WorldWideScience

Sample records for subjects hit targets

  1. 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 ...

  2. 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

  3. LHC Report: LHC hit the target!

    CERN Multimedia

    Enrico Bravin for the LHC team

    2016-01-01

    Last week, the accumulated integrated luminosity reached the target value for 2016 of 25 fb-1 in both ATLAS and CMS.   The integrated luminosity delivered to ATLAS and CMS reached (and already passed!) 25 fb-1– the target for the whole year! Tuesday, 30 August was just a regular day for the 2016 LHC run. However,  on that day, the integrated luminosity delivered to ATLAS and CMS reached 25 fb-1 – the target for the whole year! How did we get here? A large group of committed scientists and technical experts work behind the scenes at the LHC, ready to adapt to the quirks of this truly impressive machine. After the push to produce as many proton-proton collisions as possible before the summer conferences, several new ideas and production techniques (such as Bunch Compression Multiple Splitting, BCMS) have been incorporated in the operation of LHC in order to boost its performance even further. Thanks to these improvements, the LHC was routinely operated with peak luminos...

  4. 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

  5. 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

  6. Hitting the Target: How T Cells Detect and Eliminate Tumors.

    Science.gov (United States)

    Zamora, Anthony E; Crawford, Jeremy Chase; Thomas, Paul G

    2018-01-15

    The successes of antitumor immuno-based therapies and the application of next-generation sequencing to mutation profiling have produced insights into the specific targets of antitumor T cells. Mutated proteins have tremendous potential as targets for interventions using autologous T cells or engineered cell therapies and may serve as important correlates of efficacy for immunoregulatory interventions including immune checkpoint blockade. As mutated self, tumors present an exceptional case for host immunity, which has primarily evolved in response to foreign pathogens. Tumor Ags' resemblance to self may limit immune recognition, but key features appear to be the same between antipathogen and antitumor responses. Determining which targets will make efficacious Ags and which responses might be elicited therapeutically are key questions for the field. Here we discuss current knowledge on antitumor specificity, the mutations that provide immunogenic targets, and how cross-reactivity and immunodominance may contribute to variation in immune responses among tumor types. Copyright © 2018 by The American Association of Immunologists, Inc.

  7. Hitting Hotspots: Spatial Targeting of Malaria for Control and Elimination

    NARCIS (Netherlands)

    Bousema, T.; Griffin, J.T.; Sauerwein, R.W.; Smith, D.L.; Churcher, T.S.; Takken, W.; Ghani, A.; Drakeley, C.; Gosling, R.

    2012-01-01

    Current malaria elimination guidelines are based on the concept that malaria transmission becomes heterogeneous in the later phases of malaria elimination [1]. In the pre-elimination and elimination phases, interventions have to be targeted to entire villages or towns with higher malaria incidence

  8. The role of biofilms: are we hitting the right target?

    Science.gov (United States)

    Wolcott, Randall; Dowd, Scot

    2011-01-01

    Chronic infections affect 17 million people yearly, and approximately 550,000 people die each year from, or with, their chronic infections. Acute and chornic infection differences are well known to clinicians, but the role of bacteria in producing these clinical differences remains poorly understood. This review relies on basic science, clinical studies, and a general review of the medical biofilm literature. The basic science studies are level A and B quality of evidence. The clinical studies are mainly retrospective cohort (level B) and case studies (level C). The biofilm literature includes reviews with varying levels of evidence. All articles have been peer reviewed and meet the standard of evidence-based medicine. Acute infections are associated with planktonic bacteria and must be diagnosed rapidly and accurately to prevent tissue damage and/or death. In contrast, biofilm behavior pursues a more parasitic course by producing sustained host hyperinflammation, with the biofilm feeding on plasma exudate. Chronic infections vacillate over long periods of time, responding only partially to antibiotics and reemerging once the antibiotics are withdrawn. Chronic wounds exhibit similar clinical behavior seen in other chronic infections and are associated with biofilm phenotype bacteria on their surface. Biofilm infections, such as chronic wounds, cannot be adequately diagnosed with current clinical cultures; therefore, molecular methods are necessary. Biofilm phenotype bacteria require multiple concurrent strategies, including débridement and targeted antibiofilm agents. Biofilm phenotype bacteria predominate on the surface of wounds, and biofilm-based management improves wound healing outcomes, indicating that biofilm is the right target for managing the bioburden barrier of chronic wounds.

  9. HYPERLEXIA AND DYSLEXIA IN AUTISM: HITTING A MOVING TARGET

    Directory of Open Access Journals (Sweden)

    Emily L. WILLIAMS

    2012-09-01

    Full Text Available The diagnostic histories of autism, dyslexia, and hyperlexia are complex. Because these conditions share both convergent and diver­gent properties, it is important to under­stand these relationships, especially in the case of research and how we interpret bodi­es of work which span decades of fluc­tuating criteria. It is also important to syn­the­size what we already know about the morpho­logy of these con­di­tions and pinpoint what we still don’t. Autism and dyslexia, for instance, share antipodal cerebral morpho­logies, such as minicolumnar den­sity, neuropil width, cell size, corpus callo­sal volume, gyral complexity, gyral window size, and cerebral volume, while hyperlexia has not been studied in this fashion, although it sha­res much in common with autism. Mean­while, the fluctuation in criteria of dyslexia over the years, means that older studies, such as some of the most highly cited in post­mortem research, have potentially used more heterogeneous groups of subjects than dys­lexia research typically uses today. Con­sider­ably, these older studies are often the basis of current animal model and genetics research. In conclusion, in consideration of the continued flux in criteria, particularly the proposed change from “Reading Disorder” to the broa­der “Specific Learning Disorder” within the DSM-5, we strongly recommend a separation of the various reading disorders under their own headings to promote specificity of diag­nosis and treatment, and to support better research.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing.

    Science.gov (United States)

    Amabile, Angelo; Migliara, Alessandro; Capasso, Paola; Biffi, Mauro; Cittaro, Davide; Naldini, Luigi; Lombardo, Angelo

    2016-09-22

    Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Siparex hits target with '146m for third mid-market fund

    CERN Multimedia

    2003-01-01

    Sigefi Private Equity has reached its target final closing of '146m ($155m) for its third mid-market buy-out and expansion capital fund. International investors contributed 26% of the capital including commitments from CERN, Switzerland (1 paragraph).

  1. HIV and Drug Resistance: Hitting a Moving Target | Center for Cancer Research

    Science.gov (United States)

    Prior research revealed how HIV-1 makes its destructive entry into the target cell by fusing together the cholesterol-rich lipid bilayer of the viral envelope—made with key glycoproteins gp120 and gp41—and the host cell’s plasma membrane. Cell-viral interactions begin with the binding of gp120 to the CD4 receptor molecule on the target cell, followed by gp120 binding to coreceptors. These coreceptors likely reside in structures called lipid rafts—areas in the cell plasma membrane that are rich in cholesterol, saturated fatty acids, and certain proteins that facilitate the entry of viruses into host cells. Finally, sequences in gp41 trigger the fusion of the viral and cellular lipid bilayers. The lipid rafts are then involved in the production of new viral particles.

  2. Lipossomas: a bala mágica acertou? Liposomes: has the magic bullet hit the target?

    Directory of Open Access Journals (Sweden)

    Nuno C. Santos

    2002-12-01

    Full Text Available Efficient drug delivery systems are as important as drug themselves. A powerful drug unable to reach the target cell is useless in practice. Ehrlich's Magic Bullet was the first carrier system to be proposed. The evolution in this domain has been quite slow as the natural mechanisms of mammals against foreign products are hard to overcome. However, lipid-based systems (liposomes and related vesicles have attained reasonable success. The basic preparations and structural features of liposomes and related vesicles as well as their applications are addressed from the chemist's and biochemist's point of view.

  3. The Latest from the LHC: hitting the target luminosity for 2010!

    CERN Document Server

    CERN Bulletin

    2010-01-01

    Thanks to a significant increase in the number of bunches in each beam, the 2010 target peak luminosity of 1032 cm-2 s-1 was reached on 14 October 2010, with further progress made in the following days. Soon, the attention of the LHC operators will turn to operation with lead ions throughout November.   In the last two weeks the number of bunches injected in each beam has steadily increased to reach 312, of which 295 collide in points 1 (ATLAS experiment), 5 (CMS experiment) and 8 (LHCb experiment). This has allowed the operators to reach a luminosity of 1.48x1032 cm-2 s-1, comfortably exceeding the target for 2010. With the present number of bunches, there are over 3.5x1013 protons per beam and around 20MJ of stored energy per beam. Since 4 October, when 204 bunches per beam were injected into the LHC, some intensity-related effects have started to be observed, notably, a significant rise in the ATLAS background. This is linked to an increase in pressure in the beam vacuum about 60m either s...

  4. Morphometry for alpha particle hits of critical targets in the lungs. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Mercer, R.R.

    1998-11-01

    The objective of this study is to provide detailed data on the number, location and type of critical target cells in the airspaces and to use these data in order to make risk assessments of the health effects of radon and radon progeny in the lungs. This will be done by quantitative morphometric study of the distribution of the various cell types and mucous lining layers in the lungs. The results provide anatomically correct models for dosimetry in the rate and human airways which significantly improve the ability to do risk assessment for radon exposures by providing quantitative data for specific cell types and provide a basis for mechanism based comparison between data available in animal exposures and human epidemiology.

  5. Mammalian Target of Rapamycin: Hitting the Bull's-Eye for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Zhao Zhong Chong

    2010-01-01

    Full Text Available The mammalian target of rapamycin (mTOR and its associated cell signaling pathways have garnered significant attention for their roles in cell biology and oncology. Interestingly,the explosion of information in this field has linked mTOR to neurological diseases with promising initial studies. mTOR, a 289 kDa serine/threonine protein kinase, plays an important role in cell growth and proliferation and is activated through phosphorylation in response to growth factors, mitogens and hormones. Growth factors, amino acids, cellular nutrients and oxygen deficiency can downregulate mTOR activity. The function of mTOR signaling is mediated primarily through two mTOR complexes: mTORC1 and mTORC2. mTORC1 initiates cap-dependent protein translation, a rate-limiting step of protein synthesis, through the phosphorylation of the targets eukaryotic initiation factor 4E-binding protein 1 (4EBP1 and p70 ribosomal S6 kinase (p70S6K. In contrast, mTORC2 regulates development of the cytoskeleton and also controls cell survival. Although closely tied to tumorigenesis, mTOR and the downstream signaling pathways are significantly involved in the central nervous system (CNS with synaptic plasticity, memory retention, neuroendocrine regulation associated with food intake and puberty and modulation of neuronal repair following injury. The signaling pathways of mTOR also are believed to be a significant component in a number of neurological diseases, such as Alzheimer disease, Parkinson disease and Huntington disease, tuberous sclerosis, neurofibromatosis, fragile X syndrome, epilepsy, traumatic brain injury and ischemic stroke. Here we describe the role of mTOR in the CNS and illustrate the potential for new strategies directed against neurological disorders.

  6. 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.

  7. 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 ...

  8. 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.

  9. A tax on output of the polluting industry is not a tax on pollution: The importance of hitting the target

    OpenAIRE

    Fullerton, Don; Hong, Inkee; Metcalf, Gilbert E.

    2000-01-01

    We explore the effects of environmental taxes that imprecisely target pollution. A review of actual policies indicates few (if any) examples of a true tax on pollution. More typically, environmental taxes target an input or output that is correlated with pollution. We construct a simple analytical general equilibrium model to calculate the optimum tax rate on the output of the polluting industry, in terms of key behavioural parameters, and we compare this imprecisely-targeted tax to an ideal ...

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Unmarked gene deletion mutagenesis of gtfB and gtfC in Streptococcus mutans using a targeted hit-and-run strategy with a thermosensitive plasmid.

    Science.gov (United States)

    Atlagic, D; Kiliç, A O; Tao, L

    2006-04-01

    Unmarked gene deletion of the Streptococcus mutans gtfB-gtfC locus was achieved using a thermosensitive plasmid. DNA fragments flanking the locus were amplified by polymerase chain reaction and jointly ligated into pG+host5, which was transformed into S. mutans at 37 degrees C to facilitate integration. A transformant was then grown at 28 degrees C for 60 generations without antibiotics to facilitate excision. Antibiotic sensitive clones appeared at a frequency of about 99% and were analyzed for deletions of gtfB, gtfC and a part of mbrA by the lack of insoluble glucan synthesis, sensitivity to bacitracin, and polymerase chain reaction. Targeted gene deletions occurred at a frequency of 2.5%.

  15. Antibacterial effects of quaternary bis-phosphonium and ammonium salts of pyridoxine on Staphylococcus aureus cells: A single base hitting two distinct targets?

    Science.gov (United States)

    Nikitina, Elena V; Zeldi, Marina I; Pugachev, Mikhail V; Sapozhnikov, Sergey V; Shtyrlin, Nikita V; Kuznetsova, Svetlana V; Evtygin, Vladimir E; Bogachev, Mikhail I; Kayumov, Airat R; Shtyrlin, Yurii G

    2016-01-01

    We studied the effects of quaternary bis-phosphonium and bis-ammonium salts of pyridoxine with lipophilic substituents on the survival and morphology of Staphylococcus aureus cells. We found that, while originating from the same base, they exhibit considerably different antimicrobial mechanisms. In the presence of Ca(2+) ions the MIC and MBC values of ammonium salt increased 100-fold, suggesting that Ca(2+) ions can successfully impede the membrane Ca(2+) ions exchange required for ammonium salt incorporation. In contrast, in the presence of quaternary phosphonium salt, the artificial capsular-like material was formed around the cells and the filamentous and chain-like growth of the cells was observed suggesting the disruption of the cell division mechanisms. Altogether, both pyridoxine derivatives successfully inhibited the growth of gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis) and Escherichia coli considerably, while demonstrated nearly no effect against Klebsiella pneumoniae and Pseudomonas aeruginosa. We suggest that due to their effects on distinct and likely complementary targets the derivatives of pyridoxine represent potentially perspective antibacterials with complicated adaptation and thus with lower risk of drug resistance development.

  16. 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.

  17. Hitting the target with antithrombotic therapy.

    Science.gov (United States)

    Fritsma, Margaret G; Rodak, Bernadette F

    2007-05-01

    Thrombus treatment and prevention can be regulated by a number of intravenous or subcutaneous drugs, as well as oral warfarin. Many therapies require laboratory monitoring for efficacy and for detection of dangerous sequelae, such as bleeding, thrombosis, or heparin induced thrombocytopenia.

  18. Subjectivity

    Directory of Open Access Journals (Sweden)

    Jesús Vega Encabo

    2015-11-01

    Full Text Available In this paper, I claim that subjectivity is a way of being that is constituted through a set of practices in which the self is subject to the dangers of fictionalizing and plotting her life and self-image. I examine some ways of becoming subject through narratives and through theatrical performance before others. Through these practices, a real and active subjectivity is revealed, capable of self-knowledge and self-transformation. 

  19. 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

  20. 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...

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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...

  6. 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.

  7. 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.

  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. A data mining approach to selecting herbs with similar efficacy: Targeted selection methods based on medical subject headings (MeSH).

    Science.gov (United States)

    Yea, Sang-Jun; Seong, BoSeok; Jang, Yunji; Kim, Chul

    2016-04-22

    Natural products have long been the most important source of ingredients in the discovery of new drugs. Moreover, since the Nagoya Protocol, finding alternative herbs with similar efficacy in traditional medicine has become a very important issue. Although random selection is a common method of finding ethno-medicinal herbs of similar efficacy, it proved to be less effective; therefore, this paper proposes a novel targeted selection method using data mining approaches in the MEDLINE database in order to identify and select herbs with a similar degree of efficacy. From among sixteen categories of medical subject headings (MeSH) descriptors, three categories containing terms related to herbal compounds, efficacy, toxicity, and the metabolic process were selected. In order to select herbs of similar efficacy in a targeted way, we adopted the similarity measurement method based on MeSH. In order to evaluate the proposed algorithm, we built up three different validation datasets which contain lists of original herbs and corresponding medicinal herbs of similar efficacy. The average area under curve (AUC) of the proposed algorithm was found to be about 500% larger than the random selection method. We found that the proposed algorithm puts more hits at the front of the top-10 list than the random selection method, and precisely discerns the efficacy of the herbs. It was also found that the AUC of the experiments either remained the same or increased slightly in all three validation datasets as the search range was increased. This study reveals and proves that the proposed algorithm is significantly more accurate and efficient in finding alternative herbs of similar efficacy than the random selection method. As such, it is hoped that this approach will be used in diverse applications in the ethno-pharmacology field. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  10. Medication adherence interventions that target subjects with adherence problems: Systematic review and meta-analysis.

