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Sample records for oral direct selective

  1. Direct oral anticoagulants and venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Massimo Franchini

    2016-09-01

    Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

  2. Optimal selection for direct mail

    NARCIS (Netherlands)

    Bult, [No Value; Wansbeek, T

    1995-01-01

    Direct marketing (mail) is a growing area of marketing practice, yet the academic journals contain very little research on this topic. The most important issue for direct marketers is how to sample targets from a population for a direct mail campaign. Although some selection methods are described in

  3. Optimal selection for direct mail

    NARCIS (Netherlands)

    Bult, [No Value; Wansbeek, T

    1995-01-01

    Direct marketing (mail) is a growing area of marketing practice, yet the academic journals contain very little research on this topic. The most important issue for direct marketers is how to sample targets from a population for a direct mail campaign. Although some selection methods are described in

  4. Clinical considerations on the posology of direct oral anticoagulants.

    Science.gov (United States)

    Sáez-Peñataro, J; Avendaño-Solá, C; González-Juanatey, J R

    2016-10-01

    The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  5. [Antidotes to novel direct oral anticoagulants].

    Science.gov (United States)

    Khorev, N G; Momot, A P; Kon'kova, V O

    During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation). The review contains the data on the existing therapeutic regimens of treating haemorrhage on the background of taking these coagulants. This is followed by analysing the present-day results of clinical trials aimed at working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors. Administration of these agents makes it possible to reverse coagulation and minimize the aftermaths of haemorrhage in patients taking these drugs, in emergency situations.

  6. [Oral medicine in Israel: Current status and future directions].

    Science.gov (United States)

    Aframian, D J; Vered, M

    2016-04-01

    The oral cavity-body relationships are bi-directional: oral diseases affect the welfare and health of the individual, while diseases and conditions of organs and tissues in the human body affect oral health. The global policy of the World Health Organization is to improve oral health in the 21st century as an integral part of promoting our general health. During the recent years the knowledge of the dental profession has grown exponentially and widened its fields of interest and this has led to impressive advances at both clinical and research levels. Oral medicine, which is a recognized, licensed specialty in Israel, is a definite example that reflects this process. In the last decade residency programs in oral medicine are in the process of constant increased demand. The authors discuss this trend and comment on the need to maintain excellence in this specialty.

  7. Unplanned pregnancy on a direct oral anticoagulant (Rivaroxaban): A warning.

    Science.gov (United States)

    Myers, B; Neal, R; Myers, O; Ruparelia, M

    2016-03-01

    Direct oral anticoagulants (DOACs or NOACs -non-vitamin K oral anticoagulants), as the name suggests, are oral anticoagulants with a direct inhibitory action either against factor X or factor II (thrombin). Pregnant women were excluded from participating in all the large trials of the DOACs and they are considered contra-indicated in pregnancy and breast feeding. We present a case of inadvertent exposure to rivaroxaban in a woman who presented at 25 weeks' gestation. The management of her pregnancy and delivery is described, and the previous published case reports are reviewed with a discussion about the use of DOACs in woman of childbearing age.

  8. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.

    2013-09-12

    Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

  9. Suboptimal Use of Oral Anticoagulants in Atrial Fibrillation: Has the Introduction of Direct Oral Anticoagulants Improved Prescribing Practices?

    Science.gov (United States)

    Alamneh, Endalkachew A; Chalmers, Leanne; Bereznicki, Luke R

    2016-06-01

    Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation. In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic. Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice. Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs.

  10. In vitro Increased Respiratory Activity of Selected Oral Bacteria May Explain Competitive and Collaborative Interactions in the Oral Microbiome

    Directory of Open Access Journals (Sweden)

    Emma Hernandez-Sanabria

    2017-06-01

    Full Text Available Understanding the driving forces behind the shifts in the ecological balance of the oral microbiota will become essential for the future management and treatment of periodontitis. As the use of competitive approaches for modulating bacterial outgrowth is unexplored in the oral ecosystem, our study aimed to investigate both the associations among groups of functional compounds and the impact of individual substrates on selected members of the oral microbiome. We employed the Phenotype Microarray high-throughput technology to analyse the microbial cellular phenotypes of 15 oral bacteria. Multivariate statistical analysis was used to detect respiratory activity triggers and to assess similar metabolic activities. Carbon and nitrogen were relevant for the respiration of health-associated bacteria, explaining competitive interactions when grown in biofilms. Carbon, nitrogen, and peptides tended to decrease the respiratory activity of all pathobionts, but not significantly. None of the evaluated compounds significantly increased activity of pathobionts at both 24 and 48 h. Additionally, metabolite requirements of pathobionts were dissimilar, suggesting that collective modulation of their respiratory activity may be challenging. Flow cytometry indicated that the metabolic activity detected in the Biolog plates may not be a direct result of the number of bacterial cells. In addition, damage to the cell membrane may not influence overall respiratory activity. Our methodology confirmed previously reported competitive and collaborative interactions among bacterial groups, which could be used either as marker of health status or as targets for modulation of the oral environment.

  11. In vitro Increased Respiratory Activity of Selected Oral Bacteria May Explain Competitive and Collaborative Interactions in the Oral Microbiome.

    Science.gov (United States)

    Hernandez-Sanabria, Emma; Slomka, Vera; Herrero, Esteban R; Kerckhof, Frederiek-Maarten; Zaidel, Lynette; Teughels, Wim; Boon, Nico

    2017-01-01

    Understanding the driving forces behind the shifts in the ecological balance of the oral microbiota will become essential for the future management and treatment of periodontitis. As the use of competitive approaches for modulating bacterial outgrowth is unexplored in the oral ecosystem, our study aimed to investigate both the associations among groups of functional compounds and the impact of individual substrates on selected members of the oral microbiome. We employed the Phenotype Microarray high-throughput technology to analyse the microbial cellular phenotypes of 15 oral bacteria. Multivariate statistical analysis was used to detect respiratory activity triggers and to assess similar metabolic activities. Carbon and nitrogen were relevant for the respiration of health-associated bacteria, explaining competitive interactions when grown in biofilms. Carbon, nitrogen, and peptides tended to decrease the respiratory activity of all pathobionts, but not significantly. None of the evaluated compounds significantly increased activity of pathobionts at both 24 and 48 h. Additionally, metabolite requirements of pathobionts were dissimilar, suggesting that collective modulation of their respiratory activity may be challenging. Flow cytometry indicated that the metabolic activity detected in the Biolog plates may not be a direct result of the number of bacterial cells. In addition, damage to the cell membrane may not influence overall respiratory activity. Our methodology confirmed previously reported competitive and collaborative interactions among bacterial groups, which could be used either as marker of health status or as targets for modulation of the oral environment.

  12. Oral Health Disparities as Determined by Selected Healthy People 2020 Oral Health Objectives for the United States, ...

    Science.gov (United States)

    ... Order from the National Technical Information Service NCHS Oral Health Disparities as Determined by Selected Healthy People 2020 Oral Health Objectives for the United States, 2009–2010 Recommend ...

  13. New Direct Oral Anticoagulants (DOAC and Their Use Today

    Directory of Open Access Journals (Sweden)

    Heike Schwarb

    2016-03-01

    Full Text Available The ideal anticoagulant is oral, has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects and minimal interactions with other drugs or food. With the development of the novel direct oral anticoagulants (DOAC, we now have an alternative to the traditional vitamin K antagonists (VKA for the prevention and treatment of thrombosis. DOACs have limited monitoring requirements and very predictable pharmacokinetic profiles. They were shown to be non-inferior or superior to VKA in the prophylaxis or treatment of thromboembolic events. Particularly in terms of safety they were associated with less major bleeding, including intracranial bleeding, thus providing a superior benefit for the prevention of stroke in patients with atrial fibrillation. Despite these advantages, there are remaining limitations with DOACs: their dependence on renal and hepatic function for clearance and the lack of an approved reversal agent, whereas such antidotes are successively being made available. DOACs do not need regular monitoring to assess the treatment effect but, on the other hand, they interact with other drugs and interfere with functional coagulation assays. From a practical point of view, the properties of oral administration, simple dosing without monitoring, a short half-life allowing for the possibility of uncomplicated switching or bridging, and proven safety overwhelm the disadvantages, making them an attractive option for short- or long-term anticoagulation.

  14. Interface Pattern Selection in Directional Solidification

    Science.gov (United States)

    Trivedi, Rohit; Tewari, Surendra N.

    2001-01-01

    The central focus of this research is to establish key scientific concepts that govern the selection of cellular and dendritic patterns during the directional solidification of alloys. Ground-based studies have established that the conditions under which cellular and dendritic microstructures form are precisely where convection effects are dominant in bulk samples. Thus, experimental data can not be obtained terrestrially under pure diffusive regime. Furthermore, reliable theoretical models are not yet possible which can quantitatively incorporate fluid flow in the pattern selection criterion. Consequently, microgravity experiments on cellular and dendritic growth are designed to obtain benchmark data under diffusive growth conditions that can be quantitatively analyzed and compared with the rigorous theoretical model to establish the fundamental principles that govern the selection of specific microstructure and its length scales. In the cellular structure, different cells in an array are strongly coupled so that the cellular pattern evolution is controlled by complex interactions between thermal diffusion, solute diffusion and interface effects. These interactions give infinity of solutions, and the system selects only a narrow band of solutions. The aim of this investigation is to obtain benchmark data and develop a rigorous theoretical model that will allow us to quantitatively establish the physics of this selection process.

  15. Critical review of oral drug treatments for diabetic neuropathic pain-clinical outcomes based on efficacy and safety data from placebo-controlled and direct comparative studies.

    NARCIS (Netherlands)

    Adriaensen, H.F.M; Plaghki, L.; Mathieu, C.; Joffroy, A.; Vissers, K.C.P.

    2005-01-01

    The present review aims to evaluate the efficacy and safety of a selection of oral treatments for the management of painful diabetic neuropathy. A literature review was conducted retrieving placebo-controlled and direct comparative studies with a selection of oral treatments for painful diabetic neu

  16. Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial.

    Science.gov (United States)

    Alexander, John H; Becker, Richard C; Bhatt, Deepak L; Cools, Frank; Crea, Filippo; Dellborg, Mikael; Fox, Keith A A; Goodman, Shaun G; Harrington, Robert A; Huber, Kurt; Husted, Steen; Lewis, Basil S; Lopez-Sendon, Jose; Mohan, Puneet; Montalescot, Gilles; Ruda, Mikhail; Ruzyllo, Witold; Verheugt, Freek; Wallentin, Lars

    2009-06-09

    After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding. Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone. We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome

  17. Exploring Mechanisms of Selective Directed Forgetting

    Science.gov (United States)

    Aguirre, Carmen; Gómez-Ariza, Carlos J.; Andrés, Pilar; Mazzoni, Giuliana; Bajo, Ma T.

    2017-01-01

    While some studies have shown that providing a cue to selectively forget one subset of previously learned facts may cause specific forgetting of this information, little is known about the mechanisms underlying this memory phenomenon. In three experiments, we aimed to better understand the nature of the selective directed forgetting (SDF) effect. Participants studied a List 1 consisting of 18 sentences regarding two (or three) different characters and a List 2 consisting of sentences regarding an additional character. In Experiment 1, we explored the role of rehearsal as the mechanism producing SDF by examining the effect of articulatory suppression after List 1 and during List 2 presentation. In Experiments 2 and 3, we explored the role of attentional control mechanisms by introducing a concurrent updating task after List 1 and during List 2 (Experiment 2) and by manipulating the number of characters to be selectively forgotten (1 out of 3 vs. 2 out of 3). Results from the three experiments suggest that neither rehearsal nor context change seem to be the mechanisms underlying SDF, while the pattern of results is consistent with an inhibitory account. In addition, whatever the responsible mechanism is, SDF seems to rely on the available attentional resources and the demands of the task. Our results join other findings to show that SDF is a robust phenomenon and suggest boundary conditions for the effect to be observed. PMID:28316584

  18. Bacteriostatic effect of simvastatin on selected oral streptococci in vitro

    Directory of Open Access Journals (Sweden)

    Eugene J Whitaker

    2017-01-01

    Full Text Available Context and Objective: Simvastatin is a widely used cholesterol-lowering drug, which has been found to have a number of pleiotropic effects. The aim of this study was to evaluate the antimicrobial effectiveness of simvastatin against selected oral streptococci as determined by the minimum inhibitory concentration (MIC. Methods: Streptococcus mutans, Streptococcus sanguis, Streptococcus anginosus, and Streptococcus salivarius were the test microorganisms. The serial dilution method was used to determine the MIC of simvastatin against these organisms. The MIC was defined as the lowest concentration of simvastatin that completely inhibited growth of the test organisms. Results: The data indicate that simvastatin inhibits the growth of the test organisms, with MIC's ranging from 7.8 to 15.6 μg/ml. Conclusions: Simvastatin has MIC's against the selected bacteria that compare favorably with reported values for topical agents such as essential oil, chlorhexidine gluconate, and triclosan. The levels of simvastatin required to inhibit bacterial growth of oral bacteria exceed the reported levels of the drug found in plasma or crevicular fluid of patients who are treated with this cholesterol-lowering drug. However, clinical studies are warranted to investigate the potential use of simvastatin as a novel antiplaque agent that could be used in local drug delivery to the oral cavity of those patients who are prescribed this cholesterol-lowering drug.

  19. Evaluation of bleeding in patients receiving direct oral anticoagulants.

    Science.gov (United States)

    Hellenbart, Erika L; Faulkenberg, Kathleen D; Finks, Shannon W

    2017-01-01

    Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants.

  20. Measurement and reversal of the direct oral anticoagulants.

    Science.gov (United States)

    Samuelson, Bethany T; Cuker, Adam

    2017-01-01

    Direct oral anticoagulants (DOACs) offer noninferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors. We also discuss reversal strategies, both specific and nonspecific, for each drug, including the preferential use of idarucizumab for the reversal of dabigatran and two agents, andexanet and ciraparantag, currently under development for the reversal of rivaroxaban, apixaban, and edoxaban. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Methodology of oral formulation selection in the pharmaceutical industry.

