efficiency of the algrothim.The results shows that the efficiency reduced with the blocksize increased,while the efficiency increased gradually when cluster scale had been expanded properly.

  1. A short note on hit-and-miss hyperspaces

    Directory of Open Access Journals (Sweden)

    René Bartsch

    2003-10-01

    Full Text Available Based on some set-theoretical observations, compactness results are given for general hit-and-miss hyperspaces. Compactness here is sometimes viewed splitting into “κ-Lindelöfness” and “κ-compactness” for cardinals κ. To focus only hit-and-miss structures, could look quite old-fashioned, but some importance, at least for the techniques, is given by a recent result, [8], of Som Naimpally, to who this article is hearty dedicated.

  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. 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.

  4. 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

  5. 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.

  6. B-HIT - A Tool for Harvesting and Indexing Biodiversity Data.

    Science.gov (United States)

    Kelbert, Patricia; Droege, Gabriele; Barker, Katharine; Braak, Kyle; Cawsey, E Margaret; Coddington, Jonathan; Robertson, Tim; Whitacre, Jamie; Güntsch, Anton

    2015-01-01

    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.

  7. 42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

    Science.gov (United States)

    2010-10-01

    ... and future visions: (1) A baseline assessment of the current HIT landscape environment in the State...) Description of the HIT “as-is” landscape; (ii) Description of the HIT “to-be” landscape; and (iii) HIT roadmap... Medicaid Information Technology Architecture (MITA) principles as described in the Medicaid Information...

  8. Applications of Biophysics in High-Throughput Screening Hit Validation.

    Science.gov (United States)

    Genick, Christine Clougherty; Barlier, Danielle; Monna, Dominique; Brunner, Reto; Bé, Céline; Scheufler, Clemens; Ottl, Johannes

    2014-06-01

    For approximately a decade, biophysical methods have been used to validate positive hits selected from high-throughput screening (HTS) campaigns with the goal to verify binding interactions using label-free assays. By applying label-free readouts, screen artifacts created by compound interference and fluorescence are discovered, enabling further characterization of the hits for their target specificity and selectivity. The use of several biophysical methods to extract this type of high-content information is required to prevent the promotion of false positives to the next level of hit validation and to select the best candidates for further chemical optimization. The typical technologies applied in this arena include dynamic light scattering, turbidometry, resonance waveguide, surface plasmon resonance, differential scanning fluorimetry, mass spectrometry, and others. Each technology can provide different types of information to enable the characterization of the binding interaction. Thus, these technologies can be incorporated in a hit-validation strategy not only according to the profile of chemical matter that is desired by the medicinal chemists, but also in a manner that is in agreement with the target protein's amenability to the screening format. Here, we present the results of screening strategies using biophysics with the objective to evaluate the approaches, discuss the advantages and challenges, and summarize the benefits in reference to lead discovery. In summary, the biophysics screens presented here demonstrated various hit rates from a list of ~2000 preselected, IC50-validated hits from HTS (an IC50 is the inhibitor concentration at which 50% inhibition of activity is observed). There are several lessons learned from these biophysical screens, which will be discussed in this article. © 2014 Society for Laboratory Automation and Screening.

  9. Experience with Video Head Impulse Testing (vHIT

    Directory of Open Access Journals (Sweden)

    Carmen ÁLVAREZ-SANTACRUZ

    2017-03-01

    Full Text Available Introduction and objective: The diagnosis and study of vestibular pathology has been always guided by the medical history, exploration and caloric test. The caloric test has some limitations because it only allows the study of horizontal semicircular canal and it is also poorly tolerated by patients. Alternatively, the vHIT (Video Head Impulse Test, allows the analysis of all semicircular channels being quicker to perform and less obtrusive. The objective of the following study is to reflect our initial experience with the vHIT and compare it with another diagnosis tests. Method: This is a observational, prospective and descriptive study, of one year of observation in our Healthcare center for all patients who described symptoms of dizziness, unsteadiness or vertigo. Results: A total of 155 patients were included. There was a clear predominance of females, being Meniere's disease the most frequently diagnosed entity. The diagnosis was reached by vHIT. Caloric test was also performed in patients without definite or doubt in the diagnosis. With the data, the statistical relationships were established, being significant between sex with vestibular neuritis and vestibular migraine. There was a statistically significant relationship between vestibule-ocular reflex and caloric test associated with the previous pathologies. Discussion: The head impulse assisted video is a quick, simple and well tolerated technique without adverse symptoms like the caloric test. The disparities of results are due to differences in the stimulated frequencies, being the vHIT more physiological. Conclusions: vHIT facilitates the complementary diagnosis of acute pathology, being a well-tolerated technique. However, in pathologies with central compensation the results by vHIT may be normal, requiring the caloric test for better diagnostic approach.

  10. HitWalker2: visual analytics for precision medicine and beyond.

    Science.gov (United States)

    Bottomly, Daniel; McWeeney, Shannon K; Wilmot, Beth

    2016-04-15

    The lack of visualization frameworks to guide interpretation and facilitate discovery is a potential bottleneck for precision medicine, systems genetics and other studies. To address this we have developed an interactive, reproducible, web-based prioritization approach that builds on our earlier work. HitWalker2 is highly flexible and can utilize many data types and prioritization methods based upon available data and desired questions, allowing it to be utilized in a diverse range of studies such as cancer, infectious disease and psychiatric disorders. Source code is freely available at https://github.com/biodev/HitWalker2 and implemented using Python/Django, Neo4j and Javascript (D3.js and jQuery). We support major open source browsers (e.g. Firefox and Chromium/Chrome). wilmotb@ohsu.edu Supplementary data are available at Bioinformatics online. Additional information/instructions are available at https://github.com/biodev/HitWalker2/wiki. © The Author 2015. Published by Oxford University Press.

  11. 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.

  12. 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....... In the latter case, a nonparametric estimator for the first hitting probability is proposed and the asymptotic properties of strong consistency and asymptotic normality are proven. Finally, a numerical application on a five-state system is presented to illustrate the performance of this estimator....

  13. 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.

  14. Double-hit primary unilateral adrenal lymphoma with good outcome

    Directory of Open Access Journals (Sweden)

    Marković Olivera

    2014-01-01

    Full Text Available Introduction. Primary adrenal non-Hodgkin’s lymphoma (NHL is a rare neoplasm with poor prognosis. On the other side, double-hit lymphomas with BCL2 and MYC translocation are characterized by advanced disease stage, extranodal and central nervous system involvements at presentation or disease progression. Case report. We reported a 73-year-old male patient with double-hit primary adrenal lymphoma and preserved adrenal function, showing a favorable clinical course. Computed tomography of abdomen showed a 9 7 cm mass of the left adrenal gland. Laparatomy with left adrenalectomy was done and histological examination revealed diagnosis of a diffuse large B-cell NHL (DLBCL, non-GCB subtype. The patient was treated with 6 cycles of R-CHOP chemotherapy with reduced doses of doxorubicin because of the decreased left verticle ejection fraction. The patient was followed up regularly for 20 months with no evidence of tumor recurrence despite the inherently poor prognostic profile and double-hit phenotype of the disease. Conclusion. R-CHOP chemotherapy in combination with adrenalectomy can be an effective first-line regimen for primary adrenal DLBCL, despite the inherently poor prognostic profile (non-GCB subtype, bulky disease, elevated lactate dehydrogenase and double-hit phenotype of the disease.

  15. 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.

  16. Staff Responses When Parents Hit Children in a Hospital Setting.

    Science.gov (United States)

    Font, Sarah A; Gershoff, Elizabeth T; Taylor, Catherine A; Terreros, Amy; Nielsen-Parker, Monica; Spector, Lisa; Foster, Rebecca H; Budzak Garza, Ann; Olson-Dorff, Denyse

    Physical punishment of children is a prevalent practice that is condemned by most medical professionals given its link with increased risk of child physical abuse and other adverse child outcomes. This study examined the prevalence of parent-to-child hitting in medical settings and the intervention behaviors of staff who witness it. Staff at a children's medical center and a general medical center completed a voluntary, anonymous survey. We used descriptive statistics to examine differences in the experiences of physicians, nurses, and other medical staff. We used logistic regression to predict intervention behaviors among staff who witnessed parent-to-child hitting. Of the hospital staff who completed the survey (N = 2863), we found that 50% of physicians, 24% of nurses, 27% of other direct care staff, and 17% of nondirect care staff witnessed parent-to-child hitting at their medical center in the past year. A majority of physicians, nurses, and other direct care staff reported intervening sometimes or always. Nondirect care staff rarely intervened. Believing staff have the responsibility to intervene, and having comfortable strategies with which to intervene were strongly predictive of intervention behavior. Staff who did not intervene commonly reported that they did not know how to respond. Many medical center staff witness parent-to-child hitting. Although some of the staff reported that they intervened when they witnessed this behavior, the findings indicate that staff may need training to identify when and how they should respond.

  17. 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

  18. 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…

  19. 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...

  20. 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.

  1. Dealing with Hitting and Aggression in the Classroom.

    Science.gov (United States)

    Saifer, Steffen

    1996-01-01

    Notes that while hitting-aggressive behavior is probably the greatest single behavior concern of teachers, children can be taught appropriate behavior for the classroom. Offers tips for dealing with: roughhousing; existing problems; grabbing toys; and war games, guns, or violent play. Suggests allowing children the choice of an alternative…

  2. Soft Play Detection in Shooter Games Using Hit Matrix Analysis

    Directory of Open Access Journals (Sweden)

    Jussi Laasonen

    2015-08-01

    Full Text Available Soft play is a form of cheating where players deliberately play easy against each other. We evaluate different methods for detecting the players engaging in soft play in shooter games using data generated with synthetic players. These methods are used when analysing the hit matrix of the game.

  3. A flow cytometric assay of platelet activation marker P-selectin (CD62P) distinguishes heparin-induced thrombocytopenia (HIT) from HIT with thrombosis (HITT).

    Science.gov (United States)

    Jy, W; Mao, W W; Horstman, L L; Valant, P A; Ahn, Y S

    1999-10-01

    Heparin induced thrombocytopenia (HIT) is a well-known complication of heparin administration but usually resolves upon discontinuation without sequelae. However, a small proportion of HIT patients develop thrombosis associated with HIT, designated as HITT, which is often life-threatening and may lead to gangrene and amputations. Existing laboratory methods of confirming HIT/HITT do not distinguish between HIT and HITT. We report a flow cytometric assay of platelet activation marker CD62P to distinguish the effects of addition of HIT vs. HITT plasma to normal blood. Briefly, normal whole blood was incubated with platelet-poor plasma from 12 patients with HITT, 30 with HIT, and 65 controls, in presence and absence of heparin, and expression of CD62P was assayed by flow cytometry. When the ratios of fluorescent intensity of CD62P with heparin divided by that without heparin were compared, HITT plasma induced significantly higher ratios than HIT plasma (HITT ratios approximately 2.5 vs. HIT ratios approximately 1.2; p HITT patients were positive by this test but only 5 of 30 HIT patients were positive (p HITT from HIT and may be clinically useful in the detection of HITT, allowing early intervention for preventing catastrophic thrombosis.

  4. Computational Breakthrough of Natural Lead Hits from the Genus ofArisaemaagainst 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.

  5. Hitting times of local and global optima in genetic algorithms with very high selection pressure

    Directory of Open Access Journals (Sweden)

    Eremeev Anton V.

    2017-01-01

    Full Text Available The paper is devoted to upper bounds on the expected first hitting times of the sets of local or global optima for non-elitist genetic algorithms with very high selection pressure. The results of this paper extend the range of situations where the upper bounds on the expected runtime are known for genetic algorithms and apply, in particular, to the Canonical Genetic Algorithm. The obtained bounds do not require the probability of fitness-decreasing mutation to be bounded by a constant which is less than one.

  6. A memory model for internet hits after media exposure

    Science.gov (United States)

    Chessa, Antonio G.; Murre, Jaap M. J.

    2004-02-01

    We present a cognitive model, based on the mathematical theory of point processes, which extends the results of two studies by Johansen (Physica A 276 (2000) 338; Physica A 296 (2001) 539) on download relaxation dynamics. Responses from subjects are considered as single events, which are received from original listeners or readers and from a network of social contacts, through which a message may propagate further. We collected data on the number of daily visits at our web site after a radio interview with the second author, in which the name of the web site was mentioned. A model based on an exponential hit time distribution and a homogeneous point process for regular visitors fits our data and Johansen's very well and is superior to both the power law and the logarithmic function. The fits suggest that hit data from different sources share the same cognitive mechanism, which are controlled merely by the encoding and retrieval of the target information memorised.

  7. Business Model and Replication Study of BIG HIT

    DEFF Research Database (Denmark)

    Zhao, Guangling; Ravn Nielsen, Eva

    and infrastructure investment and operation cost of electricity and water consumption. The functional unit is 1 kg hydrogen produced and consumed. The data collected from the project patterns and suppliers. The current analysis is based on the estimation of hydrogen production and consumption on both Shapinsay....... The BIG HIT project is creating a replicable hydrogen territory in Orkney (An island archipelago six miles offshore from North of Mainland Scotland.) by implementing a fully integrated model of hydrogen production, storage, distribution of the hydrogen across Orkney and utilised for mobility, heat...... and power. The BIG HIT project will use otherwise curtailed electricity from one wind turbine on Shapinsay and one wind turbine and a tidal test sites on Eday, and use 1.5 MW of Polymer Electrolyte Membrane (PEM) electrolyser to convert it into ~50 t pa of hydrogen. This will be used to provide heat...

  8. A Direct Simulation Method for Calculating Multiple-hit Vulnerability of Aircraft with Overlapping Components

    National Research Council Canada - National Science Library

    Pei Yang Song Bifeng Han Qing Ou Baiyu

    2009-01-01

    .... In this method, random method is adopted to produce the multiple-hit locations and Bernoulli trial is used to determine the kill or no kill of each component hit by one shot line, and kill tree...

  9. Progress on the HIT-SI3 Experiment

    Science.gov (United States)

    Golingo, R. P.; Rogers, J. A.; Ennis, D. A.; Hansen, C. J.; Hossack, A. C.; Jarboe, T. R.; Nelson, B. A.; Marklin, G. J.; Victor, B. S.

    2012-10-01

    The HIT-SI program at the University of Washington is investigating the formation and sustainment of toroidal current using steady inductive helicity injection (SIHI). The HIT-SI experiment consists of a bow tie shaped flux conserver with two helicity injectors on opposite sides of the machine. All plasma facing surfaces are coated with an insulting material to prevent arcing. The injectors are driven 90 degrees out of phase leading to a constant rate of helicity injection. Presently toroidal currents up to three times the injector current are created in the device. Discoveries made during the operation have guided the design of an improved injection geometry. Three injectors, which will operate with 120 degree phase differences, are presently being assembled to be mounted on one side of the device. These injectors will have the same preferred direction and produce a rotating structure with less n=1 than presently used. The injectors will operate at a higher frequency. The IDCD model predicts this will lead to a further reduction of the perturbations in the confinement volume. Additional diagnostic access has been gained by placing the injectors on one of the device. The present assembly status of the injectors and additional diagnostics for HIT-SI3 will be presented.

  10. 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.

  11. 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.

  12. Liquid Argon TPC Signal Formation, Signal Processing and Hit Reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Baller, Bruce [Fermilab

    2017-03-11

    This document describes the early stage of the reconstruction chain that was developed for the ArgoNeuT and MicroBooNE experiments at Fermilab. These experiments study accelerator neutrino interactions that occur in a Liquid Argon Time Projection Chamber. Reconstructing the properties of particles produced in these interactions requires knowledge of the micro-physics processes that affect the creation and transport of ionization electrons to the readout system. A wire signal deconvolution technique was developed to convert wire signals to a standard form for hit reconstruction, to remove artifacts in the electronics chain and to remove coherent noise.

  13. Hit efficiency study of CMS prototype forward pixel detectors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dongwook; /Johns Hopkins U.

    2006-01-01

    In this paper the author describes the measurement of the hit efficiency of a prototype pixel device for the CMS forward pixel detector. These pixel detectors were FM type sensors with PSI46V1 chip readout. The data were taken with the 120 GeV proton beam at Fermilab during the period of December 2004 to February 2005. The detectors proved to be highly efficient (99.27 {+-} 0.02%). The inefficiency was primarily located near the corners of the individual pixels.

  14. Water transfer and loss in hit-and-run collisions

    Science.gov (United States)

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

    2017-09-01

    This work focuses on transfer and loss of volatiles, like water, in hit-and-run collisions, where especially the smaller one of the colliding pair is often stripped of considerable amounts of its initial volatile content, but still survives the encounter more or less intact. We find water losses up to 75 percent in a single collision, depending on various parameters, especially velocity, impact angle and mass ratio, but also on the total colliding mass. The physical state, especially vaporization of volatiles, is found to be particularly important in collisions of approximately Mars-sized bodies, with high impact energies, but still potentially easy volatile escape.

  15. Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb.

    Science.gov (United States)

    Castellanos, Elisabeth; Bielsa, Isabel; Carrato, Cristina; Rosas, Imma; Solanes, Ares; Hostalot, Cristina; Amilibia, Emilio; Prades, José; Roca-Ribas, Francesc; Lázaro, Conxi; Blanco, Ignacio; Serra, Eduard

    2015-01-24

    A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivation of the NF2 gene. However, SMARCB1-associated schwannomas follow a four-hit, three-step model, in which both alleles of SMARCB1 and NF2 genes are inactivated in the tumor, with one of the steps being always the loss of a big part of chromosome 22 involving both loci. Here we report a 36-year-old woman who only presented multiple subcutaneous schwannomas on her right leg. To help discriminate between both possible diagnoses, an exhaustive molecular genetic and genomic analysis was performed on two schwannomas of the patient, consisting in cDNA and DNA sequencing, MLPA, microsatellite multiplex PCR and SNP-array analyses. The loss of a big part of chromosome 22 (22q12.1q13.33) was identified in both tumors. However, this loss involved the NF2 but not the SMARCB1 locus. SNP-array analysis revealed the presence of the same deletion breakpoint in both schwannomas, indicating that this alteration was actually the first NF2 inactivating hit. In addition, a distinct NF2 point mutation in each tumor was identified, representing independent second hits. In accordance with these results, no deletions or point mutations in the SMARCB1 gene were identified. None of the mutations were present in the blood. Two of the patient's children inherited chromosome 22 deleted in schwannomas of the mother, but in its wild type form. These results conclusively confirm the segmental mosaic NF2 nature of the clinical phenotype presented.

  16. Calibration of the ATLAS electromagnetic calorimeter using calibration hits

    CERN Document Server

    Banfi, D; Mandelli, L

    2007-01-01

    In the present note a method to determine the electron energy from the energies measured in an electron cluster is discussed. The method is based on a detailed Monte-Carlo simulation (labeled \\textit{Calibration Hits}) of electrons in the ATLAS detector in which also the energies deposited in the passive and dead materials are recorded. It allows also to compute the different contributions (energy deposited in front, in and behind the Accordion) to the total electron energy. To better understand the various contributions to the energy reconstruction three rounds of simulations have been performed: electrons hitting the middle cell centre, electrons spread uniformly over a cell in absence of magnetic field and electrons spread uniformly over a cell in presence of magnetic field. The method is applied to the Barrel calorimeter and to electrons. Its extension to the End Caps and to photons does not pose problems. In the operative ATLAS conditions an energy resolution sampling term varying from 9.9$\\%$ at $\\eta$=...

  17. Towards Optimal and Expressive Kernelization for d-Hitting Set

    CERN Document Server

    van Bevern, René

    2011-01-01

    A sunflower in a hypergraph is a set of hyperedges pairwise intersecting in exactly the same vertex set. Sunflowers are a useful tool in polynomial-time data reduction for problems formalizable as d-Hitting Set, the problem of covering all hyperedges (of cardinality at most d) of a hypergraph by at most k vertices. Additionally, in fault diagnosis, sunflowers yield concise explanations for "highly defective structures". We provide a linear-time algorithm that, by finding sunflowers, transforms an instance of d-Hitting Set into an equivalent instance comprising at most O(k^d) hyperedges and vertices. In terms of parameterized complexity theory, we show a problem kernel with asymptotically optimal size (unless coNP in NP/poly). We show that the number of vertices can be reduced to O(k^(d-1)) with additional processing in O(k^(1.5d)) time---nontrivially combining the sunflower technique with a known problem kernel that uses crown reductions.

  18. 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.

  19. Overview of the HIT-SI3 Experiment and Ion Doppler Spectroscopy Results from HIT-SI

    Science.gov (United States)

    Hossack, A. C.; Morgan, K. D.; Hansen, C. J.; Everson, C. J.; Sutherland, D. A.; Summers, A. W.; Chandra, R. N.; Nguyen, N. H.; Nelson, B. A.; Jarboe, T. R.; Elliott, D. B.; Victor, B. S.

    2015-11-01

    HIT-SI3 is a one-meter diameter spheromak current drive experiment. The plasma is formed and sustained by three inductive helicity injectors. The loop voltage and magnetic flux in each injector are oscillated in phase. The three injectors can be phased 120 or 60 degrees apart giving constant helicity injection. Operating frequencies include 14.5 kHz, 47.5 kHz, and higher. Toroidal current 3 times greater than the quadrature sum of injector currents has been achieved. Results are presented from a new, internal magnetic probe which spans the entire major radius of the flux conserver. Initial results will also be presented from the multi-point Thomson scattering diagnostic, ion Doppler spectrometer (IDS), and laser-induced fluorescence neutral density diagnostic. IDS results from the previous experiment, HIT-SI, are also presented. The spheromak plasma exhibits coherent motion driven by the injector currents and higher injector driving frequencies yielded higher betas than low frequency. Measurements are also compared with NIMROD and PSI-TET simulations and show qualitative agreement with temperature and velocity profiles. Work supported by USDoE.

  20. 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.

  1. Hit-Validation Methodologies for Ligands Isolated from DNA-Encoded Chemical Libraries.

    Science.gov (United States)

    Zimmermann, Gunther; Li, Yizhou; Rieder, Ulrike; Mattarella, Martin; Neri, Dario; Scheuermann, Jörg

    2017-05-04

    DNA-encoded chemical libraries (DECLs) are large collections of compounds linked to DNA fragments, serving as amplifiable barcodes, which can be screened on target proteins of interest. In typical DECL selections, preferential binders are identified by high-throughput DNA sequencing, by comparing their frequency before and after the affinity capture step. Hits identified in this procedure need to be confirmed, by resynthesis and by performing affinity measurements. In this article we present new methods based on hybridization of oligonucleotide conjugates with fluorescently labeled complementary oligonucleotides; these facilitate the determination of affinity constants and kinetic dissociation constants. The experimental procedures were demonstrated with acetazolamide, a binder to carbonic anhydrase IX with a dissociation constant in the nanomolar range. The detection of binding events was compatible not only with fluorescence polarization methodologies, but also with Alphascreen technology and with microscale thermophoresis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Pathomechanisms Underlying X-Adrenoleukodystrophy: A Three-Hit Hypothesis

    Science.gov (United States)

    Singh, Inderjit; Pujol, Aurora

    2011-01-01

    X-adrenoleukodystrophy (X-ALD) is a complex disease where inactivation of ABCD1 gene results in clinically diverse phenotypes, the fatal disorder of cerebral ALD (cALD) or a milder disorder of adrenomyeloneuropathy (AMN). Loss of ABCD1 function results in defective beta oxidation of very long chain fatty acids (VLCFA) resulting in excessive accumulation of VLCFA, the biochemical “hall mark” of X-ALD. At present, the ABCD1-mediated mechanisms that determine the different phenotype of X-ALD are not well understood. The studies reviewed here suggest for a “three-hit hypothesis” for neuropathology of cALD. An improved understanding of the molecular mechanisms associated with these three phases of cALD disease should facilitate the development of effective pharmacological therapeutics for X-ALD. PMID:20626745

  3. 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

  4. Tracking, aiming, and hitting the UAV with ordinary assault rifle

    Science.gov (United States)

    Racek, František; Baláž, Teodor; Krejčí, Jaroslav; Procházka, Stanislav; Macko, Martin

    2017-10-01

    The usage small-unmanned aerial vehicles (UAVs) is significantly increasing nowadays. They are being used as a carrier of military spy and reconnaissance devices (taking photos, live video streaming and so on), or as a carrier of potentially dangerous cargo (intended for destruction and killing). Both ways of utilizing the UAV cause the necessity to disable it. From the military point of view, to disable the UAV means to bring it down by a weapon of an ordinary soldier that is the assault rifle. This task can be challenging for the soldier because he needs visually detect and identify the target, track the target visually and aim on the target. The final success of the soldier's mission depends not only on the said visual tasks, but also on the properties of the weapon and ammunition. The paper deals with possible methods of prediction of probability of hitting the UAV targets.

  5. Locating sweet spots for screening hits and evaluating pan-assay interference filters from the performance analysis of two lead-like libraries.

    Science.gov (United States)

    Mok, N Yi; Maxe, Sara; Brenk, Ruth

    2013-03-25

    The efficiency of automated compound screening is heavily influenced by the design and the quality of the screening libraries used. We recently reported on the assembly of one diverse and one target-focused lead-like screening library. Using data from 15 enzyme-based screenings conducted using these libraries, their performance was investigated. Both libraries delivered screening hits across a range of targets, with the hits distributed across the entire chemical space represented by both libraries. On closer inspection, however, hit distribution was uneven across the chemical space, with enrichments observed in octants characterized by compounds at the higher end of the molecular weight and lipophilicity spectrum for lead-like compounds, while polar and sp(3)-carbon atom rich compounds were underrepresented among the screening hits. Based on these observations, we propose that screening libraries should not be evenly distributed in lead-like chemical space but be enriched in polar, aliphatic compounds. In conjunction with variable concentration screening, this could lead to more balanced hit rates across the chemical space and screening hits of higher ligand efficiency will be captured. Apart from chemical diversity, both screening libraries were shown to be clean from any pan-assay interference (PAINS) behavior. Even though some compounds were flagged to contain PAINS structural motifs, some of these motifs were demonstrated to be less problematic than previously suggested. To maximize the diversity of the chemical space sampled in a screening campaign, we therefore consider it justifiable to retain compounds containing PAINS structural motifs that were apparently clean in this analysis when assembling screening libraries.

  6. Verbalizations Affect Visuomotor Control in Hitting Objects to Distant Targets

    Directory of Open Access Journals (Sweden)

    Simone Caljouw

    2017-04-01

    Full Text Available There is a long-standing proposal for the existence of two neuroanatomically and functionally separate visual systems; one supported by the dorsal pathway to control action and the second supported by the ventral pathway to handle explicit perceptual judgments. The dorsal pathway requires fast access to egocentric information, while the ventral pathway primarily requires allocentric information. Despite the evidence for functionally distinct systems, researchers have posited important interactions. This paper examines evidence to what degree the interaction becomes more important when target-identity, the perception of which is supported by the ventral stream, is verbalized during the execution of a target-directed far-aiming movement. In the experiment reported here participants hit balls toward distant targets while concurrently making explicit perceptual judgments of target properties. The endpoint of a shaft served as the target, with conditions including illusory arrow fins at the endpoint. Participants verbalized the location of the target by comparing it to a reference line and calling out “closer” or “further” while propelling the ball to the target. The impact velocity at ball contact was compared for hits toward three shafts of lengths, 94, 100, and 106 cm, with and without verbalizations and delays. It was observed that the meaning of the expressed words modulated movement execution when the verbalizations were consistent with the action characteristics. This effect of semantic content was evident regardless of target visibility during movement execution, demonstrating it was not restricted to movements that rely on visual memory. In addition to a direct effect of semantic content we anticipated an indirect effect of verbalization to result in action shifting toward the use of context-dependent allocentric information. This would result in an illusion bias on the impact velocity when the target is embedded in a M

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

    NARCIS (Netherlands)

    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

  8. Scientific impact: the story of your big hit

    Science.gov (United States)

    Sinatra, Roberta; Wang, Dashun; Deville, Pierre; Song, Chaoming; Barabasi, Albert-Laszlo

    2014-03-01

    A gradual increase in performance through learning and practice characterize most trades, from sport to music or engineering, and common sense suggests this to be true in science as well. This prompts us to ask: what are the precise patterns that lead to scientific excellence? Does performance indeed improve throughout a scientific career? Are there quantifiable signs of an impending scientific hit? Using citation-based measures as a proxy of impact, we show that (i) major discoveries are not preceded by works of increasing impact, nor are followed by work of higher impact, (ii) the precise time ranking of the highest impact work in a scientist's career is uniformly random, with the higher probability to have a major discovery in the middle of scientific careers being due only to changes in productivity, (iii) there is a strong correlation between the highest impact work and average impact of a scientist's work. These findings suggest that the impact of a paper is drawn randomly from an impact distribution that is unique for each scientist. We present a model which allows to reconstruct the individual impact distribution, making possible to create synthetic careers that exhibit the same properties of the real data and to define a ranking based on the overall impact of a scientist. RS acknowledges support from the James McDonnell Foundation.

  9. 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.

  10. HIT implementation in critical access hospitals: extent of implementation and business strategies supporting IT use.

    Science.gov (United States)

    Bahensky, James A; Ward, Marcia M; Nyarko, Kwame; Li, Pengxiang

    2011-08-01

    Small rural hospitals face considerable financial and personnel resource shortages which hinder their efforts to implement complex health information technology (HIT) systems. A survey on the use of HIT was completed by 85% of Iowa's 82 Critical Access Hospitals (CAH). Analyses indicate that low IT staffing in CAHs is a barrier to implementing HIT solutions. CAHs with fewer staff tend to employ alternative business strategies. There is a clear relationship between having IT staff at a CAH and the types of technologies used. Many CAHs report having difficulty expanding upon HIT functionalities due to the challenges of finding IT staff with healthcare expertise. Most CAHs are in the transition point of planning for or beginning implementation of complex clinical information systems. Strategies for addressing these challenges will need to evolve as the HIT investments by rural hospitals race to keep pace with the goals for the nation.

  11. Construction of the Helicity Injected Torus with Steady Inductive Helicity Injection (HIT-SI)

    Science.gov (United States)

    Sieck, P. E.; Gu, P.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; Rogers, J. A.

    2001-10-01

    HIT-SI is a ``bow tie'' spheromak designed to implement Steady Inductive Helicity Injection (SIHI). The engineering requirements of SIHI lead to several unique design features, including a multiply connected electrically insulating o-ring seal and a close-fitting passive flux conserver that is electrically insulated from the plasma. Prototype tests have been performed to verify the performance of the o-ring seal and the plasma sprayed zirconia insulation. An engineering test of the new HIT-SI front end will be done before it replaces the present HIT-II front end on HIT. Startup and one millisecond of sustainment will be done to test breakdown and verify power supply requirements. The power supplies and external coils are designed to provide 20 MW at 5 kHz to 50 kHz for 1 ms to the helicity injection circuits for this test. Progress in the construction and assembly of HIT-SI will be presented.

  12. 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.

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

    Science.gov (United States)

    Bassler, N.; Hansen, D. C.; Lühr, A.; Thomsen, B.; Petersen, J. B.; Sobolevsky, N.

    2014-03-01

    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-HIT to a heavy ion dose optimization algorithm to provide MC-optimized treatment plans that include radiobiology. Methods: SHIELD-HIT12A is written in FORTRAN and carefully retains platform independence. A powerful scoring engine is implemented scoring relevant quantities such as dose and track-average LET. 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. 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 of computation time. Scheduled for later release are CT import and photon-electron transport. Conclusions: SHIELD-HIT12A is an interesting alternative ion transport engine. Apart from being a flexible particle therapy research tool, it can also serve as a back end for a MC ion treatment planning system. More information about SHIELD-HIT12A and a demo version can be found on http://www.shieldhit.org.

  14. The "first hit" toward alcohol reinforcement: role of ethanol metabolites.

    Science.gov (United States)

    Israel, Yedy; Quintanilla, María Elena; Karahanian, Eduardo; Rivera-Meza, Mario; Herrera-Marschitz, Mario

    2015-05-01

    This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self-administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu-opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge-like drinking in the condition known as the "alcohol deprivation effect"; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re-access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain-generated EtOH metabolites play a major role in the early ("first-hit") development of alcohol reinforcement and in the generation of relapse-like drinking. Copyright © 2015 by the Research Society on Alcoholism.

  15. 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...... of computation time. Scheduled for later release are CT import and photon-electron transport. Conclusions: SHIELD-HIT12A is an interesting alternative ion transport engine. Apart from being a flexible particle therapy research tool, it can also serve as a back end for a MC ion treatment planning system. More...

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

    Science.gov (United States)

    Korsager, Leise Elisabeth Hviid; Schmidt, Jesper Hvass; Faber, Christian; Wanscher, Jens Højberg

    2016-12-01

    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. 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. 25 subjects who had undergone cochlear implant (CI) surgery. Subjects were tested using the vHIT by two of four different examiners. Two judges interpreted the occurrence of saccades in the diagram. VOR gain values and the occurrence of saccades in the diagram. Differences in gain values between examiners varied from 0.2 to 0.58 with an average of 0.14 (95 % CI 0.12-0.16) on the right ear and 0.17 (95 % CI 0.15-0.19) on the left ear. Occurrences of saccades in the same patient were reproduced in 93 % of the cases by all examiners. Kappa's coefficient on the occurrence of saccades was 0.83. Interclass correlation 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 of the vestibular function. Interpretation of vHIT results should, therefore, first depend on the occurrence of saccades and second on the gain value.

  17. 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.

  18. Precocity of fine motor control and task context: hitting a ball while stepping.

    Science.gov (United States)

    Rosey, Florence; Golomer, Eveline Marie Elisabeth; Keller, Jean

    2008-07-01

    To determine if children under 5 years were able to intercept a moving object while stepping, the authors had 9 3-year-olds hit a ball that the authors dropped from a ramp from 5 heights (1.5, 2.0, 2.5, 3.0, and 3.5 m). The statistical analysis showed that the hand movement times were similar regardless of ball rolling heights and that the hand initiation times were dependent on the ball rolling times. Children under 5 years were able to hit a moving ball, and they performed this hitting according to a temporal coupling between ball displacements and the hand contact with it. The participants' behavior of hitting while stepping supports the idea that the motor system implicitly knows what the cognitive system ignores.

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

    Directory of Open Access Journals (Sweden)

    Chun-You Wei

    2013-11-01

    Full Text Available 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.

  20. 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...

  1. Force, Frequency of Head Hits Jump as Young Football Players Get Older

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_166906.html Force, Frequency of Head Hits Jump as Young Football Players ... is based on a comparison of head impact frequency and impact force among groups of kids between ...

  2. 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.

  3. Validation of the Headache Impact Test (HIT-6™) across episodic and chronic migraine

    Science.gov (United States)

    Yang, Min; Rendas-Baum, Regina; Varon, Sepideh F; Kosinski, Mark

    2011-01-01

    Objective: The purpose of this study was to assess psychometric properties of the six-item Headache Impact Text (HIT-6™) across episodic and chronic migraine. Methods: Using a migraine screener and number of headache days per month (HDPM), participants from the National Survey of Headache Impact (NSHI) study and the HIT-6 validation study (HIT6-V) were selected for this study. Eligible participants were categorized into three groups: chronic migraine (CM: ≥ 15 HDPM); episodic migraine (EM: migraine headaches. Reliability and validity of the HIT-6 were evaluated. Results: A total of 2,049 survey participants met the inclusion/exclusion criteria for this study. Participants were identified as 6.4% CM; 42.1% EM; 51.5% non-migraine, with respective mean HIT-6 scores: 62.5 ± 7.8; 60.2 ± 6.8; and 49.1 ± 8.7. High reliability was demonstrated with internal consistency (time1/time2) of 0.83/0.87 in NSHI, and 0.82/0.92 in HIT6-V. Intra-class correlation for test-retest reliability was very good at 0.77. HIT-6 scores correlated significantly (p Migraine Disability Assessment Scale scores (r = 0.56), headache pain severity (r = 0.46), and HDPM (r = 0.29). Discriminant validity analysis showed significantly different HIT-6 scores (F = 488.02, p migraine. PMID:20819842

  4. Predictability of Harmonic Complexity Across 75 Years of Popular Music Hits

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer; Hebert, David

    2015-01-01

    This study applies a novel computational strategy––Jensen Chroma Complexity (JCC)––to develop robust harmonic profiles of music recordings. This feature has been calculated on all US Billboard Top 100 hits across a 75-year period (n=6,394). Results indicate a clear historical trajectory of harmonic...... corroborate the effectiveness of JCC in generating ro- bust harmonic profiles that enable identification of the approximate year in which a hit song was popularized....

  5. HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology.

    Science.gov (United States)

    Shrestha, Raunak; Hodzic, Ermin; Sauerwald, Thomas; Dao, Phuong; Wang, Kendric; Yeung, Jake; Anderson, Shawn; Vandin, Fabio; Haffari, Gholamreza; Collins, Colin C; Sahinalp, S Cenk

    2017-09-01

    Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the "random walk facility location" (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: "multihitting time," the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients' survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology. © 2017 Shrestha et al.; Published by Cold Spring Harbor Laboratory Press.

  6. 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.

  7. Efficient hit-finding approaches for histone methyltransferases: the key parameters.

    Science.gov (United States)

    Ahrens, Thomas; Bergner, Andreas; Sheppard, David; Hafenbradl, Doris

    2012-01-01

    For many novel epigenetics targets the chemical ligand space and structural information were limited until recently and are still largely unknown for some targets. Hit-finding campaigns are therefore dependent on large and chemically diverse libraries. In the specific case of the histone methyltransferase G9a, the authors have been able to apply an efficient process of intelligent selection of compounds for primary screening, rather than screening the full diverse deck of 900 000 compounds to identify hit compounds. A number of different virtual screening methods have been applied for the compound selection, and the results have been analyzed in the context of their individual success rates. For the primary screening of 2112 compounds, a FlashPlate assay format and full-length histone H3.1 substrate were employed. Validation of hit compounds was performed using the orthogonal fluorescence lifetime technology. Rated by purity and IC(50) value, 18 compounds (0.9% of compound screening deck) were finally considered validated primary G9a hits. The hit-finding approach has led to novel chemotypes being identified, which can facilitate hit-to-lead projects. This study demonstrates the power of virtual screening technologies for novel, therapeutically relevant epigenetics protein targets.

  8. 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.

  9. 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. PMID:26958238

  10. The rationale and design of the national familial hypercholesterolemia registries in Turkey: A-HIT1 and A-HIT2 studies.

    Science.gov (United States)

    Kayıkçıoğlu, Meral; Tokgözoğlu, Lale

    2017-04-01

    Familial hypercholesterolemia (FH) is a genetic disease characterized by extremely high levels of cholesterol, leading to premature atherosclerosis. Although many countries have already addressed the burden of FH by means of national registries, Turkey has no national FH registry or national screening program to detect FH. Creation of a series of FH registries is planned as part of Turkish FH Initiative endorsed by the Turkish Society of Cardiology to meet this need. This article provides detailed information on the rationale and design of the first 2 FH registries (A-HIT1 and A-HIT2). A-HIT1 is a nationwide survey of adult homozygous FH (HoFH) patients undergoing low-density lipoprotein (LDL) apheresis (LA) in Turkey. A-HIT1 will provide insight into the clinical status of HoFH patients undergoing LA. Primary objective of this cross-sectional study is to identify how HoFH patients on LA are managed. Inclusion criteria are age >12 years, diagnosis of HoFH, and regular LA treatment. All available apheresis centers were electronically invited to participate in the study. The principal physicians of each center will respond to a questionnaire regarding their attitude toward LA. For each patient, another questionnaire will be used to collect data on clinical status, medication use, and disease data. In addition, patients will be asked to complete self-report questionnaires that provide information on quality of life, disease-related anxiety, and depression. A-HIT2 is a registry of adult FH patients presenting at outpatient clinics. At least 1000 FH patients will be recruited from 30 outpatient clinics representing the 12 statistical regions in Turkey based on the EU NUTS classification. Sites specializing in cardiology, internal medicine, and endocrinology were invited to participate. The primary objective of this cross-sectional study is to determine clinical status and management of patients in Turkey diagnosed with FH. Eligibility for screening was defined as having

  11. Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual-hit hypothesis of neurodegeneration.