    Science.gov (United States)

    Conn, Vicki S; Ruppar, Todd M; Enriquez, Maithe; Cooper, Pam

    2016-01-01

    Inadequate medication adherence is a pervasive, under-recognized cause of poor health outcomes. Many intervention trials designed to improve medication adherence have targeted adults with adherence problems. No previous reviews have synthesized the effectiveness of medication adherence interventions focused on subjects with medication adherence difficulties. This systematic review and meta-analysis synthesized findings from medication adherence intervention studies conducted among adults with medication adherence difficulties. Primary research studies were eligible for inclusion if they tested an intervention designed to increase medication adherence among adults with documented adherence difficulties and reported medication adherence behavior outcomes. Comprehensive search strategies of 13 computerized databases, author and ancestry searches, and hand searches of 57 journals were used to locate eligible primary research. Participant demographics, intervention characteristics, and methodological features were reliably coded from reports along with medication adherence outcomes. Effect sizes for outcomes were calculated as standardized mean differences, and random effects models were used to estimate overall mean effects. Exploratory dichotomous and continuous variable moderator analyses were employed to examine potential associations between medication adherence effect size and sample, intervention, and methodological characteristics. Data were extracted from 53 reports of studies involving 8243 individual primary study participants. The overall standardized mean difference effect size for treatment vs. control subjects was 0.301. For treatment pre- vs. post-intervention comparisons, the overall effect size was 0.533. Significantly larger effect sizes were associated with interventions incorporating prompts to take medications than interventions lacking medication prompts (0.497 vs. 0.234). Larger effect sizes were also found for interventions that linked

  11. Medication Adherence Interventions That Target Subjects with Adherence Problems: Systematic Review and Meta-analysis

    Science.gov (United States)

    Conn, Vicki S.; Ruppar, Todd M.; Enriquez, Maithe; Cooper, Pam

    2015-01-01

    Background Inadequate medication adherence is a pervasive, under-recognized cause of poor health outcomes. Many intervention trials designed to improve medication adherence have targeted adults with adherence problems. No previous reviews have synthesized the effectiveness of medication adherence interventions focused on subjects with medication adherence difficulties. Objective This systematic review and meta-analysis synthesized findings from medication adherence intervention studies conducted among adults with medication adherence difficulties. Methods Primary research studies were eligible for inclusion if they tested an intervention designed to increase medication adherence among adults with documented adherence difficulties and reported medication adherence behavior outcomes. Comprehensive search strategies of 13 computerized databases, author and ancestry searches, and hand searches of 57 journals were used to locate eligible primary research. Participant demographics, intervention characteristics, and methodological features were reliably coded from reports along with medication adherence outcomes. Effect sizes for outcomes were calculated as standardized mean differences, and random effects models were used to estimate overall mean effects. Exploratory dichotomous and continuous variable moderator analyses were employed to examine potential associations between medication adherence effect size and sample, intervention, and methodological characteristics. Results Data were extracted from 53 reports of studies involving 8,243 individual primary study participants. The overall standardized mean difference effect size for treatment vs. control subjects was 0.301. For treatment pre- vs. post-intervention comparisons, the overall effect size was 0.533. Significantly larger effect sizes were associated with interventions incorporating prompts to take medications than interventions lacking medication prompts (0.497 vs. 0.234). Larger effect sizes were also found

  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. 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.

  14. Illusions of integration are subjectively impenetrable: Phenomenological experience of Lag 1 percepts during dual-target RSVP.

    Science.gov (United States)

    Simione, Luca; Akyürek, Elkan G; Vastola, Valentina; Raffone, Antonino; Bowman, Howard

    2017-05-01

    We investigated the relationship between different kinds of target reports in a rapid serial visual presentation task, and their associated perceptual experience. Participants reported the identity of two targets embedded in a stream of stimuli and their associated subjective visibility. In our task, target stimuli could be combined together to form more complex ones, thus allowing participants to report temporally integrated percepts. We found that integrated percepts were associated with high subjective visibility scores, whereas reports in which the order of targets was reversed led to a poorer perceptual experience. We also found a reciprocal relationship between the chance of the second target not being reported correctly and the perceptual experience associated with the first one. Principally, our results indicate that integrated percepts are experienced as a unique, clear perceptual event, whereas order reversals are experienced as confused, similar to cases in which an entirely wrong response was given. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Influence of age, spatial memory, and ocular fixation on localization of auditory, visual, and bimodal targets by human subjects.

    Science.gov (United States)

    Dobreva, Marina S; O'Neill, William E; Paige, Gary D

    2012-12-01

    A common complaint of the elderly is difficulty identifying and localizing auditory and visual sources, particularly in competing background noise. Spatial errors in the elderly may pose challenges and even threats to self and others during everyday activities, such as localizing sounds in a crowded room or driving in traffic. In this study, we investigated the influence of aging, spatial memory, and ocular fixation on the localization of auditory, visual, and combined auditory-visual (bimodal) targets. Head-restrained young and elderly subjects localized targets in a dark, echo-attenuated room using a manual laser pointer. Localization accuracy and precision (repeatability) were quantified for both ongoing and transient (remembered) targets at response delays up to 10 s. Because eye movements bias auditory spatial perception, localization was assessed under target fixation (eyes free, pointer guided by foveal vision) and central fixation (eyes fixed straight ahead, pointer guided by peripheral vision) conditions. Spatial localization across the frontal field in young adults demonstrated (1) horizontal overshoot and vertical undershoot for ongoing auditory targets under target fixation conditions, but near-ideal horizontal localization with central fixation; (2) accurate and precise localization of ongoing visual targets guided by foveal vision under target fixation that degraded when guided by peripheral vision during central fixation; (3) overestimation in horizontal central space (±10°) of remembered auditory, visual, and bimodal targets with increasing response delay. In comparison with young adults, elderly subjects showed (1) worse precision in most paradigms, especially when localizing with peripheral vision under central fixation; (2) greatly impaired vertical localization of auditory and bimodal targets; (3) increased horizontal overshoot in the central field for remembered visual and bimodal targets across response delays; (4) greater vulnerability to

  16. 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...

  17. 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…

  18. 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…

  19. 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...

  20. Clearing the air : The effect of experimenter race on target's test performance and subjective experience

    NARCIS (Netherlands)

    Marx, DM; Goff, PA

    2005-01-01

    According to stereotype threat theory (Steele, 1997), stereotyped targets under-perform on challenging tests, in part because they are worried about being viewed in terms of the negative stereotype that they are intellectually inferior. How then are the negative effects of stereotype threat reduced

  1. The Effects of CLIL Education on the Subject Matter (Mathematics) and the Target Language (English)

    Science.gov (United States)

    Ouazizi, Khalid

    2016-01-01

    This paper investigates the effects of Content and Language Integrated Learning, CLIL for short, on both the attainment of the subject matter, mathematics in our case, hence the content aspect of CLIL. The second axes of research focuses on the effect of CLIL on the learners' proficiency vis-à-vis the language of instruction, epitomized here by…

  2. Neutrophils are immune cells preferentially targeted by retinoic acid in elderly subjects

    Directory of Open Access Journals (Sweden)

    Minet-Quinard Régine

    2010-08-01

    Full Text Available Abstract Background The immune system gradually deteriorates with age and nutritional status is a major factor in immunosenescence. Of the many nutritional factors implicated in age-related immune dysfunction, vitamin A may be a good candidate, since vitamin A concentrations classically decrease during aging whereas it may possess important immunomodulatory properties via its active metabolites, the retinoic acids. This prompted us to investigate the immune response induced by retinoids in adults and elderly healthy subjects. Before and after oral supplementation with 13cis retinoic acid (0.5 mg/kg/day during 28 days, whole blood cells were phenotyped, and functions of peripheral blood mononuclear cells (PBMC and polymorphonuclear cells (PMN were investigated by flow cytometry and ELISA tests. Results In both young adults (n = 20, 25 ± 4 years and older subjects (n = 20, 65 ± 4 years, retinoic acid supplementation had no effect on the distribution of leukocyte subpopulations or on the functions of PBMC (Il-2 and sIl-2R production, membrane expression of CD25. Concerning PMN, retinoic acid induced an increase in both spontaneous migration and cell surface expression of CD11b in the two different age populations, whereas bactericidal activity and phagocytosis remained unchanged. Conclusions We demonstrated that retinoic acid induces the same intensity of immune response between adult and older subjects, and more specifically affects PMN functions, i.e. adhesion and migration, than PBMC functions.

  3. 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.

  4. 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).

  5. 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.

  6. Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

    Science.gov (United States)

    Vasylyeva, Tetyana I; Friedman, Samuel R; Lourenco, Jose; Gupta, Sunetra; Hatzakis, Angelos; Pybus, Oliver G; Katzourakis, Aris; Smyrnov, Pavlo; Karamitros, Timokratis; Paraskevis, Dimitrios; Magiorkinis, Gkikas

    2016-11-28

    Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post-first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.

  7. 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.

  8. Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects

    Science.gov (United States)

    Vasylyeva, Tetyana I.; Friedman, Samuel R.; Lourenco, Jose; Gupta, Sunetra; Hatzakis, Angelos; Pybus, Oliver G.; Katzourakis, Aris; Smyrnov, Pavlo; Karamitros, Timokratis; Paraskevis, Dimitrios; Magiorkinis, Gkikas

    2016-01-01

    Objective: Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Design: Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. Method: We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. Results: In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post–first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. Conclusion: As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb. PMID:27824626

  9. 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.

  10. 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...

  11. 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...

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  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. Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Xuan Shang

    2017-09-01

    Full Text Available Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.

  20. 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.

  1. 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.

  2. Exercise after You Eat: Hitting the Postprandial Glucose Target

    Directory of Open Access Journals (Sweden)

    Melissa L. Erickson

    2017-09-01

    Full Text Available We discuss a novel hypothesis: the effect size of postmeal exercise for attenuating postprandial glucose will be a function of the exercise bout vs. the size of the postprandial glucose response, specifically peak and duration of the postprandial glucose excursion.

  3. 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.

  4. 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

  5. Theoretical analysis of the surface temperature regulation of an infrared false target subjected to periodical ambient conditions

    Directory of Open Access Journals (Sweden)

    Shi-min Li

    2016-10-01

    Full Text Available Infrared false target is an important mean to induce the infrared-guided weapons, and the key issue is how to keep the surface temperature of the infrared false target to be the same as that of the object to be protected. One-dimensional heat transfer models of a metal plate and imitative material were established to explore the influences of the thermophysical properties of imitative material on the surface temperature difference (STD between the metal plate and imitative material which were subjected to periodical ambient conditions. It is elucidated that the STD is determined by the imitative material's dimensionless thickness (dim* and the thermal inertia (Pim. When dim* is above 1.0, the STD is invariable as long as Pim is a constant. And if the dimensionless thickness of metal plate (dm* is also larger than 1.0, the STD approaches to zero as long as Pim is the same as the thermal inertia of metal plate (Pm. When dim* is between 0.08 and 1, the STD varies irregularly with Pim and dim*. However, if dm* is also in the range of 0.08–1, the STD approaches to zero on condition that Pim=Pm and dim*=dm*. If dim* is below 0.08, the STD is unchanged when Pimdim* is a constant. And if dm* is also less than 0.08, the STD approaches to zero as long as Pimdim*=Pmdm*. Furthermore, an application-oriented discussion indicates that the imitative material can be both light and thin via the application of the phase change material with a preset STD because of its high specific heat capacity during the phase transition process.

  6. 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.

  7. 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.

  8. 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.

  9. Starkweather Target Game for Preschool Children.

    Science.gov (United States)

    Starkweather, Elizabeth K.

    The Starkweather Target Game is designed to measure preschool children's willingness to try difficult tasks independent of ability. The game consists of a box-shaped target which responds, when the target is hit by a rolled ball, somewhat like a jack-in-a-box. When the bull's eye is hit, the lid opens and a surprise picture appears. After being…

  10. Improving Middle School Students' Subjective Well-Being: Efficacy of a Multicomponent Positive Psychology Intervention Targeting Small Groups of Youth

    Science.gov (United States)

    Roth, Rachel A.; Suldo, Shannon M.; Ferron, John M.

    2017-01-01

    Most interventions intended to improve subjective well-being, termed "positive psychology interventions" (PPIs), have neglected to include relevant stakeholders in youth's lives and have not included booster sessions intended to maintain gains in subjective well-being. The current study investigated the impact of a multitarget,…

  11. 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)

  12. 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

  13. Head repositioning accuracy in patients with neck pain and asymptomatic subjects: concurrent validity, influence of motion speed, motion direction and target distance.

    Science.gov (United States)

    Dugailly, Pierre-Michel; De Santis, Roberta; Tits, Mathieu; Sobczak, Stéphane; Vigne, Anna; Feipel, Véronique

    2015-12-01

    Cervicocephalic kinesthetic deficiencies have been demonstrated in patients with chronic neck pain (NP). On the other hand, authors emphasized the use of different motion speeds for assessing functional impairment of the cervical spine. The objectives of this study were (1) to investigate the head repositioning accuracy in NP patients and control subjects and (2) to assess the influence of target distance, motion speed, motion direction and pain. Seventy-one subjects (36 healthy subjects and 35 NP patients; age 30-55 years) performed the head repositioning test (HRT) at two different speeds for horizontal and vertical movements and at two different distances. For each condition, six consecutive trials were sampled. The study showed the validity and reproducibility of the HRT, confirming a dysfunctional threshold of 4.5°. Normative values of head repositioning error up to 3.6° and 7.1° were identified for healthy and NP subjects, respectively. A distance of 180 cm from the target and a natural motion speed increased HRT accuracy. Repositioning after extension movement showed a significantly larger error in both groups. Intensity, duration of pain as well as pain level did not significantly alter head repositioning error. The assessment of proprioceptive performance in healthy and NP subjects allowed the validation of the HRT. The HRT is a simple, not expensive and fast test, easily implementable in daily practice to assess and monitor treatment and evolution of proprioceptive cervical deficits.

  14. 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...

  15. 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

  16. Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.

    Science.gov (United States)

    Caira, Simonetta; Iannelli, Antonio; Sciarrillo, Rosaria; Picariello, Gianluca; Renzone, Giovanni; Scaloni, Andrea; Addeo, Pietro

    2017-12-01

    The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.

  17. New biomarkers of coffee consumption identified by the non-targeted metabolomic profiling of cohort study subjects.

    Directory of Open Access Journals (Sweden)

    Joseph A Rothwell

    Full Text Available Coffee contains various bioactives implicated with human health and disease risk. To accurately assess the effects of overall consumption upon health and disease, individual intake must be measured in large epidemiological studies. Metabolomics has emerged as a powerful approach to discover biomarkers of intake for a large range of foods. Here we report the profiling of the urinary metabolome of cohort study subjects to search for new biomarkers of coffee intake. Using repeated 24-hour dietary records and a food frequency questionnaire, 20 high coffee consumers (183-540 mL/d and 19 low consumers were selected from the French SU.VI.MAX2 cohort. Morning spot urine samples from each subject were profiled by high-resolution mass spectrometry. Partial least-square discriminant analysis of multidimensional liquid chromatography-mass spectrometry data clearly distinguished high consumers from low via 132 significant (p-value<0.05 discriminating features. Ion clusters whose intensities were most elevated in the high consumers were annotated using online and in-house databases and their identities checked using commercial standards and MS-MS fragmentation. The best discriminants, and thus potential markers of coffee consumption, were the glucuronide of the diterpenoid atractyligenin, the diketopiperazine cyclo(isoleucyl-prolyl, and the alkaloid trigonelline. Some caffeine metabolites, such as 1-methylxanthine, were also among the discriminants, however caffeine may be consumed from other sources and its metabolism is subject to inter-individual variation. Receiver operating characteristics curve analysis showed that the biomarkers identified could be used effectively in combination for increased sensitivity and specificity. Once validated in other cohorts or intervention studies, these specific single or combined biomarkers will become a valuable alternative to assessment of coffee intake by dietary survey and finally lead to a better understanding of

  18. Study Identifies New Lymphoma Treatment Target

    Science.gov (United States)

    NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

  19. 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

  20. 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.

  1. 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

  2. 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…

  3. 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.

  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...

  5. 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.

  6. 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.

  7. Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response in subjects with cat allergy.

    Science.gov (United States)

    Hulse, Kathryn E; Reefer, Amanda J; Engelhard, Victor H; Satinover, Shama M; Patrie, James T; Chapman, Martin D; Woodfolk, Judith A

    2008-03-01

    Induction of CD4+ T cells that produce IL-10 or IFN-gamma is central to the protective effects of conventional allergen immunotherapy. We examined the T-cell modulatory capacity of a fusion protein (H22-Fel d 1) that targets Fel d 1 to the high-affinity IgG receptor (FcgammaRI) on antigen-presenting cells. Monocyte-derived dendritic cells pulsed with H22-Fel d 1 were analyzed for surface phenotype and cytokine secretion by flow cytometry and cytometric bead assay, respectively. CD4+ T cells generated after coculture with H22-Fel d 1-pulsed dendritic cells were analyzed at the single-cell level by flow cytometry after intracellular cytokine staining. The T-cell repertoire was compared for subjects with (IgE+) and without cat allergy (IgE(neg)IgG(neg)), including subjects with a modified T(H)2 response (IgE(neg)IgG+). H22-Fel d 1 induced a semimature phenotype in dendritic cells in conjunction with a selective increase in IL-5+ and IL-10+ CD4+ T cells compared with nonreceptor-targeted Fel d 1. Amplified T cells included diverse subtypes characteristic of T(H)0 (IL-5+IFN-gamma+), regulatory T(H)1 (IL-10+IFN-gamma+) and regulatory T(H)2 (IL-10+IL-5+ cells. T-cell qualitative changes were restricted to subjects with allergy and were distinct from a modified T(H)2 response. Blocking IL-10 induced by H22-Fel d 1 selectively increased IL-5+ CD4+ T cells, suggesting that T(H)2 responses were controlled. Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response that incorporates major elements of a protective T-cell response.

  8. 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.

  9. 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.

  10. CXCR4 Ligands : The Next Big Hit?

    NARCIS (Netherlands)

    Walenkamp, Annemiek M. E.; Lapa, Constantin; Herrmann, Ken; Wester, Hans-Juergen

    2017-01-01

    The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and

  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. 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.

  13. SUBJECT INDEX

    Indian Academy of Sciences (India)

    Subject Index. Variation of surface electric field during geomagnetic disturbed period at Maitri, Antarctica. 1721. Geomorphology. A simple depression-filling method for raster and irregular elevation datasets. 1653. Decision Support System integrated with Geographic. Information System to target restoration actions in water-.

  14. 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...

  15. 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.

  16. 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....

  17. 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.

  18. Targeted metabolomic analysis reveals the association between the postprandial change in palmitic acid, branched-chain amino acids and insulin resistance in young obese subjects.