    Science.gov (United States)

    Kuentz, Martin; Holm, René; Elder, David P

    2016-05-25

    Pharmaceutical formulations have to fulfil various requirements with respect to their intended use, either in the development phase or as a commercial product. New drug candidates with their specific properties confront the formulation scientist with industrial challenges for which a strategy is needed to cope with limited resources, stretched timelines as well as regulatory requirements. This paper aims at reviewing different methodologies to select a suitable formulation approach for oral delivery. Exclusively small-molecular drugs are considered and the review is written from an industrial perspective. Specific cases are discussed starting with an emphasis on poorly soluble compounds, then the topics of chemically labile drugs, low-dose compounds, and modified release are reviewed. Due to the broad scope of this work, a primary focus is on explaining basic concepts as well as recent trends. Different strategies are discussed to approach industrial formulation selection, which includes a structured product development. Examples for such structured development aim to provide guidance to formulators and finally, the recent topic of a manufacturing classification system is presented. It can be concluded that the field of oral formulation selection is particularly complex due to both multiple challenges as well as opportunities so that industrial scientists have to employ tailored approaches to design formulations successfully.

  2. Selectivity of Direct Methanol Fuel Cell Membranes

    Directory of Open Access Journals (Sweden)

    Antonino S. Aricò

    2015-11-01

    Full Text Available Sulfonic acid-functionalized polymer electrolyte membranes alternative to Nafion® were developed. These were hydrocarbon systems, such as blend sulfonated polyetheretherketone (s-PEEK, new generation perfluorosulfonic acid (PFSA systems, and composite zirconium phosphate–PFSA polymers. The membranes varied in terms of composition, equivalent weight, thickness, and filler and were investigated with regard to their methanol permeation characteristics and proton conductivity for application in direct methanol fuel cells. The behavior of the membrane electrode assemblies (MEA was investigated in fuel cell with the aim to individuate a correlation between membrane characteristics and their performance in a direct methanol fuel cell (DMFC. The power density of the DMFC at 60 °C increased according to a square root-like function of the membrane selectivity. This was defined as the reciprocal of the product between area specific resistance and crossover. The power density achieved at 60 °C for the most promising s-PEEK-based membrane-electrode assembly (MEA was higher than the benchmark Nafion® 115-based MEA (77 mW·cm−2 vs. 64 mW·cm−2. This result was due to a lower methanol crossover (47 mA·cm−2 equivalent current density for s-PEEK vs. 120 mA·cm−2 for Nafion® 115 at 60 °C as recorded at OCV with 2 M methanol and a suitable area specific resistance (0.15 Ohm cm2 for s-PEEK vs. 0.22 Ohm cm2 for Nafion® 115.

  3. Selectivity of Direct Methanol Fuel Cell Membranes

    Science.gov (United States)

    Aricò, Antonino S.; Sebastian, David; Schuster, Michael; Bauer, Bernd; D’Urso, Claudia; Lufrano, Francesco; Baglio, Vincenzo

    2015-01-01

    Sulfonic acid-functionalized polymer electrolyte membranes alternative to Nafion® were developed. These were hydrocarbon systems, such as blend sulfonated polyetheretherketone (s-PEEK), new generation perfluorosulfonic acid (PFSA) systems, and composite zirconium phosphate–PFSA polymers. The membranes varied in terms of composition, equivalent weight, thickness, and filler and were investigated with regard to their methanol permeation characteristics and proton conductivity for application in direct methanol fuel cells. The behavior of the membrane electrode assemblies (MEA) was investigated in fuel cell with the aim to individuate a correlation between membrane characteristics and their performance in a direct methanol fuel cell (DMFC). The power density of the DMFC at 60 °C increased according to a square root-like function of the membrane selectivity. This was defined as the reciprocal of the product between area specific resistance and crossover. The power density achieved at 60 °C for the most promising s-PEEK-based membrane-electrode assembly (MEA) was higher than the benchmark Nafion® 115-based MEA (77 mW·cm−2 vs. 64 mW·cm−2). This result was due to a lower methanol crossover (47 mA·cm−2 equivalent current density for s-PEEK vs. 120 mA·cm−2 for Nafion® 115 at 60 °C as recorded at OCV with 2 M methanol) and a suitable area specific resistance (0.15 Ohm cm2 for s-PEEK vs. 0.22 Ohm cm2 for Nafion® 115). PMID:26610582

  4. Child passenger safety: direction, selection, location, installation.

    Science.gov (United States)

    Agran, Phyllis F; Hoffman, Benjamin

    2008-09-01

    The most significant risk factor for death and serious injury in a car crash is the failure to use a size-appropriate restraint system. Providing accurate car safety seat anticipatory guidance to families is the standard of care. Guiding families on the best car seat for best protection can be done with the four messages, direction, selection, location, and refer, if needed, to community resources for correct installation. Addressing special issues that impact use of a car seat on each and every ride, including challenging behaviors and obesity, will transfer to many other situations. Data support a new recommendation that children stay rear-facing in size-appropriate car seats until they reach the highest weight and height allowed for rear-facing by the manufacturer of the convertible seat. Premature graduation to the next seat type/size/position increases risk of injury. A driver who is distracted by a cell phone, food, or something else, becomes a risk factor for a car crash. State laws may lag behind best practices. Advocacy for stronger laws, better enforcement, and best practices at the local, state, and national levels is a critical role for the pediatric professional community.

  5. Retinal Origin of Direction Selectivity in the Superior Colliculus

    Science.gov (United States)

    Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron; Koren, David; Jin, Yanjiao; Liu, Xiaorong; Wei, Wei; Cang, Jianhua

    2017-01-01

    Detecting visual features in the environment such as motion direction is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. Here, we optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly-tuned retinal ganglion cells. The direction selective retinal input is linearly amplified by the intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using 2-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC, and reveal a central visual deficit as a consequence of altered feature selectivity in the retina. PMID:28192394

  6. Retinal origin of direction selectivity in the superior colliculus.

    Science.gov (United States)

    Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron; Koren, David; Jin, Yanjiao; Liu, Xiaorong; Wei, Wei; Cang, Jianhua

    2017-04-01

    Detecting visual features in the environment, such as motion direction, is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. We optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly tuned retinal ganglion cells. The direction-selective retinal input is linearly amplified by intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using two-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC and reveal a central visual deficit as a consequence of altered feature selectivity in the retina.

  7. Development of synaptic connectivity in the retinal direction selective circuit.

    Science.gov (United States)

    Morrie, Ryan D; Feller, Marla B

    2016-10-01

    Direction selectivity is a classic neuronal computation that has been described in many different sensory systems. The circuit basis of this computation is perhaps best understood in the retina, where direction selectivity is the result of asymmetric connectivity patterns between excitatory and inhibitory circuit components. Retinal direction selective circuits emerge before eye-opening, though components of the circuit undergo refinement after vision begins. These features make the direction selective circuit a rich model in which to investigate neuronal circuit assembly. In this Opinion, we highlight recent experiments investigating the contribution of various molecular cues, as well as neuronal activity, to the development of the retinal direction selective circuit.

  8. Association between selected oral pathogens and gastric precancerous lesions.

    Directory of Open Access Journals (Sweden)

    Christian R Salazar

    Full Text Available We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans and dental caries (Streptococcus mutans and S. sobrinus. There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87-2.12, P. gingivalis (OR = 1.12, 0.67-1.88 and T. denticola (OR = 1.34, 0.83-2.12 measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13-5.56 among those with ≥ median of percent tooth sites with PD ≥ 3 mm, compared with no association among those below the median (OR = 0.86, 0.43-1.72. A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03-0.06. Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions.

  9. Research directions in oral health promotion for older adults.

    Science.gov (United States)

    Gift, H C

    1992-09-01

    Health education and health promotion facilitate voluntary adoption of behaviors and provide educational, organizational, economic, and environmental supports for behaviors conductive to health. Health education and health promotion are complementary and any effort to eliminate oral disease requires both activities. Federal research initiatives in oral health promotion have encouraged more biomedical and behavioral research on oral health and aging through the establishment of research centers. Other initiatives have been established to speed the generation of basic and clinical research. Recent initiatives encourage research on aging and provide opportunities for oral health promotion during the coming decade. These include Healthy People 2000, the nation's health objectives for the decade; the NIH framework for the development of a strategic plan, and the NIDR Long-Range Research Plan, Broadening the Scope.

  10. Oral Metaphor Construct--New Directions in Cognitive Linguistics

    OpenAIRE

    Stepak, Asa M.

    2002-01-01

    Abstract: Oral Metaphor Construct,(OMC), is a new concept in Cognitive Linguistics based upon metaphor dynamics that ,also, has significance in numerous related fields such as Artificial Intelligence, Anthropology, Automated Voice Systems, Clinical Psychology, Psychiatry, Communicative Disorders, Second Language Acquisition, etc. The Oral Metaphor Construct is a language imprint that identifies the predisposed space time metaphorical configuration of articulation and semantic objects of t...

  11. ASTDD Synopses of State Oral Health Programs - Selected indicators

    Data.gov (United States)

    U.S. Department of Health & Human Services — 2011-2015. The ASTDD Synopses of State Oral Health Programs contain information useful in tracking states’ efforts to improve oral health and contributions to...

  12. ASTDD Synopses of State Oral Health Programs - Selected indicators

    Data.gov (United States)

    U.S. Department of Health & Human Services — 2011-2016. The ASTDD Synopses of State Oral Health Programs contain information useful in tracking states’ efforts to improve oral health and contributions to...

  13. The retrieval and selection of arithmetic facts in oral arithmetic.

    Science.gov (United States)

    Megías, Patricia; Macizo, Pedro

    2016-10-01

    We examined the co-activation and the selection of arithmetic facts in oral arithmetic. In two experiments, participants had to verify whether simple additions were correct or not. In Experiment 1, additions were presented in the auditory-verbal format; in Experiment 2, additions were presented in the digit format but simulating the temporal sequence of auditory problems of Experiment 1. Results were similar in both experiments. Firstly, participants took the same time to respond when an addition was incorrect but the result was that of multiplying the operands (e.g., 2+4=8) relative to a control addition with unrelated result. Secondly, participants took more time to respond when the result of multiplying the operands of the first trial was presented again in a correct addition problem (e.g., 2+6=8) relative to a control addition. This pattern of results is discussed in terms of the temporal resolution to which auditory problems are resolved and the role of an inhibitory mechanism involved in the selection of arithmetic facts.

  14. Project Selection Directed By Intellectual Capital Scorecards

    NARCIS (Netherlands)

    H.A.M. Daniels (Hennie); B. de Jonge

    2003-01-01

    textabstractManagement of intellectual capital is an important issue in knowledge intensive organizations. Part of this is the composition of the optimal project portfolio the organization will carry out in the future. Standard methods that guide this process mostly focus on project selection on the

  15. Project Selection Directed By Intellectual Capital Scorecards

    NARCIS (Netherlands)

    H.A.M. Daniels (Hennie); B. de Jonge

    2003-01-01

    textabstractManagement of intellectual capital is an important issue in knowledge intensive organizations. Part of this is the composition of the optimal project portfolio the organization will carry out in the future. Standard methods that guide this process mostly focus on project selection on the

  16. SELF-DIRECTED LEARNING, TEAMWORK, HOLISTIC VIEW AND ORAL HEALTH.

    Science.gov (United States)

    Leisnert, Leif

    2014-01-01

    The dental program at the Malmö Dental School, the so called Malmö-model, is guided by four linked principles: self-directed learning, teamwork, a holistic view of patient care, and oral health (Fig.1). Self-assessment ability is a critical competence for healthcare professionals, necessary for the successful adaptation to the modern life-long learning environment. Educational research seems to point out two critical factors for the development of such skills, continuous practice of self-assessment and constructive feedback. The first study presented in this thesis assessed students' self-assessment ability by means of the Interactive Examination in a cohort of senior dental students, who had gone through an identical assessment procedure during their second year of studies. The results indicated that self-assessment ability was not directly relevant to subject knowledge. Upon graduation, there were a number of students (10%) with significant self-assessment difficulties. Early detection of students with weak self-assessment abilities appears possible to achieve. The aim of the second study, concerning teamwork and holistic view, was to investigate if highlighting teamwork between dental and dental hygienist students could improve the students' holistic view on patients, as well as their knowledge of, and insight into, each other's future professions. This project showed that by initiating teamwork between dental and dental hygienist students, it was possible to increase students' knowledge on dental hygienists competence, develop students' perceived holistic view on patients, and prepare students for teamwork. The third study explored findings clinicians used when diagnosing chronic periodontitis. A questionnaire was distributed to students, dental teachers and clinical supervisors in the Public Dental Services. Within all categories of clinicians, the majority of the clinicians used deepened pocket, bone loss on x-rays, and bleeding as findings. There were

  17. The Direct-Method: A Good Start to Teach Oral Language

    Directory of Open Access Journals (Sweden)

    Cagri Tugrul Mart

    2013-11-01

    Full Text Available Oral language development has always played a big role in foreign language learning process. Oral proficiency is considered as the major goal of foreign language learning. The use of communication strategies highly contributes to oral proficiency in the target language. This study focuses on developing students’ communicative abilities through using the target language constantly in the classroom. And this study emphasizes the benefits of the Direct Method to teach how to communicate in the target language.

  18. Selection of direct restorative and rooting filling materials by Kenyan ...

    African Journals Online (AJOL)

    Selection of direct restorative and rooting filling materials by Kenyan dentists in 2014. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... To establish the categories of direct restorative and root filling materials used by ...