    Science.gov (United States)

    Heinemann, Scott D; Posimo, Jessica M; Mason, Daniel M; Hutchison, Daniel F; Leak, Rehana K

    2016-08-01

    The dual-hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, a relatively high-throughput dual-hit model of stress synergy was developed in primary hippocampal neurons. In order to increase the rigor of the study and strengthen the interpretations, three independent, unbiased viability assays were employed at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48 h. MG132 and paraquat only elicited additive effects 24 h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48 h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. These findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, a new model of hippocampal vulnerability was developed for the testing of therapies

  12. 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.

  13. Use of HIT for adverse event reporting in nursing homes: barriers and facilitators.

    Science.gov (United States)

    Wagner, Laura M; Castle, Nicholas G; Handler, Steven M

    2013-01-01

    Approximately 8 million adverse events occur annually in nursing homes (NHs). The focus of this research is to determine barriers and health information technology (HIT)-related facilitators to adverse event reporting among U.S. NHs. Surveys were returned by 399 nursing home administrators using a mailed survey approach. Respondents were asked to report on their adverse event reporting processes focusing on barriers and role of HIT facilitators. About 15% of NHs had computerized entry by the nurse on the unit and almost 18% used no computer technology to track, monitor, or maintain adverse event data. One-third of nursing directors conducted data analysis "by-hand." NHs without HIT were more likely to not be accredited (p = 0.04) and not part of a chain/corporation (p = 0.03). Two of the top three barriers focused on fears of reporting as a barrier. This study found numerous barriers and few HIT-related facilitators to assist with adverse event reporting. Improvements in facilitating adverse event reporting through the use of HIT approaches may be warranted. Copyright © 2013 Mosby, Inc. All rights reserved.

  14. Microdosimetric one hit detector model for calculation of dose and energy response of some solid state detectors.

    Science.gov (United States)

    Olko, P; Waligórski, M P R

    2002-01-01

    A microdosimetric one hit detector model has been applied to calculate dose response, energy response and relative efficiency of thermoluminescent LiF:Mg,Cu,P (MCP-N), CaF2:Tm (TLD-300) and ESR alanine detectors on radiation of different qualities. For each detector type two model parameters, the target size and the saturation parameter, alpha, have been derived. Using those parameters and the microdosimetric distributions in nanometre size targets calculated using Monte Carlo track structure codes TRION and MOCA-14 it was possible to predict a great variety of experimental data for photons, X rays, beta electrons, protons, alpha particles and heavy ions. Due to a good reproducibility of experimental data some solid state detectors might be useful to test biophysical models of radiation action. Furthermore, these models can give some insight into the physics of radiation action in solid state detectors such as the range of charge interaction, energy levels etc.

  15. Stochastic dynamics and the predictability of big hits in online videos

    CERN Document Server

    Miotto, Jose M; Altmann, Eduardo G

    2016-01-01

    The competition for the attention of users is a central element of the Internet. Crucial issues are the origin and predictability of big hits, the few items that capture a big portion of the total attention. We address these issues analyzing 10 million time series of videos' views from YouTube. We find that the average gain of views is linearly proportional to the number of views a video already has, in agreement with usual rich-get-richer mechanisms and Gibrat's law, but this fails to explain the prevalence of big hits. The reason is that the fluctuations around the average views are themselves heavy tailed. Based on these empirical observations, we propose a stochastic differential equation with Le\\'evy noise as a model of the dynamics of videos. We show how this model is substantially better in estimating the probability of an ordinary item becoming a big hit, which is considerably underestimated in the traditional proportional-growth models.

  16. Mathematical model for hit phenomena and its application to analyze popularity of weekly tv drama

    CERN Document Server

    Ishii, Akira; Usui, Tsukasa; Uchiyama, Koki

    2015-01-01

    Mathematical model for hit phenomena presented by A Ishii et al in 2012 has been extended to analyze and predict a lot of hit subject using social network system. The equation for each individual consumers is assumed and the equation of social response to each hit subject is derived as stochastic process of statistical physics. The advertisement effect is included as external force and the communication effects are included as two-body and three-body interaction. The applications of this model are demonstrated for analyzing population of weekly TV drama. Including both the realtime view data and the playback view data, we found that the indirect communication correlate strongly to the TV viewing rate data for recent Japanese 20 TV drama.

  17. Hit expansion approaches using multiple similarity methods and virtualized query structures.

    Science.gov (United States)

    Bergner, Andreas; Parel, Serge P

    2013-05-24

    Ligand-based virtual screening and computational hit expansion methods undoubtedly facilitate the finding of novel active chemical entities, utilizing already existing knowledge of active compounds. It has been demonstrated that the parallel execution of complementary similarity search methods enhances the performance of such virtual screening campaigns. In this article, we examine the use of virtualized template (query, seed) structures as an extension to common search methods, such as fingerprint and pharmacophore graph-based similarity searches. We demonstrate that template virtualization by bioisosteric enumeration and other rule-based methods, in combination with standard similarity search techniques, represents a powerful approach for hit expansion following high-throughput screening campaigns. The reliability of the methods is demonstrated by four different test data sets representing different target classes and two hit finding case studies on the epigenetic targets G9a and LSD1.

  18. Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol.

    Science.gov (United States)

    von Bueren, André O; Friedrich, Carsten; von Hoff, Katja; Kwiecien, Robert; Müller, Klaus; Pietsch, Torsten; Warmuth-Metz, Monika; Hau, Peter; Benesch, Martin; Kuehl, Joachim; Kortmann, Rolf D; Rutkowski, Stefan

    2015-11-01

    Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited. Adults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT'91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy. Twenty-three patients (median age: 30.7years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99years. The 4-year event-free survival (EFS) and overall survival (OS)±standard error (SE) were 52%±12% and 91%±6%, respectively. The survival was similar in both treatment groups (HIT'91 maintenance strategy, n=9; MET-HIT2000AB4 sandwich strategy, n=14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n=2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n=11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n=10; 4-year EFS/OS: 48%/100%), respectively (p=0.161 for EFS and p=0.033 for OS). Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10). Treatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease. Copyright © 2015 Elsevier Ltd. All rights

  19. 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.

  20. Study of neutron-induced background hits in the CMS endcap muon system

    CERN Document Server

    Dasgupta, Abhigyan

    2017-01-01

    Among the many challenges arising from the high luminosities of the HL-LHC is the impact of increased hit rates in the cathode strip chambers of the CMS endcap muon system. These chambers detect muons as part of the CMS muon trigger, and their data is used offline for muon track reconstruction. Neutrons (both fast and thermal) induce background hits via nuclear interactions and capture, followed by gamma emission and (mainly) Compton scatter off electrons that subsequently ionize the chamber gas. This note presents recent efforts to improve the understanding of such neutron-induced background through detailed comparison of CMS pp collision data and GEANT4 simulation.

  1. 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.

  2. Hitting moving targets : A dissociation between the use of the target's speed and direction of motion

    NARCIS (Netherlands)

    Brouwer, Anne Marie; Middelburg, Tom; Smeets, Jeroen B J; Brenner, Eli

    2003-01-01

    Previous work has indicated that people do not use their judgment of a target's speed to determine where to hit it. Instead, they use their judgment of the target's changing position and an expected speed (based on the speed of previous targets). In the present study we investigate whether people

  3. 42 CFR 495.336 - Health information technology planning advance planning document requirements (HIT PAPD).

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Health information technology planning advance planning document requirements (HIT PAPD). 495.336 Section 495.336 Public Health CENTERS FOR MEDICARE... Medicaid Program § 495.336 Health information technology planning advance planning document requirements...

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

    NARCIS (Netherlands)

    Goldschmidt, A.|info:eu-repo/dai/nl/372729789; Zwarts, J.|info:eu-repo/dai/nl/094993025

    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

  5. Sub-concussive hit characteristics predict deviant brain metabolism in football athletes.

    Science.gov (United States)

    Poole, Victoria N; Breedlove, Evan L; Shenk, Trey E; Abbas, Kausar; Robinson, Meghan E; Leverenz, Larry J; Nauman, Eric A; Dydak, Ulrike; Talavage, Thomas M

    2015-01-01

    Magnetic resonance spectroscopy and helmet telemetry were used to monitor the neural metabolic response to repetitive head collisions in 25 high school American football athletes. Specific hit characteristics were determined highly predictive of metabolic alterations, suggesting that sub-concussive blows can produce biochemical changes and potentially lead to neurological problems.

  6. 75 FR 51820 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-08-23

    ...] [FR Doc No: 2010-20829] 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... Coordinator on a policy framework for the development and adoption of a nationwide health information...

  7. 75 FR 29762 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-05-27

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  8. 76 FR 9784 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2011-02-22

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  9. 76 FR 9782 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2011-02-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  10. 75 FR 8078 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-02-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  11. 75 FR 42091 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-07-20

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  12. 76 FR 4352 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2011-01-25

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

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

    Science.gov (United States)

    2011-01-25

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  14. 75 FR 57276 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-09-20

    ... HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Technology (ONC). The meeting will be open to the public. Name of Committee: Health IT Policy Committee's Governance Workgroup. General Function of the Health IT Policy Committee: To provide recommendations to the...

  15. 75 FR 3906 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-01-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  16. 75 FR 33811 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-06-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a...

  17. 75 FR 21630 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-04-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  18. 75 FR 57026 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-09-17

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  19. 75 FR 36658 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-06-28

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  20. 75 FR 65485 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-10-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  1. 75 FR 70923 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-11-19

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  2. 75 FR 17744 - Office of the National Coordinator for Health Information Technology HIT Policy Committee...

    Science.gov (United States)

    2010-04-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee... Coordinator on a policy framework for the development and adoption of a nationwide health information...

  3. 75 FR 369 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-01-05

    ... Policy, Strategic Plan, and Nationwide Health Information Infrastructure (NHIN) workgroups. General...: E9-31348] DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the...

  4. 75 FR 12752 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-03-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  5. 75 FR 6398 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-02-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a...

  6. 75 FR 57026 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-09-17

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  7. 76 FR 1432 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2011-01-10

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  8. 75 FR 70924 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-11-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  9. 75 FR 34141 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-06-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health...

  10. 75 FR 51819 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-08-23

    ...] [FR Doc No: 2010-20828] 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... Coordinator on a policy framework for the development and adoption of a nationwide health [[Page 51820...

  11. 75 FR 151 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-01-04

    ... Coordinator on a policy framework for the development and adoption of a nationwide health information... No: E9-31186] 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...

  12. 75 FR 65486 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-10-25

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  13. 75 FR 5595 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-02-03

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  14. 75 FR 8953 - Office of the National Coordinator for Health Information Technology HIT Policy Committee...

    Science.gov (United States)

    2010-02-26

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health Information...

  15. 75 FR 16126 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

    Science.gov (United States)

    2010-03-31

    ... From the Federal Register Online via the Government Publishing Office 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 Coordinator for Health...

  16. 75 FR 51819 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Science.gov (United States)

    2010-08-23

    ... No: 2010-20826] DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice...

  17. Visits, Hits, Caching and Counting on the World Wide Web: Old Wine in New Bottles?

    Science.gov (United States)

    Berthon, Pierre; Pitt, Leyland; Prendergast, Gerard

    1997-01-01

    Although web browser caching speeds up retrieval, reduces network traffic, and decreases the load on servers and browser's computers, an unintended consequence for marketing research is that Web servers undercount hits. This article explores counting problems, caching, proxy servers, trawler software and presents a series of correction factors…

  18. An orthogonal-polynomial approach to first-hitting times of birth-death processes

    NARCIS (Netherlands)

    van Doorn, Erik A.

    In a recent paper in this journal, Gong, Mao and Zhang, using the theory of Dirichlet forms, extended Karlin and McGregor’s classical results on first-hitting times of a birth–death process on the nonnegative integers by establishing a representation for the Laplace transform E[exp(sTij)] of the

  19. An orthogonal-polynomial approach to first-hitting times of birth-death processes

    NARCIS (Netherlands)

    van Doorn, Erik A.

    In a recent paper [J. Theor. Probab. 25 (2012) 950-980] Gong, Mao and Zhang, using the theory of Dirichlet forms, extended Karlin and McGregor's classical results on first-hitting times of a birth-death process on the nonnegative integers by establishing a representation for the Laplace transform

  20. Our Young People and Hard Hit Communities: Recovery Has Passed Them By. A First Friday Report.

    Science.gov (United States)

    Full Employment Action Council, Washington, DC.

    Although the joblessness and underemployment that characterize the labor market status of American youth are worst for Hispanic and Black youth, they also reflect the absence of job opportunities, irrespective of race, in depressed rural areas and urban communities hard hit by sustained high levels of unemployment. In December 1984, teenagers had…

  1. 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.

  2. Towards verb modification in frames : A case study on German “schlagen” (to hit)

    NARCIS (Netherlands)

    Goldschmidt, A.; Petersen, Wiebke; Geuder, Wilhelm; Gamerschlag, Thomas; Gabrovska, Ekaterina

    2017-01-01

    Hit-verbs have three basic meaning components, namely movement, contact and force (e.g. [12], Levin 1993), which interact with the verbs’ argument structure in various ways. In this paper, we map out the different grammatical constructions of the German verb schlagen (usually, though loosely,

  3. 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

    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...

  4. FedWeb Greatest Hits: Presenting the New Test Collection for Federated Web Search

    NARCIS (Netherlands)

    Demeester, Thomas; Trieschnigg, Rudolf Berend; Zhou, Ke; Nguyen, Dong-Phuong; Hiemstra, Djoerd

    This paper presents 'FedWeb Greatest Hits', a large new test collection for research in web information retrieval. As a combination and extension of the datasets used in the TREC Federated Web Search Track, this collection opens up new research possibilities on federated web search challenges, as

  5. Hit detection in serial femtosecond crystallography using X-ray spectroscopy of plasma emission

    Directory of Open Access Journals (Sweden)

    H. Olof Jönsson

    2017-11-01

    Full Text Available Serial femtosecond crystallography is an emerging and promising method for determining protein structures, making use of the ultrafast and bright X-ray pulses from X-ray free-electron lasers. The upcoming X-ray laser sources will produce well above 1000 pulses per second and will pose a new challenge: how to quickly determine successful crystal hits and avoid a high-rate data deluge. Proposed here is a hit-finding scheme based on detecting photons from plasma emission after the sample has been intercepted by the X-ray laser. Plasma emission spectra are simulated for systems exposed to high-intensity femtosecond pulses, for both protein crystals and the liquid carrier systems that are used for sample delivery. The thermal radiation from the glowing plasma gives a strong background in the XUV region that depends on the intensity of the pulse, around the emission lines from light elements (carbon, nitrogen, oxygen. Sample hits can be reliably distinguished from the carrier liquid based on the characteristic emission lines from heavier elements present only in the sample, such as sulfur. For buffer systems with sulfur present, selenomethionine substitution is suggested, where the selenium emission lines could be used both as an indication of a hit and as an aid in phasing and structural reconstruction of the protein.

  6. The enzyme DXS as an anti-infective target : Exploiting multiple hit-identification strategies

    NARCIS (Netherlands)

    Masini, Tiziana

    2015-01-01

    We exploited multiple hit-identification strategies toward the development of inhibitors for the enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS). DXS belongs to the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the biosynthesis of isopentenyl diphosphate (IDP) and dimethylallyl

  7. Independent control of acceleration and direction of the hand when hitting moving targets

    NARCIS (Netherlands)

    Brenner, Eli; De Lussanet, Marc H.E.; Smeets, J. B J

    2002-01-01

    Human subjects were asked to hit moving targets as quickly as they could. Nevertheless the speed with which the subjects moved toward identical stimuli differed between trials. We examined whether the subjects compensated for a lower initial acceleration by aiming further ahead of the target. We

  8. Maximal Aerobic Frequency of Ball Hitting: A New Training Load Parameter in Tennis.

    Science.gov (United States)

    Baiget, Ernest; Iglesias, Xavier; Rodríguez, Ferran A

    2017-01-01

    Baiget, E, Iglesias, X, and Rodríguez, FA. Maximal aerobic frequency of ball hitting: a new training load parameter in tennis. J Strength Cond Res 31(1): 106-114, 2017-This study aimed (a) to evaluate a new training load parameter in tennis based on the ball-hitting frequency (Ballf) at V[Combining Dot Above]O2max occurs (maximal aerobic frequency of ball hitting, MAF) and (b) to assess the accuracy of a specific endurance tennis test (SET-Test) for predicting MAF. Thirty-five male competitive tennis players performed the SET-Test and selected physiological and performance parameters at maximal workload (MAX), and last completed stage (LS) and MAF were compared. Performance parameters (Ballf, time, stage, and hits per test) at LS were higher than at MAF (20.2 ± 1.7 vs. 18.1 ± 1.5 shots·min, 6.6 ± 0.8 vs. 5.6 ± 0.8 stages, and 189 ± 33 vs. 147 ± 27 hits; p training, and that the SET-Test is a valid method for assessing MAF. Gas exchange measurements not being available, as a rule of thumb, most players reach their MAF at ∼1 stage (95% confidence interval: 0.9-1.2) and ∼2 shots·min (95% confidence interval: 1.7-2.5) less than their completed LS. A model for specific on-court training protocols for optimizing aerobic fitness in competitive tennis player is proposed.

  9. 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.

  10. 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…

  11. Transfer effects on training the refraction of light when hitting the target in the water

    Directory of Open Access Journals (Sweden)

    Nešić Blagoje V.

    2014-01-01

    Full Text Available This paper presents experimental research of the effects of training students in the principles of light refraction to succeed in hitting the target in the water. The aim of this experiment was to investigate the veracity of the conclusions reached by Judd in 1908, since this experiment has been crucial in educational psychology - it represents the experimental basis of the generalized theory of transfers. Namely, Judd demonstrated that general experience (not identical elements is transferred in the process of transfer. There were two groups in the research: the experimental and the control group. The following variables were controlled: hitting the target in the air; the knowledge of the refraction of light, age, gender, and number. Unlike the control group, the experimental group received training in the principles of light reflection. Having completed the training of the experimental group, the hitting of the target in the water was performed, firstly at the depth of 50 cm and then at the depth of 20 cm. The sample included two classes of eighth - grade students from the elementary school in Pečenjevac (the experimental group and Razgojna (the control group. The research was conducted at the beginning of the school year (1975/76. In the process, there were errors in hitting the target. For the processing of data, the analyses of variance and measures of statistical descriptions have shown the following: 1 the success of the experimental group in hitting the targets at the first depth of water is significantly better than the success of the control group F (1,102 = 5.240 , p <0.05; 2 the experimental group has achieved significantly better results than the control group when hitting the targets at the altered depth of water F (1,102 = 27.767 , p <0.01; 3 when comparing the progresses of groups or differences of differences showed that the experimental group was significantly better than the control group F (1,192=9,5300, p<0.01. Even though

  12. Methods to identify, study and understand end-user participation in HIT development.

    Science.gov (United States)

    Høstgaard, Anna Marie; Bertelsen, Pernille; Nøhr, Christian

    2011-09-28

    Experience has shown that for new health-information-technology (HIT) to be suc-cessful clinicians must obtain positive clinical benefits as a result of its implementation and joint-ownership of the decisions made during the development process. A prerequisite for achieving both success criteria is real end-user-participation. Experience has also shown that further research into developing improved methods to collect more detailed information on social groups participating in HIT development is needed in order to support, facilitate and improve real end-user participation. A case study of an EHR planning-process in a Danish county from October 2003 until April 2006 was conducted using process-analysis. Three social groups (physicians, IT-professionals and administrators) were identified and studied in the local, present perspective. In order to understand the interactions between the three groups, the national, historic perspective was included through a literature-study. Data were collected through observations, interviews, insight gathered from documents and relevant literature. In the local, present perspective, the administrator's strategy for the EHR planning process meant that there was no clinical workload-reduction. This was seen as one of the main barriers to the physicians to achieving real influence. In the national, historic perspective, physicians and administrators have had/have different perceptions of the purpose of the patient record and they have both struggled to influence this definition. To date, the administrators have won the battle. This explains the conditions made available for the physicians' participation in this case, which led to their role being reduced to that of clinical consultants--rather than real participants. In HIT-development the interests of and the balance of power between the different social groups involved are decisive in determining whether or not the end-users become real participants in the development process. Real

  13. Methods to identify, study and understand End-user participation in HIT development

    Directory of Open Access Journals (Sweden)

    Nøhr Christian

    2011-09-01

    Full Text Available Abstract Background Experience has shown that for new health-information-technology (HIT to be suc-cessful clinicians must obtain positive clinical benefits as a result of its implementation and joint-ownership of the decisions made during the development process. A prerequisite for achieving both success criteria is real end-user-participation. Experience has also shown that further research into developing improved methods to collect more detailed information on social groups participating in HIT development is needed in order to support, facilitate and improve real end-user participation. Methods A case study of an EHR planning-process in a Danish county from October 2003 until April 2006 was conducted using process-analysis. Three social groups (physicians, IT-professionals and administrators were identified and studied in the local, present perspective. In order to understand the interactions between the three groups, the national, historic perspective was included through a literature-study. Data were collected through observations, interviews, insight gathered from documents and relevant literature. Results In the local, present perspective, the administrator's strategy for the EHR planning process meant that there was no clinical workload-reduction. This was seen as one of the main barriers to the physicians to achieving real influence. In the national, historic perspective, physicians and administrators have had/have different perceptions of the purpose of the patient record and they have both struggled to influence this definition. To date, the administrators have won the battle. This explains the conditions made available for the physicians' participation in this case, which led to their role being reduced to that of clinical consultants - rather than real participants. Conclusion In HIT-development the interests of and the balance of power between the different social groups involved are decisive in determining whether or not the end

  14. Uniformly discrete hit-and-miss hypertopology. A missing link in hypertopologies

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Maio

    2006-10-01

    Full Text Available Recently it was shown that the lower Hausdorff metric (uniform topology is generated by families of uniformly discrete sets as hit sets. This result leads to a new hypertopology which is the join of the above topology and the upper Vietoris topology. This uniformly discrete hit-and-miss hypertopology is coarser than the locally finite hypertopology and finer than both Hausdorff metric (uniform topology and Vietoris topology. In this paper this new hypertopology is studied. Here is a Hasse diagram in which each arrow goes from a coarser topology to a finer one and equality follows UC or TB as indicated. The diagram clearly shows that the new (underlined topology provides the missing link.

  15. Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.

    Science.gov (United States)

    Evangelista, Wilfredo; Weir, Rebecca L; Ellingson, Sally R; Harris, Jason B; Kapoor, Karan; Smith, Jeremy C; Baudry, Jerome

    2016-10-15

    This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. "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".

  17. Organizations disseminating health messages: the roles of organizational identification and HITs.

    Science.gov (United States)

    Stephens, Keri K; Goins, Elizabeth S; Dailey, Stephanie L

    2014-01-01

    Research into the dissemination of health information now includes more focus on how various organizations (e.g., beauty shops, schools, workplaces, and churches) and health information technologies (HITs) reach and affect audiences. One relational feature of organizations is identification--the feeling of belongingness. Our study explores how it influences audiences, especially in combination with HITs such as e-mail, websites, and social media. We use social identity theory to predict how organizational identification and social media might function in health communication. Using a 3 × 2 experimental design, we find that people's identification with a message source mediates the effect of social media on outcomes. These findings improve our understanding of when organizations might be most helpful for disseminating health information.

  18. 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.

  19. Flaws in the LNT single-hit model for cancer risk: An historical assessment.

    Science.gov (United States)

    Calabrese, Edward J

    2017-10-01

    The LNT single-hit model was derived from the Nobel Prize-winning research of Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila and that the dose response for these so-called mutational events was linear. Lewis J. Stadler, another well-known and respected geneticist at the time, strongly disagreed with and challenged Muller's claims. Detailed evaluations by Stadler over a prolonged series of investigations revealed that Muller's experiments had induced gross heritable chromosomal damage instead of specific gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray-induced alterations became progressively more frequent and were of larger magnitude (more destructive) with increasing doses. Thus, Muller's claim of having induced discrete gene mutations represented a substantial speculative overreach and was, in fact, without proof. The post hoc arguments of Muller to support his gene mutation hypothesis were significantly challenged and weakened by a series of new findings in the areas of cytogenetics, reverse mutation, adaptive and repair processes, and modern molecular methods for estimating induced genetic damage. These findings represented critical and substantial limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore, they challenged the scientific foundations used in support of the LNT single-hit model by severing the logical nexus between Muller's data on radiation-induced inheritable alterations and the LNT single-hit model. These findings exposed fundamental scientific flaws that undermined not only the seminal recommendation of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk assessment but also any rationale for its continued use in the present day. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Rapid and simple IgG specific test for the exclusion of heparin induced thrombocytopenia (HIT).

    Science.gov (United States)

    Kolde, Hans-Jürgen; Dostatni, Ralf; Mauracher, Susanne

    2011-08-29

    The exclusion of heparin induced thrombocytopenia (HIT) is required for selecting the most appropriate anticoagulation therapy in affected patients. It requires the combination of clinical data with the detection of antibodies directed against platelet factor 4 (PF4) in complex with polyanions (PA) such as heparin. We developed a lateral flow immunoassay (LFIA) for PF4/PA complex specific IgG antibodies based on gold nanoparticles. Unlike most other assays, the initial immune reaction takes place in the liquid phase. The sensitivity of the assay has been adjusted with clinical samples aiming in the reliable detection of sera which are positive in a functional platelet activation assay. Sera from 60 patients with suspected HIT were investigated. LFIA identified correctly all samples (n=20) which were positive in a functional assay (HIPA) and an IgG specific ELISA. It correlated with ELISA, but false positive results were less frequent (7 samples were negative with LFIA and HIPA but positive with ELISA). The LFIA may be a suitable tool for the rapid exclusion of HIT within 10 min.

  1. CHRR: coordinate hit-and-run with rounding for uniform sampling of constraint-based models.

    Science.gov (United States)

    Haraldsdóttir, Hulda S; Cousins, Ben; Thiele, Ines; Fleming, Ronan M T; Vempala, Santosh

    2017-06-01

    In constraint-based metabolic modelling, physical and biochemical constraints define a polyhedral convex set of feasible flux vectors. Uniform sampling of this set provides an unbiased characterization of the metabolic capabilities of a biochemical network. However, reliable uniform sampling of genome-scale biochemical networks is challenging due to their high dimensionality and inherent anisotropy. Here, we present an implementation of a new sampling algorithm, coordinate hit-and-run with rounding (CHRR). This algorithm is based on the provably efficient hit-and-run random walk and crucially uses a preprocessing step to round the anisotropic flux set. CHRR provably converges to a uniform stationary sampling distribution. We apply it to metabolic networks of increasing dimensionality. We show that it converges several times faster than a popular artificial centering hit-and-run algorithm, enabling reliable and tractable sampling of genome-scale biochemical networks. https://github.com/opencobra/cobratoolbox . ronan.mt.fleming@gmail.com or vempala@cc.gatech.edu. Supplementary data are available at Bioinformatics online.

  2. Chlamydia Spreading from the Genital Tract to the Gastrointestinal Tract - A Two-Hit Hypothesis.

    Science.gov (United States)

    Zhong, Guangming

    2017-12-27

    Chlamydia trachomatis, a leading bacterial cause of sexually transmitted infection-induced infertility, is frequently detected in the gastrointestinal tract. Chlamydia muridarum, a model pathogen for investigating C. trachomatis pathogenesis, readily spreads from the mouse genital tract to the gastrointestinal tract, establishing long-lasting colonization. C. muridarum mutants, despite their ability to activate acute oviduct inflammation, are attenuated in inducing tubal fibrosis and are no longer able to colonize the gastrointestinal tract, suggesting that the spread of C. muridarum to the gastrointestinal tract may contribute to its pathogenicity in the upper genital tract. However, gastrointestinal C. muridarum cannot directly autoinoculate the genital tract. Both antigen-specific CD8+ T cells and profibrotic cytokines, such as TNFα and IL-13, are essential for C. muridarum to induce tubal fibrosis; this may be induced by the gastrointestinal C. muridarum, as a second hit, to transmucosally convert tubal repairing - initiated by C. muridarum infection of tubal epithelial cells (serving as the first hit) - into pathogenic fibrosis. Testing the two-hit mouse model should both add new knowledge to the growing list of mechanisms by which gastrointestinal microbes contribute to pathologies in extragastrointestinal tissues and provide information for investigating the potential role of gastrointestinal C. trachomatis in human chlamydial pathogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Ionoluminescence analysis of glass scintillators and application to single-ion-hit real-time detection

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Akihito, E-mail: yokoyama.akihito@jaea.go.jp [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Takasaki Advanced Radiation Research Institute (TARRI), Japan Atomic Energy Agency (JAEA), 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Kada, Wataru [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Satoh, Takahiro; Koka, Masashi [Takasaki Advanced Radiation Research Institute (TARRI), Japan Atomic Energy Agency (JAEA), 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Shimada, Keisuke; Yokoata, Yuya; Miura, Kenta; Hanaizumi, Osamu [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan)

    2016-03-15

    In this paper, we propose and test a real-time detection system for single-ion hits using mega-electronvolt (MeV)-heavy ions. The system was constructed using G2000 and G9 glass scintillators, as well as an electron-multiplying charge-coupled device (EMCCD) camera combined with an inverted microscope with a 10× objective lens. Commercially available G2000 and G9 glass scintillators, which have been reported to exhibit strong photoluminescence at 489, 543, 585, and 622 nm as a result of the Tb{sup 3+} f–f transition, were employed for highly accurate ionized particle detection. The EMCCD camera had a resolution of 512 × 512 pixels, each with a size of 16 μm × 16 μm, and a maximum linear gain of 8 × 10{sup 5} electrons. For 260-MeV Ne, 3 ion hits/s were detected by our system. The intensity of the ionoluminescence (IL) peak induced by the heavy ions was 140 times the noise intensity. In contrast, the luminous diameter at the full width at half maximum (FWHM) in both the horizontal and vertical directions was calculated to be approximately 4.5 μm. These results suggest that our detection system can accurately detect single-ion hits with a diameter of the order of 1 μm.

  4. 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.

  5. Hit-and-run crashes in urban river-crossing road tunnels.

    Science.gov (United States)

    Jiang, Chenming; Lu, Linjun; Chen, Shengdi; Lu, Jian John

    2016-10-01

    Hit-and-run crashes are a relatively infrequent but severe offense worldwide because the identification and emergency rescue of victims is delayed, which increases the injury severities and the mortality rate. However, no studies have been conducted on hit-and-run crashes in urban river-crossing road tunnels (URCRTs), which can greatly threaten the safety of motorists driving in the tunnels. This study, which employs a dataset of vehicle crashes that happened in thirteen urban road tunnels traversing the Huangpu River, established a binary logistic regression model to identify thirteen factors that contribute to escaping after crashes in Shanghai related to the offending drivers, the vehicular and environmental conditions, the tunnel characteristics and crash information. Among the thirty-five variables considered, this study found that a perpetrator's tendency to leave the crash scene without reporting an accident was higher at night, in the tunnel exit, near to or in short tunnels, when a two-wheeled vehicle or heavy goods vehicle (HGV) was involved and when alcohol was involved. While a perpetrator was more likely to remain on the scene in the tunnel entrance, on a rainy day, in a rear end collision, when a bus was involved, in a single vehicle or a multi-vehicle accident. Based on these findings, several countermeasures for better supervision and hit-and-run prevention are proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Video head-impulse test (vHIT) in dizzy children with normal caloric responses.

    Science.gov (United States)

    Khater, Ahmed Mohammed; Afifi, Pretty O

    2016-08-01

    The caloric test and the video head-impulse test are diagnostic tools to examine dizzy patients through assessing the function of the semicircular canals. There are major differences between the two tests as regards stimulus characteristics, methodology, and function examined. The aim of this study is to evaluate the results of vHIT in children and adolescents with normal caloric test. This work was performed on 63 patients, but 14 were excluded because of technical problems in the caloric test. So, this is a prospective work in 49 patients (27 females and 22 males) with different types of vestibular disease seen because of vertigo in which both procedures were performed the same day. The caloric test was performed with air at two different temperatures in which both ears were irrigated alternately. Then, the video head-impulse test was carried out. Main outcome measures were the gain of vestibulo-ocular reflex, gain asymmetry, and refixation saccades in the vHIT. in all studied cases, caloric test was normal. The mean age of patients was 16 years. By vHIT, in 8 patients (16%) no abnormality was detected, while abnormal findings were found in 41 patients. Single canal affection was seen in 29 patients whereas 12 patients had combined canal affection. The right side was affected in 27 and left side in 22 patients. In single canal affection, isolated horizontal canals were affected in 4, anterior canals in 5 and posterior canals in 20 patients. While in combined canal affection, the affection is seen in the same ear. Moreover the most common pattern seen is affection of left anterior and left posterior canals. The caloric and vHIT is very important tests in diagnosis of dizzy patients. The information from both methods is redundant in some cases but complementary in most. vHIT is a "child friendly," relatively easy-to-use, and simple tool to evaluate each of the 6 semicircular canals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Successful management of acute thromboembolic disease complicated with heparin induced thrombocytopenia type II (HIT II: a case series

    Directory of Open Access Journals (Sweden)

    Trellopoulos George

    2008-07-01

    Full Text Available Abstract Heparin-induced thrombocytopenia type II (HIT II is a rare immune-mediated complication of heparin. The diagnosis of HIT is considered in patients exposed to heparin, presenting with thrombocytopenia and thrombosis. We present two cases with massive pulmonary embolism and HIT, successfully treated with the administration of fondaparinux, an alternative anticoagulant, combined with the insertion of an inferior vena cava filter for the prevention of new thromboembolic events. The two cases supplement the available data of the use of fondaparinux in patients with HIT and pulmonary embolism, before further large studies establish its efficacy and safety in this group of patients. Moreover, the management of these patients reveals the need for future evaluation of the combined therapy of alternative anticoagulant agents with the placement of vena cava filters.

  8. HIT, hallucination focused integrative treatment as early intervention in psychotic adolescents with auditory hallucinations : a pilot study

    NARCIS (Netherlands)

    Jenner, JA; van de Willige, G

    Objective: Early intervention in psychosis is considered important in relapse prevention. Limited results of monotherapies prompt to development of multimodular programmes. The present study tests feasibility and effectiveness of HIT, an integrative early intervention treatment for auditory

  9. HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism

    National Research Council Canada - National Science Library

    Weyn-Vanhentenryck, Sebastien M; Mele, Aldo; Yan, Qinghong; Sun, Shuying; Farny, Natalie; Zhang, Zuo; Xue, Chenghai; Herre, Margaret; Silver, Pamela A; Zhang, Michael Q; Krainer, Adrian R; Darnell, Robert B; Zhang, Chaolin

    2014-01-01

    .... However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution...

  10. 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.

  11. The Hydrogen Infrastructure Transition Model (HIT) & Its Application in Optimizing a 50-year Hydrogen Infrastructure for Urban Beijing

    OpenAIRE

    Lin, Zhenhong; Ogden, J; Fan, Yueyue; Sperling, Dan

    2006-01-01

    Beijing could be an attractive region to initiate a hydrogen infrastructure for transportation. Air quality is poor, oil imports are soaring, and there is a desire to introduce innovative responses for the 2008 Olympics. If Beijing were to proceed to build hydrogen infrastructure before and after 2008, how they might proceed has not been addressed empirically or theoretically. We introduce the Hydrogen Infrastructure Transition (HIT) model and apply it to urban Beijing. HIT is a dynamic progr...

  12. The Hydrogen Infrastructure Transition (HIT) Model and Its Application in Optimizing a 50-year Hydrogen Infrastructure for Urban Beijing

    OpenAIRE

    Lin, Zhenhong; Ogden, Joan M; Fan, Yueyue; Sperling, Dan

    2006-01-01

    Beijing could be an attractive region to initiate a hydrogen infrastructure for transportation. Air quality is poor, oil imports are soaring, and there is a desire to introduce innovative responses for the 2008 Olympics. If Beijing were to proceed to build hydrogen infrastructure before and after 2008, how they might proceed has not been addressed empirically or theoretically. We introduce the Hydrogen Infrastructure Transition (HIT) model and apply it to urban Beijing. HIT is a dynamic progr...

  13. Identification and hit-to-lead optimization of a novel class of CB1 antagonists.

    Science.gov (United States)

    Letourneau, Jeffrey J; Jokiel, Patrick; Olson, John; Riviello, Christopher M; Ho, Koc-Kan; McAleer, Lihong; Yang, Jingchun; Swanson, Robert N; Baker, James; Cowley, Phillip; Edwards, Darren; Ward, Nick; Ohlmeyer, Michael H J; Webb, Maria L

    2010-09-15

    The discovery, synthesis and preliminary structure-activity relationships (SARs) of a novel class of CB1 antagonists is described. Initial optimization of benzimidazole-based screening hit 4 led to the identification of 'inverted' indole-based lead compound 18c with improved properties versus compound 4 including reduced AlogP, improved microsomal stability and improved aqueous solubility. Compound 18c demonstrates in vivo CB1 antagonist efficacy (CB1 agonist induced hypothermia model) and is orally bioavailable in rat. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. 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.

  15. The REH theory of protein and nucleic acid divergence - A retrospective update. [Random Evolutionary Hits

    Science.gov (United States)

    Holmquist, R.

    1978-01-01

    The random evolutionary hits (REH) theory of evolutionary divergence, originally proposed in 1972, is restated with attention to certain aspects of the theory that have caused confusion. The theory assumes that natural selection and stochastic processes interact and that natural selection restricts those codon sites which may fix mutations. The predicted total number of fixed nucleotide replacements agrees with data for cytochrome c, a-hemoglobin, beta-hemoglobin, and myoglobin. The restatement analyzes the magnitude of possible sources of errors and simplifies calculational methodology by supplying polynomial expressions to replace tables and graphs.

  16. Using the QBO to predict the number of hurricanes hitting the U.S

    CERN Document Server

    Coughlin, Katie

    2007-01-01

    A simple study of the relationship between the QBO and the number of hurricanes in the Atlantic, both in the Basin and hitting the U.S. coastline, demonstrates that the QBO is not a particularly useful index to help predict hurricane numbers on five-year time scales. It is shown that there is very little difference between the number of hurricanes following easterly winds in the equatorial stratosphere and the number that follow westerly winds. Given this it is reasonable one would make better predictions just using the mean number of hurricanes in lieu of using the QBO and this is also simply demonstrated here.