    Science.gov (United States)

    Liu, Liyan; Feng, Rennan; Guo, Fuchuan; Li, Ying; Jiao, Jundong; Sun, Changhao

    2015-04-01

    Obesity is the result of a positive energy balance and often leads to difficulties in maintaining normal postprandial metabolism. The changes in postprandial metabolites after an oral glucose tolerance test (OGTT) in young obese Chinese men are unclear. In this work, the aim is to investigate the complex metabolic alterations in obesity provoked by an OGTT using targeted metabolomics. We used gas chromatography-mass spectrometry and ultra high performance liquid chromatography-triple quadrupole mass spectrometry to analyze serum fatty acids, amino acids and biogenic amines profiles from 15 control and 15 obese subjects at 0, 30, 60, 90 and 120 min during an OGTT. Metabolite profiles from 30 obese subjects as independent samples were detected in order to validate the change of metabolites. There were the decreased levels of fatty acid, amino acids and biogenic amines after OGTT in obesity. At 120 min, percent change of 20 metabolites in obesity has statistical significance when comparing with the controls. The obese parameters was positively associated with changes in arginine and histidine (Pchange in palmitic acid (PA), branched-chain amino acids (BCAAs) and phenylalanine between 1 and 120 min were positively associated with fasting insulin and HOMA-IR (all Presistance in obesity. Our findings offer new insights in the complex physiological regulation of the metabolism during an OGTT in obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Ozone's Threat Hits Back Mexico City

    Science.gov (United States)

    Velasco, E.; Retama, A.; Guzman, D.

    2016-12-01

    Last March the Mexican authorities activated after 13 years the environmental alarm when ozone (O3) reached 210 ppb. The emergency measures created confusion among the public, who had lost memory of previous air quality crisis. Despite Mexico City has experienced a significant progress towards achieving cleaner air during the last 20 years, a recent relaxation in traffic regulations and meteorology favorable for photochemical activity triggered this new episode. All criteria pollutants of primary origin have been controlled and are in compliance with the Mexican Air Quality Standards. However, O3 and fine particles still exceed the standard threshold concentrations. For instance, 49-64% of the days have exceeded the 1-hour O3 standard of 95 ppb during the last 5 years. The current control policies, which responded to the integration of air quality information by authorities and scientists, have apparently started to lose effectiveness. Although precursor gases, such as alkanes and aromatics have shown an important decrease, reactive olefins have gained importance. The increase of motor-vehicles in recent years seems to fuel again the atmosphere's reactivity. This paper analyses the effectiveness of the emergency measures during the crisis based on the knowledge obtained from previous large field studies and the comprehensive data collected by the local air quality monitoring network. It is 10 years from MILAGRO, the last interdisciplinary study that examined the air pollution of the most populous city in North America. We call for a new collaborative research initiative based on a major field measurement campaign with the target of revealing new insights into the meteorology, emission of primary pollutants and precursor gases, photochemical production and formation of secondary particles in the atmosphere of Mexico City to improve its air quality, as well as of similar cities in the developing world.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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…

  6. 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…

  7. 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.

  8. 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.

  9. [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.

  10. 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.

  11. 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...

  12. 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...

  13. 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.

  14. 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

  15. 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.

  16. Recognition of Zinc Transporter 8 and MAP3865c Homologous Epitopes by Hashimoto's Thyroiditis Subjects from Sardinia: A Common Target with Type 1 Diabetes?

    Science.gov (United States)

    Masala, Speranza; Cossu, Davide; Palermo, Mario; Sechi, Leonardo Antonio

    2014-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) asymptomatic infection has been previously linked to Type 1 diabetes (T1D) and Multiple Sclerosis. An association between MAP infection and Hashimoto's thyroiditis (HT) was also proposed only in a case report. This study aimed to investigate the robustness of the latter association, testing a large cohort of HT and healthy control (HCs) subjects, all from Sardinia. Prevalence of anti-MAP3865c Abs was assessed by indirect enzyme-linked immunosorbent assay (ELISA). Moreover, given that human ZnT8 is specifically expressed in the pancreatic β-cells, in the follicle epithelial cells and in the parafollicular cells of the thyroid gland, we also tested ZnT8 epitopes homologues to the MAP3865c immunodominant peptides previously identified. Indeed, Abs targeting MAP3865c and ZnT8 homologous regions display similar frequencies in patients and controls, thus suggesting that Abs recognizing these epitopes could be cross-reactive. A statistically significant difference was found between HT patients and HCs when analyzing the humoral response mounted against MAP3865c/ZnT8 homologues epitopes. To our knowledge, this is the first report, which provides statistically significant evidence sustaining the existence of an association between MAP sero-reactivity and HT. Further studies are required to investigate the relevance of MAP to HT, aimed at deciphering if this pathogen can be at play in triggering this autoimmune disease. Likewise, genetic polymorphism of the host, and other environmental factors need to be investigated. PMID:24830306

  17. Recognition of zinc transporter 8 and MAP3865c homologous epitopes by Hashimoto's thyroiditis subjects from Sardinia: a common target with type 1 diabetes?

    Directory of Open Access Journals (Sweden)

    Speranza Masala

    Full Text Available Mycobacterium avium subspecies paratuberculosis (MAP asymptomatic infection has been previously linked to Type 1 diabetes (T1D and Multiple Sclerosis. An association between MAP infection and Hashimoto's thyroiditis (HT was also proposed only in a case report. This study aimed to investigate the robustness of the latter association, testing a large cohort of HT and healthy control (HCs subjects, all from Sardinia. Prevalence of anti-MAP3865c Abs was assessed by indirect enzyme-linked immunosorbent assay (ELISA. Moreover, given that human ZnT8 is specifically expressed in the pancreatic β-cells, in the follicle epithelial cells and in the parafollicular cells of the thyroid gland, we also tested ZnT8 epitopes homologues to the MAP3865c immunodominant peptides previously identified. Indeed, Abs targeting MAP3865c and ZnT8 homologous regions display similar frequencies in patients and controls, thus suggesting that Abs recognizing these epitopes could be cross-reactive. A statistically significant difference was found between HT patients and HCs when analyzing the humoral response mounted against MAP3865c/ZnT8 homologues epitopes. To our knowledge, this is the first report, which provides statistically significant evidence sustaining the existence of an association between MAP sero-reactivity and HT. Further studies are required to investigate the relevance of MAP to HT, aimed at deciphering if this pathogen can be at play in triggering this autoimmune disease. Likewise, genetic polymorphism of the host, and other environmental factors need to be investigated.

  18. 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.

  19. "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)

  20. In silico Target Fishing for Rationalized Ligand Discovery Exemplified on Constituents of Ruta graveolens

    Science.gov (United States)

    Rollinger, Judith M.; Schuster, Daniela; Danzl, Birgit; Schwaiger, Stefan; Markt, Patrick; Schmidtke, Michaela; Gertsch, Jürg; Raduner, Stefan; Wolber, Gerhard; Langer, Thierry; Stuppner, Hermann

    2012-01-01

    The identification of targets whose interaction is likely to result in the successful treatment of a disease is of growing interest for natural product scientists. In the current study we performed an exemplary application of a virtual parallel screening approach to identify potential targets for 16 secondary metabolites isolated and identified from the aerial parts of the medicinal plant Ruta graveolens L. Low energy conformers of the isolated constituents were simultaneously screened against a set of 2208 pharmacophore models generated in-house for the in silico prediction of putative biological targets, i. e., target fishing. Based on the predicted ligand-target interactions, we focused on three biological targets, namely acetylcholinesterase (AChE), the human rhinovirus (HRV) coat protein and the cannabinoid receptor type-2 (CB2). For a critical evaluation of the applied parallel screening approach, virtual hits and non-hits were assayed on the respective targets. For AChE the highest scoring virtual hit, arborinine, showed the best inhibitory in vitro activity on AChE (IC50 34.7 μM). Determination of the anti-HRV-2 effect revealed 6,7,8-trimethoxycoumarin and arborinine to be the most active antiviral constituents with IC50 values of 11.98 μM and 3.19 μM, respectively. Of these, arborinine was predicted virtually. Of all the molecules subjected to parallel screening, one virtual CB2 ligand was obtained, i.e., rutamarin. Interestingly, in experimental studies only this compound showed a selective activity to the CB2 receptor (Ki of 7.4 μM) by using a radioligand displacement assay. The applied parallel screening paradigm with constituents of R. graveolens on three different proteins has shown promise as an in silico tool for rational target fishing and pharmacological profiling of extracts and single chemical entities in natural product research. PMID:19096995

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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 $\\eta$=...

  10. 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.

  11. 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.

  12. Low intensity beam target unit

    CERN Multimedia

    CERN PhotoLab

    1976-01-01

    This is a wheel fitted with many targets around its periphery (each with three longitudinally arranged thin rods) of which one is placed into the beam via a rotation of the wheel. Upstream of each target is placed a luminescent screen, aligbed on each target axis and viewed with a TV camera, to make sure that one is hitting the target. This target unit was probably used to study target's behaviour (like beam heating). Gualtiero Del Torre stands on the left, Pierre Gerdil on the right.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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...

  19. Oral magnesium supplements decrease high blood pressure (SBP>155 mmHg) in hypertensive subjects on anti-hypertensive medications: a targeted meta-analysis.

    Science.gov (United States)

    Rosanoff, Andrea; Plesset, Michael R

    2013-01-01

    Previously, we examined 44 human studies involving oral magnesium (Mg) supplementation for hypertension (HT), sorting them according to HT status, Mg dose and anti-hypertensive medication usage. We found that while some studies reported a significant lowering of blood pressure with Mg supplementation, others did not. We present here our first meta-analysis of a uniform subset from this series of studies. Seven studies, involving 135 hypertensive subjects on anti-hypertensive medication continuously for at least six months, with no more than a two-week washout and with a mean starting systolic blood pressure (SBP)>155 mmHg, demonstrated a mean change of -18.7 mmHg [95% CI=-14.95 to -22.45] p155 mmHg starting SBP values or not complying as regards anti-hypertensive medication usage, showed mean changes in both SBP and DBP with oral Mg that, while not approaching the high-responder values of the present study, appeared to include some high-responder subjects combined with low- or non-responder subjects. This uniform subset of seven studies showed a strong effect of Mg treatment in hypertension, which is in stark contrast to results of three other meta-analyses. Using non-uniform sets of studies, the small effects reported in previous meta-analyses may reflect a blending of dissimilar studies, which acted to seriously underestimate the potential of Mg in hypertension in some (but not all) subjects. Within studies, blending of non-, moderate and highresponder subjects in any one study might mask strong effects of Mg treatment in some subjects.

  20. 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.

  1. 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.

  2. Hitting the Moving Target Known as Reading Development: Some thoughts on Screening Children for Secondary Interventions

    Science.gov (United States)

    Speece, Deborah L.

    2005-01-01

    Attention to growth may net more accurate screening results than have been apparent in the long history of early identification research. Instead of relying solely on measures administered at one time point, including a measure of children's growth or responsiveness may add an important dimension to the screening equation and provide a clearer…

  3. Hitting the target! A no tears approach to writing an abstract for a conference presentation.

    Science.gov (United States)

    Happell, Brenda

    2007-12-01

    From the author's experience in reviewing abstracts for conference presentations, nurses do not find it easy or straightforward to write an abstract, nor do they appear to fully understand its aim and purpose. The aim of this paper is to provide a clear understanding of the role of the abstract in the context of conference presentations and to provide a practical tool to guide nurses through the process of writing an abstract for a conference presentation in terms of both the structure and the content. Tips on what to avoid when writing an abstract are included.

  4. Hitting a Moving Target: A Model for Malaria Elimination in the Presence of Population Movement.

    Directory of Open Access Journals (Sweden)

    Sheetal Prakash Silal

    Full Text Available South Africa is committed to eliminating malaria with a goal of zero local transmission by 2018. Malaria elimination strategies may be unsuccessful if they focus only on vector biology, and ignore the mobility patterns of humans, particularly where the majority of infections are imported. In the first study in Mpumalanga Province in South Africa designed for this purpose, a metapopulation model is developed to assess the impact of their proposed elimination-focused policy interventions. A stochastic, non-linear, ordinary-differential equation model is fitted to malaria data from Mpumalanga and neighbouring Maputo Province in Mozambique. Further scaling-up of vector control is predicted to lead to a minimal reduction in local infections, while mass drug administration and focal screening and treatment at the Mpumalanga-Maputo border are predicted to have only a short-lived impact. Source reduction in Maputo Province is predicted to generate large reductions in local infections through stemming imported infections. The mathematical model predicts malaria elimination to be possible only when imported infections are treated before entry or eliminated at the source suggesting that a regionally focused strategy appears needed, for achieving malaria elimination in Mpumalanga and South Africa.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Cross-national invariance of dimensions of parental rearing behaviour: comparison of psychometric data of Swedish depressives and healthy subjects with Dutch target ratings on the EMBU.

    Science.gov (United States)

    Arrindell, W A; Perris, C; Perris, H; Eisemann, M; van der Ende, J; von Knorring, L

    1986-03-01

    A psychometric study on Swedish and Dutch samples used the EMBU, a self-report instrument designed to assess memories of parents' rearing behaviour. Of the four primary factors identified previously with Dutch individuals (Rejection, Emotional Warmth, Over-protection, and Favouring Subject), the first three were retrieved in a similar form in the two Swedish groups (depressives and healthy, non-patients). Examination of the metric equivalence of the scales and the strength of the factors for each group indicated that comparisons of patterns and levels between groups from the respective countries on the three factors showing cross-national constancy would be warranted. Scale-level factor analyses of these dimensions produced identical two-factor compositions (CARE and PROTECTION) across national groups which further supported this conclusion.

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

    Science.gov (United States)

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

    2014-07-01

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

  12. 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.

  13. SU-G-BRA-16: Target Dose Comparison for Dynamic MLC Tracking and Mid- Ventilation Planning in Lung Radiotherapy Subject to Intrafractional Baseline Drifts

    Energy Technology Data Exchange (ETDEWEB)

    Menten, MJ; Fast, MF; Nill, S; Oelfke, U [Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom)

    2016-06-15

    Purpose: Lung tumor motion during radiotherapy can be accounted for by expanded treatment margins, for example using a mid-ventilation planning approach, or by localizing the tumor in real-time and adapting the treatment beam with multileaf collimator (MLC) tracking. This study evaluates the effect of intrafractional changes in the average tumor position (baseline drifts) on these two treatment techniques. Methods: Lung stereotactic treatment plans (9-beam IMRT, 54Gy/3 fractions, mean treatment time: 9.63min) were generated for three patients: either for delivery with MLC tracking (isotropic GTV-to-PTV margin: 2.6mm) or planned with a mid-ventilation approach and delivered without online motion compensation (GTV-to-PTV margin: 4.4-6.3mm). Delivery to a breathing patient was simulated using DynaTrack, our in-house tracking and delivery software. Baseline drifts in cranial and posterior direction were simulated at a rate of 0.5, 1.0 or 1.5mm/min. For dose reconstruction, the corresponding 4DCT phase was selected for each time point of the delivery. Baseline drifts were accounted for by rigidly shifting the CT to ensure correct relative beam-to-target positioning. Afterwards, the doses delivered to each 4DCT phase were accumulated deformably on the mid-ventilation phase using research RayStation v4.6 and dose coverage of the GTV was evaluated. Results: When using the mid-ventilation planning approach, dose coverage of the tumor deteriorated substantially in the presence of baseline drifts. The reduction in D98% coverage of the GTV in a single fraction ranged from 0.4-1.2, 0.6-3.3 and 4.5-6.2Gy, respectively, for the different drift rates. With MLC tracking the GTV D98% coverage remained unchanged (+/− 0.1Gy) regardless of drift. Conclusion: Intrafractional baseline drifts reduce the tumor dose in treatments based on mid-ventilation planning. In rare, large target baseline drifts tumor dose coverage may drop below the prescription, potentially affecting clinical

  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. Targeted metabolomics reveals differences in the extended postprandial plasma metabolome of healthy subjects after intake of whole-grain rye porridges versus refined wheat bread.

    Science.gov (United States)

    Shi, Lin; Brunius, Carl; Lindelöf, Magnus; Shameh, Souad Abou; Wu, Huaxing; Lee, Isabella; Landberg, Rikard; Moazzami, Ali A

    2017-07-01

    We previously found that whole-grain (WG) rye porridges suppressed appetite and improved glucose metabolism. This study aimed to investigate potential plasma metabolites that may be related to differences in those appetite and glucose responses. Twenty-one health subjects consumed six isocaloric breakfasts in a randomized cross-over study. Plain WG rye porridges (40 and 55 g), rye porridge enriched with different inulin: gluten proportions (9:3 g; 6:6 g; 3:9 g), and a 55 g refined wheat bread (control) were served as part of complete breakfast, followed by a standardized lunch. NMR metabolomics assessed 36 plasma metabolites and short chain fatty acids were measured by GC-MS from baseline up to 8 h. Pre-lunch plasma essential amino acids reflected protein composition and post-lunch plasma short chain fatty acids varied with fiber content in breakfasts. No correlations were observed between measured metabolites and glucose, insulin, or appetite responses. Differences in protein and fiber contents in breakfasts altered postprandial plasma amino acids and short chain fatty acids, respectively, but were unrelated to appetite and glucose responses. Further studies are warrant to identify the underlying mechanisms for the beneficial effects on appetite and second meal glucose responses after rye-based foods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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.

  17. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  18. 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.

  19. 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...

  20. Design of the LBNF Beamline Target Station

    OpenAIRE

    Tariq, S.; Ammigan, K.; Anderson, K.; Buccellato, S. A.; Crowley, C. F.; Hartsell, B. D.; Hurh, P.; Hylen, J.; Kasper, P.; Krafczyk, G. E.; Lee, A.; Lundberg, B.; Marchionni, A; Mokhov, N. V.; Moore, C. D.

    2016-01-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-fil...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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 ...

  7. 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

  8. Insulin degludec/insulin aspart versus biphasic insulin aspart 30 twice daily in insulin-experienced Japanese subjects with uncontrolled type 2 diabetes: Subgroup analysis of a Pan-Asian, treat-to-target Phase 3 Trial.