  19. Oral pemphigus vulgaris: A case report with direct immunofluorescence study

    Science.gov (United States)

    Kumar, Sangeetha Jeevan; Nehru Anand, SP; Gunasekaran, Nandhini; Krishnan, Rajkumar

    2016-01-01

    Pemphigus vulgaris (PV) is a chronic, autoimmune, intraepidermal blistering disease of the skin and mucous membranes. The initial clinical manifestation is frequently the development of intraoral lesions, and later, the lesions involve the other mucous membranes and skin. The etiology of this disease still remains obscure although the presence of autoantibodies is consistent with an autoimmune disease. These antibodies are targeted against the adhesion proteins of keratinocytes, leading to acantholysis (disruption of spinous layer, leading to intraepidermal clefting) and blister formation. Because only oral lesions are present initially, the chances of misdiagnosing the disease as another condition are increased, leading to inappropriate therapy. In this article, we report a case of PV with only oral manifestations in a 36-year-old male. PMID:27721634

  20. Modeling HIV-1 drug resistance as episodic directional selection.

    Directory of Open Access Journals (Sweden)

    Ben Murrell

    Full Text Available The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  1. Selectivity of Crystal Growth Direction in Layered Double Hydroxides

    Institute of Scientific and Technical Information of China (English)

    赵芸; 梁吉; 李峰; 段雪

    2004-01-01

    Investigation of selectivity of crystal growth direction in layered double hydroxides is helpful to control their particle sizes in different directions. Mg-Al layered double hydroxides (LDHs) were synthesized using a coprecipitation method. The influences of aging temperature, aging time, and Mg/Al molar ratio on the crystal structure, the LDHs particle size, and the selectivity of crystal growth in different directions were investigated. The results show that the size of the crystallites in the a direction is larger than that in the c direction for all experimental conditions, indicating faster crystal growth in the a direction than in the c direction. The crystallite sizes in the a and c directions both increase with decreasing Mg/Al molar ratio but with less difference between the sizes in the two directions. Therefore, the crystal growth rate in the c direction increases more than that in the a direction as the Mg/Al molar ratio decreases. The influence of the aging time, aging temperature, and Mg/Al molar ratio on the selectivity of the crystal growth direction can be used to prepare LDHs with selected sizes in the a and c directions.

  2. Le discours oral en elaboration: Directions de recherche (Oral Discourse in Process: Research in Progress).

    Science.gov (United States)

    Carton, Francis M.

    Research is in progress on oral interactive discourse, that is, discourse produced by several participants working in collaboration. The intent of the research is to investigate how the discourse is organized at several different levels of structure (acts, sequences of acts, interactive structure, propositional content, and formal realizations).…

  3. Minimizing bleeding risk in patients receiving direct oral anticoagulants for stroke prevention

    Directory of Open Access Journals (Sweden)

    Habert JS

    2016-10-01

    Full Text Available Jeffrey Steven Habert Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada Abstract: Many primary care physicians are wary about using direct oral anticoagulants (DOACs in patients with nonvalvular atrial fibrillation (AF. Factors such as comorbidities, concomitant medications, and alcohol misuse increase concerns over bleeding risk, especially in elderly and frail patients with AF. This article discusses strategies to minimize the risk of major bleeding events in patients with AF who may benefit from oral anticoagulant therapy for stroke prevention. The potential benefits of the DOACs compared with vitamin K antagonists, in terms of a lower risk of intracranial hemorrhage, are discussed, together with the identification of reversible risk factors for bleeding and correct dose selection of the DOACs based on a patient’s characteristics and concomitant medications. Current bleeding management strategies, including the new reversal agents for the DOACs and the prevention of bleeding during preoperative anticoagulation treatment, in addition to health care resource use associated with anticoagulation treatment and bleeding, are also discussed. Implementing a structured approach at an individual patient level will minimize the overall risk of bleeding and should increase physician confidence in using the DOACs for stroke prevention in their patients with nonvalvular AF. Keywords: anticoagulants, atrial fibrillation, bleeding, primary care

  4. Minimizing bleeding risk in patients receiving direct oral anticoagulants for stroke prevention

    Science.gov (United States)

    Habert, Jeffrey Steven

    2016-01-01

    Many primary care physicians are wary about using direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AF). Factors such as comorbidities, concomitant medications, and alcohol misuse increase concerns over bleeding risk, especially in elderly and frail patients with AF. This article discusses strategies to minimize the risk of major bleeding events in patients with AF who may benefit from oral anticoagulant therapy for stroke prevention. The potential benefits of the DOACs compared with vitamin K antagonists, in terms of a lower risk of intracranial hemorrhage, are discussed, together with the identification of reversible risk factors for bleeding and correct dose selection of the DOACs based on a patient’s characteristics and concomitant medications. Current bleeding management strategies, including the new reversal agents for the DOACs and the prevention of bleeding during preoperative anticoagulation treatment, in addition to health care resource use associated with anticoagulation treatment and bleeding, are also discussed. Implementing a structured approach at an individual patient level will minimize the overall risk of bleeding and should increase physician confidence in using the DOACs for stroke prevention in their patients with nonvalvular AF.

  5. Direct oral anticoagulants for secondary prevention in patients with non-valvular atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2013-12-01

    Full Text Available The patients with non-valvular atrial fibrillation (NVAF, both permanent and paroxysmal, and history of previous transient ischemic attack (TIA or stroke represent a category of patients at high risk of new embolic events, independently of the presence of other risk factors. In these patients, national and international guidelines recommend oral anticoagulants as first choice for antithrombotic prevention. Direct oral anticoagulants (DOACs have been demonstrated to be not inferior to warfarin for many end points in NVAF patients in terms of efficacy and safety. The post hoc analysis in selected subgroups of patients enrolled in the three mega trials of phase III comparing DOACs (RE-LY, ROCKET-AF and ARISTOTLE with warfarin help to evaluate whether superiority and non-inferiority persist in these subgroups. Here, patients with NVAF and history of previous TIA/stroke receiving DOACs as secondary prevention are compared with patients with the same characteristics receiving warfarin. An analysis of these patients has been recently published (separately for each of three DOACs. This analysis shows that DOACs maintain their non-inferiority when compared with warfarin in secondary prevention, representing a real alternative in this context of patients at high risk for ischemic and bleeding events.

  6. The identification, selection and use of oral contraceptives.

    Science.gov (United States)

    Flowers, C E; Griffith, S F

    1975-01-01

    Facts about oral contraceptives and their use are provided for the practcing generalist and specialist. Identification of oral contraceptives is given in chart form including company, name, contents, pill color, number in pack and special markings. Section 2 entitled "facts that may be helpful in prescribing or changing the prescription of oral contraceptives" includes potency of progestins and estrogens and symptoms indicating excessive or deficient progestin and estrogen activity. Contraindications such as migraine headaches, epilepsy, hepatic disease, renal disease and hypertension are among the reasons for obtaining a complete family history prior to prescription of oral contraceptives. This information provides the basis for choice of contraception tailored to the individual. A 100 pound 17 year old with a normal menstrual history and with adequate estrogen production would be safest with a medication low in estrogen and progestin. An older heavier woman with prolonged menstruation and cramps would require a pill which is potent in progestins since these are excellent for causing endometrium regression and vascular reduction. Length of time on oral c ontraceptives depends upon the patient's general health. If responding well to contraceptives the patient should continue to use them because 1) the body is programmed for lengthy periods of ovulation suppression; 2) the patient becomes accustomed to infertility and 3) too many unplanned pregnancies occur during rest intervals. Complaints of nausea, migraine headaches, change in libido, chloasma or thrombophlebitis determine the termination of the drug.

  7. MUCOSITIS PREVENTION BY SELECTIVE ELIMINATION OF ORAL FLORA IN IRRADIATED HEAD AND NECK-CANCER PATIENTS

    NARCIS (Netherlands)

    SPIJKERVET, FKL; VANSAENE, HKF; VANSAENE, JJM; PANDERS, AK; VERMEY, A; MEHTA, DM

    1990-01-01

    Mucositis induced by irradiation is the reactive inflammatory-like process of the oropharyngeal mucous membranes following irradiation. Bacteria colonizing the oral tissues are thought to contribute to this inflammatory process. The eradication of Gram-negative bacilli (selective elimination of oral

  8. Hardness, Cohesiveness, and Adhesiveness of Oral Moisturizers and Denture Adhesives: Selection Criteria for Denture Wearers

    Directory of Open Access Journals (Sweden)

    Keiko Fujimoto

    2016-10-01

    Full Text Available The mechanical properties of seven denture adhesives and eight oral moisturizers, all of which are commercially available, were evaluated using a texture profile analysis. A new assessment chart is proposed for the selection criteria of denture adhesive and oral moisturizers using a radar chart with three axes: hardness, cohesiveness, and adhesiveness.

  9. MUCOSITIS PREVENTION BY SELECTIVE ELIMINATION OF ORAL FLORA IN IRRADIATED HEAD AND NECK-CANCER PATIENTS

    NARCIS (Netherlands)

    SPIJKERVET, FKL; VANSAENE, HKF; VANSAENE, JJM; PANDERS, AK; VERMEY, A; MEHTA, DM

    1990-01-01

    Mucositis induced by irradiation is the reactive inflammatory-like process of the oropharyngeal mucous membranes following irradiation. Bacteria colonizing the oral tissues are thought to contribute to this inflammatory process. The eradication of Gram-negative bacilli (selective elimination of oral

  10. Characteristic Oral and Written Business Communication Problems of Selected Managerial Trainees.

    Science.gov (United States)

    Woodcock, Barry E.

    1979-01-01

    Presents a study to determine characteristic oral and written business communication problems of selected managerial trainees and to assess whether the problems defined by these trainees were those recognized by their immediate supervisors and secretaries. (JMF)

  11. Ex Vivo Produced Oral Mucosa Equivalent by Using the Direct Explant Cell Culture Technique

    Directory of Open Access Journals (Sweden)

    Kamile Öztürk

    2012-09-01

    Full Text Available Objective: The aim of this study is the histological and immunohistochemical evaluation of ex vivo produced oral mucosal equivalents using keratinocytes cultured by direct explant technique.Material and Methods: Oral mucosa tissue samples were obtained from the keratinized gingival tissues of 14 healthy human subjects. Human oral mucosa keratinocytes from an oral mucosa biopsy specimen were dissociated by the explant technique. Once a sufficient population of keratinocytes was reached, they were seeded onto the type IV collagen coated “AlloDerm” and taken for histological and immunohistochemical examinations at 11 days postseeding of the keratinocytes on the cadaveric human dermal matrix.Results: Histopathologically and immunohistochemically, 12 out of 14 successful ex vivo produced oral mucosa equivalents (EVPOME that consisted of a stratified epidermis on a dermal matrix have been developed with keratinocytes cultured by the explant technique.Conclusion: The technical handling involved in the direct explant method at the beginning of the process has fewer steps than the enzymatic method and use of the direct explant technique protocol for culturing of human oral mucosa keratinocyte may be more adequate for EVPOME production.

  12. Nonlinear dynamics of direction-selective recurrent neural media.

    Science.gov (United States)

    Xie, Xiaohui; Giese, Martin A

    2002-05-01

    The direction selectivity of cortical neurons can be accounted for by asymmetric lateral connections. Such lateral connectivity leads to a network dynamics with characteristic properties that can be exploited for distinguishing in neurophysiological experiments this mechanism for direction selectivity from other possible mechanisms. We present a mathematical analysis for a class of direction-selective neural models with asymmetric lateral connections. Contrasting with earlier theoretical studies that have analyzed approximations of the network dynamics by neglecting nonlinearities using methods from linear systems theory, we study the network dynamics with nonlinearity taken into consideration. We show that asymmetrically coupled networks can stabilize stimulus-locked traveling pulse solutions that are appropriate for the modeling of the responses of direction-selective neurons. In addition, our analysis shows that outside a certain regime of stimulus speeds the stability of these solutions breaks down, giving rise to lurching activity waves with specific spatiotemporal periodicity. These solutions, and the bifurcation by which they arise, cannot be easily accounted for by classical models for direction selectivity.

  13. Selecting the optimal oral antihistamine for patients with allergic rhinitis.

    Science.gov (United States)

    Lehman, Jeffrey M; Blaiss, Michael S

    2006-01-01

    Allergic rhinitis (AR) is now recognised as a global health problem that affects 10-30% of adults and up to 40% of children. Each year, millions of patients seek treatment from their healthcare provider. However, the prevalence of AR maybe significantly underestimated because of misdiagnosis, under diagnosis and failure of patients to seek medical attention. In addition to the classical symptoms such as sneezing, nasal pruritus, congestion and rhinorrhoea, it is now recognised that AR has a significant impact on quality of life (QOL). This condition can lead to sleep disturbance as a result of nasal congestion, which leads to significant impairment in daily activities such as work and school. Traditionally, AR has been subdivided into seasonal AR (SAR) or perennial AR (PAR). SAR symptoms usually appear during a specific season in which aeroallergens are present in the outdoor air such as tree and grass pollen in the spring and summer and weed pollens in the autumn (fall); and PAR symptoms are present year-round and are triggered by dust mite, animal dander, indoor molds and cockroaches. Oral histamine H(1)-receptor antagonists (H(1) antihistamines) are one of the most commonly prescribed medications for the treatment of AR. There are several oral H(1) antihistamines available and it is important to know the pharmacology, such as administration interval, onset of action, metabolism and conditions that require administration adjustments. When prescribing oral H(1) antihistamines, the healthcare provider must take into account the clinical efficacy and weigh this against the risk of adverse effects from the agent. In addition to the clinical efficacy, potential for improvement in QOL with a particular treatment should also be considered.