  17. Effect of hydrogen plasma passivation on performance of HIT solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Jik Lee, Seung; Hwan Kim, Se; Jang, Jin [Deptartment of Information Display, Kyung Hee University, Seoul (Korea, Republic of); Won Kim, Dae; Hyung Kim, Ki; Kyu Kim, Beom [PV Technology Team, Hyosung Co. Ltd., Seoul (Korea, Republic of)

    2011-01-15

    We studied the performance improvement of HIT solar cells by optimizing H{sub 2} plasma exposure and deposition of thin a-S:H layer on c-Si. With increasing H{sub 2} treatment time, the V{sub OC} increases until 80 s and then decreases, indicating the optimum time is 80 s. It is found that the cell performance is almost the same with and without a thin a-Si:H layer when 80 s plasma is treated on the c-Si before i-layer deposition. The conversion efficiency of 14.04% was achieved at the substrate temperature of 160 C. (author)

  18. Hubs and Authorities in the World Trade Network Using a Weighted HITS Algorithm

    Science.gov (United States)

    Deguchi, Tsuyoshi; Takahashi, Katsuhide; Takayasu, Hideki; Takayasu, Misako

    2014-01-01

    We investigate the economic hubs and authorities of the world trade network (WTN) from to , an era of rapid economic globalization. Using a well-defined weighted hyperlink-induced topic search (HITS) algorithm, we can calculate the values of the weighted HITS hub and authority for each country in a conjugate way. In the context of the WTN, authority values are large for countries with significant imports from large hub countries, and hub values are large for countries with significant exports to high-authority countries. The United States was the largest economic authority in the WTN from to . The authority value of the United States has declined since , and China has now become the largest hub in the WTN. At the same time, China's authority value has grown as China is transforming itself from the “factory of the world” to the “market of the world.” European countries show a tendency to trade mostly within the European Union, which has decreased Europe's hub and authority values. Japan's authority value has increased slowly, while its hub value has declined. These changes are consistent with Japan's transition from being an export-driven economy in its high economic growth era in the latter half of the twentieth century to being a more mature, economically balanced nation. PMID:25050940

  19. Being hit twice: The psychological consequences of the economic crisis and an earthquake.

    Science.gov (United States)

    Starace, Fabrizio; Mungai, Francesco; Sarti, Elena; Addabbo, Tindara

    2016-06-01

    The Great Recession has caused worldwide tangible costs in terms of cuts in employment and income, which have been widely recognised also as major social determinants of mental health. Italy has not been spared from the financial crisis with severe societal and mental health consequences. In addition, a strong earthquake hit the province of Modena, Italy, in 2012, that is, amid the crisis. In this study, we explored and investigated the possible additional impact of concurrent events such as economic crisis and a natural disaster. Our analysis elaborated data from two local surveys, ICESmo2 (2006) and ICESmo3 (2012), and a national survey carried out in 2013 by the Italian National Institute of Statistics (Istituto Nazionale di Statistica (ISTAT)). A regression model was adopted to distinguish the effect of the crisis and the earthquake. Our analysis confirmed the negative effect of the economic crisis on psychological wellbeing, but within the province of Modena such an effect resulted as even stronger compared with the rest of Italy, particularly within those areas struck by the earthquake. Being hit by a combination of two major negative events might have a significantly increased negative effect on psychological health. The higher repercussion observed is not only attributable to the occurrence of a natural disaster but can be reasonably related to the additional effect of unemployment on psychological dimensions. © The Author(s) 2016.

  20. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH

    Directory of Open Access Journals (Sweden)

    Daisuke Kawai

    2013-10-01

    Full Text Available Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH. Multiple hits induce adipokine secretion, endoplasmic reticulum (ER and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease.

  1. 4SCan/vADME: intelligent library screening as a shortcut from hits to lead compounds.

    Science.gov (United States)

    Herz, Thomas; Wolf, Kristina; Kraus, Juergen; Kramer, Bernd

    2006-06-01

    Managing to solve the first step in drug discovery - the hit finding - can be a quite elaborate task, but it is only the initial step to the final goal; hit-to-lead optimisation still lies ahead and consumes even more time and resources. The solution is rather simple, that is, to take only the most promising compounds into account; but who is going to decide which ones are the most promising among a list of tens of millions of compounds in a virtual combinatorial library? 4SCan/vADME helps by bridging the gap between virtual (combinatorial) libraries designed by chemists and the in silico methods, docking and alignment, for screening databases. After choosing a random starting set, the implemented learning and prediction algorithm iteratively considers only combinations of fragments that have shown to result in more suitable interactions by the chosen method. ADME properties of the final list are then calculated via several in silico methods, resulting in a combined evaluation of the individual compound's target-specific, as well as ADME, properties. Based on the latter list of evaluated compounds, medicinal chemists can then decide which compounds might be the best ones to synthesise first and to serve as possible lead candidates. Following a brief introduction to virtual high-throughput screening techniques, the 4SCan/vADME method is outlined and discussed in this paper, using an example coming out of the 4SC pipeline.

  2. Spatio-temporal constraints on upright children's coordination when hitting a moving target.

    Science.gov (United States)

    Rosey, Florence; Keller, Jean; Golomer, Eveline

    2007-12-01

    To determine if the spatial and/or temporal context affected the coordination patterns of children under five in upright interceptive tasks, 3-year-olds hit a ball dropped from a ramp from five heights (1.5, 2, 2.5, 3, and 3.5 m) to control drop time. We studied the initiation time of hitting a ball with a cinematic analysis of the different joint movements (foot, knee, hip, shoulder, and hand). Two patterns of joint coordination were observed according to the rolling height of the ball: a de-synchronized pattern for heights of 2 m or above where the foot was the first to move and the hand the last, and a "synchronized" pattern, for the lowest height (1.5 m) where all joints started moving at the same time due to a strong temporal pressure. These two coordination patterns highlight a functional adaptation of body joints according to the spatio-temporal constraints among children from the age of three.

  3. Engineering and Design of the Steady Inductive Helicity Injected Torus (HIT--SI)

    Science.gov (United States)

    Sieck, P. E.; Jarboe, T. R.; Nelson, B. A.; Rogers, J. A.; Shumlak, U.

    1999-11-01

    Steady Inductive Helicity Injection (SIHI) is an inductive helicity injection method that injects helicity at a nearly constant rate, without open field lines, and without removing any helicity or magnetic energy from the plasma.(T.R. Jarboe, Fusion Technology, 36) (1), p. 85, 1999 SIHI directly produces a rotating magnetic field structure, and in the frame of the rotating field the current profile is nearly time independent. The Steady Inductive Helicity Injected Torus (HIT--SI) is a spheromak designed to implement SIHI so that the current profile in the rotating frame is optimized. The geometry of HIT--SI will be presented, including the manufacturing techniques and metallurgical processes planned for construction of the close-fitting flux conserver. The flux conserver is made of aged chromium copper with 80% the conductivity of pure copper. The detailed electrical insulation requirements in the helicity injector design lead to a complex o-ring seal and a plasma-sprayed alumina insulation coating. This has prompted the construction of an o-ring prototype test fixture having the main features of the o-ring design and the alumina coating. The design and evaluation of this fixture will also be presented with vacuum and voltage test results.

  4. Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

    Science.gov (United States)

    Shalev, Idan; Belsky, Jay

    2016-05-01

    Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. "I Wish the Hitting Would Stop . . . " An Assessment of a Domestic Violence Education Program for Elementary Students.

    Science.gov (United States)

    Dahle, Thorvald O; Archbold, Carol A

    2014-09-01

    School officials across the country have recognized that many of their students live in homes where domestic violence occurs. As a result, several elementary schools have implemented education-based programs focused on this issue. The current study evaluates the efficacy of the "I Wish the Hitting Would Stop . . . " program that was presented to elementary school children in two school districts in the Midwest. This study examines the level of knowledge retention by students who participated in the "I Wish the Hitting Would Stop . . . " program during the 2010-2011 and 2011-2012 academic years. Fourth- and fifth-grade students responded to open-ended questions regarding their understanding of domestic violence and their retention of the concepts presented in the "I Wish the Hitting Would Stop . . . " curriculum. While the results suggest that students retain the information presented in the program, there also appears to be a gender difference in knowledge retention. © The Author(s) 2014.

  6. Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program.

    Science.gov (United States)

    Wang, Ying; Edalji, Rohinton P; Panchal, Sanjay C; Sun, Chaohong; Djuric, Stevan W; Vasudevan, Anil

    2017-10-26

    It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k off ) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K i and k off . Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.

  7. 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.

  8. Applications of SU-8 in the development of a Single Ion Hit Facility

    Energy Technology Data Exchange (ETDEWEB)

    Arteaga-Marrero, N. [Division of Nuclear Physics, Department of Physics, Lund University, Professorsgatan 1, Box 118, SE-22100 Lund (Sweden)], E-mail: natalia.arteaga@nuclear.lu.se; Astromskas, G. [Division of Solid State Physics, Department of Physics, Lund University, Professorsgatan 1, Box 118, SE-22100 Lund (Sweden); Olsson, M.G. [Department of Infection Medicine, Lund University, Soelvegatan 19, B14, SE-22184 Lund (Sweden); Elfman, M.; Kristiansson, P.; Nilsson, E.J.C.; Nilsson, C.; Pallon, J. [Division of Nuclear Physics, Department of Physics, Lund University, Professorsgatan 1, Box 118, SE-22100 Lund (Sweden)

    2009-06-15

    The Lund Nuclear Microprobe (LNM) has been adapted to be used as a Single Ion Hit Facility (SIHF) for proton cell irradiation experiments at low dose. In order to test the capabilities of the system, Ni dot arrays and artificial cells have been fabricated with the photopolymer SU-8 and common lithographic techniques. The primary purpose of the Ni dot arrays was to determine the targeting accuracy of the beam in vacuum and in air. Additionally, this sample was employed to evaluate the system performance during cell target irradiation experiments. The Ni dot arrays were also used for beam characterization. The artificial cells were originally fabricated to test the software for cell recognition and localization, developed and implemented at the LNM. However, this sample became very functional to make small adjustments at the irradiation chamber for cell irradiation experiments. A description of the samples, fabrication procedure and applications are presented in this paper.

  9. 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...... antagonistic effect of 66nM in a BRET and 12nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27muM in cAMP)....

  10. Is "hit and run" a single word? The processing of irreversible binomials in neglect dyslexia.

    Science.gov (United States)

    Arcara, Giorgio; Lacaita, Graziano; Mattaloni, Elisa; Passarini, Laura; Mondini, Sara; Benincà, Paola; Semenza, Carlo

    2012-01-01

    The present study is the first neuropsychological investigation into the problem of the mental representation and processing of irreversible binomials (IBs), i.e., word pairs linked by a conjunction (e.g., "hit and run," "dead or alive"). In order to test their lexical status, the phenomenon of neglect dyslexia is explored. People with left-sided neglect dyslexia show a clear lexical effect: they can read IBs better (i.e., by dropping the leftmost words less frequently) when their components are presented in their correct order. This may be taken as an indication that they treat these constructions as lexical, not decomposable, elements. This finding therefore constitutes strong evidence that IBs tend to be stored in the mental lexicon as a whole and that this whole form is preferably addressed in the retrieval process.

  11. Hit, Robbed, and Put Down (but not Bullied): Underreporting of Bullying by Minority and Male Students.

    Science.gov (United States)

    Lai, Tianjian; Kao, Grace

    2018-03-01

    To tackle adolescent bullying and identify students most vulnerable to being bullied, it is essential to examine both occurrences of bullying behaviors and students' own likelihoods of reporting bullying. This study examines ethnic and gender differences in students' odds of reporting bullying using the Education Longitudinal Study of 2002, a nationally representative study of United States high school sophomores (N = 15,362; ages 15-19; 50.2% female). Compared to White and female students, minority (particularly Black and Hispanic) and male students report comparable or greater experiences of bullying behaviors (such as being threatened, hit, put down by peers, or having belongings forced from them, stolen or damaged), but are less likely to report that they have been "bullied." These findings point to racialized and gendered differences in reporting bullying experiences such that indicators of "weakness" in peer relations may carry a greater stigma for minority and male students.

  12. Double-Hit Lymphoma Presenting as Primary Renal Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Vikas Mehta

    2013-04-01

    Full Text Available B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as “double hit” lymphomas (DHL, are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathological features overlapping with Burkitt lymphoma (BL and diffuse large B-cell lymphoma (DLBCL. Primary renal lymphoma (PRL by definition is a renal lymphoma without evidence of systemic involvement. PRL is extremely rare with less than 100 cases of both Hodgkin disease and non-Hodgkin lymphoma reported in literature. Double hit lymphomas have extremely poor prognosis, and high resistance to intensive chemotherapy, including high-dose chemotherapy. We describe a very rare case of DHL arising in kidney as PRL in whom concurrent IGH-BCL2 and MYC rearrangements were detected. [J Interdiscipl Histopathol 2013; 1(2.000: 93-97

  13. Medicinal and Biological Chemistry (MBC) Library: An Efficient Source of New Hits.

    Science.gov (United States)

    Sebastián-Pérez, Víctor; Roca, Carlos; Awale, Mahendra; Reymond, Jean-Louis; Martinez, Ana; Gil, Carmen; Campillo, Nuria E

    2017-09-25

    Identification of new hits is one of the biggest challenges in drug discovery. Creating a library of well-characterized drug-like compounds is a key step in this process. Our group has developed an in-house chemical library called the Medicinal and Biological Chemistry (MBC) library. This collection has been successfully used to start several medicinal chemistry programs and developed in an accumulation of more than 30 years of experience in drug design and discovery of new drugs for unmet diseases. It contains over 1000 compounds, mainly heterocyclic scaffolds. In this work, analysis of drug-like properties and comparative study with well-known libraries by using different computer software are presented here.

  14. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit.

    Science.gov (United States)

    Gerstenberger, Brian S; Trzupek, John D; Tallant, Cynthia; Fedorov, Oleg; Filippakopoulos, Panagis; Brennan, Paul E; Fedele, Vita; Martin, Sarah; Picaud, Sarah; Rogers, Catherine; Parikh, Mihir; Taylor, Alexandria; Samas, Brian; O'Mahony, Alison; Berg, Ellen; Pallares, Gabriel; Torrey, Adam D; Treiber, Daniel K; Samardjiev, Ivan J; Nasipak, Brian T; Padilla-Benavides, Teresita; Wu, Qiong; Imbalzano, Anthony N; Nickerson, Jeffrey A; Bunnage, Mark E; Müller, Susanne; Knapp, Stefan; Owen, Dafydd R

    2016-05-26

    The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date. The medicinal chemistry program that led to PFI-3 from an initial fragment screening hit is described in detail, and additional analogues with differing family VIII bromodomain selectivity profiles are also reported. We also describe the full pharmacological characterization of PFI-3 as a chemical probe, along with phenotypic data on adipocyte and myoblast cell differentiation assays.

  15. Collision victim travels for "seven kilometres" on top of the car that hit him.

    Science.gov (United States)

    Heide, Steffen; Stiller, Dankwart; Kleiber, Manfred; Bluemke, Karen

    2012-10-01

    A 26-year-old man, after a drinking binge, drove into a tram building site and collided with a track-grinding machine which left a fist-size hole in his windscreen. He then hit a construction worker who was catapulted onto the car roof. The worker held on to the antenna and the windscreen hole, while the car drove on for 7 km, reaching speeds of 90 km h(-1). The victim suffered several fractures and survived with relatively little consequential damage. The investigation showed the driver to have been under the influence of alcohol and cannabis. In trial, he claimed loss of memory and stated that he had noticed neither the accident nor the man on his car roof. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  16. QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.

    Science.gov (United States)

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed. © 2016 Society for Risk Analysis.

  17. 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.

  18. The three-hit concept of vulnerability and resilience: towards 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.

    2013-01-01

    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. PMID:23838101

  19. Integrated Computational Approach for Virtual Hit Identification against Ebola Viral Proteins VP35 and VP40

    Directory of Open Access Journals (Sweden)

    Muhammad Usman Mirza

    2016-10-01

    Full Text Available The Ebola virus (EBOV has been recognised for nearly 40 years, with the most recent EBOV outbreak being in West Africa, where it created a humanitarian crisis. Mortalities reported up to 30 March 2016 totalled 11,307. However, up until now, EBOV drugs have been far from achieving regulatory (FDA approval. It is therefore essential to identify parent compounds that have the potential to be developed into effective drugs. Studies on Ebola viral proteins have shown that some can elicit an immunological response in mice, and these are now considered essential components of a vaccine designed to protect against Ebola haemorrhagic fever. The current study focuses on chemoinformatic approaches to identify virtual hits against Ebola viral proteins (VP35 and VP40, including protein binding site prediction, drug-likeness, pharmacokinetic and pharmacodynamic properties, metabolic site prediction, and molecular docking. Retrospective validation was performed using a database of non-active compounds, and early enrichment of EBOV actives at different false positive rates was calculated. Homology modelling and subsequent superimposition of binding site residues on other strains of EBOV were carried out to check residual conformations, and hence to confirm the efficacy of potential compounds. As a mechanism for artefactual inhibition of proteins through non-specific compounds, virtual hits were assessed for their aggregator potential compared with previously reported aggregators. These systematic studies have indicated that a few compounds may be effective inhibitors of EBOV replication and therefore might have the potential to be developed as anti-EBOV drugs after subsequent testing and validation in experiments in vivo.

  20. Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

    Science.gov (United States)

    Barnett, Madeleine L; Tusor, Nora; Ball, Gareth; Chew, Andrew; Falconer, Shona; Aljabar, Paul; Kimpton, Jessica A; Kennea, Nigel; Rutherford, Mary; David Edwards, A; Counsell, Serena J

    2018-01-01

    Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). We studied 491 infants (52% male) without focal destructive brain lesions born at hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white

  1. Heidelberg Ion Therapy Center (HIT): Initial clinical experience in the first 80 patients

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E. (Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)), E-mail: Stephanie.Combs@med.uni-heidelberg.de; Ellerbrock, Malte; Haberer, Thomas (Heidelberger Ionenstrahl Therapiezentrum (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg (Germany)) (and others)

    2010-10-15

    The Heidelberg Ion Therapy Center (HIT) started clinical operation in November 2009. In this report we present the first 80 patients treated with proton and carbon ion radiotherapy and describe patient selection, treatment planning and daily treatment for different indications. Patients and methods. Between November 15, 2009 and April 15, 2010, 80 patients were treated at the Heidelberg Ion Therapy Center (HIT) with carbon ion and proton radiotherapy. Main treated indications consisted of skull base chordoma (n = 9) and chondrosarcoma (n = 18), malignant salivary gland tumors (n=29), chordomas of the sacrum (n = 5), low grade glioma (n=3), primary and recurrent malignant astrocytoma and glioblastoma (n=7) and well as osteosarcoma (n = 3). Of these patients, four pediatric patients aged under 18 years were treated. Results. All patients were treated using the intensity-modulated rasterscanning technique. Seventy-six patients were treated with carbon ions (95%), and four patients were treated with protons. In all patients x-ray imaging was performed prior to each fraction. Treatment concepts were based on the initial experiences with carbon ion therapy at the Gesellschaft fuer Schwerionenforschung (GSI) including carbon-only treatments and carbon-boost treatments with photon-IMRT. The average time per fraction in the treatment room per patient was 29 minutes; for irradiation only, the mean time including all patients was 16 minutes. Position verification was performed prior to every treatment fraction with orthogonal x-ray imaging. Conclusion. Particle therapy could be included successfully into the clinical routine at the Dept. of Radiation Oncology in Heidelberg. Numerous clinical trials will subsequently be initiated to precisely define the role of proton and carbon ion radiotherapy in radiation oncology.

  2. Spreading of amyotrophic lateral sclerosis lesions--multifocal hits and local propagation?

    Science.gov (United States)

    Sekiguchi, Teruhiko; Kanouchi, Tadashi; Shibuya, Kazumoto; Noto, Yu-ichi; Yagi, Yohsuke; Inaba, Akira; Abe, Keisuke; Misawa, Sonoko; Orimo, Satoshi; Kobayashi, Takayoshi; Kamata, Tomoyuki; Nakagawa, Masanori; Kuwabara, Satoshi; Mizusawa, Hidehiro; Yokota, Takanori

    2014-01-01

    To investigate whether or not the lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation in the rostrocaudal direction along the spinal cord, as has been hypothesised (the 'single seed and simple propagation' hypothesis). Subjects included 36 patients with sporadic ALS and initial symptoms in the bulbar, respiratory or upper limb regions. Abnormal spontaneous activities in needle electromyography (nEMG)-that is, fibrillation potentials, positive sharp waves (Fib/PSWs) or fasciculation potentials (FPs)-were compared among the unilateral muscles innervated by different spinal segments, especially between the T10 and L5 paraspinal muscles, and between the vastus medialis and biceps femoris. Axon length and the proportion of muscle fibre types, which are both related to motoneuronal vulnerability in ALS, are similar in the paired muscles. Fourteen of 36 patients showed a non-contiguous distribution of nEMG abnormalities from the onset site, with skipping of intermediate segments. In eight of them, the non-contiguous pattern was evident between paired muscles with the same motoneuronal vulnerability. The non-contiguously affected lumbosacral lesions involved motoneuron columns horizontally or radially proximate to one another, appearing to form a cluster in four of the eight patients. FPs, known to precede Fib/PSWs, were shown more frequently than Fib/PSWs in all the lumbosacral segments but L5, suggesting that 2nd hits occur at L5 and then spread to other lumbosacral segments. In sporadic ALS, the distribution of lower motoneuron involvement cannot be explained by the 'single seed and simple propagation' hypothesis alone. We propose a 'multifocal hits and local propagation' hypothesis instead.

  3. Measurements of Ion Temperature and Velocity in HIT-SI with Comparison to NIMROD Calculations, Development of Piezoelectric Valve

    Science.gov (United States)

    Hossack, A. C.; Akcay, C.; Jarboe, T. R.; Rogers, J. A.; Kirkpatrick, A. M.; Smith, R. J.

    2012-10-01

    A one meter ion Doppler spectrometer has been upgraded to multichord capability using an image intensifier and high-speed camera. Two linear arrays of 36 fibers each simultaneously collect light across a toroidal and poloidal section of HIT-SI. Temperature and velocity data will be presented and compared with NIMROD calculation results. Additionally, a fast, piezoelectric valve has been developed which achieves a gas flow rates of over 325 Torr liters per second and response time of approximately 0.5 ms. Flow rate is proportional to voltage, so the valve will offer arbitrary fueling profile for HIT-SI3. Work supported by USDoE and ARRA.

  4. A Polynomial Time Construction of a Hitting Set for Read-Once Branching Programs of Width 3

    Czech Academy of Sciences Publication Activity Database

    Šíma, Jiří; Žák, Stanislav

    -, subm. 2015 (2018) ISSN 0022-0000 R&D Projects: GA ČR GBP202/12/G061; GA ČR GAP202/10/1333 Institutional support: RVO:67985807 Keywords : derandomization * Hitting Set * read-once branching programs * bounded width Subject RIV: IN - Informatics, Computer Science Impact factor: 1.678, year: 2016

  5. Relationships between Parents' Use of Corporal Punishment and Their Children's Endorsement of Spanking and Hitting Other Children

    Science.gov (United States)

    Simons, Dominique A.; Wurtele, Sandy K.

    2010-01-01

    Objectives: To explore the intergenerational cycle of violence, the present study examined the relationship between parental approval and children's approval of corporal punishment (CP) and the subsequent relationship between children's CP experience and preference for hitting to resolve interpersonal conflict. Method: Participants consisted of…

  6. The Case against Spanking: How to Discipline Your Child without Hitting. The Jossey-Bass Psychology Series.

    Science.gov (United States)

    Hyman, Irwin A.

    The research on discipline is synthesized and presented in a highly readable form making the case against corporal punishment of children. The negative results are presented through examples. Although popular opinion on the subject of hitting has shifted so that many parents as well as educators and therapists realize the connection between…

  7. A test of the hypothesis that time to tumor in humans fits the "one-hit" model.

    Science.gov (United States)

    Dorvlo, A S; Enslein, K; Salsburg, D

    1980-08-01

    Data from the Connecticut Tumor Registry for 1935-1968 for 14 tumor sites were subjected to formal statistical tests of the hypothesis that the time to tumor has an exponential distribution (and hence is a result of one random "hit"). All of the resulting 270 test statistics rejected the hypothesis.

  8. [Longitudinal study on adolescents' psychological resilience and its impact factors in 5.12 earthquake-hit areas].

    Science.gov (United States)

    Liu, Qiaolan; He, Furong; Jiang, Min; Zhou, Yanyang

    2013-11-01

    To explore the trajectory of psychological resilience and its impact factors of adolescents in earthquake-hit areas by latent variable growth curve model (LGM) and to find out protective factors for psychological resilience. Longitudinal design was administrated. All grade one students in two junior high schools in the heavily and slightly earthquake-hit areas respectively were investigated by follow-up study in one year. Repeated measures analysis of variance and latent variable growth curve model were used for statistical analysis. The three-time measurements of psychological resilience of adolescents in the heavily earthquake-hit areas were significantly lower than corresponding measurements of the slightly earthquake-hit areas all along. There was an ascending trend of adolescent's psychological resilience and objective support over one year (P protective factors of resilience were self-esteem and subjective support and indirectly protective factors were objective support and utilization of social support. The psychological resilience of boys was higher than that of girl, but the change trend of psychological resilience was no difference between boys and girls. Psychological resilience of adolescents had dynamic characteristics. Psychological resilience of adolescents would be damaged in disasters but it could be recovered through enhance internal and external protective factors.

  9. Combined use of pharmacophoric models together with drug metabolism and genotoxicity "in silico" studies in the hit finding process.

    Science.gov (United States)

    Jerez, Ma José; Jerez, Miguel; González-García, Coral; Ballester, Sara; Castro, Ana

    2013-01-01

    In this study we propose a virtual screening strategy based on the generation of a pharmacophore hypothesis, followed by an in silico evaluation of some ADME-TOX properties with the aim to apply it to the hit finding process and, specifically, to characterize new chemical entities with potential to control inflammatory processes mediated by T lymphocytes such as multiple sclerosis, systemic lupus erithematosus or rheumatoid arthritis. As a result, three compounds with completely novel scaffolds were selected as final hits for future hit-to-lead optimization due to their anti-inflammatory profile. The biological results showed that the selected compounds increased the intracellular cAMP levels and inhibited cell proliferation in T lymphocytes. Moreover, two of these compounds were able to increase the production of IL-4, an immunoregulatory cytokine involved in the selective deviation of T helper (Th) immune response Th type 2 (Th2), which has been proved to have anti-inflammatory properties in several animal models for autoimmune pathologies as multiple sclerosis or rheumatoid arthritis. Thus our pharmacological strategy has shown to be useful to find molecules with biological activity to control immune responses involved in many inflammatory disorders. Such promising data suggested that this in silico strategy might be useful as hit finding process for future drug development.

  10. Comparing among the Experiences of Self-Cutting, Hitting, and Scratching in Chinese Adolescents Attending Secondary Schools: An Interview Study

    Science.gov (United States)

    You, Jianing; Ma, Congfen; Lin, Min-Pei; Leung, Freedom

    2015-01-01

    This study examined adolescents' experiences associated with nonsuicidal self-injury (NSSI) and compared among the experiences of self-cutting, hitting, and scratching. Participants included 42 Chinese adolescents attending secondary schools. They had at least three NSSI episodes in the preceding year. Information about their experiences of NSSI…

  11. Genomes to Hits In Silico - A Country Path Today, A Highway Tomorrow: A Case Study of Chikungunya

    Science.gov (United States)

    Soni, Anjali; Pandey, Khushhali M; Ray, Pratima; Jayaram, B

    2013-01-01

    These are exciting times for bioinformaticians, computational biologists and drug designers with the genome and proteome sequences and related structural databases growing at an accelerated pace. The post-genomic era has triggered high expectations for a rapid and successful treatment of diseases. However, in this biological information rich and functional knowledge poor scenario, the challenges are indeed grand, no less than the assembly of the genome of the whole organism. These include functional annotation of genes, identification of druggable targets, prediction of three-dimensional structures of protein targets from their amino acid sequences, arriving at lead compounds for these targets followed by a transition from bench to bedside. We propose here a “Genome to Hits In Silico“ strategy (called Dhanvantari) and illustrate it on Chikungunya virus (CHIKV). “Genome to hits” is a novel pathway incorporating a series of steps such as gene prediction, protein tertiary structure determination, active site identification, hit molecule generation, docking and scoring of hits to arrive at lead compounds. The current state of the art for each of the steps in the pathway is high-lighted and the feasibility of creating an automated genome to hits assembly line is discussed. PMID:23260020

  12. The distribution of first hitting times of random walks on directed Erdős-Rényi networks

    Science.gov (United States)

    Tishby, Ido; Biham, Ofer; Katzav, Eytan

    2017-04-01

    We present analytical results for the distribution of first hitting times of random walkers (RWs) on directed Erdős-Rényi (ER) networks. Starting from a random initial node, a random walker hops randomly along directed edges between adjacent nodes in the network. The path terminates either by the retracing scenario, when the walker enters a node which it has already visited before, or by the trapping scenario, when it becomes trapped in a dead-end node from which it cannot exit. The path length, namely the number of steps, d, pursued by the random walker from the initial node up to its termination, is called the first hitting time. Using recursion equations, we obtain analytical results for the tail distribution of first hitting times, P≤ft(d>\\ell \\right) . The results are found to be in excellent agreement with numerical simulations. It turns out that the distribution P≤ft(d>\\ell \\right) can be expressed as a product of an exponential distribution and a Rayleigh distribution. We obtain expressions for the mean, median and standard deviation of this distribution in terms of the network size and its mean degree. We also calculate the distribution of last hitting times, namely the path lengths of self-avoiding walks on directed ER networks, which do not retrace their paths. The last hitting times are found to be much longer than the first hitting times. The results are compared to those obtained for undirected ER networks. It is found that the first hitting times of RWs in a directed ER network are much longer than in the corresponding undirected network. This is due to the fact that RWs on directed networks do not exhibit the backtracking scenario, which is a dominant termination mechanism of RWs on undirected networks. It is shown that our approach also applies to a broader class of networks, referred to as semi-ER networks, in which the distribution of in-degrees is Poisson, while the out-degrees may follow any desired distribution with the same mean as

  13. Identifying "Hitting Bottom" Among Individuals with Alcohol Problems: Development and Evaluation of the Noteworthy Aspects of Drinking Important to Recovery (NADIR).

    Science.gov (United States)

    Kirouac, Megan; Witkiewitz, Katie

    2017-10-15

    Alcohol use disorder (AUD) is a costly public health concern; yet, many individuals with AUD never receive formal treatment. Prior studies have identified that "hitting bottom" may be an important factor in seeking treatment for AUD) and the notion that "hitting bottom" is necessary for recovery is commonly portrayed in the popular media. Yet, "hitting bottom" has never been formally operationalized. The present article aimed to operationalize "hitting bottom." A multiphase process was used to develop a measure of hitting bottom among individuals experiencing alcohol problems: The Noteworthy Aspects of Drinking Important to Recovery (NADIR). Psychometric evaluation of the measure was conducted using online data collected from individuals who identified as moderate to heavy drinkers (N = 597). The NADIR included five lower-order dimensions and one higher-order dimension ("hitting bottom"), had strong concurrent validity with measures of alcohol use severity and alcohol-related problems, and was found to have excellent internal consistency reliability (α > 0.90). An overall summary score on the NADIR of 50+ (factor scores>0) differentiated individuals who had previously sought treatment for AUD and reported more excessive alcohol use compared to those with no treatment history and lower levels of alcohol use. Thus, the NADIR with a cutoff of 50 may be a good starting point for future researchers to test as a method to identify individuals who have hit bottom. Conclusions/Importance: The NADIR provides a viable operational definition of hitting bottom. Future research should evaluate the predictive validity of the NADIR.

  14. "I Feel like I'm Being Hit from All Directions": Enduring the Bombardment as a Mature-Age Learner Returning to Formal Learning

    Science.gov (United States)

    Willans, Julie; Seary, Karen

    2011-01-01

    The mature-age learner's re-engagement with a formal learning environment may be somewhat akin to the novice Paintball player who, unless well positioned and attuned to the rules of the combative game, is bombarded and worn down by constant "hits". For the mature-age learner, such "hits" may come in the form of tensions…

  15. Recurrent first hitting times in Wiener diffusion under several observation schemes.

    Science.gov (United States)

    Whitmore, G A; Ramsay, T; Aaron, S D

    2012-04-01

    Recurrent events are commonly encountered in the natural sciences, engineering, and medicine. The theory of renewal and regenerative processes provides an elegant mathematical foundation for idealized recurrent event processes. In real-world applications, however, the contexts tend to be complicated by a variety of practical intricacies, including observation schemes with different phase and data structures. This paper formulates a recurrent event process as a succession of independent and identically distributed first hitting times for a Wiener sample path as it passes through successive equally-spaced levels. We develop exact mathematical results for statistical inferences based on several observation schemes that include observation initiated at a renewal point, observation of a stationary process over a finite window, and other variants. We also consider inferences drawn from different data structures, including gap times between renewal points (or fragments thereof) and counts of renewal events occurring within an observation window. We explore the precision of estimates using simulated scenarios and develop empirical regression functions for planning the sample size of a recurrent event study. We demonstrate our results using data from a clinical trial for chronic obstructive pulmonary disease in which the recurrent events are successive exacerbations of the condition. The case study demonstrates how covariates can be incorporated into the analysis using threshold regression.

  16. In silico prediction of anti-malarial hit molecules based on machine learning methods.

    Science.gov (United States)

    Kumari, Madhulata; Chandra, Subhash

    2015-01-01

    Machine learning techniques have been widely used in drug discovery and development in the areas of cheminformatics. Aspartyl aminopeptidase (M18AAP) of Plasmodium falciparum is crucial for survival of malaria parasite. We have created predictive models using weka and evaluated their performance based on various statistical parameters. Random Forest based model was found to be the most specificity (97.94%), with best accuracy (97.3%), MCC (0.306) as well as ROC (86.1%). The accuracy and MCC of these models indicated that they could be used to classify huge dataset of unknown compounds to predict their antimalarial compounds to develop effective drugs. Further, we deployed best predictive model on NCI diversity set IV. As result we found 59 bioactive anti-malarial molecules inhibiting M18AAP. Further, we obtained 18 non-toxic hit molecules out of 59 bioactive compounds. We suggest that such machine learning approaches could be applied to reduce the cost and length of time of drug discovery.

  17. Dimensional measurement of micro parts with high aspect ratio in HIT-UOI

    Science.gov (United States)

    Dang, Hong; Cui, Jiwen; Feng, Kunpeng; Li, Junying; Zhao, Shiyuan; Zhang, Haoran; Tan, Jiubin

    2016-11-01

    Micro parts with high aspect ratios have been widely used in different fields including aerospace and defense industries, while the dimensional measurement of these micro parts becomes a challenge in the field of precision measurement and instrument. To deal with this contradiction, several probes for the micro parts precision measurement have been proposed by researchers in Center of Ultra-precision Optoelectronic Instrument (UOI), Harbin Institute of Technology (HIT). In this paper, optical fiber probes with structures of spherical coupling(SC) with double optical fibers, micro focal-length collimation (MFL-collimation) and fiber Bragg grating (FBG) are described in detail. After introducing the sensing principles, both advantages and disadvantages of these probes are analyzed respectively. In order to improve the performances of these probes, several approaches are proposed. A two-dimensional orthogonal path arrangement is propounded to enhance the dimensional measurement ability of MFL-collimation probes, while a high resolution and response speed interrogation method based on differential method is used to improve the accuracy and dynamic characteristics of the FBG probes. The experiments for these special structural fiber probes are given with a focus on the characteristics of these probes, and engineering applications will also be presented to prove the availability of them. In order to improve the accuracy and the instantaneity of the engineering applications, several techniques are used in probe integration. The effectiveness of these fiber probes were therefore verified through both the analysis and experiments.

  18. Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens.

    Science.gov (United States)

    Rice, Christopher A; Colon, Beatrice L; Alp, Mehmet; Göker, Hakan; Boykin, David W; Kyle, Dennis E

    2015-04-01

    Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of 500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. 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.

  20. The current status of REH theory. [Random Evolutionary Hits in biological molecular evolution

    Science.gov (United States)

    Holmquist, R.; Jukes, T. H.

    1981-01-01

    A response is made to the evaluation of Fitch (1980) of REH (random evolutionary hits) theory for the evolutionary divergence of proteins and nucleic acids. Correct calculations for the beta hemoglobin mRNAs of the human, mouse and rabbit in the absence and presence of selective constraints are summarized, and it is shown that the alternative evolutionary analysis of Fitch underestimates the total fixed mutations. It is further shown that the model used by Fitch to test for the completeness of the count of total base substitutions is in fact a variant of REH theory. Considerations of the variance inherent in evolutionary estimations are also presented which show the REH model to produce no more variance than other evolutionary models. In the reply, it is argued that, despite the objections raised, REH theory applied to proteins gives inaccurate estimates of total gene substitutions. It is further contended that REH theory developed for nucleic sequences suffers from problems relating to the frequency of nucleotide substitutions, the identity of the codons accepting silent and amino acid-changing substitutions, and estimate uncertainties.

  1. Does the Strategy of Risk Group Testing for Hepatitis C Hit the Target?

    Directory of Open Access Journals (Sweden)

    Mirjana R. Jovanovic

    2017-06-01

    Full Text Available In the European Union, it is estimated that there are 5.5 million individuals with chronic infection of hepatitis C. Intravenous drug abuse is undoubtedly the key source of the hepatitis C epidemic in Europe and the most efficient mode of transmission of HCV infections (primarily due to short incubation time, but also because the virus is introduced directly into the blood stream with the infected needle. Potentially high-risk and vulnerable populations in Europe (and the world include immigrants, prisoners, sex workers, men having sex with men, individuals infected with HIV, psychoactive substance users etc. Since there is a lack of direct evidence of clinical benefits of HCV testing, decisions related to testing are made based on indirect evidence. Clinical practice has shown that HCV antibody tests are mostly adequate for identification of HCV infection, but the problem is that this testing strategy does not hit the target. As a result of this health care system strategy, a large number of infected patients remain undetected or they are diagnosed late. There is only a vague link between screening and treatment outcomes since there is a lack of evidence on transmission risks, multiple causes, risk behavior, ways of reaching screening decisions, treatment efficiency, etc. According to results of limited number of studies it can be concluded that there is a need to develop targeted programmes for detection of HCV and other infections, but there also a need to decrease potential harms.

  2. Some recent advances of intelligent health monitoring systems for civil infrastructures in HIT

    Science.gov (United States)

    Ou, Jinping

    2005-06-01

    The intelligent health monitoring systems more and more become a technique for ensuring the health and safety of civil infrastructures and also an important approach for research of the damage accumulation or even disaster evolving characteristics of civil infrastructures, and attracts prodigious research interests and active development interests of scientists and engineers since a great number of civil infrastructures are planning and building each year in mainland China. In this paper, some recent advances on research, development nad implementation of intelligent health monitoring systems for civil infrastructuresin mainland China, especially in Harbin Institute of Technology (HIT), P.R.China. The main contents include smart sensors such as optical fiber Bragg grating (OFBG) and polivinyllidene fluoride (PVDF) sensors, fatigue life gauges, self-sensing mortar and carbon fiber reinforced polymer (CFRP), wireless sensor networks and their implementation in practical infrastructures such as offshore platform structures, hydraulic engineering structures, large span bridges and large space structures. Finally, the relative research projects supported by the national foundation agencies of China are briefly introduced.

  3. Ice Hockey Summit II: zero tolerance for head hits and fighting.

    Science.gov (United States)

    Smith, Aynsley M; Stuart, Michael J; Dodick, David W; Roberts, William O; Alford, Patrick W; Ashare, Alan B; Aubrey, Mark; Benson, Brian W; Burke, Chip J; Dick, Randall; Eickhoff, Chad; Emery, Carolyn A; Flashman, Laura A; Gaz, Daniel V; Giza, Chris C; Greenwald, Richard M; Herring, Stanley A; Hoshizaki, T Blaine; Hudziak, James J; Huston, John; Krause, David; LaVoi, Nicole; Leaf, Matt; Leddy, John J; MacPherson, Alison; McKee, Ann C; Mihalik, Jason P; Moessner, Anne M; Montelpare, William J; Putukian, Margot; Schneider, Kathryn J; Szalkowski, Ron; Tabrum, Mark; Whitehead, James R; Wiese-Bjornstal, Diane M

    2015-01-01

    This study aimed to present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building upon the Ice Hockey Summit I action plan (2011) to reduce SRC. The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure for the science and discussion held during Summit II (Mayo Clinic, Rochester, MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward, (2) Acute and Chronic Concussion Care: Making a Difference, (3) Preventing Concussions via Behavior, Rules, Education, and Measuring Effectiveness, (4) Updates in Equipment: Their Relationship to Industry Standards, and (5) Policies and Plans at State, National, and Federal Levels To Reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were voted on subsequently for purposes of prioritization. The following proceedings include the knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. The highest-priority action items identified from the Summit include the following: (1) eliminate head hits from all levels of ice hockey, (2) change body checking policies, and (3) eliminate fighting in all amateur and professional hockey.