    Science.gov (United States)

    Taneda, Shinji; Hyllested-Winge, Jacob; Gall, Mari-Anne; Kaneko, Shizuka; Hirao, Koichi

    2017-03-01

    The present study was a subgroup analysis of a Pan-Asian Phase 3 open-label randomized treat-to-target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin. Eligible subjects (n = 178) were randomized (2: 1) to twice-daily (b.i.d.) IDegAsp or BIAsp 30 with or without metformin for 26 weeks, titrated to a blood glucose target of between 3.9 and <5.0 mmol/L. Changes in HbA1c , the proportion of responders reaching the HbA1c target, and changes in fasting plasma glucose, nine-point self-monitored plasma glucose profiles, and body weight were assessed. At 26 weeks, the decrease in HbA1c was similar in both groups. Fasting plasma glucose was lower with IDegAsp than BIAsp 30 (estimated treatment difference -1.50 mmol/L; 95 % confidence interval [CI] -1.98, -1.01). Overall confirmed hypoglycemia rates were similar; the nocturnal confirmed hypoglycemia rate was lower with IDegAsp than BIAsp 30 (estimated rate ratio 0.44; 95 % CI 0.20, 0.99). No severe hypoglycemic episodes were reported. The results indicate that IDegAsp b.i.d. improves glycemic control and, compared with BIAsp 30, lowers the rate of nocturnal confirmed hypoglycemia. © 2016 The Authors. Journal of Diabetes published John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

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

    Directory of Open Access Journals (Sweden)

    Xing Yang

    2018-01-01

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

  10. 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

  11. 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....

  12. 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.

  13. 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

  14. Replication is more than hitting the lottery twice

    NARCIS (Netherlands)

    Asendorpf, J.B.; Conner, M.; de Fruyt, F.; de Houwer, J.; Denissen, J.J.A.; Fiedler, K.; Fiedler, S.; Funder, D.C.; Kliegl, R.; Nosek, B.A.; Perugini, M.; Roberts, B.W.; Schmitt, M.; van Aken, M.A.G.; Weber, H.; Wicherts, J.M.

    2013-01-01

    The main goal of our target article was to provide concrete recommendations for improving the replicability of research findings. Most of the comments focus on this point. In addition, a few comments were concerned with the distinction between replicability and generalizability and the role of

  15. 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

  16. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa...

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia

    Directory of Open Access Journals (Sweden)

    Simon Chiu

    2014-01-01

    Full Text Available Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4 plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB. Objective. The primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (total n=21 to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12 entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P<0.032 and executive function (P<0.022, compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer’s dementia. This trial is registered with ClinicalTrials.gov NCT01805518.

  4. 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.

  5. 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.

  6. Exercise for Bone in Childhood-Hitting the Sweet Spot.

    Science.gov (United States)

    Beck, Belinda R

    2017-11-01

    The goal of the current work is to challenge the enduring notion that prepuberty is the optimum timing for maximum bone response to exercise in childhood and to present the evidence that early puberty is a more potently receptive period. The relevant literature is reviewed and the causes of the misconception are addressed in detail. Contrary to prevailing opinion, ample evidence exists to suggest that the peripubertal years represent the developmental period during which bone is likely to respond most robustly to exercise intervention. Public health initiatives that target bone-specific exercise interventions during the pubertal years are likely to be the most effective strategy to harness the increased receptiveness of the growing skeleton to mechanical loading.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. High speed cryogenic monodisperse targets

    Science.gov (United States)

    Boukharov, A.; Vishnevkii, E.

    2017-11-01

    The basic possibility of creation of high speed cryogenic monodisperse targets is shown. According to calculations at input of thin liquid cryogenic jets with a velocity of bigger 100 m/s in vacuum the jets don’t manage to freeze at distance to 1 mm and can be broken into monodisperse drops. Drops due to evaporation are cooled and become granules. High speed cryogenic monodisperse targets have the following advantages: direct input in vacuum (there is no need for a chamber of a triple point chamber and sluices), it is possible to use the equipment of a cluster target, it is possible to receive targets with a diameter of D 100m/s), exact synchronization of the target hitting moment in a beam with the moment of sensors turning on.

  13. The Floor's the Limit (Antiproton energies to hit new low)

    CERN Multimedia

    2000-01-01

    Celebrating the success of the RFQ in Aarhus. Left to right: Alessanda Lombardi (CERN), Iouri Bylinskii (CERN), Alex Csete (Aarhus), Ulrik Uggerhøj (Aarhus), Ryu Hayano (Tokyo, spokesman ASACUSA), Helge Knudsen (Aarhus), Werner Pirkl (CERN), Ryan Thompson (Aarhus), Søren P. Møller (Aarhus). Although in particle physics we are accustomed to strive for higher and higher energies, this is not always the most interesting thing to do with antiprotons. Indeed, as recent issues of the Bulletin have suggested, the signpost on the road to a closer look at the antiproton points towards ever-lower energies. The CERN Antiproton Decelerator decelerates antipro-tons emerging from a target placed in the path of a 26 GeV/c proton beam from 90 % of to about 10 % of the speed of light. However, even this is far too fast for many of the most interesting experiments on antiprotons planned by Danish and Japanese members of the ASACUSA collaboration. Tokyo University has therefore financed the con...

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

    Science.gov (United States)

    Kazandjian, Vahé A; Lipitz-Snyderman, Allison

    2011-12-01

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

  15. Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery.

    Science.gov (United States)

    Coutard, Bruno; Decroly, Etienne; Li, Changqing; Sharff, Andrew; Lescar, Julien; Bricogne, Gérard; Barral, Karine

    2014-06-01

    Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based experimental approach was applied to identify small molecule ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, respectively. In a second stage, we set up a fragment-based X-ray crystallographic screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymatic assays to assess their inhibition effect on the N7- and 2'-O-MTase enzymatic activities: five of these fragment hits inhibit at least one of the two activities with IC50 ranging from 180μM to 9mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity molecules that bind to novel allosteric sites. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. 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

  17. 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...

  18. 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

  19. 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.

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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…

  12. 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

  13. 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

  14. 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…

  15. 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.

  16. 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,

  17. 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...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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…

  3. Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation.

    Science.gov (United States)

    Girotra, Priti; Thakur, Aman; Kumar, Ajay; Singh, Shailendra Kumar

    2017-03-01

    The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (β2 adrenoceptor, Dopamine D3, 5HT1B, TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), β2 adrenoceptor (3NYA) and Dopamine D3 (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. 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

  5. ISOLDE back on target

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    Today, Friday 1 August, the ISOLDE installation, supplied by the beams of the PS Booster, restarted its physics programme. After a shutdown of almost a year and a half, there was a real buzz in the air as the first beam of protons hit the target of the first post-LS1 ISOLDE experiment.   One of the new target-handling robots installed by ISOLDE during LS1. Many improvements have been made to the ISOLDE installation during LS1. One of the main projects was the installation of new robots for handling the targets (see photo 1). “Our targets are bombarded by protons from the PS Booster’s beams and become very radioactive,” explains Maria Jose Garcia Borge, spokesperson for the ISOLDE collaboration. “They therefore need to be handled carefully, which is where the robots come in. The robots we had until now were already over 20 years old and were starting to suffer from the effects of radiation. So LS1 was a perfect opportunity to replace them with more moder...

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. "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".

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Literature evidence in open targets - a target validation platform.

    Science.gov (United States)

    Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

    2017-06-06

    We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

  3. 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.

  4. 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

  5. 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

  6. Integrated targeted and non-targeted analysis of water sample extracts with micro-scale UHPLC–MS

    Directory of Open Access Journals (Sweden)

    Dominik Deyerling

    2015-01-01

    • The filtering of database hits for two criteria (exact mass and partition coefficient significantly reduced the list of suspects and at the same time rendered it possible to perform non-target analysis with lower mass accuracy (no lock-spray in the range of 20–500 ppm.

  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. 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.

  10. 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...

  11. 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...

  12. 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.

  13. 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.

  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. Professional soldier assessment of a rifle-mounted target hand-off system

    NARCIS (Netherlands)

    Levesque, J.; Banko, K.; Binsch, O.

    2015-01-01

    The miniaturization of digital image acquisition and processing hardware, positional sensors, and batteries has enabled the creation of assisted targeting systems light enough to be integrated onto small firearms to increase the probability of soldiers detecting and hitting targets. As well, the

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  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. 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)....

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Nuclear Targeting Terms for Engineers and Scientists

    Energy Technology Data Exchange (ETDEWEB)

    St Ledger, John W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-01

    The Department of Defense has a methodology for targeting nuclear weapons, and a jargon that is used to communicate between the analysts, planners, aircrews, and missile crews. The typical engineer or scientist in the Department of Energy may not have been exposed to the nuclear weapons targeting terms and methods. This report provides an introduction to the terms and methodologies used for nuclear targeting. Its purpose is to prepare engineers and scientists to participate in wargames, exercises, and discussions with the Department of Defense. Terms such as Circular Error Probable, probability of hit and damage, damage expectancy, and the physical vulnerability system are discussed. Methods for compounding damage from multiple weapons applied to one target are presented.

  3. 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…

  4. 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.

  5. 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…

  6. Sensibility and Subjectivity: Levinas’ Traumatic Subject

    Directory of Open Access Journals (Sweden)

    Rashmika Pandya

    2011-02-01

    Full Text Available The importance of Levinas’ notions of sensibility and subjectivity are evident in the revision of phenomenological method by current phenomenologists such as Jean-Luc Marion and Michel Henry. The criticisms of key tenants of classical phenomenology, intentionality and reduction, are of a particular note. However, there are problems with Levinas’ characterization of subjectivity as essentially sensible. In “Totality and Infinity” and “Otherwise than Being”, Levinas criticizes and recasts a traditional notion of subjectivity, particularly the notion of the subject as the first and foremost rational subject. The subject in Levinas’ works is characterized more by its sensibility and affectedness than by its capacity to reason or affect its world. Levinas ties rationality to economy and suggests an alternative notion of reason that leads to his analysis of the ethical relation as the face-to-face encounter. The ‘origin’ of the social relation is located not in our capacity to know but rather in a sensibility that is diametrically opposed to the reason understood as economy. I argue that the opposition in Levinas’ thought between reason and sensibility is problematic and essentially leads to a self-conflicted subject. In fact, it would seem that violence characterizes the subject’s self-relation and, thus, is also inscribed at the base of the social relation. Rather than overcoming a problematic tendency to dualistic thought in philosophy Levinas merely reverses traditional hierarchies of reason/emotion, subject/object and self/other. 

  7. 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

  8. Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51.

    Directory of Open Access Journals (Sweden)

    Shamila S Gunatilleke

    Full Text Available Chagas Disease, a WHO- and NIH-designated neglected tropical disease, is endemic in Latin America and an emerging infection in North America and Europe as a result of population moves. Although a major cause of morbidity and mortality due to heart failure, as well as inflicting a heavy economic burden in affected regions, Chagas Disease elicits scant notice from the pharmaceutical industry because of adverse economic incentives. The discovery and development of new routes to chemotherapy for Chagas Disease is a clear priority.The similarity between the membrane sterol requirements of pathogenic fungi and those of the parasitic protozoon Trypanosoma cruzi, the causative agent of Chagas human cardiopathy, has led to repurposing anti-fungal azole inhibitors of sterol 14α-demethylase (CYP51 for the treatment of Chagas Disease. To diversify the therapeutic pipeline of anti-Chagasic drug candidates we exploited an approach that included directly probing the T. cruzi CYP51 active site with a library of synthetic small molecules. Target-based high-throughput screening reduced the library of ∼104,000 small molecules to 185 hits with estimated nanomolar K(D values, while cross-validation against T. cruzi-infected skeletal myoblast cells yielded 57 active hits with EC(50 <10 µM. Two pools of hits partially overlapped. The top hit inhibited T. cruzi with EC(50 of 17 nM and was trypanocidal at 40 nM.The hits are structurally diverse, demonstrating that CYP51 is a rather permissive enzyme target for small molecules. Cheminformatic analysis of the hits suggests that CYP51 pharmacology is similar to that of other cytochromes P450 therapeutic targets, including thromboxane synthase (CYP5, fatty acid ω-hydroxylases (CYP4, 17α-hydroxylase/17,20-lyase (CYP17 and aromatase (CYP19. Surprisingly, strong similarity is suggested to glutaminyl-peptide cyclotransferase, which is unrelated to CYP51 by sequence or structure. Lead compounds developed by pharmaceutical

  9. 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.

  10. "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…

  11. Targeted Inhibition of Leucine-Rich Repeat and Immunoglobulin Domain-Containing Protein 1 in Transplanted Neural Stem Cells Promotes Neuronal Differentiation and Functional Recovery in Rats Subjected to Spinal Cord Injury.

    Science.gov (United States)

    Chen, Ningning; Cen, Jing-Sheng; Wang, Jingnan; Qin, Gangjian; Long, Lingli; Wang, Le; Wei, Fuxin; Xiang, Qingfeng; Deng, David Y B; Wan, Yong

    2016-03-01

    Leucine-rich repeat and immunoglobulin domain-containing protein (LINGO)-1 is expressed in neural stem cells, and its neutralization results in sustained neuronal immaturity. Thus, targeted inhibition of LINGO-1 via RNA interference may enhance transplanted neural stem cell survival and neuronal differentiation in vivo. Furthermore, LINGO-1 RNA interference in neural stem cells represents a potential therapeutic strategy for spinal cord injury. Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University. Translational Medicine Center Research Laboratory, First Affiliated Hospital of Sun Yat-sen University. Female Sprague-Dawley rats. The animals were divided into three groups that underwent laminectomy and complete spinal cord transection accompanied by transplantation of control-RNA interference-treated or LINGO-1-RNA interference-treated neural stem cells at the injured site in vivo. In vitro, neural stem cells were divided into four groups for the following treatments: control, control RNA interference lentivirus, LINGO-1 RNA interference lentivirus and LINGO-1 complementary DNA lentivirusand the Key Projects of the Natural Science Foundation of Guangdong Province (No. S2013020012818). Neural stem cells in each treatment group were examined for cell survival and neuronal differentiation in vitro and in vivo via immunofluorescence and Western blot analysis. Axonal regeneration and tissue repair were assessed via retrograde tracing using Fluorogold, electron microscopy, hematoxylin-eosin staining and MRI. Rats were also examined for functional recovery based on the measurement of spinal cord-evoked potentials and the Basso-Beattie-Bresnahan score. LINGO-1-RNA interference-treated neural stem cell transplantation increased tissue repair and functional recovery of the injured spinal cord in rats. Similarly, LINGO-1 RNA interference increased neural stem cell survival and neuronal differentiation in vitro. The mechanism underlying the effect of

  12. Why to Treat Subjects as Fixed Effects

    Science.gov (United States)

    Adelman, James S.; Estes, Zachary

    2015-01-01

    Adelman, Marquis, Sabatos-DeVito, and Estes (2013) collected word naming latencies from 4 participants who read 2,820 words 50 times each. Their recommendation and practice was that R2 targets set for models should take into account subject idiosyncrasies as replicable patterns, equivalent to a subjects-as-fixed-effects assumption. In light of an…

  13. AA, entrance of proton beam to antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    Please look up 8010295 first. The intense proton beam from the 26 GeV PS arrives from the right, through the vacuum chamber. The big flange contains a thin window, after which the proton beam continues through free air. A beam transformer, affixed to the shielding block, measures its intensity, before it enters the hole in the concrete to hit the target behind it.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. 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.

  3. 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.

  4. A ligand's view of target similarity

    DEFF Research Database (Denmark)

    Garland, Stephen L; Gloriam, David E

    2011-01-01

    shows with several examples how focusing on the binding site(s) has a clear advantage when it comes to establishing sequence-correlated pharmacological profiles. By organizing and comparing sequence and structural data it is possible to "borrow" SAR from similar targets to increase the speed of lead......-finding and, potentially, to produce ligands for previously intractable receptors. Sequence motifs correlated with ligands can be applied in the design of target-specific focused libraries that are both efficient and cost-effective and should provide increased hit-rates over diversity screening. Furthermore......, in the optimization phase, the binding motif approach offers the possibility to identify quickly the most likely off-target candidates to be chosen for selectivity screening, as well as potentially characterizing those pockets which may best be exploited for improved selectivity....

  5. EEG and Eye Tracking Signatures of Target Encoding during Structured Visual Search

    Directory of Open Access Journals (Sweden)

    Anne-Marie Brouwer

    2017-05-01

    Full Text Available EEG and eye tracking variables are potential sources of information about the underlying processes of target detection and storage during visual search. Fixation duration, pupil size and event related potentials (ERPs locked to the onset of fixation or saccade (saccade-related potentials, SRPs have been reported to differ dependent on whether a target or a non-target is currently fixated. Here we focus on the question of whether these variables also differ between targets that are subsequently reported (hits and targets that are not (misses. Observers were asked to scan 15 locations that were consecutively highlighted for 1 s in pseudo-random order. Highlighted locations displayed either a target or a non-target stimulus with two, three or four targets per trial. After scanning, participants indicated which locations had displayed a target. To induce memory encoding failures, participants concurrently performed an aurally presented math task (high load condition. In a low load condition, participants ignored the math task. As expected, more targets were missed in the high compared with the low load condition. For both conditions, eye tracking features distinguished better between hits and misses than between targets and non-targets (with larger pupil size and shorter fixations for missed compared with correctly encoded targets. In contrast, SRP features distinguished better between targets and non-targets than between hits and misses (with average SRPs showing larger P300 waveforms for targets than for non-targets. Single trial classification results were consistent with these averages. This work suggests complementary contributions of eye and EEG measures in potential applications to support search and detect tasks. SRPs may be useful to monitor what objects are relevant to an observer, and eye variables may indicate whether the observer should be reminded of them later.