  14. Synaptic plasticity can produce and enhance direction selectivity.

    Directory of Open Access Journals (Sweden)

    Sean Carver

    2008-02-01

    Full Text Available The discrimination of the direction of movement of sensory images is critical to the control of many animal behaviors. We propose a parsimonious model of motion processing that generates direction selective responses using short-term synaptic depression and can reproduce salient features of direction selectivity found in a population of neurons in the midbrain of the weakly electric fish Eigenmannia virescens. The model achieves direction selectivity with an elementary Reichardt motion detector: information from spatially separated receptive fields converges onto a neuron via dynamically different pathways. In the model, these differences arise from convergence of information through distinct synapses that either exhibit or do not exhibit short-term synaptic depression--short-term depression produces phase-advances relative to nondepressing synapses. Short-term depression is modeled using two state-variables, a fast process with a time constant on the order of tens to hundreds of milliseconds, and a slow process with a time constant on the order of seconds to tens of seconds. These processes correspond to naturally occurring time constants observed at synapses that exhibit short-term depression. Inclusion of the fast process is sufficient for the generation of temporal disparities that are necessary for direction selectivity in the elementary Reichardt circuit. The addition of the slow process can enhance direction selectivity over time for stimuli that are sustained for periods of seconds or more. Transient (i.e., short-duration stimuli do not evoke the slow process and therefore do not elicit enhanced direction selectivity. The addition of a sustained global, synchronous oscillation in the gamma frequency range can, however, drive the slow process and enhance direction selectivity to transient stimuli. This enhancement effect does not, however, occur for all combinations of model parameters. The ratio of depressing and nondepressing synapses

  15. Comparison of video and direct observation methods for measuring oral behaviour in veal calves

    Directory of Open Access Journals (Sweden)

    Marina Verga

    2010-01-01

    Full Text Available Measuring behaviour, especially oral behaviour, has always been a debated issue: therefore the aim of this paper is to closely examine the study of oral behaviour in calves and the approaching methodology. Behavioural observations were conducted by two media (direct observations by check sheets and indirect observations by videotapes recorded by cam- eras connected to a digital field switcher and a time-lapse video recorder in order to compare data and assess the reli- ability and validity of the two methods in identifying some oral behavioural patterns in calves. The study was carried out on 54 Polish Friesian calves housed in group pens and in individual crates. The behaviour of the calves was investigated during the fattening period on the 2nd, 7th, 13th, 18th and 23rd week, one hour before and one hour after each of the two meals. Two experienced observers checked the behaviour of the calves, including oral behaviours on structures and buckets and oral stereotypies, by direct observations using a scan sampling every 2 min- utes. The calves' behaviour was also video recorded on the same days in which the direct observations were carried out and analysed by the same two observers. Percentages of time spent on each type of behaviour were calculated and anal- ysed by Chi-square test. Regardless of the housing system, the comparison between direct and indirect observations revealed significant differences in almost every behavioural category. Licking, biting and nibbling structures, nibbling and sucking the bucket, playing with the bucket and the teat, chewing and oral stereotypies were significantly higher in direct observations compared to indirect (P < 0.001, while inactivity was higher in video recorded observations (P < 0.001. In conclusion, regardless of the type of housing, our results revealed an objective difficulty in analysing videotapes with very detailed behavioural categories, like oral behaviours. Although video recording can

  16. Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor

    Directory of Open Access Journals (Sweden)

    Upreti VV

    2013-04-01

    Full Text Available Vijay V Upreti,1 Yan Song,1 Jessie Wang,2 Wonkyung Byon,3 Rebecca A Boyd,3 Janice M Pursley,4 Frank LaCreta,1 Charles E Frost1 1Clinical Pharmacology and Pharmacometrics, Discovery Medicine and Clinical Pharmacology, 2Exploratory Development Global Biometric Sciences, Bristol-Myers Squibb, Princeton, NJ, 3Primary Care Clinical Pharmacology, Pfizer, Groton, CT, 4Analytical and Bioanalytical Department, Bristol-Myers Squibb, Princeton, NJ, USA Background: Apixaban is an oral, selective, direct factor Xa inhibitor approved for thromboprophylaxis after orthopedic surgery and stroke prevention in patients with atrial fibrillation, and under development for treatment of venous thromboembolism. This study investigated the effect of a gastric acid suppressant, famotidine (a histamine H2-receptor antagonist, on the pharmacokinetics of apixaban in healthy subjects. Methods: This two-period, two-treatment crossover study randomized 18 healthy subjects to receive a single oral dose of apixaban 10 mg with and without a single oral dose of famotidine 40 mg administered 3 hours before dosing with apixaban. Plasma apixaban concentrations were measured up to 60 hours post-dose and pharmacokinetic parameters were calculated. Results: Famotidine did not affect maximum apixaban plasma concentration (Cmax or area under the plasma concentration-time curve from zero to infinite time (AUC∞. Point estimates for ratios of geometric means with and without famotidine were close to unity for Cmax (0.978 and AUC∞ (1.007, and 90% confidence intervals were entirely contained within the 80%–125% no-effect interval. Administration of apixaban alone and with famotidine was well tolerated. Conclusion: Famotidine does not affect the pharmacokinetics of apixaban, consistent with the physicochemical properties of apixaban (lack of an ionizable group and pH-independent solubility. Apixaban pharmacokinetics would not be affected by an increase in gastrointestinal pH due to

  17. Direct selection on genetic robustness revealed in the yeast transcriptome.

    Directory of Open Access Journals (Sweden)

    Stephen R Proulx

    Full Text Available BACKGROUND: Evolutionary theory predicts that organisms should evolve the ability to produce high fitness phenotypes in the face of environmental disturbances (environmental robustness or genetic mutations (genetic robustness. While several studies have uncovered mechanisms that lead to both environmental and genetic robustness, we have yet to understand why some components of the genome are more robust than others. According to evolutionary theory, environmental and genetic robustness will have different responses to selective forces. Selection on environmental robustness for a trait is expected to be strong and related to the fitness costs of altering that trait. In contrast to environmental robustness, selection on genetic robustness for a trait is expected to be largely independent of the fitness cost of altering the trait and instead should correlate with the standing genetic variation for the trait that can potentially be buffered. Several mechanisms that provide both environmental and genetic robustness have been described, and this correlation could be explained by direct selection on both forms of robustness (direct selection hypothesis, or through selection on environmental robustness and a correlated response in genetic robustness (congruence hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Using both published and novel data on gene expression in the yeast Saccharomyces cerevisiae, we find that genetic robustness is correlated with environmental robustness across the yeast genome as predicted by the congruence hypothesis. However, we also show that environmental robustness, but not genetic robustness, is related to per-gene fitness effects. In contrast, genetic robustness is significantly correlated with network position, suggesting that genetic robustness has been under direct selection. CONCLUSIONS/SIGNIFICANCE: We observed a significant correlation between our measures of genetic and environmental robustness, in agreement with the

  18. Interface Pattern Selection Criterion for Cellular Structures in Directional Solidification

    Science.gov (United States)

    Trivedi, R.; Tewari, S. N.; Kurtze, D.

    1999-01-01

    The aim of this investigation is to establish key scientific concepts that govern the selection of cellular and dendritic patterns during the directional solidification of alloys. We shall first address scientific concepts that are crucial in the selection of interface patterns. Next, the results of ground-based experimental studies in the Al-4.0 wt % Cu system will be described. Both experimental studies and theoretical calculations will be presented to establish the need for microgravity experiments.

  19. Treatment of acne with oral contraceptives: criteria for pill selection.

    Science.gov (United States)

    Koulianos, G T

    2000-10-01

    Combination oral contraceptives (OCs) (those that contain estrogen and progestin) are widely used in the treatment of acne because they modify an excessively androgenic hormonal environment and can decrease lesions. Dermatologists' knowledge of the most appropriate OC may be hampered by an incomplete understanding of these agents, misleading promotion, and confusion surrounding the new generation of OCs. Despite reports attributing significance to the degree of androgenicity of the progestin components of OCs, in vitro and animal bioassays of androgenicity have little clinical relevance. Because all of today's low-dose combination OCs are estrogen dominant, they are equally beneficial in women with androgenic conditions such as acne. Use of the OC containing the lowest dose of each hormone, consistent with the patient's needs, can enhance compliance by preventing or limiting common early-cycle side effects (e.g., nausea/vomiting, breast tenderness, weight gain, headache), while providing acne improvement.

  20. Orally administered Lactobacillus strains differentially affect the direction and efficacy of the immune response

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten, J.C.A.M. van; Balk, F.; Heijne den Bak-Glashouwer, M.J.; Leer, R.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    1998-01-01

    In mice, strain dependent cytokine production profiles are induced after oral administration of Lactobacillus. Such a cytokine profile seems to determine the direction and efficacy of the humoral response. In SJL mice lactobacilli are able to enhance or inhibit the development of disease after

  1. Neural Networks for Target Selection in Direct Marketing

    NARCIS (Netherlands)

    R. Potharst (Rob); U. Kaymak (Uzay); W.H.L.M. Pijls (Wim)

    2001-01-01

    textabstractPartly due to a growing interest in direct marketing, it has become an important application field for data mining. Many techniques have been applied to select the targets in commercial applications, such as statistical regression, regression trees, neural computing, fuzzy clustering

  2. The Underexplored Species: Selective Participation in Direct Democratic Votes

    NARCIS (Netherlands)

    Sciarini, P.; Cappelletti, F.; Goldberg, A.C.; Lanz, S.

    While electoral research usually distinguishes voters from abstainers, in the Swiss direct democratic context one needs to take into account a third category of citizens, the selective voters, who decide anew at each vote whether they will participate or not. This article offers an investigation of

  3. Neural Networks for Target Selection in Direct Marketing

    NARCIS (Netherlands)

    R. Potharst (Rob); U. Kaymak (Uzay); W.H.L.M. Pijls (Wim)

    2001-01-01

    textabstractPartly due to a growing interest in direct marketing, it has become an important application field for data mining. Many techniques have been applied to select the targets in commercial applications, such as statistical regression, regression trees, neural computing, fuzzy clustering an

  4. Estimation and Direct Equalization of Doubly Selective Channels

    Directory of Open Access Journals (Sweden)

    Leus Geert

    2006-01-01

    Full Text Available We propose channel estimation and direct equalization techniques for transmission over doubly selective channels. The doubly selective channel is approximated using the basis expansion model (BEM. Linear and decision feedback equalizers implemented by time-varying finite impulse response (FIR filters may then be used to equalize the doubly selective channel, where the time-varying FIR filters are designed according to the BEM. In this sense, the equalizer BEM coefficients are obtained either based on channel estimation or directly. The proposed channel estimation and direct equalization techniques range from pilot-symbol-assisted-modulation- (PSAM- based techniques to blind and semiblind techniques. In PSAM techniques, pilot symbols are utilized to estimate the channel or directly obtain the equalizer coefficients. The training overhead can be completely eliminated by using blind techniques or reduced by combining training-based techniques with blind techniques resulting in semiblind techniques. Numerical results are conducted to verify the different proposed channel estimation and direct equalization techniques.

  5. Directional and balancing selection in human beta-defensins

    Directory of Open Access Journals (Sweden)

    Armour John AL

    2008-04-01

    Full Text Available Abstract Background In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. Results We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93, is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Conclusion Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.

  6. Directional and balancing selection in human beta-defensins.

    Science.gov (United States)

    Hollox, Edward J; Armour, John A L

    2008-04-16

    In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93), is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.

  7. A frequency selective acoustic transducer for directional Lamb wave sensing.

    Science.gov (United States)

    Senesi, Matteo; Ruzzene, Massimo

    2011-10-01

    A frequency selective acoustic transducer (FSAT) is proposed for directional sensing of guided waves. The considered FSAT design is characterized by a spiral configuration in wavenumber domain, which leads to a spatial arrangement of the sensing material producing output signals whose dominant frequency component is uniquely associated with the direction of incoming waves. The resulting spiral FSAT can be employed both for directional sensing and generation of guided waves, without relying on phasing and control of a large number of channels. The analytical expression of the shape of the spiral FSAT is obtained through the theoretical formulation for continuously distributed active material as part of a shaped piezoelectric device. Testing is performed by forming a discrete array through the points of the measurement grid of a scanning laser Doppler vibrometer. The discrete array approximates the continuous spiral FSAT geometry, and provides the flexibility to test several configurations. The experimental results demonstrate the strong frequency dependent directionality of the spiral FSAT and suggest its application for frequency selective acoustic sensors, to be employed for the localization of broadband acoustic events, or for the directional generation of Lamb waves for active interrogation of structural health.

  8. Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis.

    Science.gov (United States)

    Burr, Nick; Lummis, Katie; Sood, Ruchit; Kane, John Samuel; Corp, Aaron; Subramanian, Venkataraman

    2017-02-01

    Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]). Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with

  9. Usefulness of oral loading of oxcarbazepine suspension in selected patients with epilepsy.

    Science.gov (United States)

    Kim, Dong Wook; Gu, Namyi; Lee, Howard; Jang, In-Jin; Chu, Kon; Yu, Kyung-Sang; Cho, Joo-Youn; Yoon, Seo Hyun; Na, Hyun Jeong; Lee, Sang Kun

    2013-10-01

    Oral loading of oxcarbazepine tablet is effective and well tolerated to adequately achieve the therapeutic levels of its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD) in epilepsy patients. The present study was performed to investigate the safety, tolerability, and pharmacokinetic profiles of oral loading of oxcarbazepine suspension in epilepsy patients with a high risk of recurrent seizures. Oxcarbazepine suspension was administered orally at a single loading dose of 30 mg/kg to 38 adult patients with recurrent seizures, who required rapid seizure control or temporarily discontinued antiepileptic drugs for diagnostic or pre-surgical evaluation. Plasma concentrations of oxcarbazepine and MHD were determined, and adverse events were assessed at 2, 4, 6, 8, 10, 12, 14, 16, and 24 hours after oral loading of oxcarbazepine suspension. 30 patients experienced ≥ 1 adverse event during the first 24 hours after oral loading of oxcarbazepine (e.g., dizziness, transient diplopia, nausea or vomiting), most of which occurred within 4 hours after loading, suggesting no temporal association with MHD plasma levels. 35 (92.1%) patients were still compliant with a maintenance dose of oxcarbazepine after discharge from hospital. 34 (89.4%) patients reached the lower therapeutic level of MHD (12 mg/l) at 4 hours after oral loading of oxcarbazepine suspension, which lasted up to 24 hours in most patients. No patient reached the supratherapeutic levels of MHD (> 35 mg/l) during the study. The mean plasma concentration-time curves and pharmacokinetic profiles of oral loading of oxcarbazepine suspension were similar to those of oral loading of oxcarbazepine tablet. Oral loading of oxcarbazepine suspension followed by maintenance dosing is well tolerated and effective in steadily achieving the therapeutic level of MHD in selected patients with epilepsy.