  4. [HINT1--a novel tumor suppressor protein of the HIT superfamily].

    Science.gov (United States)

    Ozga, Magdalena

    2010-01-01

    The histidine triad nucleotide binding protein1 (Hint1) belongs to the first branch of the HIT superfamily. Hint1 catalyses the process of hydrolysis of the P-N bond in AMP-lysine, AMP-alanine, AMP-NH2. The physiological role of this enzyme is still unclear. There is accumulating evidence that HINT1 is a novel tumor suppressor protein, albeit the mechanism of action of HINT1 in respect to tumor suppression is not fully understood. Recent findings have shown that Hint1 inhibits the activity of the transcription factors AP1, MITF and USF2, as well as influences the transcription process of some genes of Wnt/beta-catenin pathway. Thereby, it seems that Hint1 exerts its major cellular function as gene transcription regulator, and thus, this function provides its potential role as a tumor suppressor protein. The clinical relevance of impairments in the Hint1 expression with the respect to specific human cancers is still a matter of extensive studies.

  5. Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis.

    Science.gov (United States)

    Unsinger, Jacqueline; Burnham, Carey-Ann D; McDonough, Jacquelyn; Morre, Michel; Prakash, Priya S; Caldwell, Charles C; Dunne, W Michael; Hotchkiss, Richard S

    2012-08-15

    Secondary hospital-acquired fungal infections are common in critically-ill patients and mortality remains high despite antimicrobial therapy. Interleukin-7 (IL-7) is a potent immunotherapeutic agent that improves host immunity and has shown efficacy in bacterial and viral models of infection. This study examined the ability of IL-7, which is currently in multiple clinical trials (including hepatitis and human immunodeficiency virus), to improve survival in a clinically relevant 2-hit model of fungal sepsis. Mice underwent cecal ligation and puncture to induce peritonitis. Four days later, surviving mice had intravenous injection with Candida albicans. Following Candida infection, mice were treated with IL-7 or saline control. The effect of IL-7 on host immunity and survival was recorded. IL-7 ameliorated the loss of immune effector cells and increased lymphocyte functions, including activation, proliferation, expression of adhesion molecules, and interferon-γ production. These beneficial effects of IL-7 were associated with an increase in global immunity as reflected by an enhanced delayed type hypersensitivity response and a 1.7-fold improvement in survival. The present findings showing that IL-7 improves survival in fungal sepsis, together with its previously reported efficacy in bacterial and viral infectious models, further supports its use as a novel immunotherapeutic in sepsis.

  6. Designing small universal k-mer hitting sets for improved analysis of high-throughput sequencing.

    Directory of Open Access Journals (Sweden)

    Yaron Orenstein

    2017-10-01

    Full Text Available With the rapidly increasing volume of deep sequencing data, more efficient algorithms and data structures are needed. Minimizers are a central recent paradigm that has improved various sequence analysis tasks, including hashing for faster read overlap detection, sparse suffix arrays for creating smaller indexes, and Bloom filters for speeding up sequence search. Here, we propose an alternative paradigm that can lead to substantial further improvement in these and other tasks. For integers k and L > k, we say that a set of k-mers is a universal hitting set (UHS if every possible L-long sequence must contain a k-mer from the set. We develop a heuristic called DOCKS to find a compact UHS, which works in two phases: The first phase is solved optimally, and for the second we propose several efficient heuristics, trading set size for speed and memory. The use of heuristics is motivated by showing the NP-hardness of a closely related problem. We show that DOCKS works well in practice and produces UHSs that are very close to a theoretical lower bound. We present results for various values of k and L and by applying them to real genomes show that UHSs indeed improve over minimizers. In particular, DOCKS uses less than 30% of the 10-mers needed to span the human genome compared to minimizers. The software and computed UHSs are freely available at github.com/Shamir-Lab/DOCKS/ and acgt.cs.tau.ac.il/docks/, respectively.

  7. Does the Strategy of Risk Group Testing for Hepatitis C Hit the Target?

    Science.gov (United States)

    Jovanovic, Mirjana R; Miljatovic, Aleksandar; Puskas, Laslo; Kapor, Slobodan; Puskas, Dijana L

    2017-01-01

    In the European Union, it is estimated that there are 5.5 million individuals with chronic infection of hepatitis C. Intravenous drug abuse is undoubtedly the key source of the hepatitis C epidemic in Europe and the most efficient mode of transmission of HCV infections (primarily due to short incubation time, but also because the virus is introduced directly into the blood stream with the infected needle). Potentially high-risk and vulnerable populations in Europe (and the world) include immigrants, prisoners, sex workers, men having sex with men, individuals infected with HIV, psychoactive substance users etc. Since there is a lack of direct evidence of clinical benefits of HCV testing, decisions related to testing are made based on indirect evidence. Clinical practice has shown that HCV antibody tests are mostly adequate for identification of HCV infection, but the problem is that this testing strategy does not hit the target. As a result of this health care system strategy, a large number of infected patients remain undetected or they are diagnosed late. There is only a vague link between screening and treatment outcomes since there is a lack of evidence on transmission risks, multiple causes, risk behavior, ways of reaching screening decisions, treatment efficiency, etc. According to results of limited number of studies it can be concluded that there is a need to develop targeted programmes for detection of HCV and other infections, but there also a need to decrease potential harms.

  8. Range management visual impacts

    Science.gov (United States)

    Bruce R. Brown; David Kissel

    1979-01-01

    Historical overgrazing of western public rangelands has resulted in the passage of the Public Rangeland Improvement Act of 1978. The main purpose of this Act is to improve unsatisfactory range conditions. A contributing factor to unfavorable range conditions is adverse visual impacts. These visual impacts can be identified in three categories of range management: range...

  9. The distribution of first hitting times of non-backtracking random walks on Erdős-Rényi networks

    Science.gov (United States)

    Tishby, Ido; Biham, Ofer; Katzav, Eytan

    2017-05-01

    We present analytical results for the distribution of first hitting times of non-backtracking random walks on finite Erdős-Rényi networks of N nodes. The walkers hop randomly between adjacent nodes on the network, without stepping back to the previous node, until they hit a node which they have already visited before or get trapped in a dead-end node. At this point, the path is terminated. The length, d, of the resulting path, is called the first hitting time. Using recursion equations, we obtain analytical results for the tail distribution of first hitting times, P(d > \\ell) , \\ell=0, 1, 2, \\dots , of non-backtracking random walks starting from a random initial node. It turns out that the distribution P(d > \\ell) is given by a product of a discrete Rayleigh distribution and an exponential distribution. We obtain analytical expressions for central measures (mean and median) and a dispersion measure (standard deviation) of this distribution. It is found that the paths of non-backtracking random walks, up to their termination at the first hitting time, are longer, on average, than those of the corresponding simple random walks. However, they are shorter than those of self avoiding walks on the same network, which terminate at the last hitting time. We obtain analytical results for the probabilities, p ret and p trap, that a path will terminate by retracing, namely stepping into an already visited node, or by trapping, namely entering a node of degree k  =  1, which has no exit link, respectively. It is shown that in dilute networks the dominant termination scenario is trapping while in dense networks most paths terminate by retracing. We obtain expressions for the conditional tail distributions of path lengths, P(d> \\ell \\vert ret) and P(d> \\ell \\vert {trap}) , for those paths which terminate by retracing or by trapping, respectively. We also study a class of generalized non-backtracking random walk models which not only avoid the backtracking step

  10. A Hurricane Hits Home: An Interactive Science Museum Exhibit on Ocean Mapping and Marine Debris

    Science.gov (United States)

    Butkiewicz, T.; Vasta, D. J.; Gager, N. C.; Fruth, B. W.; LeClair, J.

    2016-12-01

    As part of the outreach component for a project involving the detection and analysis of marine debris generated by Super Storm Sandy, The Center for Coastal and Ocean Mapping / Joint Hydrographic Center partnered with The Seacoast Science Center to develop an interactive museum exhibit that engages the public with a touchscreen based game revolving around the detection and identification of marine debris. "A Hurricane Hits Home" is a multi-station touchscreen exhibit geared towards children, and integrates a portion of a historical wooden shipwreck into its physical design. The game invites museum guests to examine a number of coastal regions and harbors in Sandy affected areas. It teaches visitors about modern mapping technology by having them control boats with multibeam sonars and airplanes with lidar sensors. They drag these vehicles around maps to reveal the underlying bathymetry below the satellite photos. They learn the applications and limitations of sonar and lidar by where the vehicles can and cannot collect survey data (e.g. lidar doesn't work in deep water, and the boat can't go in shallow areas). As users collect bathymetry data, they occasionally reveal marine debris objects on the seafloor. Once all the debris objects in a level have been located, the game challenges them to identify them based on their appearance in the bathymetry data. They must compare the simulated bathymetry images of the debris targets to photos of possible objects, and choose the correct matches to achieve a high score. The exhibit opened January 2016 at the Seacoast Science Center in Rye, NH.

  11. Outcomes of Patients With Double-Hit Lymphoma Who Achieve First Complete Remission.

    Science.gov (United States)

    Landsburg, Daniel J; Falkiewicz, Marissa K; Maly, Joseph; Blum, Kristie A; Howlett, Christina; Feldman, Tatyana; Mato, Anthony R; Hill, Brian T; Li, Shaoying; Medeiros, L Jeffrey; Torka, Pallawi; Hernandez-Ilizaliturri, Francisco; Reddy, Nishitha M; Singavi, Arun; Fenske, Timothy S; Chavez, Julio C; Kaplan, Jason B; Behdad, Amir; Petrich, Adam M; Bast, Martin A; Vose, Julie M; Olszewski, Adam J; Costa, Cristiana; Lansigan, Frederick; Gerson, James N; Barta, Stefan K; Calzada, Oscar; Cohen, Jonathon B; Lue, Jennifer K; Amengual, Jennifer E; Rivera, Xavier; Persky, Daniel O; Peace, David J; Nathan, Sunita; Cassaday, Ryan D

    2017-07-10

    Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.

  12. One For All? Hitting multiple Alzheimer’s Disease targets with one drug

    Directory of Open Access Journals (Sweden)

    Rebecca Ellen Hughes

    2016-04-01

    Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

  13. One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug.

    Science.gov (United States)

    Hughes, Rebecca E; Nikolic, Katarina; Ramsay, Rona R

    2016-01-01

    HIGHLIGHTS Many AD target combinations are being explored for multi-target drug design.New databases and models increase the potential of computational drug designLiraglutide and other antidiabetics are strong candidates for repurposing to AD.Donecopride a dual 5-HT/AChE inhibitor shows promise in pre-clinical studies Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MTD design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

  14. Assessment of current virotherapeutic application schemes: "hit hard and early" versus "killing softly"?

    Science.gov (United States)

    Ruf, Benjamin; Lauer, Ulrich M

    2015-01-01

    Over the past two decades, a considerable amount of oncolytic vector families has entered numerous clinical trials. However, to this date, the field has not yet been able to come to a common understanding regarding the best possible ways to administer oncolytic viruses to cancer patients. This is mainly due to the fact that so far clinical trials being designed for head-to-head comparisons (such as using two different virotherapeutics originating from two distinct virus families being applied via identical routes in the same types of cancer) are still missing. Hence, there is no consent (i) on the best route of virotherapeutics administration (e.g., systemic versus intratumoral), (ii) on the virus dosages to be applied, (iii) on dosing intervals, and (iv) on the numbers of repetitive courses of virus administration. As the detailed comparison of clinical virotherapy trial regimens is time-consuming and complex, we here present an overview of current state-of-the-art virotherapeutic application schemes. Notably, our comprehensive assessment culminates in raising two rough classifications of virotherapeutic strategies, i.e., "hit hard and early" versus "killing softly". In order to find out which one of these two gross alternatives might be most successful for each and every tumor entity, we here suggest the implementation of phase 1/2 studies, which primarily aim at a repetitive sampling and analysis of tumor samples in cancer patients treated with oncolytic viruses reading out (i) virus-specific, (ii) tumor-specific as well as (iii) immunotherapeutic parameters. On this basis, a rational design of significantly improved virotherapeutic application schemes should be possible in the future.

  15. Comparison of Document Index Graph Using TextRank and HITS Weighting Method in Automatic Text Summarization

    Science.gov (United States)

    Hadyan, Fadhlil; Shaufiah; Arif Bijaksana, Moch.

    2017-01-01

    Automatic summarization is a system that can help someone to take the core information of a long text instantly. The system can help by summarizing text automatically. there’s Already many summarization systems that have been developed at this time but there are still many problems in those system. In this final task proposed summarization method using document index graph. This method utilizes the PageRank and HITS formula used to assess the web page, adapted to make an assessment of words in the sentences in a text document. The expected outcome of this final task is a system that can do summarization of a single document, by utilizing document index graph with TextRank and HITS to improve the quality of the summary results automatically.

  16. 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.

  17. 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.

  18. Prospective evaluation of a rapid nanoparticle-based lateral flow immunoassay (STic Expert(®) HIT) for the diagnosis of heparin-induced thrombocytopenia.

    Science.gov (United States)

    Leroux, Dorothée; Hezard, Nathalie; Lebreton, Aurélien; Bauters, Anne; Suchon, Pierre; de Maistre, Emmanuel; Biron, Christine; Huisse, Marie-Genevieve; Ternisien, Catherine; Voisin, Sophie; Gruel, Yves; Pouplard, Claire

    2014-09-01

    A rapid lateral flow immunoassay (LFIA) (STic Expert(®) HIT), recently developed for the diagnosis of heparin-induced thrombocytopenia (HIT), was evaluated in a prospective multicentre cohort of 334 consecutive patients. The risk of HIT was estimated by the 4Ts score as low, intermediate and high in 28·7%, 61·7% and 9·6% of patients, respectively. Definite HIT was diagnosed in 40 patients (12·0%) with positive results on both enzyme-linked immunosorbent assay (Asserachrom(®) HPIA IgG) and serotonin release assay. The inter-reader reproducibility of results obtained was excellent (kappa ratio > 0·9). The negative predictive value of LFIA with plasma samples was 99·6% with a negative likelihood ratio (LR) of 0·03, and was comparable to those of the particle gel immunoassay (H/PF4-PaGIA(®) ) performed in 124 cases. Positive predictive value and positive LR were 44·4% and 5·87, respectively, and the results were similar for serum samples. The probability of HIT in intermediate risk patients decreased from 11·2% to 0·4% when the LFIA result was negative and increased to 42·5% when it was positive. In conclusion, the STic Expert(®) HIT combined with the 4Ts score is a reliable tool to rule out the diagnosis of HIT. © 2014 John Wiley & Sons Ltd.

  19. Minnesota Pheasant Range

    Data.gov (United States)

    Minnesota Department of Natural Resources — This dataset delineates the spatial range of wild pheasant populations in Minnesota as of 2002 by dividing the MN state boundary into 2 units: pheasant range and...

  20. Substring Range Reporting

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li

    2014-01-01

    We revisit various string indexing problems with range reporting features, namely, position-restricted substring searching, indexing substrings with gaps, and indexing substrings with intervals. We obtain the following main results. We give efficient reductions for each of the above problems...... to a new problem, which we call substring range reporting. Hence, we unify the previous work by showing that we may restrict our attention to a single problem rather than studying each of the above problems individually. We show how to solve substring range reporting with optimal query time and little...... for substring range reporting generalize to substring range counting and substring range emptiness variants. We also obtain non-trivial time-space trade-offs for these problems. Our bounds for substring range reporting are based on a novel combination of suffix trees and range reporting data structures...

  1. Reconciling the IPC and Two-Hit Models: Dissecting the Underlying Cellular and Molecular Mechanisms of Two Seemingly Opposing Frameworks.

    Science.gov (United States)

    Morris, Carlos F M; Tahir, Muhammad; Arshid, Samina; Castro, Mariana S; Fontes, Wagner

    2015-01-01

    Inflammatory cascades and mechanisms are ubiquitous during host responses to various types of insult. Biological models and interventional strategies have been devised as an effort to better understand and modulate inflammation-driven injuries. Amongst those the two-hit model stands as a plausible and intuitive framework that explains some of the most frequent clinical outcomes seen in injuries like trauma and sepsis. This model states that a first hit serves as a priming event upon which sequential insults can build on, culminating on maladaptive inflammatory responses. On a different front, ischemic preconditioning (IPC) has risen to light as a readily applicable tool for modulating the inflammatory response to ischemia and reperfusion. The idea is that mild ischemic insults, either remote or local, can cause organs and tissues to be more resilient to further ischemic insults. This seemingly contradictory role that the two models attribute to a first inflammatory hit, as priming in the former and protective in the latter, has set these two theories on opposing corners of the literature. The present review tries to reconcile both models by showing that, rather than debunking each other, each framework offers unique insights in understanding and modulating inflammation-related injuries.

  2. The two-hit hypothesis for neuroinflammation: role of exogenous ATP in modulating inflammation in the brain

    Directory of Open Access Journals (Sweden)

    Bernd L. Fiebich

    2014-09-01

    Full Text Available Brain inflammation is a common occurrence following responses to varied insults such as bacterial infections, stroke, traumatic brain injury and neurodegenerative disorders. A common mediator for these varied inflammatory responses is prostaglandin E2 (PGE2, produced by the enzymatic activity of cyclooxygenases (COX 1 and 2. Previous attempts to reduce neuronal inflammation through COX inhibition, by use of nonsteroidal anti-inflammatory drugs (NSAIDs, have met with limited success. We are proposing the two-hit model for neuronal injury – an initial localized inflammation mediated by PGE2 (first hit and the simultaneous release of adenosine triphosphate (ATP by injured cells (second hit, which significantly enhances the inflammatory response through increased synthesis of PGE2. Several evidences on the role of exogenous ATP in inflammation have been reported, including contrary instances where extracellular ATP reduces inflammatory events. In this review, we will examine the current literature on the role of P2 receptors, to which ATP binds, in modulating inflammatory reactions during neurodegeneration. Targeting the P2 receptors, therefore, provides a therapeutic alternative to reduce inflammation in the brain. P2 receptor-based anti-inflammatory drugs (PBAIDs will retain the activities of essential COX enzymes, yet will significantly reduce neuroinflammation by decreasing the enhanced production of PGE2 by extracellular ATP.

  3. 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

    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...... implant (CI) surgery. Subjects were tested using the vHIT by two of four different examiners. Two judges interpreted the occurrence of saccades in the diagram. MAIN OUTCOME MEASURES: VOR gain values and the occurrence of saccades in the diagram. Differences in gain values between examiners varied from 0...

  4. Substring Range Reporting

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li

    2011-01-01

    We revisit various string indexing problems with range reporting features, namely, position-restricted substring searching, indexing substrings with gaps, and indexing substrings with intervals. We obtain the following main results. – We give efficient reductions for each of the above problems...... to a new problem, which we call substring range reporting. Hence, we unify the previous work by showing that we may restrict our attention to a single problem rather than studying each of the above problems individually. – We show how to solve substring range reporting with optimal query time and little...... range reporting are based on a novel combination of suffix trees and range reporting data structures. The reductions are simple and general and may apply to other combinations of string indexing with range reporting....

  5. Compact Antenna Range

    Data.gov (United States)

    Federal Laboratory Consortium — Facility consists of a folded compact antenna range including a computer controlled three axis position table, parabolic reflector and RF sources for the measurement...

  6. Dryden Aeronautical Test Range

    Data.gov (United States)

    Federal Laboratory Consortium — Recently redesignated to honor Dr. Hugh L. Dryden, NASA's Dryden Aeronautical Test Range (DATR) supports aerospace flight research and technology integration, space...

  7. The HIT Expert Probability (HEP) Score: a novel pre‐test probability model for heparin‐induced thrombocytopenia based on broad expert opinion

    National Research Council Canada - National Science Library

    CUKER, A; AREPALLY, G; CROWTHER, M. A; RICE, L; DATKO, F; HOOK, K; PROPERT, K. J; KUTER, D. J; ORTEL, T. L; KONKLE, B. A; CINES, D. B

    2010-01-01

    .... Objectives:  To develop a pre‐test clinical scoring model for HIT based on broad expert opinion that may be useful in guiding clinical decisions regarding therapy. Patients/methods:  A pre...

  8. On Range of Skill

    DEFF Research Database (Denmark)

    Hansen, Thomas Dueholm; Miltersen, Peter Bro; Sørensen, Troels Bjerre

    2008-01-01

    size (and doubly exponential in its depth). We also provide techniques that yield concrete bounds for unbalanced game trees and apply these to estimate the Range of Skill of Tic-Tac-Toe and Heads-Up Limit Texas Hold'em Poker. In particular, we show that the Range of Skill of Tic-Tac-Toe is more than...

  9. Range Scheduling Aid (RSA)

    Science.gov (United States)

    Logan, J. R.; Pulvermacher, M. K.

    1991-01-01

    Range Scheduling Aid (RSA) is presented in the form of the viewgraphs. The following subject areas are covered: satellite control network; current and new approaches to range scheduling; MITRE tasking; RSA features; RSA display; constraint based analytic capability; RSA architecture; and RSA benefits.

  10. The United States Air Force Aims to be Fueled by Innovation, but is it Developing Leaders Who Can Hit That Target?

    Science.gov (United States)

    2014-06-13

    2001/12/ primal -leadership-the-hidden-driver-of-great-performance/ar/pr (accessed November 7, 2013). Govindarajan, Vijay. 2010. Innovation is not...THE UNITED STATES AIR FORCE AIMS TO BE FUELED BY INNOVATION , BUT IS IT DEVELOPING LEADERS WHO CAN HIT THAT TARGET? A thesis...Force Aims to be Fueled by Innovation , but is it Developing Leaders Who Can Hit That Target? 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  11. Home range and travels

    Science.gov (United States)

    Stickel, L.F.; King, John A.

    1968-01-01

    The concept of home range was expressed by Seton (1909) in the term 'home region,' which Burr (1940, 1943) clarified with a definition of home range and exemplified in a definitive study of Peromyscus in the field. Burt pointed out the ever-changing characteristics of home-range area and the consequent absence of boundaries in the usual sense--a finding verified by investigators thereafter. In the studies summarized in this paper, sizes of home ranges of Peromyscus varied within two magnitudes, approximately from 0.1 acre to ten acres, in 34 studies conducted in a variety of habitats from the seaside dunes of Florida to the Alaskan forests. Variation in sizes of home ranges was correlated with both environmental and physiological factors; with habitat it was conspicuous, both in the same and different regions. Food supply also was related to size of home range, both seasonally and in relation to habitat. Home ranges generally were smallest in winter and largest in spring, at the onset of the breeding season. Activity and size also were affected by changes in weather. Activity was least when temperatures were low and nights were bright. Effects of rainfall were variable. Sizes varied according to sex and age; young mice remained in the parents' range until they approached maturity, when they began to travel more widely. Adult males commonly had larger home ranges than females, although there were a number of exceptions. An inverse relationship between population density and size of home range was shown in several studies and probably is the usual relationship. A basic need for activity and exploration also appeared to influence size of home range. Behavior within the home range was discussed in terms of travel patterns, travels in relation to home sites and refuges, territory, and stability of size of home range. Travels within the home range consisted of repeated use of well-worn trails to sites of food, shelter, and refuge, plus more random exploratory travels

  12. Craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high-grade or diffuse intrinsic pontine gliomas. A first report from the GPOH-HIT-HGG Study Group

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, K.; Schlamann, A.; Pietschmann, S.; Kortmann, R.D. [University Medical Center Leipzig, Department of Radiation Oncology, Leipzig (Germany); Guckenberger, M. [University Medical Center Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Warmuth-Metz, M. [University Medical Center Wuerzburg, Department of Neuroradiology, Wuerzburg (Germany); Glueck, A. [Clinic for Radiation Oncology Schwabing, Muenchen (Germany); Wawer, A. [University Medical Center Muenchen Schwabing, Department of Pediatric Hematology and Oncology, Muenchen (Germany); Kramm, C.; Bueren, A.O. von [University Medical Center Goettingen, Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Goettingen (Germany)

    2014-04-15

    High-grade (HGG) and diffuse intrinsic pontine gliomas (DIPG) with primary metastatic spread are extremely rare and have a dismal prognosis. Analogous to simultaneous radiochemotherapy in non-metastatic HGG and DIPG, concurrent craniospinal irradiation (CSI) and metronomic temozolomide (metroTMZ) may represent a reasonable therapeutic approach. However, the antitumor efficacy and toxicity of this treatment still have to be investigated. Between March 2007 and December 2012, six children with primary metastatic HGG (n=4) or DIPG (n=2) received CSI and concurrent metroTMZ based on individual treatment recommendations and, in some cases, within the HIT-HGG 2007 multicenter trial. Outcome and treatment-related toxicities were evaluated. All patients received irradiation to the entire craniospinal axis (35.2 Gy, n=5; 36 Gy, n=1:) and 5 received a local boost to macroscopic tumor deposits. Simultaneously, metroTMZ (75 mg/m{sup 2}/day, n=5; 60 mg/m{sup 2}/day, n=1) was administered. Additionally, 1 patient received nimotuzumab once per week. Within a median follow-up of 10.0 months (range 6.5-18.7 months), all patients experienced disease progression and 5 patients died. Median progression-free survival was 4.0±0.8 months (range 2.4-10.7 months) and median overall survival was 7.6±3.5 months (range 4.0-17.6 months). Acute myelosuppression most severely limited application of this aggressive treatment strategy. Severe hematotoxicities (= grade 3) occurred in all patients and metroTMZ had to be interrupted or discontinued in 4 out of 6 cases. Concurrent CSI and metroTMZ might represent a feasible treatment approach for primary metastatic HGG and DIPG. On the basis of our experience, severe but manageable acute hematotoxicity has to be expected. An international effort is warranted to reassess the efficacy and toxicity of this approach within a prospective study. (orig.)

  13. 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.

  14. Range of plasma ions in cold cluster gases near the critical point

    Science.gov (United States)

    Zhang, G.; Quevedo, H. J.; Bonasera, A.; Donovan, M.; Dyer, G.; Gaul, E.; Guardo, G. L.; Gulino, M.; La Cognata, M.; Lattuada, D.; Palmerini, S.; Pizzone, R. G.; Romano, S.; Smith, H.; Trippella, O.; Anzalone, A.; Spitaleri, C.; Ditmire, T.

    2017-05-01

    We measure the range of plasma ions in cold cluster gases by using the Petawatt laser at the University of Texas-Austin. The produced plasma propagated in all directions some hitting the cold cluster gas not illuminated by the laser. From the ratio of the measured ion distributions at different angles we can estimate the range of the ions in the cold cluster gas. It is much smaller than estimated using popular models, which take only into account the slowing down of charged particles in uniform matter. We discuss the ion range in systems prepared near a liquid-gas phase transition.

  15. Long range image enhancement

    CSIR Research Space (South Africa)

    Duvenhage, B

    2015-11-01

    Full Text Available and Vision Computing, Auckland, New Zealand, 23-24 November 2015 Long Range Image Enhancement Bernardt Duvenhage Council for Scientific and Industrial Research South Africa Email: bduvenhage@csir.co.za Abstract Turbulent pockets of air...

  16. SNOWY RANGE WILDERNESS, WYOMING.

    Science.gov (United States)

    Houston, Robert S.; Bigsby, Philip R.

    1984-01-01

    A mineral survey of the Snowy Range Wilderness in Wyoming was undertaken and was followed up with more detailed geologic and geochemical surveys, culminating in diamond drilling of one hole in the Snowy Range Wilderness. No mineral deposits were identified in the Snowy Range Wilderness, but inasmuch as low-grade uranium and associated gold resources were identified in rocks similar to those of the northern Snowy Range Wilderness in an area about 5 mi northeast of the wilderness boundary, the authors conclude that the northern half of the wilderness has a probable-resource potential for uranium and gold. Closely spaced drilling would be required to completely evaluate this mineral potential. The geologic terrane precludes the occurrence of fossil fuels.

  17. Atlantic Test Range (ATR)

    Data.gov (United States)

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

  18. Light Detection And Ranging

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — LiDAR (Light Detection and Ranging) discrete-return point cloud data are available in the American Society for Photogrammetry and Remote Sensing (ASPRS) LAS format....

  19. Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

    Directory of Open Access Journals (Sweden)

    Irina Haecker

    Full Text Available KSHV is the etiological agent of Kaposi's sarcoma (KS, primary effusion lymphoma (PEL, and a subset of multicentricCastleman's disease (MCD. The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regulation of gene expression is a complex network with each miRNA having many potential targets, and to date only few KSHV miRNA targets have been experimentally determined. A detailed understanding of KSHV miRNA functions requires high-through putribonomics to globally analyze putative miRNA targets in a cell type-specific manner. We performed Ago HITS-CLIP to identify viral and cellular miRNAs and their cognate targets in two latently KSHV-infected PEL cell lines. Ago HITS-CLIP recovered 1170 and 950 cellular KSHV miRNA targets from BCBL-1 and BC-3, respectively. Importantly, enriched clusters contained KSHV miRNA seed matches in the 3'UTRs of numerous well characterized targets, among them THBS1, BACH1, and C/EBPβ. KSHV miRNA targets were strongly enriched for genes involved in multiple pathways central for KSHV biology, such as apoptosis, cell cycle regulation, lymphocyte proliferation, and immune evasion, thus further supporting a role in KSHV pathogenesis and potentially tumorigenesis. A limited number of viral transcripts were also enriched by HITS-CLIP including vIL-6 expressed only in a subset of PEL cells during latency. Interestingly, Ago HITS-CLIP revealed extremely high levels of Ago-associated KSHV miRNAs especially in BC-3 cells where more than 70% of all miRNAs are of viral origin. This suggests that in addition to seed match-specific targeting of cellular genes, KSHV miRNAs may also function by hijacking RISCs, thereby contributing to a global de-repression of cellular gene expression due to the loss of regulation by human miRNAs. In summary, we provide an extensive list of cellular and viral miRNA targets representing an

  20. HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism

    OpenAIRE

    Weyn-Vanhentenryck, Sebastien M.; Mele, Aldo; Yan, Qinghong; Sun, Shuying; Farny, Natalie; Zhang, Zuo; Xue, Chenghai; Herre, Margaret; Silver, Pamela A.; Zhang, Michael Q.; Krainer, Adrian R.; Darnell, Robert B.; Zhang, Chaolin

    2014-01-01

    The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We find that the two guanines in the Rbfox binding motif UGCAUG are critical for prot...

  1. On Range of Skill

    DEFF Research Database (Denmark)

    Hansen, Thomas Dueholm; Miltersen, Peter Bro; Sørensen, Troels Bjerre

    2008-01-01

    is a small number, but only gave heuristic arguments for this. In this paper, we provide the first methods for rigorously estimating the Range of Skill of a given game. We provide some general, asymptotic bounds that imply that the Range of Skill of a perfectly balanced game tree is almost exponential in its......At AAAI'07, Zinkevich, Bowling and Burch introduced the Range of Skill measure of a two-player game and used it as a parameter in the analysis of the running time of an algorithm for finding approximate solutions to such games. They suggested that the Range of Skill of a typical natural game...... size (and doubly exponential in its depth). We also provide techniques that yield concrete bounds for unbalanced game trees and apply these to estimate the Range of Skill of Tic-Tac-Toe and Heads-Up Limit Texas Hold'em Poker. In particular, we show that the Range of Skill of Tic-Tac-Toe is more than...

  2. Block training periodization in alpine skiing: effects of 11-day HIT on VO2max and performance.

    Science.gov (United States)

    Breil, Fabio A; Weber, Simone N; Koller, Stefan; Hoppeler, Hans; Vogt, Michael

    2010-08-01

    Attempting to achieve the high diversity of training goals in modern competitive alpine skiing simultaneously can be difficult and may lead to compromised overall adaptation. Therefore, we investigated the effect of block training periodization on maximal oxygen consumption (VO2max) and parameters of exercise performance in elite junior alpine skiers. Six female and 15 male athletes were assigned to high-intensity interval (IT, N = 13) or control training groups (CT, N = 8). IT performed 15 high-intensity aerobic interval (HIT) sessions in 11 days. Sessions were 4 x 4 min at 90-95% of maximal heart rate separated by 3-min recovery periods. CT continued their conventionally mixed training, containing endurance and strength sessions. Before and 7 days after training, subjects performed a ramp incremental test followed by a high-intensity time-to-exhaustion (tlim) test both on a cycle ergometer, a 90-s high-box jump test as well as countermovement (CMJ) and squat jumps (SJ) on a force plate. IT significantly improved relative VO2max by 6.0% (P power output by 5.5% (P power output at ventilatory threshold 2 by 9.6% (P power (CMJ -4.8%, SJ -4.1%; P < 0.01), but not height decreased in IT only. For competitive alpine skiers, block periodization of HIT offers a promising way to efficiently improve VO2max and performance. Compromised explosive jump performance might be associated with persisting muscle fatigue.

  3. Protective effects of arachidonic acid against palmitic acid-mediated lipotoxicity in HIT-T15 cells.

    Science.gov (United States)

    Cho, Young Sik; Kim, Chi Hyun; Kim, Ki Young; Cheon, Hyae Gyeong

    2012-05-01

    Saturated fatty acids have been considered major contributing factors in type 2 diabetes, whereas unsaturated fatty acids have beneficial effects for preventing the development of diabetes. However, the effects of polyunsaturated fatty acids in pancreatic β cells have not been reported. Here, we examined the effects of arachidonic acid (AA) on palmitic acid (PA)-mediated lipotoxicity in clonal HIT-T15 pancreatic β cells. AA prevented the PA-induced lipotoxicity as indicated by cell viability, DNA fragmentation and mitochondrial membrane potential, whereas eicosatetraynoic acid (ETYA), a non-metabolizable AA, had little effect on PA-induced lipotoxicity. In parallel with its protective effects against PA-induced lipotoxicity, AA restored impaired insulin expression and secretion induced by PA. AA but not ETYA increased intracellular triglyceride (TG) in the presence of PA compared with PA alone, and xanthohumol, a diacylglycerol acyltransferase (DGAT) inhibitor, reversed AA-induced protection from PA. Taken together, our results suggest that AA protects against PA-induced lipotoxicity in clonal HIT-T15 pancreatic β cells, and the protective effects may be associated with TG accumulation, possibly through sequestration of lipotoxic PA into TG.

  4. 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].

  5. Comparative transcriptomes and reciprocal best hit analysis revealed potential pigment genes in two color forms of Tetranychus urticae.

    Science.gov (United States)

    Mo, Yi-Dan; Yang, Si-Xia; Zhao, Jing-Yu; Jin, Peng-Yu; Hong, Xiao-Yue

    2017-11-07

    Tetranychus urticae Koch is a worldwide agricultural pest. There are two color forms: red and green. The molecular mechanism underlying this color variation is unknown. To elucidate the mechanism, we characterized differentially expressed pigment pathway genes shared in the transcriptomes of these two forms using RNA sequencing and reciprocal best hit analysis. Differentially expressed pigment pathway genes were determined by qRT-PCR to confirm the accuracy of RNA-Seq. The transcriptomes revealed 963 differentially expressed genes (DEGs), of which 687 DEGs were higher in the green form. KEGG enrichment analysis revealed carotenoid biosynthesis genes in T. urticae. Reciprocal best hit analysis revealed 817 putative pigment pathway genes, 38 of which were differentially expressed and mainly classified into four categories: heme, melanin, ommochrome and rhodopsin. Phylogenetic analysis of homologous ommochrome genes showed that tetur09g01950 is closely related to Ok. This study revealed putative pigment pathway genes in the two forms of T. urticae, and might provide a new resource for understanding the mechanism of color variation.

  6. 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.

  7. Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade.

    Science.gov (United States)

    De Rycker, Manu; Thomas, John; Riley, Jennifer; Brough, Stephen J; Miles, Tim J; Gray, David W

    2016-04-01

    Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-Trypanosoma cruzi activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.

  8. Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade.

    Directory of Open Access Journals (Sweden)

    Manu De Rycker

    2016-04-01

    Full Text Available Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-Trypanosoma cruzi activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.

  9. NIMROD simulations and physics assessment of possible designs for a next generation Steady Inductive Helicity Injection HIT device

    Science.gov (United States)

    Penna, James; Morgan, Kyle; Grubb, Isaac; Jarboe, Thomas

    2017-10-01

    The Helicity Injected Torus - Steady Inductive 3 (HIT-SI3) experiment forms and maintains spheromaks via Steady Inductive Helicity Injection (SIHI) using discrete injectors that inject magnetic helicity via a non-axisymmetric perturbation and drive toroidally symmetric current. Newer designs for larger SIHI-driven spheromaks incorporate a set of injectors connected to a single external manifold to allow more freedom for the toroidal structure of the applied perturbation. Simulations have been carried out using the NIMROD code to assess the effectiveness of various imposed mode structures and injector schema in driving current via Imposed Dynamo Current Drive (IDCD). The results are presented here for varying flux conserver shapes on a device approximately 1.5 times larger than the current HIT-SI3 experiment. The imposed mode structures and spectra of simulated spheromaks are analyzed in order to examine magnetic structure and stability and determine an optimal regime for IDCD sustainment in a large device. The development of scaling laws for manifold operation is also presented, and simulation results are analyzed and assessed as part of the development path for the large scale device.

  10. Range Selection and Median

    DEFF Research Database (Denmark)

    Jørgensen, Allan Grønlund; Larsen, Kasper Green

    2011-01-01

    that supports queries in constant time, needs n1+ (1) space. For data structures that uses n logO(1) n space this matches the best known upper bound. Additionally, we present a linear space data structure that supports range selection queries in O(log k= log log n + log log n) time. Finally, we prove that any...

  11. Electric vehicles: Driving range

    Science.gov (United States)

    Kempton, Willett

    2016-09-01

    For uptake of electric vehicles to increase, consumers' driving-range needs must be fulfilled. Analysis of the driving patterns of personal vehicles in the US now shows that today's electric vehicles can meet all travel needs on almost 90% of days from a single overnight charge.