  6. Preverbal subjects in null subject languages are not necessarily dislocated

    Directory of Open Access Journals (Sweden)

    João Costa

    2002-12-01

    Full Text Available In recent work on null subject languages it has been claimed that preverbal subjects are always (clitic-left dislocated. In this paper, we argue against this claim, on the grounds of empirical evidence from European Portuguese concerning agreement facts, asymmetries between preverbal subjects and clitic-left dislocated XPs with respect to minimality effects, the existence of languages with a mixed system (null expletive subjects and full referential ones, language acquisition data, the behavior of negative QPs and interpretation facts, and propose a non-uniform analysis of preverbal subjects and clitic-left dislocated XPs that derives their topic interpretation from a predication rule stated configurationally (section 2. Our account of the SVO and VSO orders displayed in European Portuguese relies on a specific formulation of the EPP parameter, on the locality constraint Attract Closest X and on the independently motivated claim that V-movement targets T in European Portuguese (section 3. Under our analysis, the computational system generates equally economical SVO and VSO derivations and discourse considerations, at the appropriate interface, rule out the unfelicitous ones.

  7. 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

  8. 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.

  9. Preventing falls in community-dwelling frail older people using a home intervention team (HIT): results from the randomized Falls-HIT trial.

    Science.gov (United States)

    Nikolaus, Thorsten; Bach, Matthias

    2003-03-01

    To evaluate the effect of an intervention by a multidisciplinary team to reduce falls in older people's homes. Randomized, controlled trial with follow-up of subjects for 1 year. University-affiliated geriatric hospital and older patients' homes. Three hundred sixty subjects (mean age +/- standard deviation = 81.5 +/- 6.4) admitted from home to a geriatric hospital and showing functional decline, especially in mobility. The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a diagnostic home visit and home intervention or a comprehensive geriatric assessment with recommendations and usual care at home. The home intervention included a diagnostic home visit, assessing the home for environmental hazards, advice about possible changes, offer of facilities for any necessary home modifications, and training in the use of technical and mobility aids. An additional home visit was made after 3 months to reinforce the recommendations. After 12 months of follow-up, a home visit was made to all study participants. Number of falls, type of recommended home modifications, and compliance with recommendations. After 1 year, there were 163 falls in the intervention group and 204 falls in the control group. The intervention group had 31% fewer falls than the control group (incidence rate ratio (IRR) = 0.69, 95% confidence interval (CI) = 0.51-0.97). The intervention was most effective in a subgroup of participants who reported having had two or more falls during the year before recruitment into the study. In this subgroup, the proportion of frequent fallers and the rate of falls was significantly reduced for the intervention group compared with the control group (21 vs 36 subjects with recurrent falls, P =.009; IRR = 0.63, 95% CI = 0.43-0.94). The compliance rate varied with the type of change recommended from 83% to 33% after 12 months of follow-up. Home intervention based on home visits to assess the home for environmental hazards

  10. Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits

    NARCIS (Netherlands)

    Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

    Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint.

  11. Virtual screening yields inhibitors of novel antifungal drug target, benzoate 4-monooxygenase.

    Science.gov (United States)

    Berne, Sabina; Podobnik, Barbara; Zupanec, Neja; Novak, Metka; Kraševec, Nada; Turk, Samo; Korošec, Branka; Lah, Ljerka; Šuligoj, Erika; Stojan, Jure; Gobec, Stanislav; Komel, Radovan

    2012-11-26

    Fungal CYP53 enzymes are highly conserved proteins, involved in phenolic detoxification, and have no homologues in higher eukaryotes, rendering them favorable drug targets. Aiming to discover novel CYP53 inhibitors, we employed two parallel virtual screening protocols and evaluated highest scoring hit compounds by analyzing the spectral binding interactions, by surveying the antifungal activity, and assessing the inhibition of catalytic activity. On the basis of combined results, we selected 3-methyl-4-(1H-pyrrol-1-yl)benzoic acid (compound 2) as the best candidate for hit-to-lead follow-up in the antifungal drug discovery process.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  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. A subjective scheduler for subjective dedicated networks

    Science.gov (United States)

    Suherman; Fakhrizal, Said Reza; Al-Akaidi, Marwan

    2017-09-01

    Multiple access technique is one of important techniques within medium access layer in TCP/IP protocol stack. Each network technology implements the selected access method. Priority can be implemented in those methods to differentiate services. Some internet networks are dedicated for specific purpose. Education browsing or tutorial video accesses are preferred in a library hotspot, while entertainment and sport contents could be subjects of limitation. Current solution may use IP address filter or access list. This paper proposes subjective properties of users or applications are used for priority determination in multiple access techniques. The NS-2 simulator is employed to evaluate the method. A video surveillance network using WiMAX is chosen as the object. Subjective priority is implemented on WiMAX scheduler based on traffic properties. Three different traffic sources from monitoring video: palace, park, and market are evaluated. The proposed subjective scheduler prioritizes palace monitoring video that results better quality, xx dB than the later monitoring spots.

  20. 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.

  1. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, S. [Fermilab; Ammigan, K. [Fermilab; Anderson, K.; ; Buccellato, S. A. [Fermilab; Crowley, C. F. [Fermilab; Hartsell, B. D. [Fermilab; Hurh, P. [Fermilab; Hylen, J. [Fermilab; Kasper, P. [Fermilab; Krafczyk, G. E. [Fermilab; Lee, A. [Fermilab; Lundberg, B. [Fermilab; Reitzner, S. D. [Fermilab; Sidorov, V. [Fermilab; Stefanik, A. M. [Fermilab; Tropin, I. S. [Fermilab; Vaziri, K. [Fermilab; Williams, K. [Fermilab; Zwaska, R. M. [Fermilab; Densham, C. [RAL, Didcot

    2016-10-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding in a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.

  2. Designing allosteric peptide ligands targeting a globular protein.

    Science.gov (United States)

    Selz, Karen A; Samoylova, Tatiana I; Samoylov, Alexandre M; Vodyanoy, Vitaly J; Mandell, Arnold J

    2007-01-01

    Patented signal analytic algorithms applied to hydrophobically transformed, numerical amino acid sequences have previously been used to design short, protein-targeted, L or D retro-inverso peptides. These peptides have demonstrated allosteric and/or indirect agonist effects on a variety of G-protein and tyrosine kinase coupled membrane receptors with 30% to over 80% hit rates. Here we extend these approaches to a globular protein target. We designed eight peptide ligands targeting an ELISA antibody responsive protein, beta-galactosidase, betaGAL. Three of the eight 14mer peptides allosterically activated betaGAL with ELISA methodology. Using Bayesian statistics, this 38% hit rate would have occurred 2 x 10(-9) by chance. These peptides demonstrated binding site competitive or noncompetitive interactions, suggesting allosteric site multiplicity with respect to their betaGAL binding-mediated ELISA signal. Kinetic studies demonstrated the temperature dependence of the betaGAL peptide binding functions. Using the van't Hoff relation, we found evidence for enthalpy-entropy compensation. This relation is often found for hydrophobic interactions in aqueous media, and is consistent with the postulated hydrophobic series encoding underlying our protein-targeted, peptide design methods. It appears that our algorithmic, hydrophobic autocovariance eigenvector template approach to the design of allosteric peptides targeting membrane receptors may also be applicable to the design of peptide ligands targeting nonmembrane involved globular proteins. Copyright 2006 Wiley Periodicals, Inc.

  3. Effects of eight weeks of aerobic interval training and of isoinertial resistance training on risk factors of cardiometabolic diseases and exercise capacity in healthy elderly subjects.

    Science.gov (United States)

    Bruseghini, Paolo; Calabria, Elisa; Tam, Enrico; Milanese, Chiara; Oliboni, Eugenio; Pezzato, Andrea; Pogliaghi, Silvia; Salvagno, Gian Luca; Schena, Federico; Mucelli, Roberto Pozzi; Capelli, Carlo

    2015-07-10

    We investigated the effect of 8 weeks of high intensity interval training (HIT) and isoinertial resistance training (IRT) on cardiovascular fitness, muscle mass-strength and risk factors of metabolic syndrome in 12 healthy older adults (68 yy ± 4). HIT consisted in 7 two-minute repetitions at 80%-90% of V˙O2max, 3 times/w. After 4 months of recovery, subjects were treated with IRT, which included 4 sets of 7 maximal, bilateral knee extensions/flexions 3 times/w on a leg-press flywheel ergometer. HIT elicited significant: i) modifications of selected anthropometrical features; ii) improvements of cardiovascular fitness and; iii) decrease of systolic pressure. HIT and IRT induced hypertrophy of the quadriceps muscle, which, however, was paralleled by significant increases in strength only after IRT. Neither HIT nor IRT induced relevant changes in blood lipid profile, with the exception of a decrease of LDL and CHO after IRT. Physiological parameters related with aerobic fitness and selected body composition values predicting cardiovascular risk remained stable during detraining and, after IRT, they were complemented by substantial increase of muscle strength, leading to further improvements of quality of life of the subjects.

  4. Action-specific judgment, not perception: Fitts' law performance is related to estimates of target width only when participants are given a performance score.

    Science.gov (United States)

    Zelaznik, Howard N; Forney, Laura A

    2016-08-01

    Proponents of the action-specific account of perception and action posit that participants perceive their environment relative to their capabilities. For example, softball players who batted well judge the ball as being larger compared to players who did not hit as well. In the present study, we examined this issue in the context of a well-known speed-accuracy movement task that can be examined in the laboratory, repetitive Fitts aiming. In the Fitts task, a performer moved as quickly and as accurately as possible between two targets, D units of distance apart (between 2.5 and 20.0 cm) and of W width (1.0 cm or less). In the Fitts task, we posited that individuals do not have access to performance quality. Thus, we asked whether individual differences in Fitts task performance was related to perception of target width. If Fitts task performance is related to perception of target width, then the action-specific effect on perception does not require explicit knowledge of performance and, furthermore, these effects reside during on-line visual control of the task. We show that only when subjects were provided with a performance score was there a relation between Fitts task performance and target width judgment error. We interpret this result to mean that action-specific effects do not occur during perceptual processing of the task, but action-specific effects are the result of postperformance evaluation processes.

  5. Distributions of secondary particles around various targets exposed to 50 MeV protons

    CERN Document Server

    Fassò, A

    1976-01-01

    The particle production in thick targets of carbon, aluminium, and copper, hit by 50 MeV protons, has been studied with activation detectors. The measured angular distribution of secondaries around the targets was compared with calculations making use of semi-empirical formulae proposed by Alsmiller et. al. In general, the agreement between experiment and theory is good, except for large angles where the experimentally found production of secondaries is greater than predicted by the calculation. (17 refs).

  6. Identification and characterization of potential druggable targets among hypothetical proteins of extensively drug resistant Mycobacterium tuberculosis (XDR KZN 605) through subtractive genomics approach.

    Science.gov (United States)

    Uddin, Reaz; Siddiqui, Quratulain Nehal; Azam, Syed Sikander; Saima, Bibi; Wadood, Abdul

    2017-11-22

    Among the resistant isolates of tuberculosis (TB), the multidrug resistance tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) are the areas of growing concern for which the front-line antibiotics are no more effective. As a result, the search of new therapeutic targets against TB is an imperative need of time. On the other hand, the target identification is an a priori step in drug discovery based research. Furthermore, the availability of the complete proteomic data of extensively drug resistant Mycobacterium tuberculosis (XDR-MTB) made it possible to carry out in silico analysis for the discovery of new drug targets. In the current study, we aimed to prioritize the potential drug targets among the hypothetical proteins of XDR-TB via subtractive genomics approach. In the subtractive genomics, we stepwise reduced the complete proteome of XDR-MTB to only two hypothetical proteins and evidently proposed them as new therapeutic targets. The 3D structure of one of the two target proteins was predicted via homology modeling and later on, validated by various analysis tools. Our study suggested that the domains identified and the motif hits found in the sequences of the shortlisted drug targets are crucial for the survival of the XDR-MTB. To the best of our knowledge, the current study is the first attempt in which the complete proteomic data of XDR-MTB was subjected to the computational subtractive genomics approach and therefore, would provide an opportunity to identify the unique therapeutic targets against deadly XDR-MTB. Copyright © 2017. Published by Elsevier B.V.

  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. Estimating Subjective Probabilities

    DEFF Research Database (Denmark)

    Andersen, Steffen; Fountain, John; Harrison, Glenn W.

    Subjective probabilities play a central role in many economic decisions, and act as an immediate confound of inferences about behavior, unless controlled for. Several procedures to recover subjective probabilities have been proposed, but in order to recover the correct latent probability one must...

  9. Estimating Subjective Probabilities

    DEFF Research Database (Denmark)

    Andersen, Steffen; Fountain, John; Harrison, Glenn W.

    2014-01-01

    Subjective probabilities play a central role in many economic decisions and act as an immediate confound of inferences about behavior, unless controlled for. Several procedures to recover subjective probabilities have been proposed, but in order to recover the correct latent probability one must ...

  10. Subjective meaning: an introduction

    NARCIS (Netherlands)

    van Wijnbergen-Huitink, Janneke; van Wijbergen-Huitink, Janneke; Meier, Cécile

    This introductory chapter traces some of the considerations on the basis of which relativistic approaches to subjective meaning became en vogue. In doing so, the chapter provides an overview of the relevant linguistic and philosophical issues when developing a treatment of subjectivity. In addition,

  11. Subjective safety in traffic.

    NARCIS (Netherlands)

    2012-01-01

    The term ‘subjective safety in traffic’ refers to people feeling unsafe in traffic or, more generally, to anxiety regarding being unsafe in traffic for oneself and/or others. Subjective safety in traffic can lead to road users limiting their mobility and social activities, which is one of the

  12. Subjective poverty line definitions

    NARCIS (Netherlands)

    J. Flik; B.M.S. van Praag (Bernard)

    1991-01-01

    textabstractIn this paper we will deal with definitions of subjective poverty lines. To measure a poverty threshold value in terms of household income, which separates the poor from the non-poor, we take into account the opinions of all people in society. Three subjective methods will be discussed

  13. Counting only the hits? The risk of underestimating the costs of stringent climate policy: A letter

    NARCIS (Netherlands)

    Tavoni, M.; Tol, R.S.J.

    2010-01-01

    This paper warns against the risk of underestimating the costs-and the uncertainty about the costs-of achieving stringent stabilization targets. We argue that a straightforward review of integrated assessment models results produces biased estimates for the more ambitious climate objectives such as

  14. Robust adaptive control modeling of human arm movements subject to altered gravity and mechanical loads

    Science.gov (United States)

    Tryfonidis, Michail

    It has been observed that during orbital spaceflight the absence of gravitation related sensory inputs causes incongruence between the expected and the actual sensory feedback resulting from voluntary movements. This incongruence results in a reinterpretation or neglect of gravity-induced sensory input signals. Over time, new internal models develop, gradually compensating for the loss of spatial reference. The study of adaptation of goal-directed movements is the main focus of this thesis. The hypothesis is that during the adaptive learning process the neural connections behave in ways that can be described by an adaptive control method. The investigation presented in this thesis includes two different sets of experiments. A series of dart throwing experiments took place onboard the space station Mir. Experiments also took place at the Biomechanics lab at MIT, where the subjects performed a series of continuous trajectory tracking movements while a planar robotic manipulandum exerted external torques on the subjects' moving arms. The experimental hypothesis for both experiments is that during the first few trials the subjects will perform poorly trying to follow a prescribed trajectory, or trying to hit a target. A theoretical framework is developed that is a modification of the sliding control method used in robotics. The new control framework is an attempt to explain the adaptive behavior of the subjects. Numerical simulations of the proposed framework are compared with experimental results and predictions from competitive models. The proposed control methodology extends the results of the sliding mode theory to human motor control. The resulting adaptive control model of the motor system is robust to external dynamics, even those of negative gain, uses only position and velocity feedback, and achieves bounded steady-state error without explicit knowledge of the system's nonlinearities. In addition, the experimental and modeling results demonstrate that

  15. 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.

  16. Unifying Subjectivity and Objectivity

    Directory of Open Access Journals (Sweden)

    Murugesan Chandrasekaran

    2016-10-01

    Full Text Available The contribution of modern science to the progress of civilization is immeasurable. Even its tendency toward exclusive concentration on the objective world has had salutary effects of great value. Modern science has wiped away much that was merely superstitious or speculative. Its rejection of unfounded opinions and prejudices has helped the thinking mind question conventional beliefs, shed preferences and prejudices, and challenge established authority. But modern systems thinking inherited from natural science is the suppression of the subjective dimension of reality. Many complex systems are an attempt to define and represent all subjective experience in physical terms. The modern man has a bias towards objectivity. The powerful influence of sense impressions on his mind and thinking makes him ignore the subjective experience and consider only objective facts as a valid, legitimate and representation of reality. Observing objective factors that are physical is easier than observing subjective factors that are subtle. The mechanistic view of reality has led to the rejection of the role of the individual in social development as insignificant. The individuals determine the development of society. Their social power has its roots both in subjective factors and objective factors. Economy, politics, society, and culture are inseparable dimensions of a single integrated reality. Subject and object constitute an integrated whole. The mind sees them as separate and independent. Or it views one as completely subordinate to the other. Unbiased approach to the study of all human experiences may prove that subject and object are interdependent dimensions or elements of reality.

  17. RUSSIAN LAW SUBJECTS

    Directory of Open Access Journals (Sweden)

    D.N. Bakhrakh

    2006-03-01

    Full Text Available The question about the subjects of law branches is concerning the number of most important and difficult in law science. Its right decision influences on the subject of law regulation, precise definition of addressees of law norms, the volume of their rights and duties, the limits of action of norms of Main part of the branch, its principles. Scientific investigations, dedicated to law subjects system, promote the development of recommendations for the legislative and law applying activity; they are needed for scientific work organization and student training, for preparing qualified lawyers.

  18. The Data Subject

    DEFF Research Database (Denmark)

    Blume, Peter

    2015-01-01

    This article considers whether it is fortunate that data protection rules, as a starting point, apply to all physical persons as data subjects, or whether it would be better to differentiate between kinds of persons on grounds of their ability to act as a data subject. In order to protect all...... persons, it is argued that a principle of care should be part of data protection law....