  10. Sex-related genes, directional sexual selection, and speciation.

    Science.gov (United States)

    Civetta, A; Singh, R S

    1998-07-01

    Reproductive isolation and speciation can result from the establishment of either premating or postmating barriers that restrict gene flow between populations. Recent studies of speciation have been dominated by a molecular approach to dissect the genetic basis of hybrid male sterility, a specific form of postmating reproductive isolation. However, relatively little attention has been paid to the evolution of genes involved in premating isolation and genes generally involved in other sex-related functions (e.g., mating behavior, fertilization, spermatogenesis, sex determination). We have assembled DNA sequences from 51 nuclear genes and classified them based on their functional characteristics. The proportion of nonsynonymous to synonymous nucleotide substitutions were compared between Drosophila melanogaster, Drosophila simulans, and Drosophila pseudoobscura, as well as between Caenorhabditis elegans and Caenorhabditis briggsae. We found a high ratio of nonsynonymous to synonymous substitutions for sex-related genes (i.e., genes involved in mating behavior, fertilization, spermatogenesis, or sex determination). The results suggest that directional sexual selection has shaped the evolution of sex-related genes and that these changes have more likely occurred during the early stages of speciation. It is possible that directional selection becomes relaxed after reproductive isolation has been completed between more distantly related species (e.g., D. melanogaster and D. pseudoobscura). However, a saturation in the number of nucleotide substitutions since the time of species separation may mask any sign of directional selection between more distantly related species.

  11. Implications of Dabigatran, a direct thrombin inhibitor, for oral surgery practice.

    Science.gov (United States)

    Davis, Clayton; Robertson, Chad; Shivakumar, Sudeep; Lee, Min

    2013-01-01

    Direct thrombin inhibitors, specifically orally administered dabigatran etexilate, are emerging as alternatives to warfarin for anticoagulation in the management of atrial fibrillation and venous thromboembolism. The risk associated with bleeding events while taking dabigatran has been documented in multiple randomized controlled trials, but to date, no studies have focused on the risk of bleeding after dental extraction. Extraction of teeth is one of the most common surgical procedures and may cause significant bleeding, so a thorough understanding of the pharmacology of anticoagulant medications is required to prevent complications. With the increasing use of direct thrombin inhibitors, the safe management of patients taking these anticoagulants must be delineated. This review compares dabigatran and warfarin, especially in terms of their effects on dental and oral surgery practice, and examines best management of these patients in light of the existing literature.

  12. Early introduction of direct oral anticoagulants in cardioembolic stroke patients with non-valvular atrial fibrillation.

    Science.gov (United States)

    Cappellari, Manuel; Carletti, Monica; Danese, Alessandra; Bovi, Paolo

    2016-10-01

    Direct oral anticoagulants (DOACs) are superior to warfarin in reduction of the intracranial bleeding risk. The aim of the present study was to assess whether early DOAC introduction (1-3 days after onset) in stroke patients with non-valvular atrial fibrillation (nVAF) may be safe and effective, compared with DOAC introduction after 4-7 days. We conducted a prospective analysis based on data collected from 147 consecutive nVAF patients who started DOAC within 7 days after stroke onset. In all patients, we performed pre-DOAC CT scan 24-36 h after onset and follow-up CT scan at 7 days after DOAC introduction. Outcome measures were post-DOAC intracranial bleeding (new any intracerebral hemorrhage (ICH) in patients with pre-DOAC infarct without hemorrhagic transformation (HT) or expansion of ICH in patients with pre-DOAC infarct with asymptomatic HT) and post-DOAC recurrent ischemic stroke (any new ischemic infarct) on follow-up CT scan. 97 patients started DOAC after 1-3 days and 50 patients started DOAC after 4-7 days. On pre-DOAC CT scan, 132 patients had an infarct without HT and 15 an infarct with asymptomatic HT. On follow-up CT scan, new any ICH was noted in seven patients (asymptomatic in 6) and asymptomatic expansion of ICH in one patient. We found no association between early DOAC introduction and intracranial bleeding. Large infarct remained the only independent predictor of post-DOAC intracranial bleeding. No patients suffered recurrent ischemic stroke after DOAC introduction. Early DOAC introduction might be safe in carefully selected patients with nVAF who experience small- and medium-sized cardioembolic ischemic strokes. Further investigation will be needed.

  13. Novel, potent, selective, and orally bioavailable human betaII-tryptase inhibitors.

    Science.gov (United States)

    Sperandio, David; Tai, Vincent W-F; Lohman, Julia; Hirschbein, Bernie; Mendonca, Rohan; Lee, Chang-Sun; Spencer, Jeffrey R; Janc, James; Nguyen, Margaret; Beltman, Jerlyn; Sprengeler, Paul; Scheerens, Heleen; Lin, Tong; Liu, Liang; Gadre, Ashwini; Kellogg, Alisha; Green, Michael J; McGrath, Mary E

    2006-08-01

    The synthesis of novel [1,2,4]oxadiazoles and their structure-activity relationship (SAR) for the inhibition of tryptase and related serine proteases is presented. Elaboration of the P'-side afforded potent, selective, and orally bioavailable tryptase inhibitors.

  14. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives.

    Science.gov (United States)

    Gómez-Outes, Antonio; Suárez-Gea, Ma Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio

    2015-11-01

    In recent years, several direct-acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto, Bayer HealthCare), apixaban (Eliquis, Bristol-Myers Squibb), and edoxaban (Lixiana/Savaysa, Daiichi-Sankyo). The new compounds have a predictable dose response and few drug-drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives.

  15. Cervical Lymph Nodes as a Selective Niche for Brucella during Oral Infections.

    Directory of Open Access Journals (Sweden)

    Kristine von Bargen

    Full Text Available Cervical lymph nodes (CLN are the first lymph nodes encountered by material taking the oral route. To study their role in orally acquired infections, we analyzed 307 patients of up to 14 years treated in the university clinic of Skopje, Macedonia, for brucellosis, a zoonotic bacterial disease frequently acquired by ingestion of contaminated dairy products. From these children, 36% had lymphadenopathy. Among orally infected children, lymphadenopathy with CLN being the only lymph nodes affected was significantly more frequent as compared to those infected by contact with animals (83% vs. 63%, suggesting a possible involvement of CLN during orally acquired human brucellosis. Using a murine model where bacteria are delivered into the oral cavity, we show that Brucella quickly and selectively colonize the CLN where they proliferate and persist over long periods of time for up to 50 days post-infection. A similar efficient though less specific drainage to CLN was found for Brucella, Salmonella typhimurium and fluorescent microspheres delivered by gavage, a pathway likely representing a mixed infection mode of intragastric and oral infection, suggesting a central pathway of drained material. Microspheres as well as bacteria drained to CLN predominately reside in cells expressing CD68 and no or low levels of CD11c. Even though no systemic response could be detected, Brucella induced a locally restricted inflammatory reaction with increased expression levels of interferon γ, interleukin (IL-6, IL-12, granzyme B and a delayed induction of Nos2. Inflammation led to pronounced lymphadenopathy, infiltration of macrophages/monocytes expressing high levels of major histocompatibility complex II and to formation of epitheloid granulomas. Together, these results highlight the role of CLN in oral infections as both, an initial and efficient trap for bacterial invaders and as possible reservoir for chronic pathogens. They likewise cast a new light on the

  16. Cervical Lymph Nodes as a Selective Niche for Brucella during Oral Infections

    Science.gov (United States)

    von Bargen, Kristine; Gagnaire, Aurélie; Arce-Gorvel, Vilma; de Bovis, Béatrice; Baudimont, Fannie; Chasson, Lionel; Bosilkovski, Mile; Papadopoulos, Alexia; Martirosyan, Anna; Henri, Sandrine; Mège, Jean-Louis; Malissen, Bernard; Gorvel, Jean-Pierre

    2015-01-01

    Cervical lymph nodes (CLN) are the first lymph nodes encountered by material taking the oral route. To study their role in orally acquired infections, we analyzed 307 patients of up to 14 years treated in the university clinic of Skopje, Macedonia, for brucellosis, a zoonotic bacterial disease frequently acquired by ingestion of contaminated dairy products. From these children, 36% had lymphadenopathy. Among orally infected children, lymphadenopathy with CLN being the only lymph nodes affected was significantly more frequent as compared to those infected by contact with animals (83% vs. 63%), suggesting a possible involvement of CLN during orally acquired human brucellosis. Using a murine model where bacteria are delivered into the oral cavity, we show that Brucella quickly and selectively colonize the CLN where they proliferate and persist over long periods of time for up to 50 days post-infection. A similar efficient though less specific drainage to CLN was found for Brucella, Salmonella typhimurium and fluorescent microspheres delivered by gavage, a pathway likely representing a mixed infection mode of intragastric and oral infection, suggesting a central pathway of drained material. Microspheres as well as bacteria drained to CLN predominately reside in cells expressing CD68 and no or low levels of CD11c. Even though no systemic response could be detected, Brucella induced a locally restricted inflammatory reaction with increased expression levels of interferon γ, interleukin (IL)-6, IL-12, granzyme B and a delayed induction of Nos2. Inflammation led to pronounced lymphadenopathy, infiltration of macrophages/monocytes expressing high levels of major histocompatibility complex II and to formation of epitheloid granulomas. Together, these results highlight the role of CLN in oral infections as both, an initial and efficient trap for bacterial invaders and as possible reservoir for chronic pathogens. They likewise cast a new light on the significance of oral

  17. How important are direct fitness benefits of sexual selection?

    Science.gov (United States)

    Møller, A. P.; Jennions, M. D.

    2001-10-01

    Females may choose mates based on the expression of secondary sexual characters that signal direct, material fitness benefits or indirect, genetic fitness benefits. Genetic benefits are acquired in the generation subsequent to that in which mate choice is performed, and the maintenance of genetic variation in viability has been considered a theoretical problem. Consequently, the magnitude of indirect benefits has traditionally been considered to be small. Direct fitness benefits can be maintained without consideration of mechanisms sustaining genetic variability, and they have thus been equated with the default benefits acquired by choosy females. There is, however, still debate as to whether or not males should honestly advertise direct benefits such as their willingness to invest in parental care. We use meta-analysis to estimate the magnitude of direct fitness benefits in terms of fertility, fecundity and two measures of paternal care (feeding rate in birds, hatching rate in male guarding ectotherms) based on an extensive literature survey. The mean coefficients of determination weighted by sample size were 6.3%, 2.3%, 1.3% and 23.6%, respectively. This compares to a mean weighted coefficient of determination of 1.5% for genetic viability benefits in studies of sexual selection. Thus, for several fitness components, direct benefits are only slightly more important than indirect ones arising from female choice. Hatching rate in male guarding ectotherms was by far the most important direct fitness component, explaining almost a quarter of the variance. Our analysis also shows that male sexual advertisements do not always reliably signal direct fitness benefits.

  18. Hierarchy-Direction Selective Approach for Locally Adaptive Sparse Grids

    Energy Technology Data Exchange (ETDEWEB)

    Stoyanov, Miroslav K [ORNL

    2013-09-01

    We consider the problem of multidimensional adaptive hierarchical interpolation. We use sparse grids points and functions that are induced from a one dimensional hierarchical rule via tensor products. The classical locally adaptive sparse grid algorithm uses an isotropic refinement from the coarser to the denser levels of the hierarchy. However, the multidimensional hierarchy provides a more complex structure that allows for various anisotropic and hierarchy selective refinement techniques. We consider the more advanced refinement techniques and apply them to a number of simple test functions chosen to demonstrate the various advantages and disadvantages of each method. While there is no refinement scheme that is optimal for all functions, the fully adaptive family-direction-selective technique is usually more stable and requires fewer samples.

  19. Direct Synthesis of Telechelic Polyethylene by Selective Insertion Polymerization

    KAUST Repository

    Jian, Zhongbao

    2016-10-14

    A single-step route to telechelic polyethylene (PE) is enabled by selective insertion polymerization. PdII-catalyzed copolymerization of ethylene and 2-vinylfuran (VF) generates α,ω-di-furan telechelic polyethylene. Orthogonally reactive exclusively in-chain anhydride groups are formed by terpolymerization with carbic anhydride. Combined experimental and theoretical DFT studies reveal the key for this direct approach to telechelics to be a match of the comonomers’ different electronics and bulk. Identified essential features of the comonomer are that it is an electron-rich olefin that forms an insertion product stabilized by an additional interaction, namely a π–η3 interaction for the case of VF.

  20. Selective anaerobic oxidation of methane enables direct synthesis of methanol.

    Science.gov (United States)

    Sushkevich, Vitaly L; Palagin, Dennis; Ranocchiari, Marco; van Bokhoven, Jeroen A

    2017-05-05

    Direct functionalization of methane in natural gas remains a key challenge. We present a direct stepwise method for converting methane into methanol with high selectivity (~97%) over a copper-containing zeolite, based on partial oxidation with water. The activation in helium at 673 kelvin (K), followed by consecutive catalyst exposures to 7 bars of methane and then water at 473 K, consistently produced 0.204 mole of CH3OH per mole of copper in zeolite. Isotopic labeling confirmed water as the source of oxygen to regenerate the zeolite active centers and renders methanol desorption energetically favorable. On the basis of in situ x-ray absorption spectroscopy, infrared spectroscopy, and density functional theory calculations, we propose a mechanism involving methane oxidation at Cu(II) oxide active centers, followed by Cu(I) reoxidation by water with concurrent formation of hydrogen. Copyright © 2017, American Association for the Advancement of Science.

  1. Indirect competitive assays on DVD for direct multiplex detection of drugs of abuse in oral fluids.

    Science.gov (United States)

    Zhang, Lingling; Li, Xiaochun; Li, Yunchao; Shi, Xiaoli; Yu, Hua-Zhong

    2015-02-03

    On-site oral fluid testing for drugs of abuse has become prominent in order to take immediate administrative action in an enforcement process. Herein, we report a DVD technology-based indirect competitive immunoassay platform for the quantitative detection of drugs of abuse. A microfluidic approach was adapted to prepare multiplex immunoassays on a standard DVD-R, an unmodified multimode DVD/Blu-Ray drive to read signal, and a free disc-quality analysis software program to process the data. The DVD assay platform was successfully demonstrated for the simultaneous, quantitative detection of drug candidates (morphine and cocaine) in oral fluids with high selectivity. The detection limit achieved was as low as 1.0 ppb for morphine and 5.0 ppb for cocaine, comparable with that of standard mass spectrometry and ELISA methods.