  12. Challenges in ethics, safety, best practices, and oversight regarding HIT vendors, their customers, and patients: a report of an AMIA special task force

    Science.gov (United States)

    Berner, Eta S; Dente, Mark A; Kaplan, Bonnie; Koppel, Ross; Rucker, Donald; Sands, Daniel Z; Winkelstein, Peter

    2010-01-01

    The current commercial health information technology (HIT) arena encompasses a number of competing firms that provide electronic health applications to hospitals, clinical practices, and other healthcare-related entities. Such applications collect, store, and analyze patient information. Some vendors incorporate contract language whereby purchasers of HIT systems, such as hospitals and clinics, must indemnify vendors for malpractice or personal injury claims, even if those events are not caused or fostered by the purchasers. Some vendors require contract clauses that force HIT system purchasers to adopt vendor-defined policies that prevent the disclosure of errors, bugs, design flaws, and other HIT-software-related hazards. To address this issue, the AMIA Board of Directors appointed a Task Force to provide an analysis and insights. Task Force findings and recommendations include: patient safety should trump all other values; corporate concerns about liability and intellectual property ownership may be valid but should not over-ride all other considerations; transparency and a commitment to patient safety should govern vendor contracts; institutions are duty-bound to provide ethics education to purchasers and users, and should commit publicly to standards of corporate conduct; and vendors, system purchasers, and users should encourage and assist in each others' efforts to adopt best practices. Finally, the HIT community should re-examine whether and how regulation of electronic health applications could foster improved care, public health, and patient safety. PMID:21075789

  13. The video head impulse test (vHIT of semicircular canal function – age dependent normative values of VOR gain in healthy subjects

    Directory of Open Access Journals (Sweden)

    Leigh Andrew McGarvie

    2015-07-01

    Full Text Available Background/Hypothesis. The video Head Impulse Test (vHIT is now widely used to test the function of each of the six semicircular canals individually by measuring the eye rotation response to an abrupt head rotation in the plane of the canal. The main measure of canal adequacy is the ratio of the eye movement response to the head movement stimulus i.e. the gain of the vestibulo-ocular reflex (VOR. However there is a need for normative data about how VOR gain is affected by age and also by head velocity, to allow the response of any particular patient to be compared to response of healthy subjects in their age range. In this study we determined for all six semicircular canals, normative values of VOR gain, for each canal across a range of head velocities, for healthy subjects in each decade of life.Study Design. The VOR gain was measured for all canals across a range of head velocities for at least 10 healthy subjects in decade age bands: 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89. Methods. The compensatory eye movement response to a small, unpredictable, abrupt head rotation (head impulse was measured by the ICS Impulse prototype system. The same operator delivered every impulse to every subject. Results. VOR gain decreased at high head velocities, but was largely unaffected by age into the 80-89 year age group. There were some small but systematic differences between the two directions of head rotation, which appear to be largely due to the fact that in this study only the right eye was measured. The results are considered in relation to recent evidence about the effect of age on VOR performance.Conclusion. These normative values allow the results of any particular patient to be compared to the values of healthy people in their age range and so allow, for example, detection of whether a patient has a bilateral vestibular loss. VOR gain, as measured directly by the eye movement response to head rotation, seems largely unaffected by

  14. Long-range antigravity

    Energy Technology Data Exchange (ETDEWEB)

    Macrae, K.I.; Riegert, R.J. (Maryland Univ., College Park (USA). Center for Theoretical Physics)

    1984-10-01

    We consider a theory in which fermionic matter interacts via long-range scalar, vector and tensor fields. In order not to be in conflict with experiment, the scalar and vector couplings for a given fermion must be equal, as is natural in a dimensionally reduced model. Assuming that the Sun is not approximately neutral with respect to these new scalar-vector charges, and if the couplings saturate the experimental bounds, then their strength can be comparable to that of gravity. Scalar-vector fields of this strength can compensate for a solar quadrupole moment contribution to Mercury's anomalous perihelion precession.

  15. Online Sorted Range Reporting

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf; Greve, Mark

    2009-01-01

    We study the following one-dimensional range reporting problem: On an arrayA of n elements, support queries that given two indices i ≤ j and an integerk report the k smallest elements in the subarray A[i..j] in sorted order. We present a data structure in the RAM model supporting such queries...... in optimal O(k) time. The structure uses O(n) words of space and can be constructed in O(n logn) time. The data structure can be extended to solve the online version of the problem, where the elements in A[i..j] are reported one-by-one in sorted order, in O(1) worst-case time per element. The problem...... is motivated by (and is a generalization of) a problem with applications in search engines: On a tree where leaves have associated rank values, report the highest ranked leaves in a given subtree. Finally, the problem studied generalizes the classic range minimum query (RMQ) problem on arrays....

  16. Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH)

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, K. [Leipzig Univ. (Germany). Dept. of Radiotherapy and Radiation Oncology; Gnekow, A.; Falkenstein, F. [General Hospital of Augsburg (Germany). Hospital for Children and Adolescents] [and others

    2013-08-15

    Purpose: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. Patients and methods: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. Results: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 {+-} 5 % after EFRT and 65 {+-} 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. Conclusion: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative. (orig.)

  17. Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A2A receptor.

    Science.gov (United States)

    Duroux, Romain; Renault, Nicolas; Cuelho, Joana Esteves; Agouridas, Laurence; Blum, David; Lopes, Luisa V; Melnyk, Patricia; Yous, Saïd

    2017-12-01

    The development of adenosine A2A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential A2AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A2A receptor. Compound F1, with an affinity of 1 μm, presented good absorption, distribution, metabolism and excretion properties with an excellent aqueous solubility (184 μm) without being cytotoxic at 100 μm. This compound, along with low-molecular weight compound D1 (Ki = 10 μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation.

  18. "Hit the ground running": perspectives of new nurses and nurse managers on role transition and integration of new graduates.

    Science.gov (United States)

    Chernomas, Wanda M; Care, W Dean; McKenzie, Jo-Ann Lapointe; Guse, Lorna; Currie, Jan

    2010-01-01

    The workplace for new graduates must be a constructive learning environment to facilitate their development. Nurse managers need new graduates who can "hit the ground running." Conflict between the needs of new nurses and the realities of the workplace often creates role confusion and tension in new graduates and threatens employers' ability to retain them. As part of a larger study that examined the effectiveness of a new strategy on new nurse retention and workplace integration, we conducted focus groups with new nurses and nurse managers. This paper discusses the perspectives of new nurses on their role transition from graduates to practising professionals and the perspectives of nurse managers on the workplace integration of new nurses. The thematic findings integrate new nurses' perspectives on their needs during role transition with the perspectives of nurse managers in meeting those needs. The discussion includes strategies to facilitate successful transition and integration of new nurses into the workplace within the context of recruitment and retention.

  19. Is “Hit and Run” a Single Word? The Processing of Irreversible Binomials in Neglect Dyslexia

    Science.gov (United States)

    Arcara, Giorgio; Lacaita, Graziano; Mattaloni, Elisa; Passarini, Laura; Mondini, Sara; Benincà, Paola; Semenza, Carlo

    2012-01-01

    The present study is the first neuropsychological investigation into the problem of the mental representation and processing of irreversible binomials (IBs), i.e., word pairs linked by a conjunction (e.g., “hit and run,” “dead or alive”). In order to test their lexical status, the phenomenon of neglect dyslexia is explored. People with left-sided neglect dyslexia show a clear lexical effect: they can read IBs better (i.e., by dropping the leftmost words less frequently) when their components are presented in their correct order. This may be taken as an indication that they treat these constructions as lexical, not decomposable, elements. This finding therefore constitutes strong evidence that IBs tend to be stored in the mental lexicon as a whole and that this whole form is preferably addressed in the retrieval process. PMID:22347199

  20. An Analytical Model for the Probability Characteristics of a Crack Hitting an Encapsulated Self-healing Agent in Concrete

    Science.gov (United States)

    Zemskov, Serguey V.; Jonkers, Henk M.; Vermolen, Fred J.

    The present study is performed in the framework of the investigation of the potential of bacteria to act as a catalyst of the self-healing process in concrete, i.e. their ability to repair occurring cracks autonomously. Spherical clay capsules containing the healing agent (calcium lactate) are embedded in the concrete structure. Water entering a freshly formed crack releases the healing agent and activates the bacteria which will seal the crack through the process of metabolically mediated calcium carbonate precipitation. In the paper, an analytic formalism is developed for the computation of the probability that a crack hits an encapsulated particle, i.e. the probability that the self-healing process starts. Most computations are performed in closed algebraic form in the computer algebra system Mathematica which allows to perform the last step of calculations numerically with a higher accuracy.

  1. A protocol for hit and control synchronous transfer for the front-end electronics at the CBM experiment

    Energy Technology Data Exchange (ETDEWEB)

    Kasinski, K., E-mail: kasinski@agh.edu.pl [AGH University of Science and Technology, Department of Measurement and Electronics, Av. Mickiewicza 30, 30-059 Cracow (Poland); Szczygiel, R. [AGH University of Science and Technology, Department of Measurement and Electronics, Av. Mickiewicza 30, 30-059 Cracow (Poland); Zabolotny, W. [Institute of Electronic Systems, Warsaw University of Technology, ul. Nowowiejska 15/19, 00-665 Warsaw (Poland); Lehnert, J.; Schmidt, C.J. [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstrasse 1, 64-291 Darmstadt (Germany); Müller, W.F.J. [FAIR Facility for Antiproton and Ion Research in Europe GmbH, Planckstrasse 1, 64-291 Darmstadt (Germany)

    2016-11-01

    The Silicon Tracking System, Muon Chamber, Transition Radiation Detector and Time-Of-Flight among others are the detector systems of the Compressed Baryonic Matter (CBM) experiment at the FAIR facility. These detector systems will be built with tens of thousands of front-end ASICs exposed to high radiation doses and difficult environmental and interference conditions. A CERN's GBTx-based solution was chosen for combining data from multiple front-end ASICs into an optical link before further concentration and preprocessing in the common Data Processing Board data hub. This paper presents the protocol design addressing the DAQ system requirements, simplifying the ASIC's back-end design and presents its adaptation for the STS and MUCH detector's conditions. A specific link synchronization technique, hit data bandwidth optimization and time synchronization method for the self-triggered front-end chip are presented.

  2. 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

    . An experimental depth dose curve obtained by the AD-4/ACE collaboration was compared with an earlier version of SHIELD-HIT, but since then inelastic annihilation cross sections for antiprotons have been updated and a more detailed geometric model of the AD-4/ACE experiment was applied. Furthermore, the Fermi...... of these updates is tested by comparing simulated data with the antiproton depth dose curve in water. It is found that the implementation of these new capture probabilities results in an overestimation of the depth dose curve in the Bragg peak. This can be mitigated by scaling the antiproton collision cross...... sections, which restores the agreement, but some small deviations still remain. Best agreement is achieved by using the most recent antiproton collision cross sections and the Fermi–Teller Z-law, even if experimental data conclude that the Z-law is inadequately describing annihilation on compounds. We...

  3. Is ‘hit and run’ a single word? The processing of irreversible binomials in neglect dyslexia

    Directory of Open Access Journals (Sweden)

    Giorgio eArcara

    2012-02-01

    Full Text Available The present study is the first neuropsychological investigation into the problem of the mental representation and processing of irreversible binomials, i.e. word pairs linked by a conjunction (e.g. ‘hit and run’, ‘dead or alive’. In order to test their lexical status, the phenomenon of neglect dyslexia is explored.People with left-sided neglect dyslexia show a clear lexical effect: they can read irreversible binomials better (i.e., by dropping the leftmost words less frequently when their components are presented in their correct order. This may be taken as an indication that they treat these constructions as lexical, not decomposable, elements. This finding therefore constitutes strong evidence that irreversible binomials tend to be stored in the mental lexicon as a whole and that this whole form is preferably addressed in the retrieval process.

  4. AMIA members' "vital signs": what the HIT implementation listserv says about goals for AMIA and for medical informatics.

    Science.gov (United States)

    Ravvaz, Kourosh; Kuziemsky, Craig; Koppel, Ross; Kaplan, Bonnie; Adams, Samantha A; Adams, Martha B

    2015-01-01

    The health information technology (HIT) implementation listserv was conceived as a way to combine a substantial portion of American Medical Informatics Association (AMIA) members who belonged to four working groups (WGs): CIS, Evaluation, ELSI, and POI. Other AMIA members joined in significant numbers. It immediately became a major forum for discussing medical informatics, informatics policies, and discussion of the purpose of AMIA itself. The listserv membership approximates 25% of AMIA's members and has generated over 6,000 posts. We report on a survey of the listserv's members: what members think about the listserv; what participants want for medical informatics; how they think those goals should be achieved, and what AMIA's role should be in this process. The listserv provides vital signs about AMIA and hopes for informatics. We combine qualitative analysis of members' comments and responses about the listserv using ATLAS.ti qualitative text analysis tool and a word cloud generator.

  5. 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.

  6. TJC: HCOs need to be on alert for HIT problems related to sociotechnical factors, take steps to improve safety culture, process, and leadership.

    Science.gov (United States)

    2015-06-01

    Noting that too many errors related to health information technology (HIT) are resulting in adverse consequences, The Joint Commission (TJC) has issued a Sentinel Event Alert, urging health care providers to take steps to improve their safety culture, approach to process improvement, and leadership in this area. In this latest alert, the accrediting agency is taking particular aim at risks posed by sociotechnical factors--or the ways in which HIT is implemented and used. Experts say that many of these risks are, in fact, exemplified at a higher level in the emergency setting, where providers are under constant pressure to see more patients and move them though the system faster. In an analysis of 3,375 sentinel events that resulted in permanent patient harm or death between January 1, 2010, and June 20, 2013, The Joint Commission (TJC) found that 120 events included HIT-related contributing factors. Many of the problems cited by TJC relate to orders or medicines being prescribed for the wrong patients. These can result from toggling errors or pop-up screens where providers are asked to click on the appropriate patient or medicine, and they mistakenly click on the wrong selection. In the ED, experts recommend the creation of a multidisciplinary performance improvement group to continuously monitor the ED information system (EDIS), recognize problems, and work with the vendor to resolve them. Also important is a quick and easy way for providers to report HIT-related problems. Experts add that emergency providers need to be fully engaged in the process of selecting HIT that they will be using, and that health care organizations should arrange for usability assessments before purchasing HIT.

  7. Characteristics of precipitating monsoon clouds over rain-shadow and drought-hit regions of India using radar

    Science.gov (United States)

    Morwal, S. B.; Narkhedkar, S. G.; Padmakumari, B.; Maheskumar, R. S.; Kulkarni, J. R.

    2017-07-01

    C-band radars were installed at Baramati and Shegaon as a part of operational cloud seeding program of Maharashtra State in the monsoon season (June-September) 2004. These provided first time a unique opportunity to study (1) characteristics of precipitating monsoon clouds (2) convection and (3) number of seedable clouds over Indian meteorological subdivisions of Madhya Maharashtra (rain-shadow) and Vidarbha (drought-hit). The monsoon season is divided into active and break periods. The cloud characteristics studied are: diurnal variation, cloud top heights and durations. Diurnal variation of cloud frequency shows maximum in the afternoon hours (10-11 UTC) and minimum in the early morning hours (3-4 UTC) in both the periods. Cloud tops show trimodal distributions with modes at 2-3, 8-9 and above 9 km. Mean cloud duration is 55 min. Congestus has been found prominent cloud type (65%) with mean top height of 6.76 km. Frequency of cumulonimbus clouds is found higher in the break periods. Cloud scale is taken as a metric for characterization of convection. Maximum frequency of cloud scale is found at C scale (mesoscale: area 100-1000 km2). Mesoscale Convective System has been found dominating convection type. The convection over the area has been shown to be hybrid type, consisting of basic oceanic type modulated by land convection. Convective clouds having maximum reflectivities between 25 and 35 dBZ, suitable for hygroscopic and glaciogenic seeding, are found in a large number. Understanding of characteristics of clouds and convection is useful for the diagnostic and precipitation enhancement studies over the rain-shadow/drought-hit regions.

  8. 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.

  9. Tanzania Health Information Technology (T-HIT) System: Pilot Test of a Tablet-Based System to Improve Prevention of Mother-to-Child Transmission of HIV.

    Science.gov (United States)

    Bull, Sheana; Thomas, Deborah Sk; Nyanza, Elias C; Ngallaba, Sospatro E

    2018-01-15

    The prevention of mother-to-child transmission (PMTCT) of HIV requires innovative solutions. Although routine monitoring is effective in some areas, standardized and easy-to-scale solutions to identify and monitor pregnant women, test them for HIV, and treat them and their children is still lacking. Mobile health (mHealth) offers opportunities for surveillance and reporting in rural areas of low- and middle-income countries. The aim of this study was to document the preliminary impacts of the Tanzania Health Information Technology (T-HIT) system mHealth intervention aimed at health workers for PMTCT care delivery and capacity building in a rural area of Tanzania. We developed T-HIT as a tablet-based system for an electronic data collection system designed to capture and report PMTCT data during antenatal, delivery, and postnatal visits in Misungwi, Tanzania. T-HIT was tested by health workers in a pilot randomized trial comparing seven sites using T-HIT assigned at random to seven control sites; all sites maintained standard paper record-keeping during the pilot intervention period. We compared numbers of antenatal visits, number of HIV tests administered, and women testing positive across all sites. Health workers recorded data from antenatal visits for 1530 women; of these, 695 (45.42%) were tested for HIV and 3.59% (55/1530) tested positive. Health workers were unable to conduct an HIV test for 103 women (6.73%, 103/1530) because of lack of reagent, which is not captured on paper logs. There was no difference in the activity level for testing when comparing sites T-HIT to non-T-HIT sites. We observed a significant postintervention increase in the numbers of women testing positive for HIV compared with the preintervention period (P=.04), but this was likely not attributable to the T-HIT system. T-HIT had a high degree of acceptability and feasibility and is perceived as useful by health workers, who documented more antenatal visits during the pilot intervention

  10. Lightning detection and ranging

    Science.gov (United States)

    Lennon, C. L.; Poehler, H. A.

    1982-01-01

    A lightning detector and ranging (LDAR) system developed at the Kennedy Space Center and recently transferred to Wallops Island is described. The system detects pulsed VHF signals due to electrical discharges occurring in a thunderstorm by means of 56-75 MHz receivers located at the hub and at the tips of 8 km radial lines. Incoming signals are transmitted by wideband links to a central computing facility which processes the times of arrival, using two independent calculations to determine position in order to guard against false data. The results are plotted on a CRT display, and an example of a thunderstorm lightning strike detection near Kennedy Space Center is outlined. The LDAR correctly identified potential ground strike zones and additionally provided a high correlation between updrafts and ground strikes.

  11. Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Nicolas U., E-mail: nicolas.gerber@kispi.uzh.ch [Department of Pediatric Oncology, University Children' s Hospital, Zurich (Switzerland); Hoff, Katja von; Resch, Anika [Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Ottensmeier, Holger [Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg (Germany); Kwiecien, Robert; Faldum, Andreas [Institute of Biostatistics and Clinical Research, University of Muenster (Germany); Matuschek, Christiane [Department of Radiation Oncology, Medical Faculty, Heinrich Heine University of Duesseldorf, Duesseldorf (Germany); Hornung, Dagmar [Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Bremer, Michael [Institute for Radiation Therapy and Special Oncology, Hannover Medical School, Hannover (Germany); Benesch, Martin [Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz (Austria); Pietsch, Torsten [Department of Neuropathology, University of Bonn, Bonn (Germany); Warmuth-Metz, Monika [Department of Neuroradiology, University of Wuerzburg, Wuerzburg (Germany); Kuehl, Joachim [Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg (Germany); Rutkowski, Stefan [Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kortmann, Rolf D. [Department of Radiation Oncology, University of Leipzig, Leipzig (Germany)

    2014-07-15

    Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. Methods and Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (±standard error [SE]) were each 58% (±10%) for the entire cohort: CNS-PNET was 53% (±13); pinealoblastoma was 64% (±15%; P=.524 and P=.627, respectively). Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

  12. Hitting our Heads on the Glass Ceiling: Women and Leadership in Education in Indonesia

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    Siti Ruhaini Dzuhayatin

    2010-08-01

    Full Text Available This paper begins by describing the present situation at the madrasah level in areas that participate in LAPIS-ELOIS activities and identifies the personal, cultural, and religious factors that contribute to women's under-representation in leadership and decision-making roles. Women's participation in leadership and decision making in Islamic universities involved in LAPIS-PGMI is discussed using data from consortium institutions. The range of factors contributing to the imbalance are discussed before turning to the policy issues that continue to contribute to gender disparity in leadership and decision making. The paper concludes by identifying some directions for action.Copyright (c 2014 by SDI. All right reserved.DOI: 10.15408/sdi.v17i2.460

  13. From hitting to tattling to gossip: an evolutionary rationale for the development of indirect aggression.

    Science.gov (United States)

    Ingram, Gordon P D

    2014-04-29

    Adult humans are characterized by low rates of intra-group physical aggression. Since children tend to be more physically aggressive, an evolutionary developmental account shows promise for explaining how physical aggression is suppressed in adults. I argue that this is achieved partly through extended dominance hierarchies, based on indirect reciprocity and linguistic transmission of reputational information, mediated by indirectly aggressive competition. Reviewing the literature on indirect and related forms of aggression provides three pieces of evidence for the claim that evolutionarily old impulses towards physical aggression are socialized into indirect aggression in humans: (i) physical aggression falls in early childhood over the same age range at which indirect aggression increases; (ii) the same individuals engage in both direct and indirect aggression; and (iii) socially dominant individuals practice indirect aggression more frequently. Consideration of the developmental course of indirect aggression is complemented by analysis of similar developments in verbal behaviors that are not always thought of as aggressive, namely tattling and gossip. An important puzzle concerns why indirect aggression becomes more covert, and tattling more derogated, in preadolescence and adolescence. This may be due to the development of new strategies aimed at renegotiating social identity and friendship alliances in the peer group.

  14. From Hitting to Tattling to Gossip: An Evolutionary Rationale for the Development of Indirect Aggression

    Directory of Open Access Journals (Sweden)

    Gordon P. D. Ingram

    2014-04-01

    Full Text Available Adult humans are characterized by low rates of intra-group physical aggression. Since children tend to be more physically aggressive, an evolutionary developmental account shows promise for explaining how physical aggression is suppressed in adults. I argue that this is achieved partly through extended dominance hierarchies, based on indirect reciprocity and linguistic transmission of reputational information, mediated by indirectly aggressive competition. Reviewing the literature on indirect and related forms of aggression provides three pieces of evidence for the claim that evolutionarily old impulses towards physical aggression are socialized into indirect aggression in humans: (i physical aggression falls in early childhood over the same age range at which indirect aggression increases; (ii the same individuals engage in both direct and indirect aggression; and (iii socially dominant individuals practice indirect aggression more frequently. Consideration of the developmental course of indirect aggression is complemented by analysis of similar developments in verbal behaviors that are not always thought of as aggressive, namely tattling and gossip. An important puzzle concerns why indirect aggression becomes more covert, and tattling more derogated, in preadolescence and adolescence. This may be due to the development of new strategies aimed at renegotiating social identity and friendship alliances in the peer group.

  15. Flexible End2End Workflow Automation of Hit-Discovery Research.

    Science.gov (United States)

    Holzmüller-Laue, Silke; Göde, Bernd; Thurow, Kerstin

    2014-08-01

    The article considers a new approach of more complex laboratory automation at the workflow layer. The authors purpose the automation of end2end workflows. The combination of all relevant subprocesses-whether automated or manually performed, independently, and in which organizational unit-results in end2end processes that include all result dependencies. The end2end approach focuses on not only the classical experiments in synthesis or screening, but also on auxiliary processes such as the production and storage of chemicals, cell culturing, and maintenance as well as preparatory activities and analyses of experiments. Furthermore, the connection of control flow and data flow in the same process model leads to reducing of effort of the data transfer between the involved systems, including the necessary data transformations. This end2end laboratory automation can be realized effectively with the modern methods of business process management (BPM). This approach is based on a new standardization of the process-modeling notation Business Process Model and Notation 2.0. In drug discovery, several scientific disciplines act together with manifold modern methods, technologies, and a wide range of automated instruments for the discovery and design of target-based drugs. The article discusses the novel BPM-based automation concept with an implemented example of a high-throughput screening of previously synthesized compound libraries. © 2014 Society for Laboratory Automation and Screening.

  16. Conventional over-the-top-aiming devices with short offset fail to hit the center of the human femoral ACL footprint in medial portal technique, whereas medial-portal-aiming devices with larger offset hit the center reliably.

    Science.gov (United States)

    Domnick, Christoph; Herbort, Mirco; Raschke, Michael J; Bremer, Susanne; Schliemann, Benedikt; Petersen, Wolf; Zantop, Thore

    2016-04-01

    Aim of this study was to investigate the accuracy of a conventional over-the-top-guide (OTG) with a typically short offset to hit the center of the native femoral ACL footprint through the anteromedial portal in comparison to a specific medial-portal-aimer (MPA) with larger offset. In 20 matched human cadaveric knees, insertion sites of the ACL were marked in medial arthrotomy. An OTG with an offset of 5.5 mm, respectively, the MPA with 9 mm offset was used in a medial portal approach to locate the center of a single bundle ACL reconstruction tunnel with k-wires. Distances from the footprint center, the OTG drilling and the MPA drilling to the roof of the intercondylar notch and to the deep cartilage margin were determined. After positioning of radiological markers, radiographic analysis was performed according to the quadrant technique as described by Bernard and Hertel. The distance from ACL origin to the roof of the notch was 10.3 (±2.1) mm, in the OTG group 6.7 (±1.5) mm and in the MPA group 9.6 (±1.9) mm. The distance to the deep cartilage margin was 9.5 (±1.7) mm from ACL origin, 4.8 (±1.3) mm with OTG and 8.7 (±1.4) mm with MPA. There were statistically significant differences between the distances of the footprint center and the OTG group after measuring and also after radiographic analysis (p  0.0001). There was an increased risk for femoral blow (9/10 vs. 0/10) in the OTG group after overdrilling with a 9 mm drill. Short (5.5 mm) offset femoral aiming devices fail to locate the native ACL footprint center in medial portal approach with an increased risk for femoral blowout when overdrilling. The special medial-portal-aiming device with 9 mm offset hit the center reliably.

  17. "Hitting" voices of schizophrenia patients may lastingly reduce persistent auditory hallucinations and their burden : 18-month outcome of a randomized controlled trial

    NARCIS (Netherlands)

    Jenner, JA; Nienhuis, FJ; van de Willige, G; Wiersma, D

    Objective: This study aimed to investigate the outcome of an 18-month randomized controlled trial (RCT) on subjective burden and psychopathology of patients suffering from schizophrenia. Method: An RCT was used to compare hallucination-focused integrative treatment (HIT) and routine treatment (RT)

  18. Hybrid individualized two-level choice-based conjoint (HIT-CBC) : A new method for measuring preference structures with many attribute levels

    NARCIS (Netherlands)

    Eggers, Felix; Sattler, Henrik

    The authors introduce hybrid individualized two-level choice-based conjoint (HIT-CBC), which combines self-explicated preference measurement (SE) with choice-based conjoint analysis (CBC). The CBC part is adapted individually to a choice design that uses only the best and worst levels of each

  19. 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.

  20. Characterisation of a pre-cell hit detector to be used in single cell irradiation experiments at the Lund Nuclear Microprobe

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, Charlotta [Division of Nuclear Physics, Department of Physics, Lund University, Box 118, SE-22100 Lund (Sweden)], E-mail: charlotta.nilsson@nuclear.lu.se; Pallon, Jan [Division of Nuclear Physics, Department of Physics, Lund University, Box 118, SE-22100 Lund (Sweden); Thungstroem, Goeran [Electronics Design Division, Department of Information Technology and Media, Mid Sweden University, Holmgatan 10, SE-85170 Sundsvall (Sweden); Marrero, Natalia Arteaga; Elfman, Mikael; Kristiansson, Per; Nilsson, Christer; Wegden, Marie [Division of Nuclear Physics, Department of Physics, Lund University, Box 118, SE-22100 Lund (Sweden)

    2008-11-15

    This paper describes the characterisation of an ultra-thin silicon semiconductor {delta}E detector to be used as a pre-cell ion hit detector in single ion experiments on individual, living cells. The characteristics of interest for this specific application are the hit detection efficiency, which has to be close to 100% to enable bombardment with either a single ion or a counted number of ions, the beam spreading, which should be as small as possible to maintain the targeting accuracy, and the vacuum tightness, since the detector is intended, if possible, to be used simultaneously as vacuum window. The hit detection efficiency was shown to be above 99% when detecting alpha particles or 2 MeV protons, the increase in beam size was about 1 {mu}m and the vacuum tightness was comparable to that of the Si{sub 3}N{sub 4} wafer which is normally used as vacuum window, thus the {delta}E detector fulfils the main criteria to function properly as a single ion hit detector.

  1. Satisfactory throat-hit is needed to switch from tobacco to e-cigarettes: a lesson from an e-liquid blind test

    Directory of Open Access Journals (Sweden)

    Bertrand Dautzenberg

    2016-04-01

    The present data justify the need to further develop e-cigarettes so that an optimal OTH is identified quickly. Further research is needed to confirm the above results in other populations and to assess the specific influence of flavour on throat hit.

  2. Biomechanics and visual-motor control: how it has, is, and will be used to reveal the secrets of hitting a cricket ball.

    NARCIS (Netherlands)

    Sarpeshkar, V.; Mann, D.L.

    2011-01-01

    Cricket batting is an incredibly complex task which requires the coordination of full-body movements to successfully hit a fast moving ball. Biomechanical studies on batting have helped to shed light on how this intricate skill may be performed, yet the many different techniques exhibited by batters

  3. Hits and Misses: Leveraging tDCS to Advance Cognitive Research

    Directory of Open Access Journals (Sweden)

    Marian E Berryhill

    2014-07-01

    Full Text Available The popularity of non-invasive brain stimulation techniques in basic, commercial, and applied settings grew tremendously over the last decade. Here, we focus on one popular neurostimulation method: transcranial direct current stimulation (tDCS. Many assumptions regarding the outcomes of tDCS are based on the results of stimulating motor cortex. For instance, the primary motor cortex is predictably suppressed by cathodal tDCS or made more excitable by anodal tDCS. However, wide-ranging studies testing cognition provide more complex and sometimes paradoxical results that challenge this heuristic. Here, we first summarize successful efforts in applying tDCS to cognitive questions, with a focus on working memory. These recent findings indicate that tDCS can result in cognitive task improvement or impairment regardless of stimulation site or direction of current flow. We then report working memory and response inhibition studies that failed to replicate and/or extend previously reported effects. From these opposing outcomes, we present a series of factors to consider that are intended to facilitate future use of tDCS when applied to cognitive questions. In short, common pitfalls include testing too few participants, using insufficiently challenging tasks, using heterogeneous participant populations, and including poorly motivated participants. Furthermore, the poorly understood underlying mechanism for long-lasting tDCS effects make it likely that other important factors predict responses. In conclusion, we argue that although tDCS can be used experimentally to understand brain function its greatest potential may be in applied or translational research.

  4. N-type compensated silicon: resistivity, crystal growth, carrier lifetime, and relevant application for HIT solar cells

    Science.gov (United States)

    Li, Shuai; Gao, Wenxiu; Li, Zhen; Cheng, Haoran; Lin, Jinxia; Cheng, Qijin

    2017-05-01

    N-type compensated silicon shows unusual distribution of resistivity as crystal grows compared to the n-type uncompensated silicon. In this paper, evolutions of resistivities with varied concentrations of boron and varied starting resistivities of the n-type silicon are intensively calculated. Moreover, reduction of carrier mobility is taken into account by Schindler’s modified model of carrier mobility for the calculation of resistivity of the compensated silicon. As for substrates of solar cells, optimized starting resistivity and corresponding concentration of boron are suggested for better uniformity of resistivity and higher yield (fraction with ρ >0.5 ~ Ω \\centerdot \\text{cm} ) of the n-type compensated Cz crystal rod. A two-step growth method is investigated to obtain better uniformity of resistivity of crystal rod, and this method is very practical especially for the n-type compensated silicon. Regarding the carrier lifetime, the recombination by shallow energy-level dopants is taken into account for the compensated silicon, and evolution of carrier lifetime is simulated by considering all main recombination centers which agrees well with our measured carrier lifetimes as crystal grows. The n-type compensated silicon shows a larger reduction of carrier lifetime compared to the uncompensated silicon at the beginning of crystal growth, and recombination with a oxygen-related deep defect is sufficient to describe the reduction of degraded lifetime. Finally, standard heterojunction with intrinsic thin-layer (HIT) solar cells are made with substrates from the n-type compensated silicon rod, and a high efficiency of 22.1% is obtained with a high concentration (0.8× {{10}16}~\\text{c}{{\\text{m}}-3} ) of boron in the n-type compensated silicon feedstock. However, experimental efficiencies of HIT solar cells based on the n-type compensated silicon show an average reduction of 4% along with the crystal length compared to the uncompensated silicon. The

  5. Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity.

    Science.gov (United States)

    Harmon, J S; Tanaka, Y; Olson, L K; Robertson, R P

    1998-06-01

    We have reported that chronic culture of HIT-T15 cells in medium containing supraphysiologic glucose concentrations (11.1 mmol/l) causes a decrease in insulin mRNA levels, insulin content, and insulin release. Furthermore, decreases in insulin gene transcription and binding activity of two essential beta-cell transcription factors, somatostatin transcription factor-1 (STF-1; also known as GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with this glucotoxic effect. In this study, we observed that the loss of RIPE-3b1 occurs much earlier (79% decrease at passage [p]81) than the loss of STF-1 (65% decrease at p104), with abolishment of both factors by p122. Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA. Basal insulin promoter activities normalized to early (p71-74) passage cells (1.000 +/- 0.069) were 0.4066 +/- 0.093 and 0.142 +/- 0.034 for intermediate (p102-106) and late (p118-122) passage cells, respectively. Early, intermediate, and late passage cells, all chronically cultured in medium containing 11.1 mmol/l glucose, were transfected with STF-1 alone or cotransfected with E2-5, an E-box factor known to be synergistically associated with STF-1. Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold). In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. Cotransfection of STF-1 and E2-5 in late passage cells stimulated insulin promoter activity 2.8-fold, which was 40% of the activity observed in early passage cells. Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter

  6. 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

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

    Science.gov (United States)

    Pietrofesa, Ralph A; Velalopoulou, Anastasia; Lehman, Stacey L; Arguiri, Evguenia; Solomides, Pantelis; Koch, Cameron J; Mishra, Om P; Koumenis, Constantinos; Goodwin, Thomas J; Christofidou-Solomidou, Melpo

    2016-06-16

    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

  8. Chronic exposure of HIT cells to high glucose concentrations paradoxically decreases insulin gene transcription and alters binding of insulin gene regulatory protein.

    Science.gov (United States)

    Olson, L K; Redmon, J B; Towle, H C; Robertson, R P

    1993-07-01

    Chronically culturing HIT-T15 cells in media containing high glucose concentrations leads to decreased insulin mRNA levels, insulin content, and insulin secretion. These changes can be prevented by culturing the cells in media containing lower glucose levels (Robertson, R. P., H.-J. Zhang, K. L. Pyzdrowski, and T. F. Walseth. 1992. J. Clin. Invest. 90:320-325). The mechanism of this seemingly paradoxical phenomenon was examined by transiently transfecting HIT cells with a chloramphenicol acetyl transferase (CAT) reporter gene controlled by the 5'-regulatory domain of the human insulin gene (INSCAT). Early passages of HIT cells readily expressed INSCAT, whereas late passages of cells chronically cultured in 11.1 mM glucose expressed only 28.7 +/- 2.3% (mean +/- SEM) of the CAT activity expressed in early passages. In contrast, late passages of HIT cells chronically cultured in 0.8 mM glucose retained the ability to express the INSCAT reporter gene to 69.6 +/- 10.0% of the CAT activity observed in early passages. The decrease in INSCAT expression in late passages of cells serially cultured in 11.1 mM glucose was associated with the inability to form a specific nuclear protein-DNA complex with the CT motifs of the human insulin promoter. Formation of this specific protein-DNA complex was preserved in late passages of HIT cells when serially cultured in 0.8 mM glucose. Mutations of the CT motifs caused markedly diminished CAT activity in all passages examined. These data indicate that chronic exposure of the beta cell to high glucose concentrations can paradoxically decrease insulin gene transcription, in part, by altering the ability of a regulatory protein (GSTF) to interact with the insulin gene promoter. This provides a potential mechanism for glucotoxic effects on the beta cell at the level of the insulin gene.

  9. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Katalin Susztak

    2005-02-01

    Full Text Available Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis.Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  10. Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein

    Directory of Open Access Journals (Sweden)

    María Angélica Suarez

    2017-07-01

    Full Text Available Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgently required to reduce global tuberculosis burden. Mycobacterium tuberculosis nucleoid associated protein (NAP HU has been shown to be druggable and essential for the organism’s survival. In this study, four diarylethenes were synthesized using a one-pot decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared compounds 1–4 were tested for their in vitro growth inhibition of M. tuberculosis H37Rv using the spot culture growth inhibition assay, displaying minimum inhibitory concentrations between 9 and 22 µM. Their cytotoxicity against BHK-21 cell line showed half inhibition at concentrations between 98 and 729 µM. The most selective hit (SI = 81, demonstrated inhibition of M. tuberculosis HU protein involved in maintaining bacterial genome architecture.

  11. Novel method for hit-position reconstruction using voltage signals in plastic scintillators and its application to Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Raczyński, L., E-mail: lech.raczynski@ncbj.gov.pl [Świerk Computing Centre, National Centre for Nuclear Research, 05-400 Otwock-Świerk (Poland); Moskal, P. [Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-059 Cracow (Poland); Kowalski, P.; Wiślicki, W. [Świerk Computing Centre, National Centre for Nuclear Research, 05-400 Otwock-Świerk (Poland); Bednarski, T.; Białas, P.; Czerwiński, E. [Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-059 Cracow (Poland); Kapłon, Ł. [Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-059 Cracow (Poland); Institute of Metallurgy and Materials Science of Polish Academy of Sciences, Cracow (Poland); Kochanowski, A. [Faculty of Chemistry, Jagiellonian University, 30-060 Cracow (Poland); Korcyl, G.; Kowal, J.; Kozik, T.; Krzemień, W.; Kubicz, E. [Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-059 Cracow (Poland); Molenda, M. [Faculty of Chemistry, Jagiellonian University, 30-060 Cracow (Poland); Moskal, I.; Niedźwiecki, Sz.; Pałka, M.; Pawlik-Niedźwiecka, M.; Rudy, Z. [Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-059 Cracow (Poland); and others

    2014-11-11

    Currently inorganic scintillator detectors are used in all commercial Time of Flight Positron Emission Tomograph (TOF-PET) devices. The J-PET collaboration investigates a possibility of construction of a PET scanner from plastic scintillators which would allow for single bed imaging of the whole human body. This paper describes a novel method of hit-position reconstruction based on sampled signals and an example of an application of the method for a single module with a 30 cm long plastic strip, read out on both ends by Hamamatsu R4998 photomultipliers. The sampling scheme to generate a vector with samples of a PET event waveform with respect to four user-defined amplitudes is introduced. The experimental setup provides irradiation of a chosen position in the plastic scintillator strip with an annihilation gamma quanta of energy 511 keV. The statistical test for a multivariate normal (MVN) distribution of measured vectors at a given position is developed, and it is shown that signals sampled at four thresholds in a voltage domain are approximately normally distributed variables. With the presented method of a vector analysis made out of waveform samples acquired with four thresholds, we obtain a spatial resolution of about 1 cm and a timing resolution of about 80 ps (σ)

  12. 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.

  13. Single-Hit Criterion in Dama/libra DM Search and Daemons — they are anything but Weakly Interacting

    Science.gov (United States)

    Drobyshevski, E. M.

    Our prediction that the more massive DAMA/LIBRA detector would detect a smaller number of events per unit of mass and time than the DAMA/NaI system has got confirmation. It is easy to understand, because DM objects are by far not the WIMPs of the Galactic halo that interact only weakly with matter but are apparently electrically charged Planckian objects, i.e. daemons which fall from Earth-crossing orbits with V = 30-50 km/s and undergo multiple interaction with condensed matter already in its outer layers, on a path of a few tens of cm. Therefore, one should use not compact massive detectors but rather systems with a large surface area, as we did to detect daemons with thin ZnS(Ag) scintillators. There are grounds to believe that correct use of the single-hit criterion in LIBRA should reveal DM particles with V = 30-50 km/s, and subsequently, with V = 10-15 km/s as well.