  19. Ballistic Transparent Armor Testing Using A Multi-Hit Rifle Pattern

    Science.gov (United States)

    2007-12-01

    had the problem of TA vendors shipping “green” glass. Green glass is caused by a high concentration of iron which tints the glass a slight shade of...the degree of BACHELOR OF SCIENCE IN MECHANICAL ENGINEERING, The original document contains color images. 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY...green. This green glass is cheaper to process than clear white water glass because it is made with a greater number of impurities. Soldiers who have

  20. Subject Gateway Sites and Search Engine Ranking.

    Science.gov (United States)

    Thelwall, Mike

    2002-01-01

    Discusses subject gateway sites and commercial search engines for the Web and presents an explanation of Google's PageRank algorithm. The principle question addressed is the conditions under which a gateway site will increase the likelihood that a target page is found in search engines. (LRW)

  1. 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.

  2. 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].

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. An alternative mode of microRNA target recognition

    Science.gov (United States)

    Chi, Sung Wook; Hannon, Gregory J.; Darnell, Robert B.

    2012-01-01

    MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (position 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing of clusters of ~50 nucleotide RNA tags associated with Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP “orphan clusters” – Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches – we have identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (position 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥ 15% (≥ 1441 sites) of all Ago-miRNA interactions in mouse brain and are evolutionally conserved. We have termed position 6 the “pivot” nucleotide and suggest a model in which a transitional “nucleation-bulge” leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites. PMID:22343717

  9. 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.

  10. Targeted caricatures.

    Science.gov (United States)

    Pappas, Dennis G

    2009-10-01

    The original Vanity Fair was an English weekly magazine from 1868 to 1914. It offered its readers articles on fashion, current events, reviews of the theater, new books, reports on social events (and the latest scandals), and other trivia.Today, the old Vanity Fair is best known for its glorious caricature prints. Over 2,000 of these caricatures were printed, varying on at least 67 subjects. One category, doctors and scientists, presents four otolaryngologists. These four well known personalities will be presented with their satirical biographies, along with a brief historical account for each of their life after Vanity Fair.

  11. Subject (of documents)

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    such as concepts, aboutness, topic, isness and ofness are also briefly presented. The conclusion is that the most fruitful way of defining “subject” (of a document) is the documents informative or epistemological potentials, that is, the documents potentials of informing users and advance the development......This article presents and discuss the concept “subject” or subject matter (of documents) as it has been examined in library and information science (LIS) for more than 100 years. Different theoretical positions are outlined and it is found that the most important distinction is between document......-oriented views versus request-oriented views. The document-oriented view conceive subject as something inherent in documents, whereas the request-oriented view (or the policy based view) understand subject as an attribution made to documents in order to facilitate certain uses of them. Related concepts...

  12. Science of the subjective.

    Science.gov (United States)

    Jahn, R G; Dunne, B J

    2007-01-01

    Over the greater portion of its long scholarly history, the particular form of human observation, reasoning, and technical deployment we properly term "science" has relied at least as much on subjective experience and inspiration as it has on objective experiments and theories. Only over the past few centuries has subjectivity been progressively excluded from the practice of science, leaving an essentially secular analytical paradigm. Quite recently, however, a compounding constellation of newly inexplicable physical evidence, coupled with a growing scholarly interest in the nature and capability of human consciousness, are beginning to suggest that this sterilization of science may have been excessive and could ultimately limit its epistemological reach and cultural relevance. In particular, an array of demonstrable consciousness-related anomalous physical phenomena, a persistent pattern of biological and medical anomalies, systematic studies of mind/brain relationships and the mechanics of human creativity, and a burgeoning catalogue of human factors effects within contemporary information processing technologies, all display empirical correlations with subjective aspects that greatly complicate, and in many cases preclude, their comprehension on strictly objective grounds. However, any disciplined re-admission of subjective elements into rigorous scientific methodology will hinge on the precision with which they can be defined, measured, and represented, and on the resilience of established scientific techniques to their inclusion. For example, any neo-subjective science, while retaining the logical rigor, empirical/theoretical dialogue, and cultural purpose of its rigidly objective predecessor, would have the following requirements: acknowledgment of a proactive role for human consciousness; more explicit and profound use of interdisciplinary metaphors; more generous interpretations of measurability, replicability, and resonance; a reduction of ontological

  13. The Subjectivity of Participation

    DEFF Research Database (Denmark)

    Nissen, Morten

    What is a 'we' – a collective – and how can we use such communal self-knowledge to help people? This book is about collectivity, participation, and subjectivity – and about the social theories that may help us understand these matters. It also seeks to learn from the innovative practices and ideas...... practices. Through this dialogue, it develops an original trans-disciplinary critical theory and practice of collective subjectivity for which the ongoing construction and overcoming of common sense, or ideology, is central. It also points to ways of relating discourse with agency, and fertilizing insights...... from interactionism and ideology theories in a cultural-historical framework....

  14. Microenvironmental targets in sarcoma

    Directory of Open Access Journals (Sweden)

    Monika eEhnman

    2015-11-01

    Full Text Available Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has lead to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject for larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells, but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma.

  15. One, Two, Three: Polycomb Proteins Hit All Dimensions of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Stefania del Prete

    2015-07-01

    Full Text Available Polycomb group (PcG proteins contribute to the formation and maintenance of a specific repressive chromatin state that prevents the expression of genes in a particular space and time. Polycomb repressive complexes (PRCs consist of several PcG proteins with specific regulatory or catalytic properties. PRCs are recruited to thousands of target genes, and various recruitment factors, including DNA-binding proteins and non-coding RNAs, are involved in the targeting. PcG proteins contribute to a multitude of biological processes by altering chromatin features at different scales. PcG proteins mediate both biochemical modifications of histone tails and biophysical modifications (e.g., chromatin fiber compaction and three-dimensional (3D chromatin conformation. Here, we review the role of PcG proteins in nuclear architecture, describing their impact on the structure of the chromatin fiber, on chromatin interactions, and on the spatial organization of the genome in nuclei. Although little is known about the role of plant PcG proteins in nuclear organization, much is known in the animal field, and we highlight similarities and differences in the roles of PcG proteins in 3D gene regulation in plants and animals.

  16. 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

  17. Subjects taught in VR

    NARCIS (Netherlands)

    van der Sluis, Frans; van den Broek, Egon; Stam, Liesbeth M.; Abrahamse, E.L.; Luursema, J.M.

    2007-01-01

    This deliverable serves to reinstate a broad view on Virtual Reality (VR), capturing all its constituting disciplines. The core target of this report is to establish a foundation for an educational program where all disciplines subordinate to VR technology will converge. Over the past decade(s) the

  18. Paying Hypertension Research Subjects

    Science.gov (United States)

    Casarett, David; Karlawish, Jason; Asch, David A

    2002-01-01

    CONTEXT Cash payments are often used to compensate subjects who participate in research. However, ethicists have argued that these payments might constitute an undue inducement. OBJECTIVES To determine whether potential subjects agree with theoretical arguments that a payment could be an undue inducement. DESIGN/SETTING/PARTICIPANTS Survey of 350 prospective jurors. MAIN OUTCOME MEASURES Belief that a $500 payment for research participation would impair their own, and others' ability to think carefully about the risks and benefits of a clinical trial. RESULTS Two hundred sixty-one jurors (74.6%) believed that a $500 payment would impair subjects' ability to think carefully about the risks and benefits of research. Ninety-six of 120 (80%) expressed this concern about subjects with a low income ($50,000). In contrast, only 69 (19.7%) of jurors believed that a $500 payment would influence them. Jurors who believed that this payment would influence them reported lower incomes and less education. CONCLUSION Members of the general public share ethical concerns about the influence of payments for research, although they believe that these concerns are more applicable to others than to themselves.

  19. Subjects, Models, Languages, Transformations

    NARCIS (Netherlands)

    Rensink, Arend; Bézivin, J.; Heckel, R.

    2005-01-01

    Discussions about model-driven approaches tend to be hampered by terminological confusion. This is at least partially caused by a lack of formal precision in defining the basic concepts, including that of "model" and "thing being modelled" - which we call subject in this paper. We propose a minimal

  20. Subjective Duration and Psychophysics

    Science.gov (United States)

    Eisler, Hannes

    1975-01-01

    Three models are proposed to describe the strategy applied by a subject when he is confronted with two successive time intervals and is required to deal with some relation between them, for example, by telling which was the longer by adjusting the second to match the first. (Author)

  1. Barron's SAT subject test

    CERN Document Server

    Jansen, MA, Robert

    2016-01-01

    Includes one diagnostic test and three complete tests, all questions answered and explained, self-assessment guides, and subject reviews. Also features test strategies, QR codes to short instructional videos, and a detailed appendix with equations, physical constants, and a basic math review.

  2. Trypanosoma Cruzi Cyp51 Inhibitor Derived from a Mycobacterium Tuberculosis Screen Hit

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chiung-Kuang; Doyle, Patricia S.; Yermalitskaya, Liudmila V.; Mackey, Zachary B.; Ang, Kenny K.H.; McKerrow, James H.; Podust, Larissa M.; (Vanderbilt); (UCSF)

    2009-02-18

    The two front-line drugs for chronic Trypanosoma cruzi infections are limited by adverse side-effects and declining efficacy. One potential new target for Chagas disease chemotherapy is sterol 14{alpha}-demethylase (CYP51), a cytochrome P450 enzyme involved in biosynthesis of membrane sterols. In a screening effort targeting Mycobacterium tuberculosis CYP51 (CYP51{sub Mt}), we previously identified the N-[4-pyridyl]-formamide moiety as a building block capable of delivering a variety of chemotypes into the CYP51 active site. In that work, the binding modes of several second generation compounds carrying this scaffold were determined by high-resolution co-crystal structures with CYP51{sub Mt}. Subsequent assays against the CYP51 orthologue in T. cruzi, CYP51{sub Tc}, demonstrated that two of the compounds tested in the earlier effort bound tightly to this enzyme. Both were tested in vitro for inhibitory effects against T. cruzi and the related protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. One of the compounds had potent, selective anti-T. cruzi activity in infected mouse macrophages. Cure of treated host cells was confirmed by prolonged incubation in the absence of the inhibiting compound. Discrimination between T. cruzi and T. brucei CYP51 by the inhibitor was largely based on the variability (phenylalanine versus isoleucine) of a single residue at a critical position in the active site. CYP51{sub Mt}-based crystal structure analysis revealed that the functional groups of the two tightly bound compounds are likely to occupy different spaces in the CYP51 active site, suggesting the possibility of combining the beneficial features of both inhibitors in a third generation of compounds to achieve more potent and selective inhibition of CYP51{sub Tc}. Enzyme sterol 14{alpha}-demethylase (CYP51) is a well-established target for anti-fungal therapy and is a prospective target for Chagas disease therapy. We previously identified a

  3. Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented selective kappa opioid receptor agonists

    DEFF Research Database (Denmark)

    Sasmal, Pradip K; Krishna, C Vamsee; Sudheerkumar Adabala, S

    2015-01-01

    Kappa opioid receptor (KOR) is an important mediator of pain signaling and it is targeted for the treatment of various pains. Pharmacophore based mining of databases led to the identification of 2-aminobenzimidazole derivative as KOR agonists with selectivity over the other opioid receptors DOR...... and MOR. A short SAR exploration with the objective of identifying more polar and hence less brain penetrant agonists is described herewith. Modeling studies of the recently published structures of KOR, DOR and MOR are used to explain the receptor selectivity. The synthesis, biological evaluation and SAR...... of novel benzimidazole derivatives as KOR agonists are described. The in vivo proof of principle for anti-nociceptive effect with a lead compound from this series is exemplified....

  4. Trypanosoma cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit.

    Directory of Open Access Journals (Sweden)

    Chiung-Kuang Chen

    Full Text Available The two front-line drugs for chronic Trypanosoma cruzi infections are limited by adverse side-effects and declining efficacy. One potential new target for Chagas' disease chemotherapy is sterol 14alpha-demethylase (CYP51, a cytochrome P450 enzyme involved in biosynthesis of membrane sterols.In a screening effort targeting Mycobacterium tuberculosis CYP51 (CYP51(Mt, we previously identified the N-[4-pyridyl]-formamide moiety as a building block capable of delivering a variety of chemotypes into the CYP51 active site. In that work, the binding modes of several second generation compounds carrying this scaffold were determined by high-resolution co-crystal structures with CYP51(Mt. Subsequent assays against the CYP51 orthologue in T. cruzi, CYP51(Tc, demonstrated that two of the compounds tested in the earlier effort bound tightly to this enzyme. Both were tested in vitro for inhibitory effects against T. cruzi and the related protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. One of the compounds had potent, selective anti-T. cruzi activity in infected mouse macrophages. Cure of treated host cells was confirmed by prolonged incubation in the absence of the inhibiting compound. Discrimination between T. cruzi and T. brucei CYP51 by the inhibitor was largely based on the variability (phenylalanine versus isoleucine of a single residue at a critical position in the active site.CYP51(Mt-based crystal structure analysis revealed that the functional groups of the two tightly bound compounds are likely to occupy different spaces in the CYP51 active site, suggesting the possibility of combining the beneficial features of both inhibitors in a third generation of compounds to achieve more potent and selective inhibition of CYP51(Tc.

  5. Hitting an Unintended Target: Phylogeography of Bombus brasiliensis Lepeletier, 1836 and the First New Brazilian Bumblebee Species in a Century (Hymenoptera: Apidae.

    Directory of Open Access Journals (Sweden)

    José Eustáquio Santos Júnior

    Full Text Available This work tested whether or not populations of Bombus brasiliensis isolated on mountain tops of southeastern Brazil belonged to the same species as populations widespread in lowland areas in the Atlantic coast and westward along the Paraná-river valley. Phylogeographic and population genetic analyses showed that those populations were all conspecific. However, they revealed a previously unrecognized, apparently rare, and potentially endangered species in one of the most threatened biodiversity hotspots of the World, the Brazilian Atlantic Forest. This species is described here as Bombus bahiensis sp. n., and included in a revised key for the identification of the bumblebee species known to occur in Brazil. Phylogenetic analyses based on two mtDNA markers suggest this new species to be sister to B. brasiliensis, from which its workers and queens can be easily distinguished by the lack of a yellow hair-band on the first metasomal tergum. The results presented here are consistent with the hypothesis that B. bahiensis sp. n. may have originated from an ancestral population isolated in an evergreen-forest refuge (the so-called Bahia refuge during cold, dry periods of the Pleistocene. This refuge is also known as an important area of endemism for several animal taxa, including other bees. Secondary contact between B. bahiensis and B. brasiliensis may be presently prevented by a strip of semi-deciduous forest in a climate zone characterized by relatively long dry seasons. Considering the relatively limited range of this new species and the current anthropic pressure on its environment, attention should be given to its conservation status.

  6. Identifying a practice-based implementation framework for sustainable interventions for improving the evolving working environment: Hitting the Moving Target Framework.

    Science.gov (United States)

    Højberg, Helene; Rasmussen, Charlotte Diana Nørregaard; Osborne, Richard H; Jørgensen, Marie Birk

    2018-02-01

    Our aim was to identify implementation components for sustainable working environment interventions in the nursing assistant sector to generate a framework to optimize the implementation of workplace improvement initiatives. The implementation framework was informed by: 1) an industry advisory group, 2) interviews with key stakeholder, 3) concept mapping workshops, and 4) an e-mail survey. Thirty five stakeholders were interviewed and contributed in the concept mapping workshops. Eleven implementation components were derived across four domains: 1) A supportive organizational platform, 2) An engaged workplace with mutual goals, 3) The intervention is sustainably fitted to the workplace, and 4) the intervention is an attractive choice. The highest rated component was "Engaged and Active Management" (mean 4.1) and the lowest rated was "Delivered in an Attractive Form" (mean 2.8). The framework provides new insights into implementation in an evolving working environment and is aiming to assist with addressing gaps in effectiveness of workplace interventions and implementation success. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. [Subjective cognition in schizophrenia].

    Science.gov (United States)

    Potvin, S; Aubin, G; Stip, E

    2017-02-01

    Given the extent, magnitude and functional significance of the neurocognitive deficits of schizophrenia, growing attention has been paid recently to patients' self-awareness of their own deficits. Thus far, the literature has shown either that patients fail to recognize their cognitive deficits or that the association between subjective and objective cognition is weak in schizophrenia. The reasons for this lack of consistency remain unexplained but may have to do, among others, with the influence of potential confounding clinical variables and the choice of the scale used to measure self-awareness of cognitive deficits. In the current study, we sought to examine the relationships between subjective and objective cognitive performance in schizophrenia, while controlling for the influence of sociodemographic and psychiatric variables. Eighty-two patients with a schizophrenia-spectrum disorder (DSM-IV criteria) were recruited. Patients' subjective cognitive complaints were evaluated with the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), the most frequently used scale to measure self-awareness of cognitive deficits in schizophrenia. Neurocognition was evaluated with working memory, planning and visual learning tasks taken from Cambridge Neuropsychological Tests Automated Battery. The Stroop Color-Word test was also administered. Psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. The relationships between subjective and objective cognition were evaluated with multivariate hierarchic linear regression analyses, taking into consideration potential confounders such as sociodemographic and psychiatric variables. Finally, a factor analysis of the SSTICS was performed. For the SSTICS total score, the regression analysis produced a model including two predictors, namely visual learning and Stoop interference performance, explaining a moderate portion of the variance

  8. 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.

  9. "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.

  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. PMID:22347199

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. The effect of varying task difficulty on subjective workload

    Science.gov (United States)

    Yeh, Y.-Y.; Wickens, C. D.; Hart, S. G.

    1985-01-01

    The effect of different difficulty distribution patterns on subjective workload, and the presence of a primacy/recency effect in subjective ratings are examined. Eight subjects performed the perceptual central processing required for response selection and manual target acquisition for response execution. The reaction time, movement time, and the percent of correct pattern matching and arithmetic equations are analyzed. The data reveal that subjective rating is unaffected by different task difficulty and no primacy/recency effects are observed in subjective ratings. It is concluded that subjective workload reflects the experience of an ongoing integration process.

  18. 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.