  2. [Acute coronary syndrome: Is there a place for direct oral anticoagulants?

    Science.gov (United States)

    Cayla, Guillaume; Leclercq, Florence; Schmutz, Laurent; Cornillet, Luc; Ledermann, Bertrand; Messner, Patrick; Lattuca, Benoit

    2016-10-01

    Venous thromboembolism and atrial fibrillation are two important indications of direct oral anticoagulants. Acute coronary syndrome is another potential indication of prolonged antithrombotic therapy in addition to antiplatelet therapy. Phase 2 and 3 studies were conducted with different molecules at different doses in acute coronary syndrome in addition to dual antiplatelet therapy. Studies have not shown a reduction of ischemic events for dabigatran and apixaban, but an excess of bleeding complications was observed. A reduction of ischemic events and stent thrombosis was observed with low dose of rivaroxaban taken twice a day but with an increased risk of major bleeding complications. This data was used to obtain a European marketing authorization but the positioning of the molecule remains difficult. A new study is currently being conducted to test rivaroxaban in association with a P2Y12 inhibitor without aspirin. Direct oral anticoagulants can also be used after percutaneous coronary intervention in patients requiring long-term oral anticoagulants. Dedicated studies are currently being conducted to confirm the optimal doses and the ideal association of antithrombotic drugs.

  3. A Study of the Management of Patients Taking Novel Oral Antiplatelet or Direct Oral Anticoagulant Medication Undergoing Dental Surgery in a Rural Setting

    OpenAIRE

    Steven Johnston

    2015-01-01

    Purpose: Novel oral antiplatelet (NOAP) (prasugrel and ticagrelor) and direct oral anticoagulant drugs (DOAC) (dabigatran, rivaroxaban and apixaban) have emerged in the last decade. This study was undertaken to determine current approaches taken to the management of patients taking these agents in dental practice in a remote and rural setting. Methods: A small retrospective study was carried out in a small island population that identified patients taking one of the above drugs. All national ...

  4. Relationship between Selected Socio-Demographic Factors and Cancer of Oral Cavity - A Case Control Study.

    Science.gov (United States)

    Madani, Abdoul Hossain; Dikshit, Madhurima; Bhaduri, Debanshu; Jahromi, Abdolreza Sotoodeh; Aghamolaei, Teamur

    2010-08-11

    The aim of this study was to recognize factors associated with cancer of oral cavity considering socio-demographic characteristics. The cases were 350 with squamous-cell carcinoma of oral cavity diagnosed between 2005 and 2006 in Morbai, Narandia, Budharani Cancer Institute, Pune, India. Similar number of controls match for age and sex selected from the background population. Cases and controls were interviewed for tobacco related habits and general characteristics; age, gender, education and possible socio-demographic factors. Chi-square test in uni-variate analysis and estimate for risk showed that education, occupation and monthly household income were significantly different between cases and controls (P currency (OR = 1.7, CI 1.2-2.3) were significant risk factors for oral cancer. While, there was no significant relationship between religious and or marital status either in males or females.

  5. Selective serotonin reuptake inhibitors and oral bleeding complications after invasive dental treatment.

    Science.gov (United States)

    Napeñas, Joel J; Hong, Catherine H L; Kempter, Eric; Brennan, Michael T; Furney, Scott L; Lockhart, Peter B

    2011-10-01

    The purpose of this study was to examine the frequency of oral bleeding complications after invasive dental procedures in patients taking selective serotonin reuptake inhibitor (SSRI) medications. In this retrospective cohort study, we included dental patients who had invasive dental treatment and were taking an SSRI medication. Data collected included demographics, medical history, dental visits and procedures, and use of adjunctive measures to control bleeding. Primary outcomes included documentation of return visits or phone calls to the dental clinic or emergency department (ED) for oral bleeding, and oral bleeding or use of blood products for inpatients. There were 92 patients taking SSRIs who had 145 invasive procedure visits, consisting of extractions, implant surgery, alveoloplasty, periodontal surgery, subgingival scaling and root planning, and biopsy. There were 110 extraction visits yielding a total of 167 extractions. Among all patients, there was 1 return visit to the clinic and 1 telephone call with a chief complaint of oral bleeding. The frequency of oral bleeding complications after invasive dental treatment is low to negligible in patients on SSRI medications. Copyright © 2011 Mosby, Inc. All rights reserved.

  6. Directional postcopulatory sexual selection revealed by artificial insemination.

    Science.gov (United States)

    Evans, Jonathan P; Zane, Lorenzo; Francescato, Samuela; Pilastro, Andrea

    2003-01-23

    Postcopulatory sexual selection comprises both sperm competition, where the sperm from different males compete for fertilization, and cryptic female choice, where females bias sperm use in favour of particular males. Despite intense current interest in both processes as potential agents of directional sexual selection, few studies have attributed the success of attractive males to events that occur exclusively after insemination. This is because the interactions between pre- and post-insemination episodes of sexual selection can be important sources of variation in paternity. The use of artificial insemination overcomes this difficulty because it controls for variation in male fertilization success attributable to the female's perception of male quality, as well as effects due to mating order and the relative contribution of sperm from competing males. Here, we adopt this technique and show that in guppies, when equal numbers of sperm from two males compete for fertilization, relatively colourful individuals achieve greater parentage than their less ornamented counterparts. This finding indicates that precopulatory female mating preferences can be reinforced exclusively through postcopulatory processes occurring at a physiological level. Our analysis also revealed that relatively small individuals were advantaged in sperm competition, suggesting a possible trade-off between sperm competitive ability and body growth.

  7. Food allergen selective thermal processing regimens may change oral tolerance in infancy.

    Science.gov (United States)

    Kosti, R I; Triga, M; Tsabouri, S; Priftis, K N

    2013-01-01

    Food allergy can be considered a failure in the induction of oral tolerance. Recently, great interest has been focused on understanding the mechanisms and the contributing factors of oral tolerance development, hoping for new definitive interventions in the prevention and treatment of food allergy. Given that food processing may modify the properties and the nature of dietary proteins, several food processing methods could affect the allergenicity of these proteins and consequently may favour oral tolerance induction to food allergic children. Indeed, effective thermal food processing regimens of altering food proteins to reduce allergenicity have been recently reported in the literature. This article is mainly focused on the effect of selective thermal processing regimens on the main infant allergenic foods, with a potential clinical relevance on their allergenicity and therefore on oral tolerance induction. In the light of recent findings, the acquisition of tolerance in younger age and consequently the ability of young children to "outgrow" food allergy could be achieved through the application of selective thermal processing regimens on certain allergenic foods. Therefore, the ability of processed foods to circumvent clinical disease and at the same time to have an impact on the immune system and facilitate tolerance induction could be invaluable as a component of a successful therapeutic strategy. The opening in the new avenues of research in the use of processed foods in clinical practice for the amelioration of the impact on the quality of life of patients and possibly in food allergy prevention is warranted.

  8. Binocular rivalry waves in a directionally selective neural field model

    Science.gov (United States)

    Carroll, Samuel R.; Bressloff, Paul C.

    2014-10-01

    We extend a neural field model of binocular rivalry waves in the visual cortex to incorporate direction selectivity of moving stimuli. For each eye, we consider a one-dimensional network of neurons that respond maximally to a fixed orientation and speed of a grating stimulus. Recurrent connections within each one-dimensional network are taken to be excitatory and asymmetric, where the asymmetry captures the direction and speed of the moving stimuli. Connections between the two networks are taken to be inhibitory (cross-inhibition). As per previous studies, we incorporate slow adaption as a symmetry breaking mechanism that allows waves to propagate. We derive an analytical expression for traveling wave solutions of the neural field equations, as well as an implicit equation for the wave speed as a function of neurophysiological parameters, and analyze their stability. Most importantly, we show that propagation of traveling waves is faster in the direction of stimulus motion than against it, which is in agreement with previous experimental and computational studies.

  9. The practical management of bleedings during treatment with direct oral anticoagulants: the emergency reversal therapy

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2013-12-01

    Full Text Available Bleeding represents the most feared complication of the new oral anticoagulants, direct oral anticoagulants (DOACs, as well as all the antithrombotic therapies. During the acute phase of bleeding in patients taking anticoagulants, restoration of an effective hemostasis represents the cornerstone of practical management. While vitamin K antagonists are effectively and promptly reversed by specific antidotes such as prothrombin complex concentrates (PCCs, fresh frozen plasma or vitamin K, it is still not clear how to manage the urgent reversal of DOACs during life-threatening or major bleedings due to the lack of specific antidotes. However, in vitro and ex vivo studies have suggested some potential strategies to reverse DOACs in clinical practice, other than general support measures that are always recommended. Activated charcoal could be used in subjects with DOAC-related bleedings presenting to the emergency department within two hours of the last oral intake. Non-activated or activated PCCs (FEIBA and recombinant activated Factor VII (raFVII seem to be the optimal strategy for urgent reversal of dabigatran, while non-activated PCCs seem to have efficacy in reversing rivaroxaban. Due to its low plasma protein binding, dabigatran could be also dialyzed in urgent cases. Clinically relevant non-major bleedings and minor bleedings should be treated with general and local measures, respectively, and, when necessary, with dose delay or drug withdrawal. In this article, the Authors describe the practical approach to bleedings occurring during DOACs treatment.

  10. Mutation directional selection sheds light on prion pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Liang [Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo 255049 (China); Ji, Hong-Fang, E-mail: jhf@sdut.edu.cn [Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo 255049 (China)

    2011-07-01

    Highlights: {yields} Most pathogenic mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. {yields} Mutation-induced changes may strengthen the interactions between PrP and facilitating factors. {yields} The findings also have significant implications for exploring potential regions involved in the conformational transition from PrP{sup C} to PrP{sup Sc}. -- Abstract: As mutations in the PRNP gene account for human hereditary prion diseases (PrDs), it is crucial to elucidating how these mutations affect the central pathogenic conformational transition of normal cellular prion protein (PrP{sup C}) to abnormal scrapie isoform (PrP{sup Sc}). Many studies proposed that these pathogenic mutations may make PrP more susceptible to conformational change through altering its structure stability. By evaluating the most recent observations regarding pathogenic mutations, it was found that the pathogenic mutations do not exert a uniform effect on the thermodynamic stability of the human PrP's structure. Through analyzing the reported PrDs-related mutations, we found that 25 out of 27 mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. Based on the triggering role reported by previous studies of facilitating factors in PrP{sup C} conversion, e.g., lipid and polyanion, we proposed that the mutation-induced changes may strengthen the interaction between PrP and facilitating factors, which will accelerate PrP conversion and cause PrDs.

  11. Direct and selective small-molecule activation of proapoptotic BAX

    Science.gov (United States)

    Gavathiotis, Evripidis; Reyna, Denis E; Bellairs, Joseph A; Leshchiner, Elizaveta S; Walensky, Loren D

    2013-01-01

    BCL-2 family proteins are key regulators of the apoptotic pathway. Antiapoptotic members sequester the BCL-2 homology 3 (BH3) death domains of proapoptotic members such as BAX to maintain cell survival. The antiapoptotic BH3-binding groove has been successfully targeted to reactivate apoptosis in cancer. We recently identified a geographically distinct BH3-binding groove that mediates direct BAX activation, suggesting a new strategy for inducing apoptosis by flipping BAX’s ‘on switch’. Here we applied computational screening to identify a BAX activator molecule that directly and selectively activates BAX. We demonstrate by NMR and biochemical analyses that the molecule engages the BAX trigger site and promotes the functional oligomerization of BAX. The molecule does not interact with the BH3-binding pocket of antiapoptotic proteins or proapoptotic BAK and induces cell death in a BAX-dependent fashion. To our knowledge, we report the first gain-of-function molecular modulator of a BCL-2 family protein and demonstrate a new paradigm for pharmacologic induction of apoptosis. PMID:22634637

  12. Selection platforms for directed evolution in synthetic biology.

    Science.gov (United States)

    Tizei, Pedro A G; Csibra, Eszter; Torres, Leticia; Pinheiro, Vitor B

    2016-08-15

    Life on Earth is incredibly diverse. Yet, underneath that diversity, there are a number of constants and highly conserved processes: all life is based on DNA and RNA; the genetic code is universal; biology is limited to a small subset of potential chemistries. A vast amount of knowledge has been accrued through describing and characterizing enzymes, biological processes and organisms. Nevertheless, much remains to be understood about the natural world. One of the goals in Synthetic Biology is to recapitulate biological complexity from simple systems made from biological molecules-gaining a deeper understanding of life in the process. Directed evolution is a powerful tool in Synthetic Biology, able to bypass gaps in knowledge and capable of engineering even the most highly conserved biological processes. It encompasses a range of methodologies to create variation in a population and to select individual variants with the desired function-be it a ligand, enzyme, pathway or even whole organisms. Here, we present some of the basic frameworks that underpin all evolution platforms and review some of the recent contributions from directed evolution to synthetic biology, in particular methods that have been used to engineer the Central Dogma and the genetic code. © 2016 The Author(s).

  13. Prescription practices and medical knowledge on direct oral anticoagulants in a reference hospital

    Directory of Open Access Journals (Sweden)

    Correa, Manuela

    2015-04-01

    Full Text Available Introduction and objective: The experience and knowledge concerning the use of direct oral anticoagulants among specialists in Medellin, Colombia, are not known. Our goal was to describe the use of these drugs in patients treated at Hospital Pablo Tobón Uribe and to assess the level of knowledge regarding this issue in professionals from this institution. Materials and methods: Cross sectional study conducted between January 2012 and January 2013. Two strategies to collect information were used, namely: Analysis of relevant medical records and evaluation of knowledge about the appropriate use and prescription of direct oral anticoagulants in the group of medical specialists. Results: 114 records were included in the analysis; rivaroxaban was the most frequently prescribed drug (87% followed by dabigatran (13%. The main indication was prophylaxis in orthopedic surgery (69%. Average of correct answers among the different specialists evaluated was 67% with no apparent difference between them. Conclusion: rivaroxaban was prescribed more often than dabigatran; however, this fact does not appear to be associated with a clear and sufficient medical knowledge about these drugs. No reports of adverse events associated with this therapy were found.