  14. HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism.

    Science.gov (United States)

    Weyn-Vanhentenryck, Sebastien M; Mele, Aldo; Yan, Qinghong; Sun, Shuying; Farny, Natalie; Zhang, Zuo; Xue, Chenghai; Herre, Margaret; Silver, Pamela A; Zhang, Michael Q; Krainer, Adrian R; Darnell, Robert B; Zhang, Chaolin

    2014-03-27

    The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We find that the two guanines in the Rbfox binding motif UGCAUG are critical for protein-RNA interactions and crosslinking. Using integrative modeling, these interaction sites, combined with additional datasets, define 1,059 direct Rbfox target alternative splicing events. Over half of the quantifiable targets show dynamic changes during brain development. Of particular interest are 111 events from 48 candidate autism-susceptibility genes, including syndromic autism genes Shank3, Cacna1c, and Tsc2. Alteration of Rbfox targets in some autistic brains is correlated with downregulation of all three Rbfox proteins, supporting the potential clinical relevance of the splicing-regulatory network. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. HITS-CLIP and Integrative Modeling Define the Rbfox Splicing-Regulatory Network Linked to Brain Development and Autism

    Directory of Open Access Journals (Sweden)

    Sebastien M. Weyn-Vanhentenryck

    2014-03-01

    Full Text Available The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We find that the two guanines in the Rbfox binding motif UGCAUG are critical for protein-RNA interactions and crosslinking. Using integrative modeling, these interaction sites, combined with additional datasets, define 1,059 direct Rbfox target alternative splicing events. Over half of the quantifiable targets show dynamic changes during brain development. Of particular interest are 111 events from 48 candidate autism-susceptibility genes, including syndromic autism genes Shank3, Cacna1c, and Tsc2. Alteration of Rbfox targets in some autistic brains is correlated with downregulation of all three Rbfox proteins, supporting the potential clinical relevance of the splicing-regulatory network.

  16. The Arabidopsis heat-intolerant 5 (hit5)/enhanced response to aba 1 (era1) mutant reveals the crucial role of protein farnesylation in plant responses to heat stress.

    Science.gov (United States)

    Wu, Jia-Rong; Wang, Lian-Chin; Lin, Yu-Ru; Weng, Chi-Pei; Yeh, Ching-Hui; Wu, Shaw-Jye

    2017-02-01

    Protein farnesylation is a post-translational modification known to regulate abscisic acid (ABA)-mediated drought tolerance in plants. However, it is unclear whether and to what extent protein farnesylation affects plant tolerance to high-temperature conditions. The Arabidopsis heat-intolerant 5 (hit5) mutant was isolated because it was thermosensitive to prolonged heat incubation at 37°C for 4 d but thermotolerant to sudden heat shock at 44°C for 40 min. Map-based cloning revealed that HIT5 encodes the β-subunit of the protein farnesyltransferase. hit5 was crossed with the aba-insensitive 3 (abi3) mutant, the aba-deficient 3 (aba3) mutant, and the heat shock protein 101 (hsp101) mutant, to characterize the HIT5-mediated heat stress response. hit5/abi3 and hit5/aba3 double mutants had the same temperature-dependent phenotypes as hit5. Additionally, exogenous supplementation of neither ABA nor the ABA synthesis inhibitor fluridone altered the temperature-dependent phenotypes of hit5. The hit5/hsp101 double mutant was still sensitive to prolonged heat incubation, yet its ability to tolerate sudden heat shock was lost. The results suggest that protein farnesylation either positively or negatively affects the ability of plants to survive heat stress, depending on the intensity and duration of high-temperature exposure, in an ABA-independent manner. HSP101 is involved in the hit5-derived heat shock tolerance phenotype. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  17. Range of plasma ions in cold cluster gases near the critical point

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, G. [Cyclotron Institute, Texas A& M University, 77843 College Station, TX (United States); Quevedo, H.J. [Center for High Energy Density Science, C1510, University of Texas at Austin, Austin, TX 78712 (United States); Bonasera, A., E-mail: abonasera@comp.tamu.edu [Cyclotron Institute, Texas A& M University, 77843 College Station, TX (United States); Laboratori Nazionali del Sud-INFN, via S. Sofia 64, 95123 Catania (Italy); Donovan, M.; Dyer, G.; Gaul, E. [Center for High Energy Density Science, C1510, University of Texas at Austin, Austin, TX 78712 (United States); Guardo, G.L. [Laboratori Nazionali del Sud-INFN, via S. Sofia 64, 95123 Catania (Italy); Gulino, M. [Laboratori Nazionali del Sud-INFN, via S. Sofia 64, 95123 Catania (Italy); Libera Universita' Kore, 94100 Enna (Italy); La Cognata, M.; Lattuada, D. [Laboratori Nazionali del Sud-INFN, via S. Sofia 64, 95123 Catania (Italy); Palmerini, S. [Department of Physics and Geology, University of Perugia, Via A. Pascoli, 06123 Perugia (Italy); Istituto Nazionale di Fisica Nucleare, Section of Perugia, Via A. Pascoli, 06123 Perugia (Italy); Pizzone, R.G.; Romano, S. [Laboratori Nazionali del Sud-INFN, via S. Sofia 64, 95123 Catania (Italy); Smith, H. [Center for High Energy Density Science, C1510, University of Texas at Austin, Austin, TX 78712 (United States); Trippella, O. [Department of Physics and Geology, University of Perugia, Via A. Pascoli, 06123 Perugia (Italy); Istituto Nazionale di Fisica Nucleare, Section of Perugia, Via A. Pascoli, 06123 Perugia (Italy); Anzalone, A.; Spitaleri, C. [Laboratori Nazionali del Sud-INFN, via S. Sofia 64, 95123 Catania (Italy); Ditmire, T. [Center for High Energy Density Science, C1510, University of Texas at Austin, Austin, TX 78712 (United States)

    2017-05-18

    We measure the range of plasma ions in cold cluster gases by using the Petawatt laser at the University of Texas-Austin. The produced plasma propagated in all directions some hitting the cold cluster gas not illuminated by the laser. From the ratio of the measured ion distributions at different angles we can estimate the range of the ions in the cold cluster gas. It is much smaller than estimated using popular models, which take only into account the slowing down of charged particles in uniform matter. We discuss the ion range in systems prepared near a liquid–gas phase transition. - Highlights: • We present experimental results obtained at the UT Petawatt laser facility, Austin, TX. • The ion range is strongly modified for cluster gases as compared to its value in a homogeneous system. • Large fluctuations are found if the cluster gas is prepared near the liquid–gas phase transition region.

  18. When the Claim Hits

    DEFF Research Database (Denmark)

    Skovgaard Poulsen, Lauge; Aisbett, Emma

    2013-01-01

    Using the international investment regime as its point of departure, the article applies notions of bounded rationality to the study of economic diplomacy. Through a multimethod approach, it shows that developing countries often ignored the risks of bilateral investment treaties (bits) until...... they themselves became subject to an investment treaty claim. Thus the behavior of developing country governments with regard to the international investment regime is consistent with that routinely observed for individuals in experiments and field studies: they tend to ignore high-impact, low-probability risks...

  19. When Globalization Hits Home

    DEFF Research Database (Denmark)

    Borrás, Susana; Haakonsson, Stine Jessen

    . The dynamics are generally differentiated according to the type of lead firm strategy, i.e. knowledge augmenting or knowledge exploiting. The qualitative and exploratory findings point towards some effects on national innovation networks. Hence, the paper concludes by hypothesizing that the globalization...... of lead firms’ innovation has a mobilization effect on preexisting national innovation networks. The hypothesis says that lead firms’ engagement in global innovation networks can mobilize the organizations that are part of the lead firms’ innovation networks at home. This mobilization effect differs......Lead firms are increasingly reorganizing their innovation activities into global innovation networks. Such reorganization has potentially major impact on their existing home-based innovation networks. Based on 31 interviews in four case studies of lead firms in the Danish food industry, the paper...

  20. ASACUSA hits antiproton jackpot

    CERN Multimedia

    2001-01-01

    The Japanese-European ASACUSA collaboration, which takes its name from the oldest district of Tokyo, approaches the antimatter enigma in a different way from the other two AD experiments, by inserting antiprotons into ordinary atoms. Last month the collaboration succeeded in trapping about a million antiprotons. The ASACUSA antiproton trap (lower cylinder), surmounted by its liquid helium reservoir. Looking on are Ken Yoshiki-Franzen, Zhigang Wang, Takahito Tasaki, Suzanne Reed, John Eades, Masaki Hori, Yasunori Yamazaki, Naofumi Kuroda, Jun Sakaguchi, Berti Juhasz, Eberhard Widmann and Ryu Hayano. A key element of the ASACUSA apparatus is its decelerating Radiofrequency Quadrupole magnet, RFQD. After tests with protons in Aarhus, this was installed in ASACUSA's antiproton beam last October (Bulletin 41/2000, 9 October 2000). Constructed by Werner Pirkl's group in PS Division, the RFQD works by applying an electric field to the AD antiproton pulse the opposite direction to its motion. As the antiprotons slo...

  1. Global smash hit

    CERN Document Server

    Fisher, Richard

    2005-01-01

    The Large Hadron Collider (LHC), a massive pound 1.3 billion experiment at particle physics hub CERN in Geneva, Switzerland, which is scheduled to be launched in 2007, is discussed. The experiment will help better understand the universe by accelerating sub-atomic particles around a 27km tube and smashing them together at energies not seen since the big bang. It will also demonstrate creation of mini-black holes, existence of the elusive Higgs Boson, the so called "Good particle" that physicists think interacts with all matter to give it mass. The LHC has 6000 magnets, 7000 km of superconducting cable and a cryogenic cooling system intstalled on it. (Edited abstract).

  2. Hitting the ground running

    Energy Technology Data Exchange (ETDEWEB)

    KEENEN,MARTHA JANE; NUSBAUM,ANNA W.

    2000-05-18

    Very few of us get to start clean: getting a new organization, new space, and hiring new people for a new information management program. In over 20 years in some aspect of this profession, the author has never faced that particular challenge. By far the majority of information management opportunities involve taking over from someone else. Sometimes, a predecessor has gone on to better things on his/her initiative; that is not always the case. Sometimes the group is one you were a part of yesterday. If the function functions, time moves on and changes may be needed to accommodate new technology, additional and/or changed tasks, and alterations in corporate missions. If the function does not, it is a good bet that you were hired or promoted as an agent of change. Each of these situations poses challenges. This presentation is about that first few months and first year in a new assignment. In other words, you have the job, now what?

  3. Kindle Annotations Quick Hit

    Science.gov (United States)

    2014-06-19

    course of conducting two So TL studies on the benefits and challenges of using e-books in place of paper books we have refined a handful of best ...more. For example, they pay attention to the genre of the text and what might be known about the author’s context. They aim to make sense of the...together from the text, pointing to the specific passages that animate their connections, questions, and objections. Third, as part of their daily work for

  4. Hurting without Hitting

    DEFF Research Database (Denmark)

    He, Yinghua; Nielsson, Ulf; Wang, Yonglei

    2017-01-01

    Political tension that causes diplomatic strain rarely escalates into direct violence or war. This paper identifies the economic effects of such non-violent political tension by examining Taiwan’s sovereignty debate. Non-violent events harming the relationship with mainland China lead to an avera...

  5. Beyond "Hitting the Books"

    Science.gov (United States)

    Entress, Cole; Wagner, Aimee

    2014-01-01

    Scientists, science teachers, and serious students recognize that success in science classes requires consistent practice--including study at home. Whether balancing chemical equations, calculating angular momentum, or memorizing the steps of cell division, students must review material repeatedly to fully understand new ideas--and must practice…

  6. Hitting the bullseye

    NARCIS (Netherlands)

    Fielke, Simon; Nelson, Tracy; Bewsell, Denise; Bayne, Karen; Park, Nicola; Rijswijk, Kelly; Small, Bruce

    2017-01-01

    Reflexive monitors (RMs) have been found to be vital to the success of co-innovation projects. While the practices utilized by RMs have been examined in various contexts, we examine the roles they have played in a new cultural context in New Zealand (NZ) and how it has been possible to embed

  7. Beware the single hit!

    CERN Multimedia

    2008-01-01

    The first time that single particle effects from cosmic rays on electronics were observed was in 1991, when one of the instruments aboard an ESA satellite broke down after only five days in space. On 5 July, the TS-LEA group will have completed the installation of monitors that will help to reduce similar dangerous effects on LHC electronics.

  8. 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.

  9. 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

  10. Experiences of patients and professionals participating in the HITS home blood pressure telemonitoring trial: a qualitative study.

    Science.gov (United States)

    Hanley, Janet; Ure, Jenny; Pagliari, Claudia; Sheikh, Aziz; McKinstry, Brian

    2013-05-28

    the HITS trial registered with ISRCTN no. 72614272.

  11. Interleukin 7 immunotherapy improves host immunity and survival in a two-hit model of Pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Shindo, Yuichiro; Fuchs, Anja G; Davis, Christopher G; Eitas, Tim; Unsinger, Jacqueline; Burnham, Carey-Ann D; Green, Jonathan M; Morre, Michel; Bochicchio, Grant V; Hotchkiss, Richard S

    2017-02-01

    Patients with protracted sepsis develop impaired immunity, which predisposes them to acquiring secondary infections. One of the most common and lethal secondary infections is Pseudomonas aeruginosa pneumonia. Immunoadjuvant therapy is a promising approach to reverse sepsis-induced immunosuppression and improve morbidity and mortality from secondary infections. Interleukin-7 is an immunoadjuvant that improves survival in clinically relevant animal models of polymicrobial peritonitis and in fungal sepsis. This study investigated the effect of recombinant human interleukin-7 (rhIL-7) on survival in a 2-hit model of sublethal cecal ligation and puncture followed by P. aeruginosa pneumonia. Potential immunologic mechanisms responsible for the rhIL-7 putative beneficial effect were also examined, focusing on IL-17, IL-22, IFN-γ, and TNF-α, cytokines that are critical in the control of sepsis and pulmonary Pseudomonas infections. Results showed that rhIL-7 was highly effective in preventing P. aeruginosa-induced death, i.e., 92% survival in rhIL-7-treated mice versus 56% survival in control mice. rhIL-7 increased absolute numbers of immune effector cells in lung and spleen and ameliorated the sepsis-induced loss of lung innate lymphoid cells (ILCs). rhIL-7 also significantly increased IL-17-, IFN-γ-, and TNF-α-producing lung ILCs and CD8 T cells as well as IFN-γ- and TNF-α-producing splenic T cell subsets and ILCs. Furthermore, rhIL-7 enhanced NF-κB and STAT3 signaling in lungs during sepsis and pneumonia. Given the high mortality associated with secondary P. aeruginosa pneumonia, the ability of rhIL-7 to improve immunity and increase survival in multiple animal models of sepsis, and the remarkable safety profile of rhIL-7, clinical trials with rhIL-7 should be considered. © Society for Leukocyte Biology.

  12. You Can’t Think and Hit at the Same Time: Neural Correlates of Baseball Pitch Classification

    Directory of Open Access Journals (Sweden)

    Jason eSherwin

    2012-12-01

    Full Text Available Hitting a baseball is often described as the most difficult thing to do in sports. A key aptitude of a good hitter is the ability to determine which pitch is coming. This rapid decision requires the batter to make a judgment in a fraction of a second based largely on the trajectory and spin of the ball. When does this decision occur relative to the ball’s trajectory and is it possible to identify neural correlates that represent how the decision evolves over a split second? Using single-trial analysis of electroencephalography (EEG we address this question within the context of subjects discriminating three types of pitches (fastball, curveball, slider based on pitch trajectories. We find clear neural signatures of pitch classification and, using signal detection theory, we identify the times of discrimination on a trial-to-trial basis. Based on these neural signatures we estimate neural discrimination distributions as a function of the distance the ball is from the plate. We find all three pitches yield unique distributions, namely the timing of the discriminating neural signatures relative to the position of the ball in its trajectory. For instance, fastballs are discriminated at the earliest points in their trajectory, relative to the two other pitches, which is consistent with the need for some constant time to generate and execute the motor plan for the swing (or inhibition of the swing. We also find incorrect discrimination of a pitch (errors yields neural sources in Brodmann Area 10 (BA 10, which has been implicated in prospective memory, recall and task difficulty. In summary, we show that single-trial analysis of EEG yields informative distributions of the relative point in a baseball’s trajectory when the batter makes a decision on which pitch is coming.

  13. Best hits of 11110110111: model-free selection and parameter-free sensitivity calculation of spaced seeds.

    Science.gov (United States)

    Noé, Laurent

    2017-01-01

    Spaced seeds, also named gapped q-grams, gapped k-mers, spaced q-grams, have been proven to be more sensitive than contiguous seeds (contiguous q-grams, contiguous k-mers) in nucleic and amino-acid sequences analysis. Initially proposed to detect sequence similarities and to anchor sequence alignments, spaced seeds have more recently been applied in several alignment-free related methods. Unfortunately, spaced seeds need to be initially designed. This task is known to be time-consuming due to the number of spaced seed candidates. Moreover, it can be altered by a set of arbitrary chosen parameters from the probabilistic alignment models used. In this general context, Dominant seeds have been introduced by Mak and Benson (Bioinformatics 25:302-308, 2009) on the Bernoulli model, in order to reduce the number of spaced seed candidates that are further processed in a parameter-free calculation of the sensitivity. We expand the scope of work of Mak and Benson on single and multiple seeds by considering the Hit Integration model of Chung and Park (BMC Bioinform 11:31, 2010), demonstrate that the same dominance definition can be applied, and that a parameter-free study can be performed without any significant additional cost. We also consider two new discrete models, namely the Heaviside and the Dirac models, where lossless seeds can be integrated. From a theoretical standpoint, we establish a generic framework on all the proposed models, by applying a counting semi-ring to quickly compute large polynomial coefficients needed by the dominance filter. From a practical standpoint, we confirm that dominant seeds reduce the set of, either single seeds to thoroughly analyse, or multiple seeds to store. Moreover, in http://bioinfo.cristal.univ-lille.fr/yass/iedera_dominance, we provide a full list of spaced seeds computed on the four aforementioned models, with one (continuous) parameter left free for each model, and with several (discrete) alignment lengths.

  14. Assessment of current virotherapeutic application schemes: “hit hard and early” versus “killing softly”?

    Directory of Open Access Journals (Sweden)

    Benjamin Ruf

    2015-01-01

    Full Text Available Over the past two decades, a considerable amount of oncolytic vector families has entered numerous clinical trials. However, to this date, the field has not yet been able to come to a common understanding regarding the best possible ways to administer oncolytic viruses to cancer patients. This is mainly due to the fact that so far clinical trials being designed for head-to-head comparisons (such as using two different virotherapeutics originating from two distinct virus families being applied via identical routes in the same types of cancer are still missing. Hence, there is no consent (i on the best route of virotherapeutics administration (e.g., systemic versus intratumoral, (ii on the virus dosages to be applied, (iii on dosing intervals, and (iv on the numbers of repetitive courses of virus administration. As the detailed comparison of clinical virotherapy trial regimens is time-consuming and complex, we here present an overview of current state-of-the-art virotherapeutic application schemes. Notably, our comprehensive assessment culminates in raising two rough classifications of virotherapeutic strategies, i.e., “hit hard and early” versus “killing softly”. In order to find out which one of these two gross alternatives might be most successful for each and every tumor entity, we here suggest the implementation of phase 1/2 studies, which primarily aim at a repetitive sampling and analysis of tumor samples in cancer patients treated with oncolytic viruses reading out (i virus-specific, (ii tumor-specific as well as (iii immunotherapeutic parameters. On this basis, a rational design of significantly improved virotherapeutic application schemes should be possible in the future.

  15. Discovery and hit-to-lead optimization of 2,6-diaminopyrimidine inhibitors of interleukin-1 receptor-associated kinase 4

    Energy Technology Data Exchange (ETDEWEB)

    McElroy, William T.; Seganish, W. Michael; Herr, R. Jason; Harding, James; Yang, Jinhai; Yet, Larry; Komanduri, Venukrishnan; Prakash, Koraboina Chandra; Lavey, Brian; Tulshian, Deen; Greenlee, William J.; Sondey, Christopher; Fischmann, Thierry O.; Niu, Xiaoda (Merck); (Albany MR)

    2015-05-01

    Interleukin receptor-associated kinase 4 (IRAK4) is a critical element of the Toll-like/interleukin-1 receptor inflammation signaling pathway. A screening campaign identified a novel diaminopyrimidine hit that exhibits weak IRAK4 inhibitory activity and a ligand efficiency of 0.25. Hit-to-lead activities were conducted through independent SAR studies of each of the four pyrimidine substituents. Optimal activity was observed upon removal of the pyrimidine C-4 chloro substituent. The intact C-6 carboribose is required for IRAK4 inhibition. Numerous heteroaryls were tolerated at the C-5 position, with azabenzothiazoles conferring the best activities. Aminoheteroaryls were preferred at the C-2 position. These studies led to the discovery of inhibitors 35, 36, and 38 that exhibit nanomolar inhibition of IRAK4, improved ligand efficiencies, and modest kinase selectivities.

  16. Biomechanics and visual-motor control: how it has, is, and will be used to reveal the secrets of hitting a cricket ball.

    Science.gov (United States)

    Sarpeshkar, Vishnu; Mann, David L

    2011-11-01

    Cricket batting is an incredibly complex task which requires the coordination of full-body movements to successfully hit a fast moving ball. Biomechanical studies on batting have helped to shed light on how this intricate skill may be performed, yet the many different techniques exhibited by batters make the systematic examination of batting difficult. This review seeks to critically evaluate the existing literature examining cricket batting, but doing so by exploring the strong but often neglected relationship between biomechanics and visual-motor control. In three separate sections, the paper seeks to address (i) the different theories of motor control which may help to explain how skilled batters can hit a ball, (ii) strategies used by batters to overcome the (at times excessive) temporal constraints, and (iii) an interpretation from a visual-motor perspective of the prevailing biomechanical data on batting.

  17. Effects of low-volume high-intensity interval training (HIT) on fitness in adults: a meta-analysis of controlled and non-controlled trials.

    Science.gov (United States)

    Weston, Matthew; Taylor, Kathryn L; Batterham, Alan M; Hopkins, Will G

    2014-07-01

    Low-volume high-intensity interval training (HIT) appears to be an efficient and practical way to develop physical fitness. Our objective was to estimate meta-analysed mean effects of HIT on aerobic power (maximum oxygen consumption [VO(2max)] in an incremental test) and sprint fitness (peak and mean power in a 30-s Wingate test). Five databases (PubMed, MEDLINE, Scopus, BIOSIS and Web of Science) were searched for original research articles published up to January 2014. Search terms included 'high intensity', 'HIT', 'sprint', 'fitness' and 'VO(2max)'. Inclusion criteria were fitness assessed pre- and post-training; training period ≥2 weeks; repetition duration 30-60 s; work/rest ratio 18 years. The final data set consisted of 55 estimates from 32 trials for VO(2max), 23 estimates from 16 trials for peak sprint power, and 19 estimates from 12 trials for mean sprint power. Effects on fitness were analysed as percentages via log transformation. Standard errors calculated from exact p values (where reported) or imputed from errors of measurement provided appropriate weightings. Fixed effects in the meta-regression model included type of study (controlled, uncontrolled), subject characteristics (sex, training status, baseline fitness) and training parameters (number of training sessions, repetition duration, work/rest ratio). Probabilistic magnitude-based inferences for meta-analysed effects were based on standardized thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject standard deviations (SDs) for baseline fitness. A mean low-volume HIT protocol (13 training sessions, 0.16 work/rest ratio) in a controlled trial produced a likely moderate improvement in the VO(2max) of active non-athletic males (6.2 %; 90 % confidence limits ±3.1 %), when compared with control. There were possibly moderate improvements in the VO(2max) of sedentary males (10.0 %; ±5.1 %) and active non-athletic females (3.6 %; ±4.3 %) and a

  18. Hit Rate of Space Weather Forecasts of the Japanese Forecast Center and Analysis of Problematic Events on the Forecasts between June 2014 and March 2015

    Science.gov (United States)

    Watari, S.; Kato, H.; Yamamoto, K.

    2015-12-01

    The hit rate of space weather forecasts issued by the Japanese forecast center in the National Institute of Information and Communications Technology (NICT) between June 2014 and March 2015 are compared with that by the persistence method. It is shown that the hit rate of the forecasts by the Japanese center is better than that by the persistence method. Several problematic events on the space weather forecasts during the same period are analyzed. Those events are (1) geomagnetic storms associated with coronal mass ejections (CMEs) on 9 September 2014 and on 15 March 2015 with different durations of southward interplanetary magnetic field (IMF), (2) a large active region, AR 12192 without CMEs, solar energetic particle events, and geomagnetic storms, (3) a geomagnetic storm on 7 January 2015 caused by a faint CME, and (4) disagreement between the in-situ observation at 1 AU and the prediction of the Potential Field Source Surface (PFSS) model on timing of sector crossing in January 2015.

  19. 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.

  20. Sugared water consumption by adult offspring of mothers fed a protein-restricted diet during pregnancy results in increased offspring adiposity: the second hit effect.

    Science.gov (United States)

    Cervantes-Rodríguez, M; Martínez-Gómez, M; Cuevas, E; Nicolás, L; Castelán, F; Nathanielsz, P W; Zambrano, E; Rodríguez-Antolín, J

    2014-02-01

    Poor maternal nutrition predisposes offspring to metabolic disease. This predisposition is modified by various postnatal factors. We hypothesised that coupled to the initial effects of developmental programming due to a maternal low-protein diet, a second hit resulting from increased offspring postnatal sugar consumption would lead to additional changes in metabolism and adipose tissue function. The objective of the present study was to determine the effects of sugared water consumption (5% sucrose in the drinking-water) on adult offspring adiposity as a 'second hit' following exposure to maternal protein restriction during pregnancy. We studied four offspring groups: (1) offspring of mothers fed the control diet (C); (2) offspring of mothers fed the restricted protein diet (R); (3) offspring of control mothers that drank sugared water (C-S); (4) offspring of restricted mothers that drank sugared water (R-S). Maternal diet in pregnancy was considered the first factor and sugared water consumption as the second factor - the second hit. Body weight and total energy consumption, before and after sugared water consumption, were similar in all the groups. Sugared water consumption increased TAG, insulin and cholesterol concentrations in both the sexes of the C-S and R-S offspring. Sugared water consumption increased leptin concentrations in the R-S females and males but not in the R offspring. There was also an interaction between sugared water and maternal diet in males. Sugared water consumption increased adipocyte size and adiposity index in both females and males, but the interaction with maternal diet was observed only in females. Adiposity index and plasma leptin concentrations were positively correlated in both the sexes. The present study shows that a second hit during adulthood can amplify the effects of higher adiposity arising due to poor maternal pregnancy diet in an offspring sex dependent fashion.

  1. Rationale and study protocol for a multi-component Health Information Technology (HIT) screening tool for depression and post-traumatic stress disorder in the primary care setting.

    Science.gov (United States)

    Biegler, Kelly; Mollica, Richard; Sim, Susan Elliott; Nicholas, Elisa; Chandler, Maria; Ngo-Metzger, Quyen; Paigne, Kittya; Paigne, Sompia; Nguyen, Danh V; Sorkin, Dara H

    2016-09-01

    The prevalence rate of depression in primary care is high. Primary care providers serve as the initial point of contact for the majority of patients with depression, yet, approximately 50% of cases remain unrecognized. The under-diagnosis of depression may be further exacerbated in limited English-language proficient (LEP) populations. Language barriers may result in less discussion of patients' mental health needs and fewer referrals to mental health services, particularly given competing priorities of other medical conditions and providers' time pressures. Recent advances in Health Information Technology (HIT) may facilitate novel ways to screen for depression and other mental health disorders in LEP populations. The purpose of this paper is to describe the rationale and protocol of a clustered randomized controlled trial that will test the effectiveness of an HIT intervention that provides a multi-component approach to delivering culturally competent, mental health care in the primary care setting. The HIT intervention has four components: 1) web-based provider training, 2) multimedia electronic screening of depression and PTSD in the patients' primary language, 3) Computer generated risk assessment scores delivered directly to the provider, and 4) clinical decision support. The outcomes of the study include assessing the potential of the HIT intervention to improve screening rates, clinical detection, provider initiation of treatment, and patient outcomes for depression and post-traumatic stress disorder (PTSD) among LEP Cambodian refugees who experienced war atrocities and trauma during the Khmer Rouge. This technology has the potential to be adapted to any LEP population in order to facilitate mental health screening and treatment in the primary care setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. It's no surprise! Men are not hit more than women by the health consequences of unemployment in the Northern Swedish Cohort.

    Science.gov (United States)

    Hammarström, Anne; Gustafsson, Per E; Strandh, Mattias; Virtanen, Pekka; Janlert, Urban

    2011-03-01

    Research often fails to ascertain whether men and women are equally hit by the health consequences of unemployment. The aim of this study was to analyze whether men's self-reported health and health behaviour were hit more by unemployment than women's in a follow-up of the Northern Swedish Cohort. A follow-up study of a cohort of all school leavers in a middle-sized industrial town in northern Sweden was performed from age 16 to age 42. Of those still alive of the original cohort, 94% (n = 1,006) participated during the whole period. A sample was made of participants in the labour force and living in Sweden (n = 916). Register data were used to assess the length of unemployment from age 40 to 42, while questionnaire data were used for the other variables. In multivariate logistic regression analyses significant relations between unemployment and mental health/smoking were found among both women and men, even after control for unemployment at the time of the investigation and indicators of health-related selection. Significant relations between unemployment and alcohol consumption were found among women, while few visits to a dentist was significant among men. Men are not hit more by the health consequences of unemployment in a Swedish context, with a high participation rate of women in the labour market. The public health relevance is that the study indicates the need to take gendered contexts into account in public health research.

  3. Beyond the cold hit: measuring the impact of the national DNA data bank on public safety at the city and county level.

    Science.gov (United States)

    Gabriel, Matthew; Boland, Cherisse; Holt, Cydne

    2010-01-01

    Over the past decade, the Combined DNA Index System (CODIS) has increased solvability of violent crimes by linking evidence DNA profiles to known offenders. At present, an in-depth analysis of the United States National DNA Data Bank effort has not assessed the success of this national public safety endeavor. Critics of this effort often focus on laboratory and police investigators unable to provide timely investigative support as a root cause(s) of CODIS' failure to increase public safety. By studying a group of nearly 200 DNA cold hits obtained in SFPD criminal investigations from 2001-2006, three key performance metrics (Significance of Cold Hits, Case Progression & Judicial Resolution, and Potential Reduction of Future Criminal Activity) provide a proper context in which to define the impact of CODIS at the City and County level. Further, the analysis of a recidivist group of cold hit offenders and their past interaction with law enforcement established five noteworthy criminal case resolution trends; these trends signify challenges to CODIS in achieving meaningful case resolutions. CODIS' effectiveness and critical activities to support case resolutions are the responsibility of all criminal justice partners in order to achieve long-lasting public safety within the United States.

  4. 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

    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...... implant (CI) surgery. Subjects were tested using the vHIT by two of four different examiners. Two judges interpreted the occurrence of saccades in the diagram. MAIN OUTCOME MEASURES: VOR gain values and the occurrence of saccades in the diagram. Differences in gain values between examiners varied from 0.......2 to 0.58 with an average of 0.14 (95 % CI 0.12-0.16) on the right ear and 0.17 (95 % CI 0.15-0.19) on the left ear. Occurrences of saccades in the same patient were reproduced in 93 % of the cases by all examiners. Kappa's coefficient on the occurrence of saccades was 0.83. Interclass correlation...

  5. Where does HIT fit? An examination of the affective response to high-intensity intervals in comparison to continuous moderate- and continuous vigorous-intensity exercise in the exercise intensity-affect continuum.

    Directory of Open Access Journals (Sweden)

    Mary E Jung

    Full Text Available Affect experienced during an exercise session is purported to predict future exercise behaviour. Compared to continuous moderate-intensity exercise (CMI, the affective response to continuous vigorous-intensity exercise (CVI has consistently been shown to be more aversive. The affective response, and overall tolerability to high-intensity interval training (HIT, is less studied. To date, there has yet to be a comparison between HIT, CVI, and CMI. The purpose of this study was to compare the tolerability and affective responses during HIT to CVI and CMI. This study utilized a repeated measures, randomized, counter-balanced design. Forty-four participants visited the laboratory on four occasions. Baseline fitness testing was conducted to establish peak power output in Watts (W peak. Three subsequent visits involved a single bout of a HIT, corresponding to 1-minute at ∼ 100% W peak and 1-minute at ∼ 20% W peak for 20 minutes, b CMI, corresponding to ∼ 40% W peak for 40 minutes, and c CVI, corresponding to ∼ 80% W peak for 20 minutes. The order of the sessions was randomized. Affective responses were measured before, during and after each session. Task self-efficacy, intentions, enjoyment and preference were measured after sessions. Participants reported greater enjoyment of HIT as compared to CMI and CVI, with over 50% of participants reporting a preference to engage in HIT as opposed to either CMI or CVI. HIT was considered more pleasurable than CVI after exercise, but less pleasurable than CMI at these times. Despite this participants reported being just as confident to engage in HIT as they were CMI, but less confident to engage in CVI. This study highlights the utility of HIT in inactive individuals, and suggests that it may be a viable alternative to traditionally prescribed continuous modalities of exercise for promoting self-efficacy and enjoyment of exercise.

  6. 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

    Full Text Available BACKGROUND: 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. METHODS: 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. FINDINGS: 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. CONCLUSIONS: To accelerate the identification of novel anti-schistosomals, we have developed a

  7. Significance of ubiquitin carboxy-terminal hydrolase L1 elevations in athletes after sub-concussive head hits.

    Directory of Open Access Journals (Sweden)

    Vikram Puvenna

    Full Text Available The impact of sub-concussive head hits (sub-CHIs has been recently investigated in American football players, a population at risk for varying degrees of post-traumatic sequelae. Results show how sub-CHIs in athletes translate in serum as the appearance of reporters of blood-brain barrier disruption (BBBD, how the number and severity of sub-CHIs correlate with elevations of putative markers of brain injury is unknown. Serum brain injury markers such as UCH-L1 depend on BBBD. We investigated the effects of sub-CHIs in collegiate football players on markers of BBBD, markers of cerebrospinal fluid leakage (serum beta 2-transferrin and markers of brain damage. Emergency room patients admitted for a clinically-diagnosed mild traumatic brain injury (mTBI were used as positive controls. Healthy volunteers were used as negative controls. Specifically this study was designed to determine the use of UCH-L1 as an aid in the diagnosis of sub-concussive head injury in athletes. The extent and intensity of head impacts and serum values of S100B, UCH-L1, and beta-2 transferrin were measured pre- and post-game from 15 college football players who did not experience a concussion after a game. S100B was elevated in players experiencing the most sub-CHIs; UCH-L1 levels were also elevated but did not correlate with S100B or sub-CHIs. Beta-2 transferrin levels remained unchanged. No correlation between UCH-L1 levels and mTBI were measured in patients. Low levels of S100B were able to rule out mTBI and high S100B levels correlated with TBI severity. UCH-L1 did not display any interpretable change in football players or in individuals with mild TBI. The significance of UCH-L1 changes in sub-concussions or mTBI needs to be further elucidated.

  8. Ranging Behaviour of Commercial Free-Range Laying Hens

    Directory of Open Access Journals (Sweden)

    Leonard Ikenna Chielo

    2016-04-01

    Full Text Available In this study, the range use and behaviour of laying hens in commercial free-range flocks was explored. Six flocks were each visited on four separate days and data collected from their outdoor area (divided into zones based on distance from shed and available resources. These were: apron (0–10 m from shed normally without cover or other enrichments; enriched belt (10–50 m from shed where resources such as manmade cover, saplings and dust baths were provided; and outer range (beyond 50 m from shed with no cover and mainly grass pasture. Data collection consisted of counting the number of hens in each zone and recording behaviour, feather condition and nearest neighbour distance (NND of 20 birds per zone on each visit day. In addition, we used techniques derived from ecological surveys to establish four transects perpendicular to the shed, running through the apron, enriched belt and outer range. Number of hens in each 10 m × 10 m quadrat was recorded four times per day as was the temperature and relative humidity of the outer range. On average, 12.5% of hens were found outside. Of these, 5.4% were found in the apron; 4.3% in the enriched zone; and 2.8% were in the outer range. This pattern was supported by data from quadrats, where the density of hens sharply dropped with increasing distance from shed. Consequently, NND was greatest in the outer range, least in the apron and intermediate in the enriched belt. Hens sampled in outer range and enriched belts had better feather condition than those from the apron. Standing, ground pecking, walking and foraging were the most commonly recorded activities with standing and pecking most likely to occur in the apron, and walking and foraging more common in the outer range. Use of the outer range declined with lower temperatures and increasing relative humidity, though use of apron and enriched belt was not affected by variation in these measures. These data support previous findings that outer range

  9. Ranging Behaviour of Commercial Free-Range Laying Hens.

    Science.gov (United States)

    Chielo, Leonard Ikenna; Pike, Tom; Cooper, Jonathan

    2016-04-26

    In this study, the range use and behaviour of laying hens in commercial free-range flocks was explored. Six flocks were each visited on four separate days and data collected from their outdoor area (divided into zones based on distance from shed and available resources). These were: apron (0-10 m from shed normally without cover or other enrichments); enriched belt (10-50 m from shed where resources such as manmade cover, saplings and dust baths were provided); and outer range (beyond 50 m from shed with no cover and mainly grass pasture). Data collection consisted of counting the number of hens in each zone and recording behaviour, feather condition and nearest neighbour distance (NND) of 20 birds per zone on each visit day. In addition, we used techniques derived from ecological surveys to establish four transects perpendicular to the shed, running through the apron, enriched belt and outer range. Number of hens in each 10 m × 10 m quadrat was recorded four times per day as was the temperature and relative humidity of the outer range. On average, 12.5% of hens were found outside. Of these, 5.4% were found in the apron; 4.3% in the enriched zone; and 2.8% were in the outer range. This pattern was supported by data from quadrats, where the density of hens sharply dropped with increasing distance from shed. Consequently, NND was greatest in the outer range, least in the apron and intermediate in the enriched belt. Hens sampled in outer range and enriched belts had better feather condition than those from the apron. Standing, ground pecking, walking and foraging were the most commonly recorded activities with standing and pecking most likely to occur in the apron, and walking and foraging more common in the outer range. Use of the outer range declined with lower temperatures and increasing relative humidity, though use of apron and enriched belt was not affected by variation in these measures. These data support previous findings that outer range areas tend to be

  10. Osprey Range - CWHR [ds601

    Data.gov (United States)

    California Department of Resources — Vector datasets of CWHR range maps are one component of California Wildlife Habitat Relationships (CWHR), a comprehensive information system and predictive model for...

  11. Short-range fundamental forces

    CERN Document Server

    Antoniadis, I; Buchner, M; Fedorov, V V; Hoedl, S; Lambrecht, A; Nesvizhevsky, V V; Pignol, G; Protasov, K V; Reynaud, S; Sobolev, Yu

    2011-01-01

    We consider theoretical motivations to search for extra short-range fundamental forces as well as experiments constraining their parameters. The forces could be of two types: 1) spin-independent forces, 2) spin-dependent axion-like forces. Differe nt experimental techniques are sensitive in respective ranges of characteristic distances. The techniques include measurements of gravity at short distances, searches for extra interactions on top of the Casimir force, precision atomic and neutron experim ents. We focus on neutron constraints, thus the range of characteristic distances considered here corresponds to the range accessible for neutron experiments.

  12. Cascade Mountain Range in Oregon

    Science.gov (United States)

    Sherrod, David R.