  19. Interaction, transference, and subjectivity

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda

    2012-01-01

    Fieldwork is one of the important methods in educational, social, and organisational research. In fieldwork, the researcher takes residence for a shorter or longer period amongst the subjects and settings to be studied. The aim of this is to study the culture of people: how people seem to make...... sense of their lives and which moral, professional, and ethical values seem to guide their behaviour and attitudes. In fieldwork, the researcher has to balance participation and observation in her attempts at representation. Consequently, the researcher’s academic and life-historical subjectivity...... are important filters for fieldwork. In general, fieldwork can be understood as processes where field reports and field analysis are determined by how the researcher interacts with and experiences the field, the events and informants in it, and how she subsequently develops an ethnography. However, fieldwork...

  20. Writing and the 'Subject'

    DEFF Research Database (Denmark)

    Greve, Charlotte

    /reading subject) manifests itself in the material mark on the page. The study shows how this indexical reference to a ‘subject’ is manipulated and used as a mask through which a writer/painter can perform a certain ‘subject’. Through analyses of the various levels on which the ‘subject’ is represented...... in the early as well as the contemporary avant-garde, it becomes clear that the ‘subject’ is an unstable category that can be exposed to manipulation and play. Handwriting is performing as a signature (as an index), but is at the same time similar to the signature of a subject (an icon) and a verbal construct...

  1. 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.

  2. 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.

  3. How are inflation targets set?

    Czech Academy of Sciences Publication Activity Database

    Horváth, R.; Matějů, Jakub

    -, č. 426 (2010), s. 1-35 ISSN 1211-3298 Grant - others:MŠk(CZ) SVV-2010-261801 Institutional research plan: CEZ:MSM0021620846 Keywords : inflation targeting * central bank * credibility Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp426.pdf

  4. 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

  5. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmacogenetic analyses

    Directory of Open Access Journals (Sweden)

    Stott David J

    2011-10-01

    Full Text Available Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5. The top SNP (rs445925, chromosome 19 with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19 with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Radomir Janković

    2004-05-01

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

  8. TARGETED AND OFF-TARGET (BYSTANDER AND ABSCOPAL) EFFECTS OF RADIATION THERAPY: REDOX MECHANISMS AND RISK-BENEFIT ANALYSIS.

    Science.gov (United States)

    Pouget, Jean-Pierre; Georgakilas, Alexandros G; Ravanat, Jean-Luc

    2018-01-19

    Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called "target" theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death. In cancer therapy, the Poisson law and linear quadratic mathematical models have been used to describe the probability of hits per cell as a function of the radiation dose. However, in the last twenty years, many studies have shown that radiation generates "danger" signals that propagate from irradiated to non-irradiated cells, leading to bystander and other off-target effects. Like for targeted effects, redox mechanisms play a key role also in off-target effects through transmission of ROS and reactive nitrogen species (RNS), but also of cytokines, ATP and extracellular DNA. Particularly, nuclear factor kappa B is essential for triggering self-sustained production of ROS and RNS, thus making the bystander response similar to inflammation. In some therapeutic situations, this phenomenon is associated with recruitment of immune cells that are involved in distant irradiation effects (called "away-from-target" i.e. abscopal effects). Determining the contribution of targeted and off-target effects in the clinic is still challenging. This has important consequences in radiotherapy, but also possibly in diagnostic procedures and in radiation protection.

  9. Timing of saccadic eye movements during visual search for multiple targets

    Science.gov (United States)

    Wu, Chia-Chien; Kowler, Eileen

    2013-01-01

    Visual search requires sequences of saccades. Many studies have focused on spatial aspects of saccadic decisions, while relatively few (e.g., Hooge & Erkelens, 1999) consider timing. We studied saccadic timing during search for targets (thin circles containing tilted lines) located among nontargets (thicker circles). Tasks required either (a) estimating the mean tilt of the lines, or (b) looking at targets without a concurrent psychophysical task. The visual similarity of targets and nontargets affected both the probability of hitting a target and the saccade rate in both tasks. Saccadic timing also depended on immediate conditions, specifically, (a) the type of currently fixated location (dwell time was longer on targets than nontargets), (b) the type of goal (dwell time was shorter prior to saccades that hit targets), and (c) the ordinal position of the saccade in the sequence. The results show that timing decisions take into account the difficulty of finding targets, as well as the cost of delays. Timing strategies may be a compromise between the attempt to find and locate targets, or other suitable landing locations, using eccentric vision (at the cost of increased dwell times) versus a strategy of exploring less selectively at a rapid rate. PMID:24049045

  10. Subject Sensitive Invariantism: In Memoriam

    NARCIS (Netherlands)

    Blaauw, M.J.

    2008-01-01

    Subject sensitive invariantism is the view that whether a subject knows depends on what is at stake for that subject: the truth-value of a knowledge-attribution is sensitive to the subject's practical interests. I argue that subject sensitive invariantism cannot accept a very plausible principle for

  11. EURISOL Multimegawatt Target Unit - MAFF Configuration: Dosimetry and Activation Studies

    CERN Document Server

    Luis, R; Kadi, Y; Tecchio, L; Kharoua, C; Vaz, P; Ene, D; David, J C; Goncalves, I F; Rocca, R; Romanets, Y; Negoita, F

    2011-01-01

    The EURopean Isotope Separation On-Line Radioactive Ion Beam (EURISOL) project aims at building a facility to produce radioactive ion beams with intensities two to three orders of magnitude higher than those presently available. A 4-MW (1-GeV, 4-mA) proton beam hits a liquid mercury converter, generating, by spallation reactions, high neutron fluxes that induce fission in surrounding fissile targets. In this work, Monte Carlo calculations of dose rate and activation were carried out to identify the necessary shielding and access restrictions for each section of the facility, including maintenance, storage, and remote control spaces. These calculations allowed an optimization of the materials chosen for the assembly, based on the radioprotection issues, while taking into account the desired performance of the system. The results of the design studies indicate that the intended performance parameters (namely neutron fluxes, fission rates, and easy fission target manipulation) of the EURISOL multimegawatt target...

  12. A comparison of low volume 'high-intensity-training' and high volume traditional resistance training methods on muscular performance, body composition, and subjective assessments of training.

    Science.gov (United States)

    Giessing, J; Eichmann, B; Steele, J; Fisher, J

    2016-09-01

    Most studies of resistance training (RT) examine methods that do not resemble typical training practices of persons participating in RT. Ecologically valid RT programs more representative of such practices are seldom compared. This study compared two such approaches to RT. Thirty participants (males, n = 13; females, n = 17) were randomised to either a group performing low volume 'High Intensity Training' (HIT; n = 16) or high volume 'Body-building' (3ST; n = 14) RT methods 2x/week for 10 weeks. Outcomes included muscular performance, body composition, and participant's subjective assessments. Both HIT and 3ST groups improved muscular performance significantly (as indicated by 95% confidence intervals) with large effect sizes (ES; 0.97 to 1.73 and 0.88 to 1.77 respectively). HIT had significantly greater muscular performance gains for 3 of 9 tested exercises compared with 3ST (p < 0.05) and larger effect sizes for 8 of 9 exercises. Body composition did not significantly change in either group. However, effect sizes for whole body muscle mass changes were slightly more favourable in the HIT group compared with the 3ST group (0.27 and -0.34 respectively) in addition to whole body fat mass (0.03 and 0.43 respectively) and whole body fat percentage (-0.10 and -0.44 respectively). Significant muscular performance gains can be produced using either HIT or 3ST. However, muscular performance gains may be greater when using HIT. Future research should look to identify which components of ecologically valid RT programs are primarily responsible for these differences in outcome.

  13. Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target.

    Science.gov (United States)

    Frei, Priska; Pang, Lijuan; Silbermann, Marleen; Eriş, Deniz; Mühlethaler, Tobias; Schwardt, Oliver; Ernst, Beat

    2017-08-25

    Target-directed dynamic combinatorial chemistry (DCC) is an emerging technique for the efficient identification of inhibitors of pharmacologically relevant targets. In this contribution, we present an application for a bacterial target, the lectin FimH, a crucial virulence factor of uropathogenic E. coli being the main cause of urinary tract infections. A small dynamic library of acylhydrazones was formed from aldehydes and hydrazides and equilibrated at neutral pH in presence of aniline as nucleophilic catalyst. The major success factors turned out to be an accordingly adjusted ratio of scaffolds and fragments, an adequate sample preparation prior to HPLC analysis, and the data processing. Only then did the ranking of the dynamic library constituents correlate well with affinity data. Furthermore, as a support of DCC applications especially to larger libraries, a new protocol for improved hit identification was established. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Safety Analysis of Dual Purpose Metal Cask Subjected to Impulsive Loads due to Aircraft Engine Crash

    Science.gov (United States)

    Shirai, Koji; Namba, Kosuke; Saegusa, Toshiari

    In Japan, the first Interim Storage Facility of spent nuclear fuel away from reactor site is being planned to start its commercial operation around 2010, in use of dual-purpose metal cask in the northern part of Main Japan Island. Business License Examination for safety design approval has started since March, 2007. To demonstrate the more scientific and rational performance of safety regulation activities on each phase for the first license procedure, CREPEI has executed demonstration tests with full scale casks, such as drop tests onto real targets without impact limiters(1) and seismic tests subjected to strong earthquake motions(2). Moreover, it is important to develop the knowledge for the inherent security of metal casks under extreme mechanical-impact conditions, especially for increasing interest since the terrorist attacks from 11th September 2001(3)-(6). This paper presents dynamic mechanical behavior of the metal cask lid closure system caused by direct aircraft engine crash and describes calculated results (especially, leak tightness based on relative dynamic displacements between metallic seals). Firstly, the local penetration damage of the interim storage facility building by a big passenger aircraft engine crash (diameter 2.7m, length 4.3m, weight 4.4ton, impact velocity 90m/s) has been examined. The reduced velocity is calculated by the local damage formula for concrete structure with its thickness of 70cm. The load vs. time function for this reduced velocity (60m/s) is estimated by the impact analysis using Finite Element code LS-DYNA with the full scale engine model onto a hypothetically rigid target. Secondly, as the most critical scenarios for the metal cask, two impact scenarios (horizontal impact hitting the cask and vertical impact onto the lid metallic seal system) are chosen. To consider the geometry of all bolts for two lids, the gasket reaction forces and the inner pressure of the cask cavity, the detailed three dimensional FEM models are

  15. 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.

  16. Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-11-01

    Full Text Available In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

  17. Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Kang, Jie; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2016-11-29

    In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

  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. 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.

  1. 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

  2. Prospective versus predictive control in timing of hitting a falling ball.

    Science.gov (United States)

    Katsumata, Hiromu; Russell, Daniel M

    2012-02-01

    need to be continuously coupled to vision of the ball to initiate the swing accurately, but instead could use predictive control based on acceleration timing information (TTC2). However, other results provide evidence for movement modulation, a characteristic of prospective control. Strong correlations between movement initiation and duration and reduced timing variability from swing onset to arrival at the interception point, both support compensatory variability. An analysis of modulation within the swing revealed that early in the swing, the movement acceleration was strongly correlated to the required mean velocity at swing onset and that later in the swing, the movement acceleration was again strongly correlated with the current required mean velocity. Rather than a consistent movement initiated at the same time, these findings show that the swing was variable but modulated for meeting the demands of each trial. A prospective model of coupling τ (bat-ball) with τ (ball-target) was found to provide a very strong linear fit for an average of 69% of the movement duration. These findings provide evidence for predictive control based on TTC2 information in initiating the swing and prospective control based on τ in guiding the bat to intercept the ball.

  3. Praxis, subjectivity and sense

    Directory of Open Access Journals (Sweden)

    Alfredo Gómez-Muller

    2006-07-01

    Full Text Available A primordial aspect of the Sartrian critique of alienation concerns understanding the analytic ideology as the domination of materiality over the symbolic, in other words as the reification of the human, and therefore as anticulture. In the context of contemporary nihilism, the decoding of the mechanisms which consign praxis to the practico-inert requires a critique of the relations between the social sciences and philosophy, which in its turn implies a new theory of the relation between what Sartre calls the "notion" (the area of subjectivity and the "concept" (objectivity, From this perspective, the deconstruction of the established frontiers between the social sciences and philosophy, and between the conceptual and the narrative, is corelative to a redefinition of the relation between theory and practice.

  4. HITS-CLIP analysis uncovers a link between the Kaposi's sarcoma-associated herpesvirus ORF57 protein and host pre-mRNA metabolism.

    Directory of Open Access Journals (Sweden)

    Emi Sei

    2015-02-01

    Full Text Available The Kaposi's sarcoma associated herpesvirus (KSHV is an oncogenic virus that causes Kaposi's sarcoma, primary effusion lymphoma (PEL, and some forms of multicentric Castleman's disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP. As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5' ends. The position of these 5'-bound fragments correlated closely with the 5'-most exon-intron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9 and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation.

  5. 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

  6. 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

  7. 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.

  8. MEET ISOLDE - Target Production

    CERN Multimedia

    2017-01-01

    MEET ISOLDE - Target Production. Everything at ISOLDE starts with a target and the target production team realise on more then 50 years of experience to build and develop new targets for ISOLDE’s wide physics program.

  9. Targeting nominal income growth or inflation?

    DEFF Research Database (Denmark)

    Jensen, Henrik

    2002-01-01

    Within a simple New Keynesian model emphasizing forward-looking behavior of private agents, I evaluate optimal nominal income growth targeting versus optimal inflation targeting. When the economy is mainly subject to shocks that do not involve monetary policy trade-offs for society, inflation...... targeting is preferable. Otherwise, nominal income growth targeting may be superior because it induces inertial policy making, which improves the inflation-output-gap trade-off. Somewhat paradoxically, inflation targeting may be relatively less favorable the more society dislikes inflation, and the more...

  10. Subjects' experiences of a nutrition education programme: a ...

    African Journals Online (AJOL)

    Subjects and outcome measures: The study subjects were adults with type 2 diabetes mellitus (n = 41, aged 40–70 years) participating in a nutrition education intervention (one-year randomised controlled trial). The intervention was based on the assessed nutrition education needs of the target group, and included the ...

  11. International Energy: Subject Thesaurus

    Energy Technology Data Exchange (ETDEWEB)

    Raridon, M.H. (ed.)

    1990-01-01

    The International Energy Subject Thesaurus contains the standard vocabulary to indexing terms (descriptors) developed and structured to build and maintain energy information databases. Involved in this cooperative task are (1) the technical staff of the USDOE Office of Scientific and Technical Information (OSTI) in cooperation with the member countries of the Energy Technology Data Exchange (ETDE) and (2) the International Nuclear Information System (INIS) staff representing the more than ninety countries and organizations recording and indexing information for the international nuclear information community. ETDE member countries are also members of the International Nuclear Information System (INIS). Nuclear information indexed and recorded for INIS by these ETDE member countries is also included in the ETDE Energy Data Base, and indexing terminology is therefore cooperatively standardized for use in both information systems. This structured vocabulary reflects the scope of international energy research, development, and technological programs and encompasses terminology derived not only from the basic sciences but also from the areas of energy resources, conservation, safety, environmental impact, and regulation.

  12. Naming the Ethological Subject.

    Science.gov (United States)

    Benson, Etienne S

    2016-03-01

    Argument In recent decades, through the work of Jane Goodall and other ethologists, the practice of giving personal names to nonhuman animals who are the subjects of scientific research has become associated with claims about animal personhood and scientific objectivity. While critics argue that such naming practices predispose the researcher toward anthropomorphism, supporters suggest that it sensitizes the researcher to individual differences and social relations. Both critics and supporters agree that naming tends to be associated with the recognition of individual animal rights. The history of the naming of research animals since the late nineteenth century shows, however, that the practice has served a variety of purposes, most of which have raised few ethical or epistemological concerns. Names have been used to identify research animals who play dual roles as pets, workers, or patients, to enhance their market value, and to facilitate their identification in the field. The multifaceted history of naming suggests both that the use of personal names by Goodall and others is less of a radical break with previous practices than it might first appear to be and that the use of personal names to recognize the individuality, sentience, or rights of nonhuman animals faces inherent limits and contradictions.

  13. A Subjective Rational Choice

    Science.gov (United States)

    Vinogradov, G. P.

    2017-01-01

    The problem of constructing a choice model of an agent with endogenous purposes of evolution is under debate. It is demonstrated that its solution requires the development of well-known methods of decision-making while taking into account the relation of action mode motivation to an agent’s ambition to implement subjectively understood interests and the environment state. The latter is submitted for consideration as a purposeful state situation model that exists only in the mind of an agent. It is the situation that is a basis for getting an insight into the agent’s ideas on the possible selected action mode results. The agent’s ambition to build his confidence in the feasibility of the action mode and the possibility of achieving the desired state requires him to use the procedures of forming an idea model based on the measured values of environment state. This leads to the gaming approach for the choice problem and its solution can be obtained on a set of trade-off alternatives.

  14. Laboratory instruction and subjectivity

    Directory of Open Access Journals (Sweden)

    Elisabeth Barolli

    1998-09-01

    Full Text Available The specific aspects which determined the way some groups of students conducted their work in a university laboratory, made us understand the articulation of these groups´s dynamics, from elements that were beyond the reach of cognition. In more specific terms the conduction and the maintenance of the groups student´s dynamics were explicited based on a intergame between the non conscious strategies, shared anonymously, and the efforts of the individuals in working based on their most objective task. The results and issues we have reached so far, using a reference the work developed by W.R.Bion, with therapeutical groups, gave us the possibility for understanding the dynamics of the student´s experimental work through a new approach that approximates the fields of cognition and subjectivity. This approximation led us to a deeper reflection about the issues which may be involved in the teaching process, particularly in situations which the teacher deals with the class, organised in groups.

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  19. Macromolecular target prediction by self-organizing feature maps.