  14. Oral methylphenidate challenge selectively decreases putaminal T2 in healthy subjects.

    Science.gov (United States)

    Silveri, Marisa M; Anderson, Carl M; McNeil, Jane F; Diaz, Claudia I; Lukas, Scott E; Mendelson, Jack H; Renshaw, Perry F; Kaufman, Marc J

    2004-11-11

    Despite the recent rise in oral methylphenidate (MPH) abuse, few studies have characterized the time course of oral MPH brain effects in human subjects. Accordingly, this study assessed the hemodynamic effects of oral MPH effects in 11 healthy young adults (six women), by measuring brain transverse relaxation times (T2). T2 can be interpreted as a surrogate marker for, and inversely correlated with, steady-state cerebral blood volume (CBV). Data were acquired from the caudate nucleus, putamen, and thalamus, using a 1.5 T MRI scanner at baseline and serially for 2 h following oral MPH administration (0.5 mg/kg). Physiological and subjective measures and plasma MPH levels also were examined. MPH induced a selective T2 decrease (-1.65+/-0.53 ms) in the putamen (F(6,54)=2.68, PHeartrate, blood pressure and plasma MPH levels increased significantly after drug administration, as well as subjective ratings of "feeling drug effect". T2 decreases may reflect MPH-induced increases in putaminal blood volume. These data suggest that T2 relaxometry can be used to study the time course of regional cerebral blood volume responses to MPH and perhaps to other stimulant drugs.

  15. Orally Active and Selective Tubulin Inhibitors as Anti-Trypanosome Agents.

    Directory of Open Access Journals (Sweden)

    Vishal Nanavaty

    Full Text Available There is an urgent need to develop a safe, effective, orally active, and inexpensive therapy for African trypanosomiasis due to the drawbacks of current drugs. Selective tubulin inhibitors have the potential to be promising drug candidates for the treatment of this disease, which is based on the tubulin protein structural difference between mammalian and trypanosome cells. We propose to identify novel tubulin inhibitors from a compound library developed based on the lead compounds that selectively target trypanosomiasis.We used Trypanosoma brucei brucei as the parasite model, and human normal kidney cells and mouse microphage cells as the host model. Growth rates of both trypanosomes and mammalian cells were determined as a means to screen compounds that selectively inhibit the proliferation of parasites. Furthermore, we examined the cell cycle profile of the parasite and compared tubulin polymerization dynamics before and after the treatment using identified compounds. Last, in vivo anti-parasite activities of these compounds were determined in T. brucei-infected mice.Three compounds were selected that are 100 fold more effective against the growth of T. brucei cells than mammalian cells. These compounds caused cell cycle progression defects in T. brucei cells. Western analyses indicated that these compounds decreased tubulin polymerization in T. brucei cells. The in vivo investigation revealed that these compounds, when admitted orally, inhibited T. brucei cell proliferation in mouse blood. However, they were not potent enough to clear up the infection completely.These compounds are promising lead compounds as orally active agents for drug development of anti-trypanosome agents. A more detail structure activity relationship (SAR was summarized that will be used to guide future lead optimization to improve the selectivity and potency of the current compounds.

  16. Role of GP82 in the selective binding to gastric mucin during oral infection with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Daniela I Staquicini

    Full Text Available Oral infection by Trypanosoma cruzi has been the primary cause of recent outbreaks of acute Chagas' diseases. This route of infection may involve selective binding of the metacyclic trypomastigote surface molecule gp82 to gastric mucin as a first step towards invasion of the gastric mucosal epithelium and subsequent systemic infection. Here we addressed that question by performing in vitro and in vivo experiments. A recombinant protein containing the complete gp82 sequence (J18, a construct lacking the gp82 central domain (J18*, and 20-mer synthetic peptides based on the gp82 central domain, were used for gastric mucin binding and HeLa cell invasion assays, or for in vivo experiments. Metacyclic trypomastigotes and J18 bound to gastric mucin whereas J18* failed to bind. Parasite or J18 binding to submaxillary mucin was negligible. HeLa cell invasion by metacyclic forms was not affected by gastric mucin but was inhibited in the presence of submaxillary mucin. Of peptides tested for inhibition of J18 binding to gastric mucin, the inhibitory peptide p7 markedly reduced parasite invasion of HeLa cells in the presence of gastric mucin. Peptide p7*, with the same composition as p7 but with a scrambled sequence, had no effect. Mice fed with peptide p7 before oral infection with metacyclic forms developed lower parasitemias than mice fed with peptide p7*. Our results indicate that selective binding of gp82 to gastric mucin may direct T. cruzi metacyclic trypomastigotes to stomach mucosal epithelium in oral infection.

  17. Oral microflora and selection of resistance after a single dose of amoxicillin.

    Science.gov (United States)

    Khalil, D; Hultin, M; Rashid, M U; Lund, B

    2016-11-01

    The study aimed to determine the effects of a single-dose antibiotic prophylaxis on normal oral microflora. A single dose of 2 g amoxicillin was given to 29 healthy volunteers. Saliva was collected before antibiotic administration (day 1), and again on days 2, 5, 10, 17 and 24 and subjected to culturing and antibiotic sensitivity analysis. Twenty-one per cent (6/29) of the individuals carried penicillin-V- and amoxicillin-resistant viridans streptococci before antibiotic administration. After a single dose of amoxicillin there was a significant reduction in Streptococcus salivarius on days 2 and 5, a significant reduction in other viridans streptococci on day 2 and the proportion of viridans streptococci with reduced susceptibility to amoxicillin was significantly increased on days 2 and 5. A single dose of amoxicillin can cause an ecological disturbance and induce selection of resistant strains in the oral microflora.

  18. The direct peptide reactivity assay: selectivity of chemical respiratory allergens.

    Science.gov (United States)

    Lalko, Jon F; Kimber, Ian; Gerberick, G Frank; Foertsch, Leslie M; Api, Anne Marie; Dearman, Rebecca J

    2012-10-01

    It is well known that some chemicals are capable of causing allergic diseases of the skin and respiratory tract. Commonly, though not exclusively, chemical allergens are associated with the selective development of skin or respiratory sensitization. The reason for this divergence is unclear, although it is hypothesized that the nature of interactions between the chemical hapten and proteins is influential. The direct peptide reactivity assay (DPRA) has been developed as a screen for the identification of skin-sensitizing chemicals, and here we describe the use of this method to explore whether differences exist between skin and respiratory allergens with respect to their peptide-binding properties. Known skin and respiratory sensitizers were reacted with synthetic peptides containing either lysine (Lys) or cysteine (Cys) for 24 h. The samples were analyzed by HPLC/UV, and the loss of peptide from the reaction mixture was expressed as the percent depletion compared with the control. The potential for preferential reactivity was evaluated by comparing the ratio of Lys to Cys depletion (Lys:Cys ratio). The results demonstrate that the majority of respiratory allergens are reactive in the DPRA, and that in contrast to most skin-sensitizing chemicals, preferentially react with the Lys peptide. These data suggest that skin and respiratory chemical allergens can result in different protein conjugates, which may in turn influence the quality of induced immune responses. Overall, these investigations reveal that the DPRA has considerable potential to be incorporated into tiered testing approaches for the identification and characterization of chemical respiratory allergens.

  19. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians.

    Science.gov (United States)

    Peacock, W Frank; Rafique, Zubaid; Singer, Adam J

    2016-01-01

    Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)-dabigatran, rivaroxaban, apixaban, and edoxaban-have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.

  20. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

    Directory of Open Access Journals (Sweden)

    W. Frank Peacock

    2016-01-01

    Full Text Available Nonvalvular atrial fibrillation- (NVAF- related stroke and venous thromboembolism (VTE are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.

  1. Direct oral anticoagulants and antiplatelet agents. Clinical relevance and options for laboratory testing.

    Science.gov (United States)

    Sibbing, D; Spannagl, M

    2014-01-01

    Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.

  2. Hot isostatic pressing of direct selective laser sintered metal components

    Science.gov (United States)

    Wohlert, Martin Steven

    2000-10-01

    A new manufacturing process combining the benefits of Selective Laser Sintering (SLS) and Hot Isostatic Pressing (HIP) has been developed to permit Rapid Prototyping of high performance metal components. The new process uses Direct Metal SLS to produce a gas impermeable HIP container from the same powdered material that will eventually compose the bulk of the part. The SLS generated capsule performs the functions of the sheet metal container in traditional HIP, but unlike a sheet metal container, the SLSed capsule becomes an integral part of the final component. Additionally, SLS can produce a capsule of far greater geometric complexity than can be achieved by sheet metal forming. Two high performance alloys, Ti-6Al-4V and Inconel 625, were selected for use in the development of the new process. HIP maps were constructed to predict the densification rate of the two materials during HIP processing. Comparison to experimentally determined densification behavior indicated that the maps provide a useful qualitative description of densification rates; however, the accuracy of quantitative predictions was greatly enhanced by tuning key material parameters based on a limited number of experimental HIP cycles. Microstructural characterization of SLS + HIP samples revealed two distinct regions within the components. The outer SLS processed capsule material exhibited a relatively coarse microstructure comparable to a cast, or multi-layer welded structure. No layer boundaries were discernible in the SLS material, with grains observed to grow epitaxially from previously deposited material. The microstructure of the HIP consolidated core material was similar to conventionally HIP processed powder materials, featuring a fine grain structure and preserved prior particle boundaries. The large variation in grain size between the capsule and core materials was reflected in hardness measurements conducted on the Alloy 625 material; however, the variation in hardness was less

  3. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2010-12-01

    Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

  4. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-12-13

    Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

  5. Selective cytotoxic activity of grape peel and seed extracts against oral tumor cell lines.

    Science.gov (United States)

    Shirataki, Y; Kawase, M; Saito, S; Kurihara, T; Tanaka, W; Satoh, K; Sakagami, H; Motohashi, N

    2000-01-01

    Grape seed extracts were more cytotoxic than grape peel extracts. Methanol and 70% methanol extracts of grape seed selectively killed two human oral tumor cell lines, more efficiently than human gingival fibroblasts. ESR spectroscopy revealed that these extracts produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate at higher concentrations. On the other hand, lower concentration of these extracts slightly reduced the radical intensity of sodium ascorbate, and scavenged superoxide anion, generated by hypoxanthine and xanthine oxidase reaction. These properties of grape seed extracts suggest their possible application for cancer prevention.

  6. Novel 3-Oxazolidinedione-6-aryl-pyridinones as Potent, Selective, and Orally Active EP3 Receptor Antagonists.

    Science.gov (United States)

    Jin, Jian; Morales-Ramos, Angel; Eidam, Patrick; Mecom, John; Li, Yue; Brooks, Carl; Hilfiker, Mark; Zhang, David; Wang, Ning; Shi, Dongchuan; Tseng, Pei-San; Wheless, Karen; Budzik, Brian; Evans, Karen; Jaworski, Jon-Paul; Jugus, Jack; Leon, Lisa; Wu, Charlene; Pullen, Mark; Karamshi, Bhumika; Rao, Parvathi; Ward, Emma; Laping, Nicholas; Evans, Christopher; Leach, Colin; Holt, Dennis; Su, Xin; Morrow, Dwight; Fries, Harvey; Thorneloe, Kevin; Edwards, Richard

    2010-10-14

    High-throughput screening and subsequent optimization led to the discovery of novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent and selective EP3 antagonists with excellent pharmacokinetic properties. Compound 2 was orally active and showed robust in vivo activities in overactive bladder models. To address potential bioactivation liabilities of compound 2, further optimization resulted in compounds 9 and 10, which maintained excellent potency, selectivity, and pharmacokinetic properties and showed no bioactivation liability in glutathione trapping studies. These highly potent, selective, and orally active EP3 antagonists are excellent tool compounds for investigating and validating potential therapeutic benefits from selectively inhibiting the EP3 receptor.

  7. Relationship between Selected Socio-Demographic Factors and Cancer of Oral Cavity - A Case Control Study

    Directory of Open Access Journals (Sweden)

    Abdoul Hossain Madani

    2010-08-01

    Full Text Available The aim of this study was to recognize factors associated with cancer of oral cavity considering socio-demographic characteristics. The cases were 350 with squamous-cell carcinoma of oral cavity diagnosed between 2005 and 2006 in Morbai, Narandia, Budharani Cancer Institute, Pune, India. Similar number of controls match for age and sex selected from the background population. Cases and controls were interviewed for tobacco related habits and general characteristics; age, gender, education and possible socio-demographic factors. Chi-square test in uni-variate analysis and estimate for risk showed that education, occupation and monthly household income were significantly different between cases and controls (P < 0.001. Irrespective to gender, relative risk, here odds ratio, (OR of low level of education (OR = 5.3, CI 3.7–7.6, working in field as a farmer (OR = 2.5, CI 1.7–3.7, and monthly household income less than 5000 Indian Rupees currency (OR = 1.7, CI 1.2–2.3 were significant risk factors for oral cancer. While, there was no significant relationship between religious and or marital status either in males or females.