    2016-01-01

    The Cascade mountain system extends from northern California to central British Columbia. In Oregon, it comprises the Cascade Range, which is 260 miles long and, at greatest breadth, 90 miles wide (fig. 1). Oregon’s Cascade Range covers roughly 17,000 square miles, or about 17 percent of the state, an area larger than each of the smallest nine of the fifty United States. The range is bounded on the east by U.S. Highways 97 and 197. On the west it reaches nearly to Interstate 5, forming the eastern margin of the Willamette Valley and, farther south, abutting the Coast Ranges

  13. Ranging Behaviour of Commercial Free-Range Laying Hens

    Science.gov (United States)

    Chielo, Leonard Ikenna; Pike, Tom; Cooper, Jonathan

    2016-01-01

    Simple Summary Commercial free-range production has become a significant sector of the fresh egg market due to legislation banning conventional cages and consumer preference for products perceived as welfare friendly, as access to outdoor range can lead to welfare benefits such as greater freedom of movement and enhanced behavioural opportunities. This study investigated dispersal patterns, feather condition and activity of laying hens in three distinct zones of the range area; the apron area near shed; enriched zone 10–50 m from shed; and outer range beyond 50 m, in six flocks of laying hens under commercial free-range conditions varying in size between 4000 and 24,000 hens. Each flock was visited for four days to record number of hens in each zone, their behaviour, feather condition and nearest neighbour distances (NND), as well as record temperature and relative humidity during the visit. Temperature and relative humidity varied across the study period in line with seasonal variations and influenced the use of range with fewer hens out of shed as temperature fell or relative humidity rose. On average, 12.5% of the hens were observed on the range and most of these hens were recorded in the apron zone as hen density decreased rapidly with increasing distance from the shed. Larger flocks appeared to have a lower proportion of hens on range. The hens used the range more in the early morning followed by a progressive decrease through to early afternoon. The NND was greatest in the outer range and decreased towards the shed. Feather condition was generally good and hens observed in the outer range had the best overall feather condition. Standing, pecking, walking and foraging were the most commonly recorded behaviours and of these, standing occurred most in the apron whereas walking and foraging behaviours were recorded most in the outer range. This study supported the findings of previous studies that reported few hens in the range and greater use of areas closer

  14. How Frequently Are Pan-Assay Interference Compounds Active? Large-Scale Analysis of Screening Data Reveals Diverse Activity Profiles, Low Global Hit Frequency, and Many Consistently Inactive Compounds.

    Science.gov (United States)

    Jasial, Swarit; Hu, Ye; Bajorath, Jürgen

    2017-05-11

    Undetected pan-assay interference compounds (PAINS) with false-positive activities in assays often propagate through medicinal chemistry programs and compromise their outcomes. Although a large number of PAINS have been classified, often on the basis of individual studies or chemical experience, little has been done so far to systematically assess their activity profiles. Herein we report a large-scale analysis of the behavior of PAINS in biological screening assays. More than 23 000 extensively tested compounds containing PAINS substructures were detected, and their hit rates were determined. Many consistently inactive compounds were identified. The hit frequency was low overall, with median values of two to five hits for PAINS tested in hundreds of assays. Only confined subsets of PAINS produced abundant hits. The same PAINS substructure was often found in consistently inactive and frequently active compounds, indicating that the structural context in which PAINS occur modulates their effects.

  15. An examination of the effect of 'Hit-Turn Tennis Test' on two different protocols in pre-pubertal tennis players to heart rate, total distance runned and perceived difficulty

    Directory of Open Access Journals (Sweden)

    Mekki ABDİOĞLU

    2016-12-01

    Full Text Available Aim: The aim of the research, Hit-Turnu Tennis test, fixed with punches against the top of this test modified by downloading thrown my heart made on kick against the top speed is defined as the total requirement distance and examine the impact of the perceived difficulty. Material and Methods: The ages of the athletes were included in our study 12.7±1.75 years, height of 155.2±3.1 cm, body weight 50.9±4.78 kg, training age was determined they did was 6.7±1.5 years and a week was 5.7±0.4 hours of training. Every athlete and tennis Hit-turn test against a stationary ball, as in the original, but they also perform this test by hitting the ball against oncoming traffic by modifying. Both tests from applying their athletes run totals, heart rate and difficulty during tests perceive degrees were recorded. After the data collected during both tests calculated descriptive statistics, the differences between the differences between the two groups paired t-test to examine test (paired-samples were analyzed. Results: Hit Tennis athlete-turn test during the test, the modified test Hit-turn compared to 124 m They travel a greater distance. This difference was statistically significant (t:2.915; p<0.006. In addition, heart rate values are observed to be similar to each other when both tests. When we look at both testes of athletes perceived degree of difficulty Modified Hit-turn test it was found to be more compelling by athletes. Conclusion: As a result, the modified test Hit-Turn tennis athletes to hit the balls by other net, than they do to kick a stationary ball is believed to spend more effort.

  16. Desert Experimental Range: Annotated bibliography

    Science.gov (United States)

    E. Durant McArthur; Stanley G. Kitchen

    2013-01-01

    Entries qualify for inclusion if they were conducted in whole or part at the Desert Experimental Range (DER, also known as the Desert Range Experiment Station) or were based on DER research in whole or part. They do not qualify merely by the author having worked at the DER when the research was performed or prepared. Entries were drawn from the original abstracts or...

  17. Foraging optimally for home ranges

    Science.gov (United States)

    Mitchell, Michael S.; Powell, Roger A.

    2012-01-01

    Economic models predict behavior of animals based on the presumption that natural selection has shaped behaviors important to an animal's fitness to maximize benefits over costs. Economic analyses have shown that territories of animals are structured by trade-offs between benefits gained from resources and costs of defending them. Intuitively, home ranges should be similarly structured, but trade-offs are difficult to assess because there are no costs of defense, thus economic models of home-range behavior are rare. We present economic models that predict how home ranges can be efficient with respect to spatially distributed resources, discounted for travel costs, under 2 strategies of optimization, resource maximization and area minimization. We show how constraints such as competitors can influence structure of homes ranges through resource depression, ultimately structuring density of animals within a population and their distribution on a landscape. We present simulations based on these models to show how they can be generally predictive of home-range behavior and the mechanisms that structure the spatial distribution of animals. We also show how contiguous home ranges estimated statistically from location data can be misleading for animals that optimize home ranges on landscapes with patchily distributed resources. We conclude with a summary of how we applied our models to nonterritorial black bears (Ursus americanus) living in the mountains of North Carolina, where we found their home ranges were best predicted by an area-minimization strategy constrained by intraspecific competition within a social hierarchy. Economic models can provide strong inference about home-range behavior and the resources that structure home ranges by offering falsifiable, a priori hypotheses that can be tested with field observations.

  18. Effectiveness of High-Intensity Interval Training (HIT) and Continuous Endurance Training for VO2max Improvements: A Systematic Review and Meta-Analysis of Controlled Trials.

    Science.gov (United States)

    Milanović, Zoran; Sporiš, Goran; Weston, Matthew

    2015-10-01

    Enhancing cardiovascular fitness can lead to substantial health benefits. High-intensity interval training (HIT) is an efficient way to develop cardiovascular fitness, yet comparisons between this type of training and traditional endurance training are equivocal. Our objective was to meta-analyse the effects of endurance training and HIT on the maximal oxygen consumption (VO2max) of healthy, young to middle-aged adults. Six electronic databases were searched (MEDLINE, PubMed, SPORTDiscus, Web of Science, CINAHL and Google Scholar) for original research articles. A search was conducted and search terms included 'high intensity', 'HIT', 'sprint interval training', 'endurance training', 'peak oxygen uptake', and 'VO2max'. Inclusion criteria were controlled trials, healthy adults aged 18-45 years, training duration ≥2 weeks, VO2max assessed pre- and post-training. Twenty-eight studies met the inclusion criteria and were included in the meta-analysis. This resulted in 723 participants with a mean ± standard deviation (SD) age and initial fitness of 25.1 ± 5 years and 40.8 ± 7.9 mL·kg(-1)·min(-1), respectively. We made probabilistic magnitude-based inferences for meta-analysed effects based on standardised thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject SDs for baseline VO2max. The meta-analysed effect of endurance training on VO2max was a possibly large beneficial effect (4.9 mL·kg(-1)·min(-1); 95 % confidence limits ±1.4 mL·kg(-1)·min(-1)), when compared with no-exercise controls. A possibly moderate additional increase was observed for typically younger subjects (2.4 mL·kg(-1)·min(-1); ±2.1 mL·kg(-1)·min(-1)) and interventions of longer duration (2.2 mL·kg(-1)·min(-1); ±3.0 mL·kg(-1)·min(-1)), and a small additional improvement for subjects with lower baseline fitness (1.4 mL·kg(-1)·min(-1); ±2.0 mL·kg(-1)·min(-1)). When compared with no-exercise controls

  19. The Effect of 8 Weeks of HIT Workouts Plasma Levels of TNF-a, IL-6 and Lipid Profile in Overweight Children

    OpenAIRE

    Abdolrezareza Kazemi; Khatereh Shahrokhi

    2016-01-01

    Introduction: The prevalence of obesity among children and adolescents around the world alarmingly are increasing. Regular exercise can reduce fat tissue and improve body composition. The aim of this study was the effect of the high intensity interval training (HIT) on plasma levels of TNF-a, IL-6 and lipid profile in overweight children. Methods: The present study was semi experimental research that performed in Tehran at 2014 year.  In this study, 32 overweight students 8 to 11 divided in t...

  20. User's guide to SUBWAR 1. [Kinematically tracks torpedo and target and shows distribution of hits; in LRLTRAN for CDC 7600 computer

    Energy Technology Data Exchange (ETDEWEB)

    Stratton, S.D.

    1976-09-27

    SUBWAR 1, a digital computer program which kinematically tracks the movements of a torpedo and its target and shows the distribution of hits on the target is described. The program is written in LRLTRAN for compilation by CHAT and execution on a CDC 7600. Output is graphical as well as numerical. Torpedo and submarine target characteristics, parameters, modeling, and simulation are briefly outlined, and a line-by-line description of the program's input file is given. Some suggestions are also provided on how SUBWAR 1 can be used to study effects of underwater weapons characteristics. 10 figures, 3 tables.

  1. Reference Ranges & What They Mean

    Science.gov (United States)

    ... Chains Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle ... If you're trying to follow a healthy lifestyle, take test results that are within range as ...

  2. Kenai National Moose Range Alaska

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This book presents a summary of the history, wildlife, recreational opportunities, economic uses, and future plans for Kenai National Moose Range.

  3. Staying Out of Range: Increasing Attacking Distance in Fencing.

    Science.gov (United States)

    Turner, Anthony N; Marshall, Geoff; Noto, Angelo; Chavda, Shyam; Atlay, Nathan; Kirby, David

    2017-03-14

    To avoid being hit, fencers typically adopt an out of range position, which was hypothesized to be governed by body- and action-scaled affordances. This theory was measured in elite and national level junior (u20) fencers. Associations between "reachability" of lunging and step-lunging attacks, was assessed against height, arm-span, leg-span, body mass and lower-body power, and then compared across level. Reachability was determined as the distance covered by fencers during these attacks and was reported as actual and estimated distances. Elite fencers are better at estimating their lunging and step-lunge distance compared to national ranked junior fencers (-0.9 vs. 7.3 % and 5.4 vs. 10.9 % respectively). Surprisingly, elite fencers' actual and estimated distances for these was less than the junior fencers' (222.6 vs. 251.5 cm and 299.3 vs. 360.2 cm respectively), and significantly so in the former. Finally only arm (r = .81) and leg span (r = .71) were significantly correlated to estimated lunging distance and this was only in elite fencers. Findings suggest that better fencers can accurately predict their attack range and that reachability appears to be positively influenced by arm and leg-span; these may feed in to talent identification. Given that distances were less in elite fencers, findings suggests that timing and distance estimation are key skills to master, and that the mastery of these in offensive actions can mitigate to a large extent, the physical benefits of an opponent's greater height.

  4. Wide Operational Range Thermal Sensor

    Science.gov (United States)

    Goebel, John H. (Inventor); McMurray, Robert E., Jr. (Inventor)

    2005-01-01

    Bolometer system and method for detecting, at BLIP levels, presence of radiation over a broad range of wavelengths in an infrared spectrum and in a temperature range from 20 K to as high as room temperature. The radiation is received by a Si crystal having a region that is doped with one or more of In, Ga, S, Se, Te, B, Al, P, As and Sb in a concentration ratio in a range such as 5 x 10(exp -11) to 5 x 10(exp -6). Change in electrical resistance delta R due to receipt of the radiation is measured through a change in voltage difference or current within the crystal, and the quantity delta R is converted to an estimate of the amount of radiation received. Optionally, incident radiation having an energy high enough to promote photoconductivity is removed before detection.

  5. Mental health problems among survivors in hard-hit areas of the 5.12 Wenchuan and 4.20 Lushan earthquakes.

    Science.gov (United States)

    Xie, Zongtang; Xu, Jiuping; Wu, Zhibin

    2017-02-01

    Earthquake exposure has often been associated with psychological distress. However, little is known about the cumulative effect of exposure to two earthquakes on psychological distress and in particular, the effect on the development of post-traumatic stress disorder (PTSD), anxiety and depression disorders. This study explored the effect of exposure on mental health outcomes after a first earthquake and again after a second earthquake. A population-based mental health survey using self-report questionnaires was conducted on 278 people in the hard-hit areas of Lushan and Baoxing Counties 13-16 months after the Wenchuan earthquake (Sample 1). 191 of these respondents were evaluated again 8-9 months after the Lushan earthquake (Sample 2), which struck almost 5 years after the Wenchuan earthquake. In Sample 1, the prevalence rates for PTSD, anxiety and depression disorders were 44.53, 54.25 and 51.82%, respectively, and in Sample 2 the corresponding rates were 27.27, 38.63 and 36.93%. Females, the middle-aged, those of Tibetan nationality, and people who reported fear during the earthquake were at an increased risk of experiencing post-traumatic symptoms. Although the incidence of PTSD, anxiety and depression disorders decreased from Sample 1 to Sample 2, the cumulative effect of exposure to two earthquakes on mental health problems was serious in the hard-hit areas. Therefore, it is important that psychological counseling be provided for earthquake victims, and especially those exposed to multiple earthquakes.

  6. GEA CRDA Range Data Analysis

    Science.gov (United States)

    1999-07-28

    E1, July-August 1998 18 3.3. Example 3: SatMex, Solidaridad 2, May-June 1998 27 3.4. Example 4: PanAmSat, Galaxy IV, May-June 1998 33 3.5...17 Millstone measurements residuals for Telstar 401 on Days 181-263. 26 3-18 Millstone measurement residuals for Solidaridad 1 on Days 141-153...with 29 SatMex range data. 3-19 Hermosillo B-- Solidaridad 1 range residuals through Days 135-144 with bias 30 removed. 3-20 Iztapalapa D

  7. Radio pill antenna range test

    Science.gov (United States)

    Cummins, W. F.; Kane, R. J.

    1992-05-01

    In order to investigate the potential of a proposed 'radio pill' beacon transmitter, a range test experiment was devised and carried out in the VHF frequency range. Calculations and previous work indicated that optimum sensitivity and, thus, distance would be obtained in this frequency range provided body radio-frequency (RF) absorption was not too great. A ferrite-core loop antenna is compatible with a pill geometry and has better radiation efficiency than an air core loop. The ferrite core may be a hollow cylinder with the electronics and batteries placed inside. However, this range test was only concerned with experimentally developing test range data on the ferrite core antenna itself. A one turn strap loop was placed around a 9.5 mm diameter by 18.3 mm long stack of ferrite cores. This was coupled to a 50 Omega transmission line by 76 mm of twisted pair line and a capacitive matching section. This assembly was excited by a signal generator at output levels of -10 to +10 dBm. Signals were received on a VHF receiver and tape recorder coupled to a 14 element, circularly polarized Yagi antenna at a height of 2.5 m. Field strength measurements taken at ranges of 440, 1100, and 1714 m. Maximum field strengths referenced to 0 dBm transmitter level were -107 to -110 dB at 440 m, -124 to -127 dBm at 1100 m, and -116 to -119 dBm at 1714 m when the antenna cylinder was horizontal. Field strengths with a vertical antenna were about 6 dB below these values. The latter transmit site was elevated and had a clear line-of-site path to the receiving site. The performance of this test antenna was better than that expected from method-of-moment field calculations. When this performance data is scaled to a narrow bandwidth receiving system, ground level receiving ranges of a few to 10 km can be expected. Clear line-of-sight ranges where either or both the transmitter and receiver are elevated could vary from several km to 100 km.

  8. Improved Range Searching Lower Bounds

    DEFF Research Database (Denmark)

    Larsen, Kasper Green; Nguyen, Huy L.

    2012-01-01

    by constructing a hard input set and query set, and then invoking Chazelle and Rosenberg's [CGTA'96] general theorem on the complexity of navigation in the pointer machine. For the group model, we show that input sets and query sets that are hard for range reporting in the pointer machine (i.e. by Chazelle...

  9. Anatomy of a Mountain Range.

    Science.gov (United States)

    Chew, Berkeley

    1993-01-01

    Provides written tour of Colorado Rockies along San Juan Skyway in which the geological features and formation of the mountain range is explored. Discusses evidence of geologic forces and products such as plate tectonic movement and the Ancestral Rockies; subduction and the Laramide Orogeny; volcanism and calderas; erosion, faulting, land…

  10. Mobile Lunar Laser Ranging Station

    Science.gov (United States)

    Intellect, 1977

    1977-01-01

    Harlan Smith, chairman of the University of Texas's Astronomy Department, discusses a mobile lunar laser ranging station which could help determine the exact rates of movement between continents and help geophysicists understand earthquakes. He also discusses its application for studying fundamental concepts of cosmology and physics. (Editor/RK)

  11. Range Compressed Holographic Aperture Ladar

    Science.gov (United States)

    2017-06-01

    step 1. This image can be obtained through any digital holography processing technique and contains no range information. Since the penny has a... digital holography, laser, active imaging , remote sensing, laser imaging 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT: SAR 8...30 15. Digital Hologram Image

  12. Mandibular movement range in children.

    Science.gov (United States)

    Machado, Barbara Cristina Zanandréa; Medeiros, Ana Paula Magalhães; Felício, Cláudia Maria de

    2009-01-01

    identification of the mandibular movement range is an important procedure in the evaluation of the stomatognathic system. However, there are few studies in children that focus on normal parameters or abnormalities. to determine the average range of mandibular movements in Brazilian children aged 6 to 12 years; to verify the difference between genders, in each age group, and between the different age groups: 6-8 years; 8.1-10 years; and 10.1-12 years. participants of the study were 240 healthy children selected among regular students from local schools of São Paulo State. The maximum mandibular opening, lateral excursion and protrusive movements, and deviation of the medium line, if present, were measured using a digital caliper. Student T test, Analysis of variance and Tukey test were considered significant for p mandibular opening; 7.71mm for lateral excursion to the right; 7.92mm for lateral excursion to the left; 7.45mm for protrusive movements. No statistical difference was observed between genders. There was a gradual increase in the range of mandibular movements, with significant differences mainly between the ages of 6-8 years and 10.1-12 years. during childhood the range of mandibular movements increases. Age should be considered in this analysis for a greater precision in the diagnosis.

  13. Short-range communication system

    Science.gov (United States)

    Alhorn, Dean C. (Inventor); Howard, David E. (Inventor); Smith, Dennis A. (Inventor)

    2012-01-01

    A short-range communication system includes an antenna, a transmitter, and a receiver. The antenna is an electrical conductor formed as a planar coil with rings thereof being uniformly spaced. The transmitter is spaced apart from the plane of the coil by a gap. An amplitude-modulated and asynchronous signal indicative of a data stream of known peak amplitude is transmitted into the gap. The receiver detects the coil's resonance and decodes same to recover the data stream.

  14. Countering short range ballistic missiles

    OpenAIRE

    Conner, George W.; Ehiers, Mark A.; Marshall, Kneale T.

    1993-01-01

    Approved for public release; distribution is unlimited. Concepts commonly found in ASW search are used to model the flow and detection of mobile launchers for short range ballistic missiles. Emphasis is on detection and destruction of the launcher before launch. The benefit of pre-hostility intelligence and pre-missile-launch prosecution, the backbone of successful ASW, is revealed through the analysis of a circulation model which reflects the standard operations of a third world mobile mi...

  15. Medium Range Forecasts Representation (and Long Range Forecasts?)

    Science.gov (United States)

    Vincendon, J.-C.

    2009-09-01

    The progress of the numerical forecasts urges us to interest us in more and more distant ranges. We thus supply more and more forecasts with term of some days. Nevertheless, precautions of use are necessary to give the most reliable and the most relevant possible information. Available in a TV bulletin or on quite other support (Internet, mobile phone), the interpretation and the representation of a medium range forecast (5 - 15 days) must be different from those of a short range forecast. Indeed, the "foresee-ability” of a meteorological phenomenon decreases gradually in the course of the ranges, it decreases all the more quickly that the phenomenon is of small scale. So, at the end of some days, the probability character of a forecast becomes very widely dominating. That is why in Meteo-France the forecasts of D+4 to D+7 are accompanied with a confidence index since around ten years. It is a figure between 1 and 5: the more we approach 5, the more the confidence in the supplied forecast is good. In the practice, an indication is supplied for period D+4 / D+5, the other one for period D+6 / D+7, every day being able to benefit from a different forecast, that is be represented in a independent way. We thus supply a global tendency over 24 hours with less and less precise symbols as the range goes away. Concrete examples will be presented. From now on two years, we also publish forecasts to D+8 / J+9, accompanied with a sign of confidence (" good reliability " or " to confirm "). These two days are grouped together on a single map because for us, the described tendency to this term is relevant on a duration about 48 hours with a spatial scale slightly superior to the synoptic scale. So, we avoid producing more than two zones of types of weather over France and we content with giving an evolution for the temperatures (still, in increase or in decline). Newspapers began to publish this information, it should soon be the case of televisions. It is particularly

  16. Activity of Bdellovibrio hit locus proteins, Bd0108 and Bd0109, links Type IVa pilus extrusion/retraction status to prey-independent growth signalling.

    Directory of Open Access Journals (Sweden)

    Michael J Capeness

    Full Text Available Bdellovibrio bacteriovorus are facultatively predatory bacteria that grow within gram-negative prey, using pili to invade their periplasmic niche. They also grow prey-independently on organic nutrients after undergoing a reversible switch. The nature of the growth switching mechanism has been elusive, but several independent reports suggested mutations in the hit (host-interaction locus on the Bdellovibrio genome were associated with the transition to prey-independent growth. Pili are essential for prey entry by Bdellovibrio and sequence analysis of the hit locus predicted that it was part of a cluster of Type IVb pilus-associated genes, containing bd0108 and bd0109. In this study we have deleted the whole bd0108 gene, which is unique to Bdellovibrio, and compared its phenotype to strains containing spontaneous mutations in bd0108 and the common natural 42 bp deletion variant of bd0108. We find that deletion of the whole bd0108 gene greatly reduced the extrusion of pili, whereas the 42 bp deletion caused greater pilus extrusion than wild-type. The pili isolated from these strains were comprised of the Type IVa pilin protein; PilA. Attempts to similarly delete gene bd0109, which like bd0108 encodes a periplasmic/secreted protein, were not successful, suggesting that it is likely to be essential for Bdellovibrio viability in any growth mode. Bd0109 has a sugar binding YD- repeat motif and an N-terminus with a putative pilin-like fold and was found to interact directly with Bd0108. These results lead us to propose that the Bd0109/Bd0108 interaction regulates pilus production in Bdellovibrio (possibly by interaction with the pilus fibre at the cell wall, and that the presence (and possibly retraction state of the pilus feeds back to alter the growth state of the Bdellovibrio cell. We further identify a novel small RNA encoded by the hit locus, the transcription of which is altered in different bd0108 mutation backgrounds.

  17. Truthful approximations to range voting

    DEFF Research Database (Denmark)

    Filos-Ratsika, Aris; Miltersen, Peter Bro

    We consider the fundamental mechanism design problem of approximate social welfare maximization under general cardinal preferences on a finite number of alternatives and without money. The well-known range voting scheme can be thought of as a non-truthful mechanism for exact social welfare......-unilateral has an approximation ratio between 0.610 and 0.611, the best ordinal mechanism has an approximation ratio between 0.616 and 0.641, while the best mixed-unilateral mechanism has an approximation ratio bigger than 0.660. In particular, the best mixed-unilateral non-ordinal (i.e., cardinal) mechanism...

  18. Nonlinear dynamic range compression deconvolution

    Science.gov (United States)

    Haji-Saeed, Bahareh; Sengupta, Sandip K.; Goodhue, William; Khoury, Jed; Woods, Charles L.; Kierstead, John

    2006-07-01

    We introduce a dynamic range image compression technique for nonlinear deconvolution; the impulse response of the distortion function and the noisy distorted image are jointly transformed to pump a clean reference beam in a two-beam coupling arrangement. The Fourier transform of the pumped reference beam contains the deconvolved image and its conjugate. In contrast to standard deconvolution approaches, for which noise can be a limiting factor in the performance, this approach allows the retrieval of distorted signals embedded in a very high-noise environment.

  19. Parameters of stochastic diffusion processes estimated from observations of first-hitting times: Application to the leaky integrate-and-fire neuronal model

    Science.gov (United States)

    Ditlevsen, Susanne; Lansky, Petr

    2007-10-01

    A theoretical model has to stand the test against the real world to be of any practical use. The first step is to identify parameters in the model estimated from experimental data. In many applications where renewal point data are available, models of first-hitting times of underlying diffusion processes arise. Despite the seemingly simplicity of the model, the problem of how to estimate parameters of the underlying stochastic process has resisted solution. The few attempts have either been unreliable, difficult to implement, or only valid in subsets of the relevant parameter space. Here we present an estimation method that overcomes these difficulties, is computationally easy and fast to implement, and also works surprisingly well on small data sets. The method is illustrated on simulated and experimental data. Two common neuronal models—the Ornstein-Uhlenbeck and Feller models—are investigated.

  20. Parameters of stochastic diffusion processes estimated from observations of first-hitting times: application to the leaky integrate-and-fire neuronal model.

    Science.gov (United States)

    Ditlevsen, Susanne; Lansky, Petr

    2007-10-01

    A theoretical model has to stand the test against the real world to be of any practical use. The first step is to identify parameters in the model estimated from experimental data. In many applications where renewal point data are available, models of first-hitting times of underlying diffusion processes arise. Despite the seemingly simplicity of the model, the problem of how to estimate parameters of the underlying stochastic process has resisted solution. The few attempts have either been unreliable, difficult to implement, or only valid in subsets of the relevant parameter space. Here we present an estimation method that overcomes these difficulties, is computationally easy and fast to implement, and also works surprisingly well on small data sets. The method is illustrated on simulated and experimental data. Two common neuronal models--the Ornstein-Uhlenbeck and Feller models--are investigated.

  1. Live Fire Range Environmental Assessment

    Energy Technology Data Exchange (ETDEWEB)

    None

    1993-08-01

    The Central Training Academy (CTA) is a DOE Headquarters Organization located in Albuquerque, New Mexico, with the mission to effectively and efficiently educate and train personnel involved in the protection of vital national security interests of DOE. The CTA Live Fire Range (LFR), where most of the firearms and tactical training occurs, is a complex separate from the main campus. The purpose of the proposed action is to expand the LFR to allow more options of implementing required training. The Department of Energy has prepared this Environmental Assessment (EA) for the proposed construction and operation of an expanded Live Fire Range Facility at the Central Training Academy in Albuquerque, New Mexico. Based on the analysis in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, the preparation of an environmental impact statement is not required and DOE is issuing this Finding of No Significant Impact (FONSI).

  2. A two-hit model of suicide-trait-related behaviors in the context of a schizophrenia-like phenotype: Distinct effects of lithium chloride and clozapine.

    Science.gov (United States)

    Deslauriers, Jessica; Belleville, Karine; Beaudet, Nicolas; Sarret, Philippe; Grignon, Sylvain

    2016-03-15

    Schizophrenia patients show a high rate of premature mortality due to suicide. The pathophysiological mechanisms of these suicidal behaviors in schizophrenia do not appear to involve serotonergic neurotransmission as found in the general population. Our aim was to develop an in vivo model of schizophrenia presenting suicide-trait-related behaviors such as aggressiveness, impulsivity, anxiety and helplessness. We opted for a two-hit model: C57BL/6 dams were injected with polyI:C on gestational day 12. The pups were submitted to social isolation for 4weeks after weaning. During the last week of social isolation and 30min before behavioral testing, the mice received vehicle, lithium chloride or clozapine. Lithium chloride is well known for its suicide preventive effects in the non-schizophrenic population, while clozapine is the antipsychotic with the best-established suicide preventive effect. The two-hit model induced several schizophrenia-related and suicide-trait-related behaviors in male, but not female, mice. Additionally, lithium chloride improved prepulse inhibition, aggressiveness, impulsivity and anxiety-like behavior in socially isolated mice only, whereas clozapine prevented behavioral abnormalities mainly in mice prenatally exposed to polyI:C and submitted to isolated rearing. The distinct effects of lithium chloride and clozapine suggested that mice prenatally exposed to polyI:C and submitted to social isolation presented a distinct phenotype from that of mice submitted to social isolation only. Because diagnosing suicidal risk in patients is a challenge for psychiatrists given the lack of specific clinical predictors, our in vivo model could help in gaining a better understanding of the mechanisms underlying suicidal behavior in the context of schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Dynamic range majority data structures

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; He, Meng; Munro, J. Ian

    2011-01-01

    data structure for answering range α-majority queries on a dynamic set of points, where α ε (0,1). Our data structure uses O(n) space, supports queries in O((lg n)/α) time, and updates in O((lg n)/α) amortized time. If the coordinates of the points are integers, then the query time can be improved to O......((lg n/(α lglg n)). For constant values of α, this improved query time matches an existing lower bound, for any data structure with polylogarithmic update time. We also generalize our data structure to handle sets of points in d-dimensions, for d ≥ 2, as well as dynamic arrays, in which each entry...

  4. A universal gyroscope driving circuit with 70dB amplitude control range

    KAUST Repository

    Abdelghany, Mohamed A.

    2010-08-01

    A CMOS variable gain driving circuit with output signal amplitude control for gyroscopes with wide range of quality factors is presented. The driving circuit can be used for gyroscopes with Q values higher than 500. The circuit uses a current-commutating switching mixer to control the gyroscope driving signal level. Conventional driving circuits use automatic gain control (AGC) which suffers from limited linear range and the need for an off-chip capacitor for the peak detector and loop filter. Two stage variable gain amplifier is used in the proposed design to ensure enough gain for oscillation for such a wide range of quality factors. Analog and digital amplitude control methods are used to cover wide range of driving signal amplitude with enough accuracy to hit the maximum driving signal level without sacrificing gyroscope linearity. Due to the high DC gain of the amplifier chain, DC offset resulting from mismatches might saturate the amplifier output. DC offset correction is employed using a secondary negative feedback loop. The proposed driving circuit is being fabricated in 0.6μm CMOS technology. © 2010 IEEE.

  5. Big hits on the small screen: an evaluation of concussion-related videos on YouTube.

    Science.gov (United States)

    Williams, David; Sullivan, S John; Schneiders, Anthony G; Ahmed, Osman Hassan; Lee, Hopin; Balasundaram, Arun Prasad; McCrory, Paul R

    2014-01-01

    YouTube is one of the largest social networking websites, allowing users to upload and view video content that provides entertainment and conveys many messages, including those related to health conditions, such as concussion. However, little is known about the content of videos relating to concussion. To identify and classify the content of concussion-related videos available on YouTube. An observational study using content analysis. YouTube's video database was systematically searched using 10 search terms selected from MeSH and Google Adwords. The 100 videos with the largest view counts were chosen from the identified videos. These videos and their accompanying text were analysed for purpose, source and description of content by a panel of assessors who classified them into data-driven thematic categories. 434 videos met the inclusion criteria and the 100 videos with the largest view counts were chosen. The most common categories of the videos were the depiction of a sporting injury (37%) and news reports (25%). News and media organisations were the predominant source (51%) of concussion-related videos on YouTube, with very few being uploaded by professional or academic organisations. The median number of views per video was 26 191. Although a wide range of concussion-related videos were identified, there is a need for healthcare and educational organisations to explore YouTube as a medium for the dissemination of quality-controlled information on sports concussion.

  6. Reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to a supraphysiologic glucose concentration is associated with loss of STF-1 transcription factor expression.

    Science.gov (United States)

    Olson, L K; Sharma, A; Peshavaria, M; Wright, C V; Towle, H C; Rodertson, R P; Stein, R

    1995-09-26

    Chronic exposure of HIT-T15 beta cells to elevated glucose concentrations leads to decreased insulin gene transcription. The reduction in expression is accompanied by diminished binding of a glucose-sensitive transcription factor (termed GSTF) that interacts with two (A+T)-rich elements within the 5' flanking control region of the insulin gene. In this study we examined whether GSTF corresponds to the recently cloned insulin gene transcription factor STF-1, a homeodomain protein whose expression is restricted to the nucleus of endodermal cells of the duodenum and pancreas. We found that an affinity-purified antibody recognizing STF-1 supershifted the GSTF activator complex formed from HIT-T15 extracts. In addition, we demonstrated a reduction in STF-1 mRNA and protein levels that closely correlated with the change in GSTF binding in HIT-T15 cells chronically cultured under supraphysiologic glucose concentrations. The reduction in STF-1 expression in these cells could be accounted for by a change in the rate of STF-1 gene transcription, suggesting a posttranscriptional control mechanism. In support of this hypothesis, no STF-1 mRNA accumulated in HIT-T15 cells passaged in 11.1 mM glucose. The only RNA species detected was a 6.4-kb STF-1 RNA species that hybridized with 5' and 3' STF-1-specific cDNA probes. We suggest that the 6.4-kb RNA represents an STF-1 mRNA precursor and that splicing of this RNA is defective in these cells. Overall, this study suggests that reduced expression of a key transcriptional regulatory factor, STF-1, contributes to the decrease in insulin gene transcription in HIT-T15 cells chronically cultured in supraphysiologic glucose concentration.

  7. An Algorithm of an X-ray Hit Allocation to a Single Pixel in a Cluster and Its Test-Circuit Implementation

    Energy Technology Data Exchange (ETDEWEB)

    Deptuch, G. W. [AGH-UST, Cracow; Fahim, F. [Fermilab; Grybos, P. [AGH-UST, Cracow; Hoff, J. [Fermilab; Maj, P. [AGH-UST, Cracow; Siddons, D. P. [Brookhaven; Kmon, P. [AGH-UST, Cracow; Trimpl, M. [Fermilab; Zimmerman, T. [Fermilab

    2017-05-06

    An on-chip implementable algorithm for allocation of an X-ray photon imprint, called a hit, to a single pixel in the presence of charge sharing in a highly segmented pixel detector is described. Its proof-of-principle implementation is also given supported by the results of tests using a highly collimated X-ray photon beam from a synchrotron source. The algorithm handles asynchronous arrivals of X-ray photons. Activation of groups of pixels, comparisons of peak amplitudes of pulses within an active neighborhood and finally latching of the results of these comparisons constitute the three procedural steps of the algorithm. A grouping of pixels to one virtual pixel that recovers composite signals and event driven strobes to control comparisons of fractional signals between neighboring pixels are the actuators of the algorithm. The circuitry necessary to implement the algorithm requires an extensive inter-pixel connection grid of analog and digital signals that are exchanged between pixels. A test-circuit implementation of the algorithm was achieved with a small array of 32×32 pixels and the device was exposed to an 8 keV highly collimated to a diameter of 3 μm X-ray beam. The results of these tests are given in the paper assessing physical implementation of the algorithm.

  8. Hitting the target: fragment screening with acoustic in situ co-crystallization of proteins plus fragment libraries on pin-mounted data-collection micromeshes.

    Science.gov (United States)

    Yin, Xingyu; Scalia, Alexander; Leroy, Ludmila; Cuttitta, Christina M; Polizzo, Gina M; Ericson, Daniel L; Roessler, Christian G; Campos, Olven; Ma, Millie Y; Agarwal, Rakhi; Jackimowicz, Rick; Allaire, Marc; Orville, Allen M; Sweet, Robert M; Soares, Alexei S

    2014-05-01

    Acoustic droplet ejection (ADE) is a powerful technology that supports crystallographic applications such as growing, improving and manipulating protein crystals. A fragment-screening strategy is described that uses ADE to co-crystallize proteins with fragment libraries directly on MiTeGen MicroMeshes. Co-crystallization trials can be prepared rapidly and economically. The high speed of specimen preparation and the low consumption of fragment and protein allow the use of individual rather than pooled fragments. The Echo 550 liquid-handling instrument (Labcyte Inc., Sunnyvale, California, USA) generates droplets with accurate trajectories, which allows multiple co-crystallization experiments to be discretely positioned on a single data-collection micromesh. This accuracy also allows all components to be transferred through small apertures. Consequently, the crystallization tray is in equilibrium with the reservoir before, during and after the transfer of protein, precipitant and fragment to the micromesh on which crystallization will occur. This strict control of the specimen environment means that the crystallography experiments remain identical as the working volumes are decreased from the few microlitres level to the few nanolitres level. Using this system, lysozyme, thermolysin, trypsin and stachydrine demethylase crystals were co-crystallized with a small 33-compound mini-library to search for fragment hits. This technology pushes towards a much faster, more automated and more flexible strategy for structure-based drug discovery using as little as 2.5 nl of each major component.

  9. Forward physics in CMS: Simulation of PMT hits in HF and Higgs mass reconstruction methods with a focus on forward jet tagging

    CERN Document Server

    Moeller, Anthony Richard

    2014-01-01

    Abnormally high energy events were seen in the Hadronic Forward (HF) calorimeter for pion and muon data during testbeam in 2004. Analysis of testbeam data suggested that such events were caused by particles traveling the entire length of HF and striking the photomultiplier (PMT) windows in the readout box behind HF. Charged particles traversing the window of the PMT emit cerenkov radiation, which creates abnormally high energy events in the data. To further study these events, a modification of the existing official CMS HF simulation was created that added the PMT windows to the simulation as sensitive detectors. In agreement with testbeam data, abnormally high energy events in the PMTs were seen in the simulation for muons and pions. The simulation was then extended to jets simulated with Pythia, and then for collision like events as well. PMT hits were seen in both of these cases. Energy sharing between PMTs for long and short fibers in HF as well as timing differences between normal HF events and PMT event...

  10. MORPHOLOGICAL HIT-OR-MISS TRANSFORM BASED APPROACH FOR BUILDING DAMAGE ESTIMATION FROM VHR AIRBORNE IMAGERY IN 2011 PACIFIC COAST OF TOHOKU EARTHQUAKE AND TSUNAMI

    Directory of Open Access Journals (Sweden)

    C. D. K. Parape

    2012-08-01

    Full Text Available The very high resolution (VHR airborne images offer the opportunity to recognize features such as road, vegetation, buildings and other kind of infrastructures. The advantage of remote sensing and its applications made it possible to extract damaged, undamaged building and vulnerability assessment of wide urban areas due to a natural disaster. In this paper, we focus on an automatic building detection method which is helpful to optimizing, recognizing, rescuing, recovery and management tasks in the event of a disaster. Objective of this study is to develop techniques for tsunami damaged building extraction, based on very high resolution (VHR airborne images acquired before and after the 2011 East coastline of Japan among Tohoku area and to carry out a damage assessment of building and vulnerable area mapping. This paper presents a methodology and results of evaluating damaged buildings detection algorithm using an object recognition task based on Mathematical Morphological (MM operators for Very High Resolution (VHR remotely sensed airborne images. The proposed approach involves several advanced morphological operators among which an adaptive hit-or-miss transform with varying size and shape of the structuring elements. VHR airborne images consisting of pre and post 2011 Pacific coast of Tohoku earthquake and Tsunami site of the Ishinomaki, Miyagi area in Japan were used. The extracted results of building were compared with ground truth data giving 76% and 88% in accuracy before and after the Tsunami event.