    Science.gov (United States)

    Schneider, Gisbert; Schneider, Petra

    2017-03-01

    Rational drug discovery would greatly benefit from a more nuanced appreciation of the activity of pharmacologically active compounds against a diverse panel of macromolecular targets. Already, computational target-prediction models assist medicinal chemists in library screening, de novo molecular design, optimization of active chemical agents, drug re-purposing, in the spotting of potential undesired off-target activities, and in the 'de-orphaning' of phenotypic screening hits. The self-organizing map (SOM) algorithm has been employed successfully for these and other purposes. Areas covered: The authors recapitulate contemporary artificial neural network methods for macromolecular target prediction, and present the basic SOM algorithm at a conceptual level. Specifically, they highlight consensus target-scoring by the employment of multiple SOMs, and discuss the opportunities and limitations of this technique. Expert opinion: Self-organizing feature maps represent a straightforward approach to ligand clustering and classification. Some of the appeal lies in their conceptual simplicity and broad applicability domain. Despite known algorithmic shortcomings, this computational target prediction concept has been proven to work in prospective settings with high success rates. It represents a prototypic technique for future advances in the in silico identification of the modes of action and macromolecular targets of bioactive molecules.

  20. Discovery of Tamoxifen and N-Desmethyl Tamoxifen Protein Targets in MCF-7 Cells Using Large-Scale Protein Folding and Stability Measurements.

    Science.gov (United States)

    Ogburn, Ryenne N; Jin, Lorrain; Meng, He; Fitzgerald, Michael C

    2017-11-03

    The proteins in an MCF-7 cell line were probed for tamoxifen (TAM) and n-desmethyl tamoxifen (NDT) induced stability changes using the Stability of Proteins from Rates of Oxidation (SPROX) technique in combination with two different quantitative proteomics strategies, including one based on SILAC and one based on isobaric mass tags. Over 1000 proteins were assayed for TAM- and NDT-induced protein stability changes, and a total of 163 and 200 protein hits were identified in the TAM and NDT studies, respectively. A subset of 27 high-confidence protein hits were reproducibly identified with both proteomics strategies and/or with multiple peptide probes. One-third of the high-confidence hits have previously established experimental links to the estrogen receptor, and nearly all of the high-confidence hits have established links to breast cancer. One high-confidence protein hit that has known estrogen receptor binding properties, Y-box binding protein 1 (YBX1), was further validated as a direct binding target of TAM using both the SPROX and pulse proteolysis techniques. Proteins with TAM- and/or NDT-induced expression level changes were also identified in the SILAC-SPROX experiments. These proteins with expression level changes included only a small fraction of those with TAM- and/or NDT-induced stability changes.

  1. 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.

  2. Bayesian models for screening and TB Mobile for target inference with Mycobacterium tuberculosis.

    Science.gov (United States)

    Ekins, Sean; Casey, Allen C; Roberts, David; Parish, Tanya; Bunin, Barry A

    2014-03-01

    The search for compounds active against Mycobacterium tuberculosis is reliant upon high-throughput screening (HTS) in whole cells. We have used Bayesian machine learning models which can predict anti-tubercular activity to filter an internal library of over 150,000 compounds prior to in vitro testing. We used this to select and test 48 compounds in vitro; 11 were active with MIC values ranging from 0.4 μM to 10.2 μM, giving a high hit rate of 22.9%. Among the hits, we identified several compounds belonging to the same series including five quinolones (including ciprofloxacin), three molecules with long aliphatic linkers and three singletons. This approach represents a rapid method to prioritize compounds for testing that can be used alongside medicinal chemistry insight and other filters to identify active molecules. Such models can significantly increase the hit rate of HTS, above the usual 1% or lower rates seen. In addition, the potential targets for the 11 molecules were predicted using TB Mobile and clustering alongside a set of over 740 molecules with known M. tuberculosis target annotations. These predictions may serve as a mechanism for prioritizing compounds for further optimization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Towards a definition of SUBJECT in binding domains and subject ...

    African Journals Online (AJOL)

    Towards a definition of SUBJECT in binding domains and subject-oriented anaphors 27 and it holds little explanatory value. At best, EPP ensures that the highest argument will move to subject position. The final property I will discuss here is the fact that, in some languages (e.g. Icelandic and. Dutch), there is a subset of ...

  4. SUBJECT AND AUTHOR INDEXS

    Directory of Open Access Journals (Sweden)

    IJBE Volume 1

    2015-09-01

    Full Text Available SUBJECT INDEX IJBE VOLUME 1EPA, 1Agrotourism, 148AHP, 148balance scorecard, 63batik tulis Rolla Junior, 23Broiler, 90business model canvas, 137business performance,32capital structure, 81cashew industry,158CHAID,106CLI,42coal transportation service,63company’s characteristics, 81competitive advantage, 12competitive strategy, 127consumer satisfaction, 51CSI, 42customer loyalty, 42customer satisfaction,42decision of visitors, 72development strategy, 23development,158entrepreneurship, 32Feasibility studies, 90FEM, 81gap analysis, 1Indonesia Stock Exchange, 177Indosat, 137investor,177Kawah Putih, 72kedai sop durian lodaya (KSDL,51klassen typology, 96leading sector, 96less cash society, 137liquidity ratio, 165location quotient, 96logistic regression, 115market, 177marketing development strategy, 148Marketing mix, 72mobile payment, 137modern and Traditional cage, 90multiple regression analyse,165multiple regression, 177net working capital, 165organic tofu product, 115Padang, 106paired comparison, 63partnership, 1, 32Pecking Order Theory, 81PLS, 81Portfolio, 96power, 32product quality, 51profitability ratio, 165Prol Tape Primadona, 127purchase decision, 115purchase intention, 51purchasing interest,115QSPM, 23, 127refilled drinking water, 106seed,1segmentation, 106SEM, 42, 51service quality, 51SMEs, 96specialty coffee, 12stock,177strategic diagnosis,137strategy, 158Sukorambi Botanic Garden, 148SWOT, 23, 127, 148, 158SWOT-AHP, 12tourists,72UD. Primadona, 127value chain, 12VRIO,12 AUTHOR INDEX IJBE VOLUME 1Adiningsih, Kartika Puspitasari,42Aknesia, Vharessa,12Amalia, Firda Rachma,90Andati, Trias, 177Anggraeni, Lukytawati,23Asriani,158Daryanto, Arief,12, 90Djamaludin, MD., 42Djohar, Setiadi,96Fachrodji, Achmad,72Fahmi, Idqan,1, 63, 127Fasyni, Awisal,106Hubeis, Musa,148Iskandar, Dodi,51Juanda, Bambang, 165Kirbrandoko, 12, 106, 115Lumbantoruan, Dewi Margareth,96Maulana, TB Nur Ahmad,81Muksin, 148Mukti Soleh, Cecep,63Najib, Mukhamad,106Noor, Tajudin,81

  5. SIMULATED PERFORMANCE OF THE PRODUCTION TARGET FOR THE MUON G-2 EXPERIMENT

    Energy Technology Data Exchange (ETDEWEB)

    Stratakis, D. [Fermilab; Convery, M. [Fermilab; Morgan, J. P. [Fermilab; Still, D. [Fermilab; Syphers, M. J. [Northern Illinois U.; Tishchenko, V. [Brookhaven Natl. Lab.

    2017-05-23

    The Muon g-2 Experiment plans to use the Fermilab Re-cycler Ring for forming the proton bunches that hit its pro-duction target. The proposed scheme uses one RF system, 80 kV of 2.5 MHz RF. In order to avoid bunch rotations in a mismatched bucket, the 2.5 MHz is ramped adiabatically from 3 to 80 kV in 90 ms. In this study, the interaction of the primary proton beam with the production target for the Muon g-2 Experiment is numerically examined.

  6. Peptide-targeted polymer cancerostatics

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Eliška; Pola, Robert

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S153-S164 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : HPMA copolymers * tumor targeting * peptides Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S153.pdf

  7. Vergence facility with stereoscopic and nonstereoscopic targets.

    Science.gov (United States)

    Momeni-Moghaddam, Hamed; Goss, David A; Dehvari, Abubakr

    2014-05-01

    To compare vergence facility with nonstereo and stereo targets in binocular symptomatic and asymptomatic subjects. Sixty-six students were divided into symptomatic and asymptomatic groups according to the Convergence Insufficiency Symptom Survey Questionnaire score. Vergence facility was tested at 40 cm by flipper prism 3Δ BI/12Δ BO (BI, base-in; BO, base-out). The targets used were a nonstereo target (a vertical column of small letter "E" of ~20/30 size), a stereo-local target (fifth set of circles of the Titmus test with stereoacuity of 100 arcsec), and a stereo-global target (page 6 of the TNO test with stereoacuity of 120 arcsec). Repeated-measures analysis of variance showed differences in the mean vergence facility with different targets in all subjects and separately in two symptom groups (p 0.05) but significant for the comparison of stereo-global targets with the other two targets. The receiver operating characteristic curve analysis showed the cutoff points 10.5, 10.5, and 9.75 cycles per minute with nonstereo, stereo-local, and stereo-global targets, respectively. The sensitivity of the three targets used was the same (97%). Specificity was 0.93 or higher with all three targets, with the highest specificity obtained with the stereo-global target (100%). The highest vergence facility was obtained with a nonstereo target and the lowest was obtained with a stereo-global target. High sensitivity with all three targets means that there are few false-negative results with them, and the high specificity is indicative of low false-positive results. Hence, the vergence facility predictive value would be high in diagnosing binocular symptomatic patients using a 3Δ BI/12Δ BO prism flipper at near and a response cutoff of about 10 cycles per minute or less.

  8. 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...

  9. 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...

  10. 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).

  11. 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?

  12. 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

  13. 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...

  14. 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…

  15. 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

  16. 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.

  17. SUBJECT AND AUTHOR INDEXS

    Directory of Open Access Journals (Sweden)

    IJBE Volume 2

    2016-09-01

    Full Text Available SUBJECT INDEX IJBE VOLUME 2access credit, 93acquisition, 177AHP, 61, 82, 165arena simulation,43BMC, 69Bojonegoro, 69brand choice, 208brand image, 208brand positioning, 208bullwhip effect, 43burger buns, 1business synergy and financial reports, 177capital structure, 130cluster, 151coal reserves, 130coffee plantation, 93competitiveness, 82consumer behaviour, 33consumer complaint behavior, 101cooking spices, 1crackers, 1cross sectional analytical, 139crosstab, 101CSI, 12direct selling, 122discriminant analysis, 33economic value added, 130, 187employee motivation, 112employee performance, 112employees, 139EOQ, 23farmer decisions, 93farmer group, 52financial performance evaluation, 187financial performance, 52, 177financial ratio, 187financial report, 187fiva food, 23food crops, 151horticulture, 151imports, 151improved capital structure, 177IPA, 12leading sector, 151life insurance, 165LotteMart, 43main product, 61marketing mix, 33, 165matrix SWOT, 69MPE, 61multiple linear regression, 122muslim clothing, 197Ogun, 139Pangasius fillet, 82Pati, 93pearson correlation, 101perceived value, 208performance suppy chain, 23PLS, 208POQ, 23portfolio analyzing, 1product, 101PT SKP, 122pulp and papers, 187purchase decision, 165purchase intention, 33remuneration, 112re-purchasing decisions, 197sales performance, 122sawmill, 52SCOR, 23sekolah peternakan rakyat, 69SEM, 112SERVQUAL, 12Sido Makmur farmer groups, 93SI-PUHH Online, 12small and medium industries (IKM, 61socio-demographic, 139sport drink, 208stress, 139supply chain, 43SWOT, 82the mix marketing, 197Tobin’s Q, 130trade partnership, 52uleg chili sauce, 1 AUTHOR INDEX IJBE VOLUME 2Achsani, Noer Azam, 177Andati, Trias, 52, 177Andihka, Galih, 208Arkeman, Yandra, 43Baga, Lukman M, 69Cahyanugroho, Aldi, 112Daryanto, Arief, 12David, Ajibade, 139Djoni, 122Fahmi, Idqan, 1Fattah, Muhammad Unggul Abdul, 61Hakim, Dedi Budiman, 187Harianto, 93Hartoyo, 101Homisah, 1Hubeis, Musa, 112Hutagaol, M. Parulian, 93Jaya, Stevana

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Pressure and stress waves in a spallation neutron source mercury target generated by high-power proton pulses

    CERN Document Server

    Futakawa, M; Conrad, H; Stechemesser, H

    2000-01-01

    The international ASTE collaboration has performed a first series of measurements on a spallation neutron source target at the Alternating Gradient Synchrotron (AGS) in Brookhaven. The dynamic response of a liquid mercury target hit by high-power proton pulses of about 40 ns duration has been measured by a laser Doppler technique and compared with finite elements calculations using the ABAQUS code. It is shown that the calculation can describe the experimental results for at least the time interval up to 100 mu s after the pulse injection. Furthermore, it has been observed that piezoelectric pressure transducers cannot be applied in the high gamma-radiation field of a spallation target.

  8. 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.

  9. 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.

  10. 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.

  11. Network-assisted target identification for haploinsufficiency and homozygous profiling screens

    Science.gov (United States)

    Wang, Sheng

    2017-01-01

    Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens. With the drug-induced phenotypic fitness defect of the deletion of a gene, GIT also incorporates the fitness defects of the gene’s neighbors in the genetic interaction network. On three genome-scale yeast chemical genomic screens, GIT substantially outperforms previous scoring methods on target identification on HIP and HOP assays, respectively. Finally, we showed that by combining HIP and HOP assays, GIT further boosts target identification and reveals potential drug’s mechanism of action. PMID:28574983

  12. 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.

  13. 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.

  14. 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.

  15. Brown adipose tissue in morbidly obese subjects.

    Directory of Open Access Journals (Sweden)

    Guy H E J Vijgen

    Full Text Available BACKGROUND: Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI and body fat percentage (BF%, suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. METHODS AND FINDINGS: After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT. Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39 from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001, respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001 and BF% (r = 0.75; P<0.001. Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26 mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001, and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001, indicating a role for BAT in CIT in humans. CONCLUSIONS: This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid obesity.

  16. Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer

    Directory of Open Access Journals (Sweden)

    Yousuf Z

    2017-06-01

    Full Text Available Zeeshan Yousuf,1 Kanzal Iman,1 Nauman Iftikhar,2 Muhammad Usman Mirza3,4 1Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, 2National Institute for Genomics and Advanced Biotechnology, National Agricultural Research Centre, Islamabad, 3Centre for Research in Molecular Medicine, The University of Lahore, Lahore, Pakistan; 4Medicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium Abstract: Breast cancer is characterized by an uncontrolled growth of cells in breast tissue. Genes that foster cell growth in breast cells are overexpressed, giving rise to breast tumors. The identification of effective inhibitors represents a rational chemopreventive strategy. The current in silico study provides a pharmacoinformatic approach for the identification of active compounds against a co-chaperone HSP90 and the human epidermal growth factor receptors EGFR and HER2/neu receptor. The elevated levels of expression of these target proteins have been documented in breast cancer. The utilization of drug-likeness filters helped to evaluate the pharmacological activity of potential lead compounds. Those fulfilling this criterion were subjected to energy minimization for 1000 steepest descent steps at a root means square gradient of 0.02 with an Amber ff12SB force field. Based on molecular docking results and binding interaction analysis, this study represents five chemical compounds (S-258282355, S-258012947, S-259417539, S-258002927, and S-259411474 that indicate high binding energies that range between −8.7 to −10.3 kcal/mol. With high cytochrome P inhibitory promiscuity activity, these multi-targeted potential hits portray not only good physiochemical interactions but also an excellent profile of absorption, distribution, metabolism, excretion, and toxicity, which hypothesizes that these compounds can be developed as anticancer

  17. Impact forces cannot explain the one-target advantage in rapid aimed hand movements

    NARCIS (Netherlands)

    Biegstraaten, Marianne; Smeets, Jeroen B J; Brenner, Eli

    A pointing movement is executed faster when a subject is allowed to stop at the first target than when the subject has to proceed to a second target ("one-target advantage"). Our hypothesis was that this is because the impact at the target helps to stop the finger when the finger does not have to

  18. Human subjects research handbook: Protecting human research subjects. Second edition

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  19. Subjective Straight Ahead Orientation in Microgravity

    Science.gov (United States)

    Clement, G.; Reschke, M. F.; Wood, S. J.

    2015-01-01

    This joint ESA NASA study will address adaptive changes in spatial orientation related to the subjective straight ahead and the use of a vibrotactile sensory aid to reduce perceptual errors. The study will be conducted before and after long-duration expeditions to the International Space Station (ISS) to examine how spatial processing of target location is altered following exposure to microgravity. This study addresses the sensorimotor research gap to "determine the changes in sensorimotor function over the course of a mission and during recovery after landing."

  20. Molecular Connectivity Predefines Polypharmacology: Aliphatic Rings, Chirality, and sp3 Centers Enhance Target Selectivity

    Directory of Open Access Journals (Sweden)

    Stefania Monteleone

    2017-08-01

    Full Text Available Dark chemical matter compounds are small molecules that have been recently identified as highly potent and selective hits. For this reason, they constitute a promising class of possible candidates in the process of drug discovery and raise the interest of the scientific community. To this purpose, Wassermann et al. (2015 have described the application of 2D descriptors to characterize dark chemical matter. However, their definition was based on the number of reported positive assays rather than the number of known targets. As there might be multiple assays for one single target, the number of assays does not fully describe target selectivity. Here, we propose an alternative classification of active molecules that is based on the number of known targets. We cluster molecules in four classes: black, gray, and white compounds are active on one, two to four, and more than four targets respectively, whilst inactive compounds are found to be inactive in the considered assays. In this study, black and inactive compounds are found to have not only higher solubility, but also a higher number of chiral centers, sp3 carbon atoms and aliphatic rings. On the contrary, white compounds contain a higher number of double bonds and fused aromatic rings. Therefore, the design of a screening compound library should consider these molecular properties in order to achieve target selectivity or polypharmacology. Furthermore, analysis of four main target classes (GPCRs, kinases, proteases, and ion channels shows that GPCR ligands are more selective than the other classes, as the number of black compounds is higher in this target superfamily. On the other side, ligands that hit kinases, proteases, and ion channels bind to GPCRs more likely than to other target classes. Consequently, depending on the target protein family, appropriate screening libraries can be designed in order to minimize the likelihood of unwanted side effects early in the drug discovery process