  11. Identification of a self-paced hitting task in freely moving rats based on adaptive spike detection in multi-unit M1 cortical signals

    Directory of Open Access Journals (Sweden)

    Sofyan Hammad Himaidan Hammad

    2013-11-01

    Full Text Available Invasive brain computer interfaces may prove to be a useful rehabilitation tool for severely disabled patients. Although some systems have shown to work well in restricted laboratory settings, their usefulness must be tested in less controlled environments. Our objective was to investigate if a specific motor task could reliably be detected from multi-unit intra-cortical signals from freely moving animals. Four rats were trained to hit a retractable paddle (defined as a ‘Hit’. Intra-cortical signals were obtained from electrodes placed in the primary motor cortex. First, the signal-to-noise-ratio was increased by wavelet denoising. Action potentials were then detected using an adaptive threshold, counted in three consecutive time intervals and were used as features to classify either a ‘Hit’ or a ‘no-Hit’ (defined as an interval between two ‘Hit’s. We found that a ‘Hit’ could be detected with an accuracy of 75 ± 6% when wavelet denoising was applied whereas the accuracy dropped to 62 ± 5% without prior denoising. We compared our approach with the common daily practice in BCI that consists of using a fixed, manually selected threshold for spike detection without denoising. The results showed the feasibility of detecting a motor task in a less restricted environment than commonly applied within invasive BCI research.

  12. Radar range measurements in the atmosphere.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2013-02-01

    The earths atmosphere affects the velocity of propagation of microwave signals. This imparts a range error to radar range measurements that assume the typical simplistic model for propagation velocity. This range error is a function of atmospheric constituents, such as water vapor, as well as the geometry of the radar data collection, notably altitude and range. Models are presented for calculating atmospheric effects on radar range measurements, and compared against more elaborate atmospheric models.

  13. When particles hit the headlines

    CERN Multimedia

    James Gillies

    2010-01-01

    With its high discovery potential and unprecedented performance, the LHC is a much-anticipated machine. Media and the public are eagerly following every development, and on 30 March, the communication teams provided wide coverage of the day’s historic events.   The LHC is a machine of superlatives, and that includes its impact on science communication. Never before has a particle accelerator been as well known as the LHC, or a fundamental science laboratory made such an impressive list of headlines in the world’s press. The news of the first 7 TeV collisions was covered by print, radio and television news around the world. At least 2,200 news articles were published in print and online on the same day (see graph). More than 100 journalists from 68 media outlets in 18 countries attended the event at CERN. CERN's public homepage recorded 205,000 visitors (unique IPs) from 185 countries, compared to a normal average of 10,000 visitors per day. The Press Office site (includes L...

  14. Psychology: Climate change hits home

    Science.gov (United States)

    Weber, Elke U.

    2011-04-01

    Engaging the public with climate change has proved difficult, in part because they see the problem as remote. New evidence suggests that direct experience of one anticipated impact -- flooding -- increases people's concern and willingness to save energy.

  15. Tragedy Hits Close to Home.

    Science.gov (United States)

    Babb, J. J.; Wahlfeldt, Stephen

    1999-01-01

    Describes how the student newspaper staff at Rocky Mountain High School covered the shootings at Columbine High School (Littleton, Colorado, only 70 miles away). Notes that the students published a six-page special edition in only two days, instead of a larger edition later on, in an attempt to bring peace to the students and provide a means to…

  16. Hitting sbottom in natural SUSY

    CERN Document Server

    Lee, Hyun Min; Trott, Michael

    2012-01-01

    We compare the experimental prospects of direct stop and sbottom pair production searches at the LHC. Such searches for stops are of great interest as they directly probe for states that are motivated by the SUSY solution to the hierarchy problem of the Higgs mass parameter - leading to a "Natural" SUSY spectrum. Noting that sbottom searches are less experimentally challenging and scale up in reach directly with the improvement on b-tagging algorithms, we discuss the interplay of small TeV scale custodial symmetry violation with sbottom direct pair production searches as a path to obtaining strong sub-TeV constraints on stops in a natural SUSY scenario. We argue that if a weak scale natural SUSY spectrum does not exist within the reach of LHC, then hopes for such a spectrum for large regions of parameter space should sbottom out. Conversely, the same arguments make clear that a discovery of such a spectrum is likely to proceed in a sbottom up manner.

  17. Stanford's gene patents hit snags.

    Science.gov (United States)

    Sun, M

    1982-11-26

    Background information is presented on the preliminary rejection of a 1978 recombinant DNA patent application by Stanley Cohen and Herbert Boyer. The Patent Office is concerned about the omission of important information from the application, the exclusion of a third collaborator as co-inventor, and the interval between public disclosure and the date of filing. The dispute could lead to a challenge of a related Cohen-Boyer patent issued in 1980, posing a financial threat to Stanford University, which holds the lucrative patent rights, and the University of California, which shares the licensing fees and royalties.

  18. Social Engineering hits Social Commerce

    Science.gov (United States)

    Degenhardt, Werner; Wiele, Johannes

    Looking at social commerce, a bunch of bewildering phenomena attracts the attention of social psychologists. The way customers participate today shows attitudes and ethical behavior which cannot be explained from the inherent conditions of Web 2.0 environments alone. Fraud often succeeds, when you do not expect it, and honesty can be found under circumstances that do not support honesty at all. The current situation seems to result from customers assigning experience and ethics from real world business to virtual business environments. But there are indications that this situation may change. Social commerce could suffer as soon as customers would use its inherent weaknesses to their own advantage. The following article outlines first approaches to research into this topic.

  19. Hit the gas: go green!

    CERN Document Server

    CERN Bulletin

    2012-01-01

    Just one year ago, CERN took delivery of its first bi-fuel vehicles (see article in Bulletin 07-08/2011). Today, the fleet comprises 100 vehicles capable of running with petrol or natural gas. At that time, Véronique Marchal, head of the Site Services section in the GS Department, told us: “We are counting on CERN car users’ environmental awareness to use natural gas fuel whenever possible.” Observations one year later show that... well, let’s say there is still plenty of room for improvement. A new awareness campaign has therefore been launched.   “Running on natural gas reduces carbon dioxide emissions by some 40%,” explains Serge Micallef of the Services Industriels de Genève (SIG), CERN’s partners for this green mobility project. CNG contains 20% biogas, which is carbon-neutral. CNG produces 60 to 95% less pollution overall than ordinary petrol, and it is entirely soot-free. It is true that filli...

  20. The PS Booster hits 40

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    Many accelerators’ "round" birthdays are being celebrated at CERN these days – the PS turned 50 in 2009, the SPS was 35 in 2011, and this year it's the turn of the PS Booster to mark its 40th anniversary. Originally designed to accelerate 1013 protons to 800 MeV, it has far exceeded its initial design performance over the years.   The PS Booster in the 1970s. Imagine the scene: a group of accelerator physicists staring expectantly at a monitor, when suddenly a shout of joy goes up as a signal flickers across the screen. Does that sound familiar? Well, turn the clock back 40 years (longer hair, wider trouser legs) and you have the situation at the PS Booster on 26 May 1972. On that day, beam was injected into the Booster for the first time. “It was a real buzz,” says Heribert Koziol, then Chairman of the Running-in Committee. “We were very happy – and also a little relieved – when the beam finally...

  1. Open Days a smash hit!

    CERN Multimedia

    2008-01-01

    The general public seized the one and only opportunity to visit the Large Hadron Collider before it goes into service. The Open Days on 5 and 6 April attracted record numbers of visitors, with 53,000 visitors on the Sunday alone!

  2. CDKN2A/B Deletion and Double-hit Mutations of the MAPK Pathway Underlie the Aggressive Behavior of Langerhans Cell Tumors.

    Science.gov (United States)

    Xerri, Luc; Adélaïde, José; Popovici, Cornel; Garnier, Séverine; Guille, Arnaud; Mescam-Mancini, Lenaïg; Laurent, Camille; Brousset, Pierre; Coze, Carole; Michel, Gérard; Chaffanet, Max; Bouabdallah, Reda; Coso, Diane; Bertucci, François; Birnbaum, Daniel

    2018-02-01

    Langerhans cell histiocytosis (LCH) has a mostly favorable outcome, whereas Langerhans cell sarcoma (LCS) is an aggressive tumor. It is still unclear whether any specific molecular alterations could underlie the aggressive behavior of Langerhans cell proliferations. We used targeted next-generation sequencing and array-comparative genomic hybridization to profile 22 LCH samples from different patients together with 3 LCS samples corresponding to different relapses from the same patient. The third LCS relapse was a composite tumor including both B-cell chronic lymphocytic leukemia and LCS components. The 22 LCH samples were mostly of bone origin and showed classic histophenotypical features. Array-comparative genomic hybridization showed in all 3 LCS samples a similar homozygous somatic loss affecting the CDKN2A/B locus, whereas the 17 informative LCH samples did not show any detectable abnormality. In the 3 LCS samples, targeted next-generation sequencing of 495 cancer genes detected common mutations in KMT2D/MLL2 and in both MAP2K1 and NRAS genes, whereas BRAF was not mutated. A NOTCH1 mutation was acquired in 2 LCS samples. The composite LCS/B-cell chronic lymphocytic leukemia tumor showed the same genetic profile in its 2 components. LCH samples showed mutually exclusive mutations of BRAF (8/20) and MAP2K1 (4/19), but no mutation of KMT2D, NRAS nor NOTCH1. These results suggest that CDKN2A/B deletion and/or simultaneous mutations of MAP2K1 and NRAS may underlie the aggressive behavior of Langerhans cell tumors, and thus could be useful for the diagnosis of malignancy in histiocytic neoplasms. The MAPK pathway "double hit" profile provides a basis for targeted therapy in LCS patients.

  3. Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patients with high-grade non-Hodgkin lymphoma.

    Science.gov (United States)

    Oliveira, Cristiano Claudino; Maciel-Guerra, Helena; Kucko, Luan; Hirama, Eric Jun; Brilhante, Américo Delgado; Quevedo, Francisco Carlos; da Cunha, Isabela Werneck; Soares, Fernando Augusto; Niero-Melo, Ligia; Dos Reis, Patrícia Pintor; Domingues, Maria Aparecida Custodio

    2017-01-07

    Double-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases. Clinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted. Immunohistochemistry (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT and Myc) and fluorescence in situ hybridization for detection of MYC, BCL2 and BCL6 gene translocations were performed in a tissue microarray platform. Three cases of DHL were detected: two with translocations of MYC and BCL2 and one with translocations of MYC and BCL6, all leading to death in less than six months. Among 90 cytogenetically evaluable biopsies, associations were determined between immunohistochemistry and fluorescence in situ hybridization for MYC (p = 0.036) and BCL2 (p = 0.001). However, these showed only regular agreement, indicated by Kappa values of 0.23 [0.0;0.49] and 0.35 [0.13;0.56], respectively. "Starry sky" morphology was strongly associated with MYC positivity (p = 0.01). The detection of three cases of DHL, all resulting in death, confirms the rarity and aggressiveness of this neoplasm. The "starry sky" morphological pattern and immunohistochemical expression of Myc and Bcl2 represent possible selection factors for additional cytogenetic diagnostic testing.

  4. Interleukin-6 displays lung anti-inflammatory properties and exerts protective hemodynamic effects in a double-hit murine acute lung injury.

    Science.gov (United States)

    Voiriot, Guillaume; Razazi, Keyvan; Amsellem, Valérie; Tran Van Nhieu, Jeanne; Abid, Shariq; Adnot, Serge; Mekontso Dessap, Armand; Maitre, Bernard

    2017-04-19

    Interleukin 6 (IL-6) is a predictive factor of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, its acute pulmonary hemodynamic effects and role in lung injury have not been investigated in a clinically relevant murine model of ARDS. We used adult C57Bl6 wild-type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical ventilation (MV) for 5 h. Before sacrifice, right ventricular systolic pressure and cardiac output were measured and total pulmonary resistance was calculated. After sacrifice, lung inflammation, edema and injury were assessed with bronchoalveolar lavage (BAL) and histology. In other experiments, right ventricular systolic pressure was recorded during hypoxic challenges in uninjured WT mice pretreated with rHuIL-6 or rHuIL-6 + non-selective nitric oxide synthase inhibitor L-NAME or vehicle. IL-6KO (LPS+MV) mice showed a faster deterioration of lung elastic properties and more severe bronchoalveolar cellular inflammation as compared to WT (LPS+MV) . Treatment with rHuIL-6 partially prevented this lung deterioration. Total pulmonary resistance was higher in IL-6KO (LPS+MV) mice and this increase was abolished in rHuIL-6-treated IL-6KO mice. Finally, rHuIL-6 reduced hypoxic pulmonary vasoconstriction in uninjured WT mice, an effect that was abolished by co-treatment with L-NAME. In a double-hit murine model of ARDS, IL-6 deficient mice experienced more severe bronchoalveolar cellular inflammation as compared to wild-type littermates. Furthermore, IL-6 deficiency caused marked acute pulmonary hypertension, which may be, at least partially, due to vasoactive mechanisms. A dysregulation of nitric oxide synthase may account for this observation, a hypothesis that will need to be investigated in future studies.

  5. Long-term psychological outcomes of flood survivors of hard-hit areas of the 1998 Dongting Lake flood in China: Prevalence and risk factors.

    Science.gov (United States)

    Dai, Wenjie; Kaminga, Atipatsa C; Tan, Hongzhuan; Wang, Jieru; Lai, Zhiwei; Wu, Xin; Liu, Aizhong

    2017-01-01

    Although numerous studies have indicated that exposure to natural disasters may increase survivors' risk of post-traumatic stress disorder (PTSD) and anxiety, studies focusing on the long-term psychological outcomes of flood survivors are limited. Thus, this study aimed to estimate the prevalence of PTSD and anxiety among flood survivors 17 years after the 1998 Dongting Lake flood and to identify the risk factors for PTSD and anxiety. This cross-sectional study was conducted in December 2015, 17 years after the 1998 Dongting Lake flood. Survivors in hard-hit areas of the flood disaster were enrolled in this study using a stratified, systematic random sampling method. Well qualified investigators conducted face-to-face interviews with participants using the PTSD Checklist-Civilian version, the Zung Self-Rating Anxiety Scale, the Chinese version of the Social Support Rating Scale and the Revised Eysenck Personality Questionnaire-Short Scale for Chinese to assess PTSD, anxiety, social support and personality traits, respectively. Logistic regression analyses were used to identify factors associated with PTSD and anxiety. A total of 325 participants were recruited in this study, and the prevalence of PTSD and anxiety was 9.5% and 9.2%, respectively. Multivariable logistic regression analyses indicated that female sex, experiencing at least three flood-related stressors, having a low level of social support, and having the trait of emotional instability were risk factors for long-term adverse psychological outcomes among flood survivors after the disaster. PTSD and anxiety were common long-term adverse psychological outcomes among flood survivors. Early and effective psychological interventions for flood survivors are needed to prevent the development of PTSD and anxiety in the long run after a flood, especially for individuals who are female, experience at least three flood-related stressors, have a low level of social support and have the trait of emotional

  6. Investigation of hit-and-run crash occurrence and severity using real-time loop detector data and hierarchical Bayesian binary logit model with random effects.

    Science.gov (United States)

    Xie, Meiquan; Cheng, Wen; Gill, Gurdiljot Singh; Zhou, Jiao; Jia, Xudong; Choi, Simon

    2017-08-24

    Most of the extensive research dedicated to identifying the influential factors of hit-and-run (HR) crashes has utilized typical maximum likelihood estimation binary logit models, and none have employed real-time traffic data. To fill this gap, this study focused on investigating factors contributing to HR crashes, as well as the severity levels of HR. This study analyzed 4-year crash and real-time loop detector data by employing hierarchical Bayesian models with random effects within a sequential logit structure. In addition to evaluation of the impact of random effects on model fitness and complexity, the prediction capability of the models was examined. Stepwise incremental sensitivity and specificity were calculated and receiver operating characteristic (ROC) curves were utilized to graphically illustrate the predictive performance of the model. Among the real-time flow variables, the average occupancy and speed from the upstream detector were observed to be positively correlated with HR crash possibility. The average upstream speed and speed difference between upstream and downstream speeds were correlated with the occurrence of severe HR crashes. In addition to real-time factors, other variables found influential for HR and severe HR crashes were length of segment, adverse weather conditions, dark lighting conditions with malfunctioning street lights, driving under the influence of alcohol, width of inner shoulder, and nighttime. This study suggests the potential traffic conditions of HR and severe HR occurrence, which refer to relatively congested upstream traffic conditions with high upstream speed and significant speed deviations on long segments. The above findings suggest that traffic enforcement should be directed toward mitigating risky driving under the aforementioned traffic conditions. Moreover, enforcement agencies may employ alcohol checkpoints to counter driving under the influence (DUI) at night. With regard to engineering improvements, wider

  7. Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route.

    Science.gov (United States)

    Duan, Song; Shen, Sheng; Bulterys, Marc; Jia, Yujiang; Yang, Yuecheng; Xiang, Lifeng; Tian, Fei; Lu, Lin; Xiao, Yao; Wang, Minjie; Jia, Manhong; Jiang, Huazhou; Vermund, Sten H; Jiang, Yan

    2010-04-07

    Since 1989 when the first 146 HIV positives in China were identified, Dehong Prefecture had been one of the areas hardest-hit by HIV in China. The local and national governments have put substantial financial resources into tackling the HIV epidemic in Dehong from 2004. The objective of this study was to track dynamic changes in HIV-1 prevalence and incidence among five focal populations in Dehong and to assess the impact of HIV prevention and control efforts. Consecutive cross-sectional surveys conducted in five focal populations between 2004 and 2008. Specimens seropositive for HIV were tested with the BED IgG capture enzyme immunoassay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments. From 2004 to 2008, estimated annual HIV incidence among injecting drug users (IDUs) decreased significantly [from 15.0% (95% CI = 11.4%-18.5%) in 2004 to 4.3% (95% CI = 2.4%-6.2%) in 2008; trend test P < 0.0001]. The incidence among other focal populations, such as HIV discordant couples (varying from 5.5% to 4.7%), female sex workers (varying from 1.4% to 1.3%), pregnant women (0.1%), and pre-marital couples (0.2 to 0.1%) remained stable. Overall, the proportion of recent HIV-1 infections was higher among females than males (P < 0.0001). The HIV epidemic in Dehong continued to expand during a five-year period but at a slowing rate among IDUs, and HIV incidence remains high among IDUs and discordant couples. Intensive prevention measures should target sub-groups at highest risk to further slow the epidemic and control the migration of HIV to other areas of China, and multivariate analysis is needed to explore which measures are more effective for different populations.

  8. Colored Range Searching in Linear Space

    DEFF Research Database (Denmark)

    Grossi, Roberto; Vind, Søren Juhl

    2014-01-01

    In colored range searching, we are given a set of n colored points in d ≥ 2 dimensions to store, and want to support orthogonal range queries taking colors into account. In the colored range counting problem, a query must report the number of distinct colors found in the query range, while...... an answer to the colored range reporting problem must report the distinct colors in the query range. We give the first linear space data structure for both problems in two dimensions (d = 2) with o(n) worst case query time. We also give the first data structure obtaining almost-linear space usage and o...

  9. WPC's Short Range Forecast Coded Bulletin

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Short Range Forecast Coded Bulletin. The Short Range Forecast Coded Bulletin describes the expected locations of high and low pressure centers, surface frontal...

  10. Range-Based Auto-Focus Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Maracel Systems and Software Technologies, LLC proposes a revolutionary Range-Based Auto Focus (RBAF) system that will combine externally input range, such as might...

  11. Report to Congress on Sustainable Ranges, 2008

    Science.gov (United States)

    2008-01-01

    Air Facility Quantico in FY2008. RAICUZ studies at Townsend Range, Chocolate Mountain Aerial Gunnery Range, and Barry M Goldwater Range-West are on...representatives from Arizona, California, Nevada, New Mexico and Utah and other interested stakeholders. Part of the working group’s tactical

  12. Arabidopsis CDS blastp result: AK102134 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102134 J033085F12 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 0.0 ...

  13. Arabidopsis CDS blastp result: AK242585 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242585 J090010M20 At4g23990.1 68417.m03448 cellulose synthase family protein similar to cellulose... synthase catalytic subunit from Arabidopsis thaliana [gi:5230423], cellulose synthase-5 from Zea mays [gi:9622882] 1e-124 ...

  14. Arabidopsis CDS blastp result: AK242601 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242601 J090014G03 At4g24000.1 68417.m03449 cellulose synthase family protein similar to cellulose... synthase from Gossypium hirsutum [gi:1706956], cellulose synthase-5 from Zea mays [gi:9622882] 5e-27 ...

  15. Arabidopsis CDS blastp result: AK242601 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242601 J090014G03 At4g38190.1 68417.m05391 cellulose synthase family protein similar to cellulose... synthase catalytic subunit gi:2827143 from [Arabidopsis thaliana], cellulose synthase-5 (gi:9622882) from Zea mays 0.0 ...

  16. Arabidopsis CDS blastp result: AK242601 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242601 J090014G03 At4g24000.1 68417.m03449 cellulose synthase family protein similar to cellulose... synthase from Gossypium hirsutum [gi:1706956], cellulose synthase-5 from Zea mays [gi:9622882] 2e-27 ...

  17. Arabidopsis CDS blastp result: AK242890 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242890 J090079L19 At1g32180.1 68414.m03958 cellulose synthase family protein similar to cellulose... synthase catalytic subunit gi:2827143 from [Arabidopsis thaliana], cellulose synthase-9 (gi:9622890) from Zea mays 1e-126 ...

  18. Arabidopsis CDS blastp result: AK242585 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242585 J090010M20 At4g38190.1 68417.m05391 cellulose synthase family protein similar to cellulose... synthase catalytic subunit gi:2827143 from [Arabidopsis thaliana], cellulose synthase-5 (gi:9622882) from Zea mays 4e-27 ...

  19. Arabidopsis CDS blastp result: AK061162 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061162 006-209-A01 At2g32540.1 cellulose synthase family protein similar to cellulose... synthase catalytic subunit from Arabidopsis thaliana [gi:5230423], cellulose synthase-5 from Zea mays [gi:9622882] 3e-35 ...

  20. Arabidopsis CDS blastp result: AK110534 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK110534 002-168-A07 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 1e-114 ...

  1. Arabidopsis CDS blastp result: AK242585 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242585 J090010M20 At4g38190.1 68417.m05391 cellulose synthase family protein similar to cellulose... synthase catalytic subunit gi:2827143 from [Arabidopsis thaliana], cellulose synthase-5 (gi:9622882) from Zea mays 8e-63 ...

  2. Arabidopsis CDS blastp result: AK242585 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242585 J090010M20 At1g55850.1 68414.m06405 cellulose synthase family protein similar to cellulose... synthase catalytic subunit [gi:13925881] from Nicotiana alata, cellulose synthase-5 [gi:9622882] from Zea mays 0.0 ...

  3. Arabidopsis CDS blastp result: AK111344 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111344 002-181-F12 At1g55850.1 cellulose synthase family protein similar to cellulose... synthase catalytic subunit [gi:13925881] from Nicotiana alata, cellulose synthase-5 [gi:9622882] from Zea mays 2e-15 ...

  4. Arabidopsis CDS blastp result: AK243353 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243353 J100061B04 At1g05990.1 68414.m00627 calcium-binding protein, putative strong similarity to calcium...-binding protein [Lotus japonicus] GI:18413495; contains INTERPRO:IPR002048 calcium-binding EF-hand domain 3e-11 ...

  5. Arabidopsis CDS blastp result: AK066468 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066468 J013066B01 At1g53210.1 sodium/calcium exchanger family protein / calcium-b...inding EF hand family protein contains Pfam profiles: PF01699 sodium/calcium exchanger protein, PF00036 EF hand 1e-171 ...

  6. Arabidopsis CDS blastp result: AK071633 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071633 J023102J23 At1g07080.1 gamma interferon responsive lysosomal thiol reducta...se family protein / GILT family protein similar to SP|P13284 Gamma-interferon inducible lysosomal thiol redu...ctase precursor {Homo sapiens}; contains Pfam profile PF03227: Gamma interferon inducible lysosomal thiol reductase (GILT) 6e-66 ...

  7. Arabidopsis CDS blastp result: AK106050 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK106050 001-206-F01 At1g07080.1 gamma interferon responsive lysosomal thiol reduct...ase family protein / GILT family protein similar to SP|P13284 Gamma-interferon inducible lysosomal thiol red...uctase precursor {Homo sapiens}; contains Pfam profile PF03227: Gamma interferon inducible lysosomal thiol reductase (GILT) 6e-63 ...

  8. Arabidopsis CDS blastp result: AK103132 [KOME

    Lifescience Database Archive (English)

    Full Text Available similarity to SP|P17213 Bactericidal permeability-increasing protein precursor (BPI) {Homo sapiens}; contains Pfam profile PF02886: LBP / BPI / CETP family, C-terminal domain 1e-91 ...

  9. Arabidopsis CDS blastp result: AK108564 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK108564 002-145-C08 At4g28088.1 hydrophobic protein, putative / low temperature an...d salt responsive protein, putative similar to Hydrophobic protein RCI2A (Low temperature and salt responsive protein LTI6A) GI:15214251 4e-11 ...

  10. Arabidopsis CDS blastp result: AK062410 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK062410 001-102-E12 At4g28088.1 hydrophobic protein, putative / low temperature an...d salt responsive protein, putative similar to Hydrophobic protein RCI2A (Low temperature and salt responsive protein LTI6A) GI:15214251 1e-13 ...

  11. Arabidopsis CDS blastp result: AK121018 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121018 J023049B21 At4g28088.1 hydrophobic protein, putative / low temperature and... salt responsive protein, putative similar to Hydrophobic protein RCI2A (Low temperature and salt responsive protein LTI6A) GI:15214251 2e-17 ...

  12. Arabidopsis CDS blastp result: AK242428 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242428 J080089P09 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 2e-14 ...

  13. Arabidopsis CDS blastp result: AK288095 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288095 J075191E21 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 2e-16 ...

  14. Arabidopsis CDS blastp result: AK242346 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242346 J080012M07 At2g41100.2 68415.m05077 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 3e-44 ...

  15. Arabidopsis CDS blastp result: AK242428 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242428 J080089P09 At2g41100.2 68415.m05077 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 3e-16 ...

  16. Arabidopsis CDS blastp result: AK242346 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242346 J080012M07 At5g37770.1 68418.m04547 touch-responsive protein / calmodulin-related protein 2, touch...-induced (TCH2) identical to calmodulin-related protein 2,touch-induced SP:P25070 from [Arabidopsis thaliana] 2e-25 ...

  17. Arabidopsis CDS blastp result: AK062711 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK062711 001-106-C02 At5g37770.1 touch-responsive protein / calmodulin-related protein 2, touch...-induced (TCH2) identical to calmodulin-related protein 2,touch-induced SP:P25070 from [Arabidopsis thaliana] 9e-34 ...

  18. Arabidopsis CDS blastp result: AK242346 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242346 J080012M07 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 8e-44 ...

  19. Arabidopsis CDS blastp result: AK108506 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK108506 002-143-H11 At5g37770.1 touch-responsive protein / calmodulin-related protein 2, touch...-induced (TCH2) identical to calmodulin-related protein 2,touch-induced SP:P25070 from [Arabidopsis thaliana] 7e-14 ...

  20. Arabidopsis CDS blastp result: AK242346 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242346 J080012M07 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 3e-26 ...

  1. Arabidopsis CDS blastp result: AK242346 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242346 J080012M07 At2g41100.2 68415.m05077 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 3e-26 ...

  2. Arabidopsis CDS blastp result: AK242428 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242428 J080089P09 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 8e-18 ...

  3. Arabidopsis CDS blastp result: AK242346 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242346 J080012M07 At5g37770.1 68418.m04547 touch-responsive protein / calmodulin-related protein 2, touch...-induced (TCH2) identical to calmodulin-related protein 2,touch-induced SP:P25070 from [Arabidopsis thaliana] 2e-11 ...

  4. Arabidopsis CDS blastp result: AK243656 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243656 J100088L22 At2g41100.2 68415.m05077 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 5e-20 ...

  5. Arabidopsis CDS blastp result: AK242346 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242346 J080012M07 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 4e-41 ...

  6. Arabidopsis CDS blastp result: AK243656 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243656 J100088L22 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 2e-17 ...

  7. Arabidopsis CDS blastp result: AK071661 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071661 J023105D07 At5g37770.1 touch-responsive protein / calmodulin-related protein 2, touch...-induced (TCH2) identical to calmodulin-related protein 2,touch-induced SP:P25070 from [Arabidopsis thaliana] 3e-33 ...

  8. Arabidopsis CDS blastp result: AK242428 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242428 J080089P09 At5g37770.1 68418.m04547 touch-responsive protein / calmodulin-related protein 2, touch...-induced (TCH2) identical to calmodulin-related protein 2,touch-induced SP:P25070 from [Arabidopsis thaliana] 9e-19 ...

  9. Arabidopsis CDS blastp result: AK288095 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288095 J075191E21 At2g41100.2 68415.m05077 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 2e-15 ...

  10. Arabidopsis CDS blastp result: AK241786 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241786 J065207F05 At5g37770.1 68418.m04547 touch-responsive protein / calmodulin-related protein 2, touch...-induced (TCH2) identical to calmodulin-related protein 2,touch-induced SP:P25070 from [Arabidopsis thaliana] 1e-19 ...

  11. Arabidopsis CDS blastp result: AK243656 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243656 J100088L22 At2g41100.1 68415.m05076 touch-responsive protein / calmodulin-related protein 3, touch...-induced (TCH3) identical to calmodulin-related protein 3, touch-induced SP:P25071 from [Arabidopsis thaliana] 1e-19 ...

  12. Arabidopsis CDS blastp result: AK060920 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060920 001-035-H02 At3g55440.1 triosephosphate isomerase, cytosolic, putative strong similarity to triosep...hosphate isomerase, cytosolic from Petunia hybrida [SP|P48495], from Coptis japonica [SP|P21820] 1e-113 ...

  13. Arabidopsis CDS blastp result: AK104017 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104017 001-007-G07 At3g55440.1 triosephosphate isomerase, cytosolic, putative strong similarity to triosep...hosphate isomerase, cytosolic from Petunia hybrida [SP|P48495], from Coptis japonica [SP|P21820] 1e-106 ...

  14. Arabidopsis CDS blastp result: AK100708 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100708 J023115C24 At3g55440.1 triosephosphate isomerase, cytosolic, putative strong similarity to trioseph...osphate isomerase, cytosolic from Petunia hybrida [SP|P48495], from Coptis japonica [SP|P21820] 1e-106 ...

  15. Arabidopsis CDS blastp result: AK104461 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104461 006-301-B11 At3g55440.1 triosephosphate isomerase, cytosolic, putative strong similarity to triosep...hosphate isomerase, cytosolic from Petunia hybrida [SP|P48495], from Coptis japonica [SP|P21820] 1e-106 ...

  16. Arabidopsis CDS blastp result: AK107494 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107494 002-129-D06 At4g24620.1 glucose-6-phosphate isomerase, putative similar to glucose...-6-phosphate isomerase [Spinacia oleracea] GI:3413511; contains Pfam profile PF00342: glucose-6-phosphate isomerase 0.0 ...

  17. Arabidopsis CDS blastp result: AK241096 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241096 J065076O13 At2g16060.1 68415.m01841 non-symbiotic hemoglobin 1 (HB1) (GLB1...) identical to SP|O24520 Non-symbiotic hemoglobin 1 (Hb1) (ARAth GLB1) {Arabidopsis thaliana} 1e-59 ...

  18. Arabidopsis CDS blastp result: AK240885 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240885 J065029A17 At3g10520.1 68416.m01262 non-symbiotic hemoglobin 2 (HB2) (GLB2...) identical to SP|O24521 Non-symbiotic hemoglobin 2 (Hb2) (ARAth GLB2) {Arabidopsis thaliana} 6e-34 ...

  19. Arabidopsis CDS blastp result: AK241096 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241096 J065076O13 At3g10520.1 68416.m01262 non-symbiotic hemoglobin 2 (HB2) (GLB2...) identical to SP|O24521 Non-symbiotic hemoglobin 2 (Hb2) (ARAth GLB2) {Arabidopsis thaliana} 1e-40 ...

  20. Arabidopsis CDS blastp result: AK240885 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240885 J065029A17 At2g16060.1 68415.m01841 non-symbiotic hemoglobin 1 (HB1) (GLB1...) identical to SP|O24520 Non-symbiotic hemoglobin 1 (Hb1) (ARAth GLB1) {Arabidopsis thaliana} 3e-49 ...

  1. Arabidopsis CDS blastp result: AK288081 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288081 J075172F18 At5g24520.3 68418.m02893 transparent testa glabra 1 protein (TTG1) identical to transpar...ent testa glabra 1 (Ttg1) protein (GI:10177852) {Arabidopsis thaliana}; contains Pfam PF00400: WD domain, G-beta repeat (4 copies,1 weak); 4e-13 ...

  2. Arabidopsis CDS blastp result: AK243285 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243285 J100051N01 At1g34790.1 68414.m04337 transparent testa 1 protein (TT1) / zi...nc finger (C2H2 type) protein TT1 identical to transparent testa 1 GI:18253279 from [Arabidopsis thaliana]; contains Pfam profile PF00096: Zinc finger, C2H2 type 1e-24 ...

  3. Arabidopsis CDS blastp result: AK243061 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243061 J100014C18 At5g24520.3 68418.m02893 transparent testa glabra 1 protein (TTG1) identical to transpar...ent testa glabra 1 (Ttg1) protein (GI:10177852) {Arabidopsis thaliana}; contains Pfam PF00400: WD domain, G-beta repeat (4 copies,1 weak); 1e-102 ...

  4. Arabidopsis CDS blastp result: AK243061 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243061 J100014C18 At5g24520.2 68418.m02892 transparent testa glabra 1 protein (TTG1) identical to transpar...ent testa glabra 1 (Ttg1) protein (GI:10177852) {Arabidopsis thaliana}; contains Pfam PF00400: WD domain, G-beta repeat (4 copies,1 weak); 1e-102 ...

  5. Arabidopsis CDS blastp result: AK289209 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK289209 J100058I16 At1g34790.1 68414.m04337 transparent testa 1 protein (TT1) / zi...nc finger (C2H2 type) protein TT1 identical to transparent testa 1 GI:18253279 from [Arabidopsis thaliana]; contains Pfam profile PF00096: Zinc finger, C2H2 type 1e-12 ...

  6. Arabidopsis CDS blastp result: AK287566 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287566 J065027L04 At1g34790.1 68414.m04337 transparent testa 1 protein (TT1) / zi...nc finger (C2H2 type) protein TT1 identical to transparent testa 1 GI:18253279 from [Arabidopsis thaliana]; contains Pfam profile PF00096: Zinc finger, C2H2 type 2e-77 ...

  7. Arabidopsis CDS blastp result: AK243061 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243061 J100014C18 At5g24520.1 68418.m02891 transparent testa glabra 1 protein (TTG1) identical to transpar...ent testa glabra 1 (Ttg1) protein (GI:10177852) {Arabidopsis thaliana}; contains Pfam PF00400: WD domain, G-beta repeat (4 copies,1 weak); 1e-102 ...

  8. Arabidopsis CDS blastp result: AK288081 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288081 J075172F18 At5g24520.2 68418.m02892 transparent testa glabra 1 protein (TTG1) identical to transpar...ent testa glabra 1 (Ttg1) protein (GI:10177852) {Arabidopsis thaliana}; contains Pfam PF00400: WD domain, G-beta repeat (4 copies,1 weak); 4e-13 ...

  9. Arabidopsis CDS blastp result: AK288081 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288081 J075172F18 At5g24520.1 68418.m02891 transparent testa glabra 1 protein (TTG1) identical to transpar...ent testa glabra 1 (Ttg1) protein (GI:10177852) {Arabidopsis thaliana}; contains Pfam PF00400: WD domain, G-beta repeat (4 copies,1 weak); 4e-13 ...

  10. Arabidopsis CDS blastp result: AK101554 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101554 J033050A06 At4g09020.1 isoamylase, putative / starch debranching enzyme, putative similar to isoamy...lase isoform 3 [Solanum tuberosum] GI:27728149, isoamylase [Oryza sativa] GI:325279...4; contains Pfam profiles PF00128: Alpha amylase catalytic domain, PF02922: Isoamylase N-terminal domain 1e-135 ...

  11. Arabidopsis CDS blastp result: AK242137 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242137 J075150A13 At4g09020.1 68417.m01489 isoamylase, putative / starch debranch...ing enzyme, putative similar to isoamylase isoform 3 [Solanum tuberosum] GI:27728149, isoamylase [Oryza sati...va] GI:3252794; contains Pfam profiles PF00128: Alpha amylase catalytic domain, PF02922: Isoamylase N-terminal domain 9e-13 ...

  12. Arabidopsis CDS blastp result: AK288307 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288307 J090020G01 At4g09020.1 68417.m01489 isoamylase, putative / starch debranch...ing enzyme, putative similar to isoamylase isoform 3 [Solanum tuberosum] GI:27728149, isoamylase [Oryza sati...va] GI:3252794; contains Pfam profiles PF00128: Alpha amylase catalytic domain, PF02922: Isoamylase N-terminal domain 8e-98 ...

  13. Arabidopsis CDS blastp result: AK100867 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100867 J023124E13 At2g29640.1 josephin family protein contains Pfam domain PF02099: Jose...phin; similar to Josephin-like protein (Swiss-Prot:O82391) [Arabidopsis thaliana] 7e-59 ...

  14. Arabidopsis CDS blastp result: AK069900 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069900 J023035E20 At5g23420.1 high mobility group (HMG1/2) family protein similar to high... mobility group protein 2 HMG2 [Ipomoea nil] GI:1052956; contains Pfam profile PF00505: HMG (high mobility group) box 8e-32 ...

  15. Arabidopsis CDS blastp result: AK108585 [KOME

    Lifescience Database Archive (English)

    Full Text Available 5358 Elongation of fatty acids protein 2 (GNS1 protein) (V-SNARE bypass mutant gene 2 protein) {Saccharomyces cerevisiae}; contains Pfam profile PF01151: GNS1/SUR4 family 1e-19 ...

  16. Arabidopsis CDS blastp result: AK059151 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059151 001-023-B10 At4g25080.3 magnesium-protoporphyrin O-methyltransferase, putative / magnesium-protopor...phyrin IX methyltransferase, putative similar to SP|Q55467 Magnesium-protoporphyrin... O-methyltransferase (EC 2.1.1.1) (Magnesium-protoporphyrin IX methyltransferase) {Synechocystis sp.} 4e-31 ...

  17. Arabidopsis CDS blastp result: AK066771 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066771 J013083K07 At1g01170.1 ozone-responsive stress-related protein, putative s...imilar to stress-related ozone-induced protein AtOZI1 (GI:790583) [Arabidopsis thaliana]; contains 1 predicted transmembrane domain; 2e-29 ...

  18. Arabidopsis CDS blastp result: AK059353 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059353 001-026-D01 At1g01170.1 ozone-responsive stress-related protein, putative ...similar to stress-related ozone-induced protein AtOZI1 (GI:790583) [Arabidopsis thaliana]; contains 1 predicted transmembrane domain; 2e-29 ...

  19. Arabidopsis CDS blastp result: AK059160 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059160 001-023-D05 At1g01170.1 ozone-responsive stress-related protein, putative ...similar to stress-related ozone-induced protein AtOZI1 (GI:790583) [Arabidopsis thaliana]; contains 1 predicted transmembrane domain; 3e-28 ...

  20. Arabidopsis CDS blastp result: AK110681 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK110681 002-169-H04 At5g09650.1 inorganic pyrophosphatase family protein similar to SP|Q15181 Inorganic... pyrophosphatase (EC 3.6.1.1) (Pyrophosphate {Homo sapiens}; contains Pfam profile PF00719: inorganic pyrophosphatase 8e-63 ...