  8. Periodontal status and selected parameters of oral condition of Poles aged 65 to 74 years.

    Science.gov (United States)

    Konopka, Tomasz; Dembowska, Elżbieta; Pietruska, Małgorzata; Dymalski, Paweł; Górska, Renata

    2015-01-01

    The goal of this study was the evaluation of the periodontal health by means of CPI score in inhabitants of big and small cities in the age range from 65 to 74 and making comparison with previous Polish and European studies from XXI century. Also an average number of natural teeth, the edentulous persons percentage, the percentage of people with oral function maintenance and prevalence of oral mucosal diseases were evaluated. There were also attempts to evaluate essential behaviours related to the oral health and the percentage of people that are treated with use of non-reimbursed or reimbursed services. Studies were conducted in 5 big cities: Warszawa, Szczecin, Wrocław, Białystok and Toruń, as well as in 4 towns, such as Oława, Police, Łobez and Ełk. From sampling 7400 people aged from 65 to 74 years for the study reported only 807 people. In the mouth evaluated CPI score, number of natural teeth and prevalence of pathological lesions on cavity mucosa. Answers for questions on selected attitudes and health-seeking behaviours related to the oral health and the range of dental treatment were also analysed. Distribution of values of CPI codes in the whole group was as follows: CPI0-1.2%, CPI1-9.4%, CPI2-16.6%, CPI3-21.8%, CPI4-19.7% and the number of people excluded from examinations (1 tooth in the sextant or edentulous 31.3%). The state of the periodontium was worse in big cities and in men. An average number of teeth was 13.7 and was higher in big cities and in men. The percentage of edentulous persons was 28.9% and was higher in towns and in woman. The percentage of people with oral function maintenance was 25.15% and was higher in big cities and in men. The most three common pathologies of the oral cavity were leukoplakia and leukokeratosis that were found in 10.5% of examined people, candidiasis 5.82% and lichen planus 2.2%. The state of the periodontium of Poles at the age from 65 to 74 has not been improved in XXI century, but also does not

  9. Prevalence of Oral Trichomoniasis in Patients with Periodontitis and Gingivitis Using PCR and Direct Smear

    OpenAIRE

    Athari, A; L Soghandi; A Haghighi; B Kazemi

    2007-01-01

    Background: Trichomonas tenax, a commensal flagellated protozoan, inhabits in human oral cavity. This parasite is cos-mopoli­tan and frequently found in patients with poor oral hygiene and advanced periodontal disease. There is only one pub­lished study that rebound the prevalence of this parasite in Iran. This PCR based study compared the prevalence of oral tricho­moni­asis in patients with oral diseases and a healthy control group.Methods: From May 2005 to Ap...

  10. Direct and indirect control of oral ectoderm regulatory gene expression by Nodal signaling in the sea urchin embryo.

    Science.gov (United States)

    Li, Enhu; Materna, Stefan C; Davidson, Eric H

    2012-09-15

    The Nodal signaling pathway is known from earlier work to be an essential mediator of oral ectoderm specification in the sea urchin embryo, and indirectly, of aboral ectoderm specification as well. Following expression of the Nodal ligand in the future oral ectoderm during cleavage, a sequence of regulatory gene activations occur within this territory which depend directly or indirectly on nodal gene expression. Here we describe additional regulatory genes that contribute to the oral ectoderm regulatory state during specification in Strongylocentrotus purpuratus, and show how their spatial expression changes dynamically during development. By means of system wide perturbation analyses we have significantly improved current knowledge of the epistatic relations among the regulatory genes of the oral ectoderm. From these studies there emerge diverse circuitries relating downstream regulatory genes directly and indirectly to Nodal signaling. A key intermediary regulator, the role of which had not previously been discerned, is the not gene. In addition to activating several genes earlier described as targets of Nodal signaling, the not gene product acts to repress other oral ectoderm genes, contributing crucially to the bilateral spatial organization of the embryonic oral ectoderm. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy

    DEFF Research Database (Denmark)

    Hansen, Morten Lock; Jepsen, Rikke Malene H G; Olesen, Jonas Bjerring;

    2015-01-01

    AIMS: To study the risk of thromboembolism in a nationwide cohort of atrial fibrillation patients undergoing direct current (DC) cardioversion with or without oral anticoagulant coverage. METHODS AND RESULTS: A retrospective study of 16 274 patients in Denmark discharged from hospital after a first......-time DC cardioversion for atrial fibrillation between 2000 and 2008. Use of oral anticoagulant therapy within 90 days prior and 360 days after DC cardioversion was obtained from the Danish Register of Medicinal Product Statistics. The risk of thromboembolism was estimated by calculating incidence rates...... and by multivariable adjusted Cox proportional-hazard models. During the initial 30 days following discharge, the thromboembolic incidence rate was 10.33 per 100 patient-years for the no prior oral anticoagulant therapy group [n = 5084 (31.2%)], as compared with 4.00 per 100 patient-years for the prior oral...

  12. DIRECT SELECTION ON LIFE-SPAN IN DROSOPHILA-MELANOGASTER

    NARCIS (Netherlands)

    ZWAAN, B; BIJLSMA, R; HOEKSTRA, RE

    1995-01-01

    An important issue in the study of the evolution of aging in Drosophila melanogaster is whether decreased early fecundity is inextricably coupled with increased life span in selection experiments on age at reproduction. Here, this problem has been tackled using an experimental design in which select

  13. Newer non-vitamin K-antagonist direct oral anticoagulants in acute coronary syndromes

    Directory of Open Access Journals (Sweden)

    Andrea Rubboli

    2013-12-01

    Full Text Available standard dual antiplatelet therapy (DAPT of aspirin and clopidogrel is associated with a substantial absolute incidence of adverse events, including death, myocardial infarction and stroke after an acute coronary syndrome (ACs. Combination therapy of an oral anticoagulant and DAPT has been previously proposed in order to improve efficacy, but has not gained popularity owing to the cumbersome management of vitamin K-antagonists (VKA. The recent introduction of newer, non-VKA, direct oral anticoagulants (NOAC, including dabigatran, apixaban, and rivaroxaban, has renewed the interest in combination therapy, owing to the more favorable pharmacokinetic and pharmacodynamic profiles of these drugs. Whereas phase II studies with dabigatran, apixaban, and rivaroxaban have consistently shown an increased bleeding risk with combination therapy, a potential increased efficacy has emerged for apixaban and rivaroxaban, thereby prompting phase III studies, namely APPRAIsE-2 with apixaban and ATLAs ACs 2-TIMI 51 with rivaroxaban. Both APPRAIsE-2 and ATLAs ACs 2-TIMI 51 studies confirmed a dose-dependent increase in major, including intracranial, bleeding with apixaban and rivaroxaban when combined with DAPT. Low-dose rivaroxaban on the other hand, was associated with significantly higher efficacy on the occurrence of combined cardiovascular death, myocardial infarction, or stroke, as well as of cardiovascular death, myocardial infarction and stent thrombosis. Owing to the persistent uncertainty regarding the net clinical benefit of combined therapy of NOAC, namely low-dose rivaroxaban, and DAPT, further studies are warranted to identify the ACs patient who will benefit most from such treatment, also in comparison to current standard DAPT of aspirin and prasugrel or ticagrelor.

  14. Management of major bleedings during anticoagulant treatment with the oral direct thrombin inhibitor ximelagatran or warfarin.

    Science.gov (United States)

    Fernlöf, Gunilla; Sjöström, Britta M; Lindell, Klas M; Wall, Ulrika E

    2009-12-01

    Several new oral anticoagulants are currently investigated in phase III programmes, mainly with inhibition of factor Xa or thrombin as their pharmacological target. Advantages are expected with these new drugs compared with vitamin K antagonists, but one potential drawback is the lack of specific antidotes. During the clinical studies with ximelagatran, an oral direct thrombin inhibitor withdrawn due to hepatic side effects, investigators were instructed to manage bleedings with routine measures. We have retrospectively tried to assess whether this was sufficient or whether there was a need for reversal strategies. The study population consisted of patients with major bleedings in three long-term studies (104 ximelagatran, 155 warfarin). All individual patient narratives were reviewed with respect to management of the bleeding. Complementary data were retrieved from the data-based case report forms. Approximately, two of three of the patients in both groups were subject to some kind of treatment. One-third (1/3) in both groups had transfusions documented and/or received specific medication. Vitamin K was given more often to warfarin patients. Two ximelagatran patients received prothrombin complex (four-factor concentrate), but one was a patient with a severe hepatopathy suspected to be drug-induced. Overall, the case descriptions did not reveal any apparent differences in the course of events between groups. We found no indications that the lack of an antidote posed a clinical problem in patients treated with ximelagatran as compared with warfarin. The relatively short half-life of melagatran, the active metabolite of ximelagatran, may have contributed to these results.

  15. Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device in patients with mild to moderate obstructive sleep apnoea.

    Science.gov (United States)

    De Corso, E; Bastanza, G; Della Marca, G; Grippaudo, C; Rizzotto, G; Marchese, M R; Fiorita, A; Sergi, B; Meucci, D; Di Nardo, W; Paludetti, G; Scarano, E

    2015-12-01

    Nowadays oral appliance therapy is recognised as an effective therapy for many patients with primary snoring and mild to moderate obstructive sleep apnoea (OSA), as well as those with more severe OSA who cannot tolerate positive airway pressure (PAP) therapies. For this reason, it is important to focus on objective criteria to indicate which subjects may benefit from treatment with a mandibular advancement device (MAD). Various anthropometric and polysomnographic predictors have been described in the literature, whereas there are still controversies about the role of drug-induced sleep endoscopy (DISE) and advancement bimanual manoeuvre as predictor factors of treatment outcome by oral device. Herein, we report our experience in treatment of mild moderate OSA by oral appliance selected by DISE. We performed a single institution, longitudinal prospective evaluation of a consecutive group of mild moderate patients with obstructive sleep apnoea syndrome who underwent DISE. During sleep endoscopy, gentle manoeuvre of mandibular advancement less than 5 mm was performed. In 30 of 65 patients (46.2%) we obtained an unsuccessful improvement of airway patency whereas in 35 of 65 patients (53.8%) the improvement was successful and patients were considered suitable for oral device application. Because 7 of 35 patients were excluded due to conditions interfering with oral appliance therapy, we finally treated 28 patients. After 3 months of treatment, we observed a significant improvement in the Epworth medium index [(7.35 ± 2.8 versus 4.1 ± 2.2 (p DISE for MAD therapy. In the current study, mandibular advancement splint therapy was successfully prescribed on the basis not only of severity of disease, as determined by the subject's initial AHI, but also by DISE findings combined with results of gentle mandibular advancement manoeuvre allowing direct view of the effects of mandibular protrusion on breathing spaces in obstruction sites, and showing good optimisation of

  16. EXEL; Experience for Children in Learning. Parent-Directed Activities to Develop: Oral Expression, Visual Discrimination, Auditory Discrimination, Motor Coordination.

    Science.gov (United States)

    Behrmann, Polly; Millman, Joan

    The activities collected in this handbook are planned for parents to use with their children in a learning experience. They can also be used in the classroom. Sections contain games designed to develop visual discrimination, auditory discrimination, motor coordination and oral expression. An objective is given for each game, and directions for…

  17. Direct current electrical fields induce apoptosis in oral mucosa cancer cells by NADPH oxidase-derived reactive oxygen species.

    Science.gov (United States)

    Wartenberg, Maria; Wirtz, Nina; Grob, Alexander; Niedermeier, Wilhelm; Hescheler, Jürgen; Peters, Saskia C; Sauer, Heinrich

    2008-01-01

    The presence of more than one dental alloy in the oral cavity often causes pathological galvanic currents and voltage resulting in superficial erosions of the oral mucosa and eventually in the emergence of oral cancer. In the present study the mechanisms of apoptosis of oral mucosa cancer cells in response to electromagnetic fields was investigated. Direct current (DC) electrical fields with field strengths between 2 and 16 V/m, applied for 24 h to UM-SCC-14-C oral mucosa cancer cells, dose-dependently resulted in decreased cell proliferation as evaluated by Ki-67 immunohistochemistry and upregulation of the cyclin-dependent kinase (CDK) inhibitors p21(cip1/waf1) and p27(kip1), which are associated with cell cycle arrest. Electrical field treatment (4 V/m, 24 h) increased apoptosis as evaluated by immunohistochemical analysis of cleaved caspase-3 and poly-(ADP-ribose)-polymerase-1 (PARP-1). Furthermore, robust reactive oxygen species (ROS) generation, increased expression of NADPH oxidase subunits as well as Hsp70 was observed. Electrical field treatment (4 V/m, 24 h) resulted in increased expression of Cu/Zn superoxide dismutase and decreased intracellular concentration of reduced glutathione (GSH), whereas the expression of catalase remained unchanged. Pre-treatment with the free radical scavenger N-acetyl cysteine (NAC) and the superoxide dismutase mimetic EUK-8 abolished caspase-3 and PARP-1 induction, suggesting that apoptosis in oral mucosa cancer cells is initated by ROS generation in response to DC electrical field treatment.

  18. Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

    Science.gov (United States)

    Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

    2016-11-01

    All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

  19. Direct oral anticoagulant use in nonvalvular atrial fibrillation with valvular heart disease: a systematic review.

    Science.gov (United States)

    Owens, Ryan E; Kabra, Rajesh; Oliphant, Carrie S

    2016-12-22

    Direct oral anticoagulants (DOACs) are indicated for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), which, according to the American College of Cardiology/American Heart Association/Heart Rhythm Society atrial fibrillation (AF) guidelines, excludes patients with rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. However, the data regarding use of DOACs in AF patients with other types of valvular heart disease (VHD) are unclear. We aimed to summarize and evaluate the literature regarding the safety and efficacy of DOAC use in NVAF patients with other types of VHD. After an extensive literature search, a total of 1 prospective controlled trial, 4 subanalyses, and 1 abstract were identified. Efficacy of the DOAC agents in NVAF patients with VHD mirrored the overall trial results. Bleeding risk was significantly increased in VHD patients treated with rivaroxaban, but not for dabigatran or apixaban. Of the bioprosthetic valve patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, no safety or efficacy concerns were identified. In conclusion, subanalyses of DOAC landmark AF trials revealed that dabigatran, rivaroxaban, and apixaban may be safely used in AF patients with certain types of VHD: aortic stenosis, aortic regurgitation, and mitral regurgitation. More evidence is needed before routinely recommending these agents for patients with bioprosthetic valves or mild mitral stenosis. Patients with moderate to severe mitral stenosis or mechanical valves should continue to receive warfarin, as these patients were excluded from all landmark AF trials.

  20. A directly converting high-resolution intra-oral X-ray imaging sensor

    CERN Document Server

    Spartiotis, K; Schulman, T; Puhakka, K; Muukkonen, K

    2003-01-01

    A digital intra-oral X-ray imaging sensor with an active area of 3.6x2.9 cm sup 2 and consisting of six charge-integrating CMOS signal readout circuits bump bonded to one high-resistivity silicon pixel detector has been developed and tested. The pixel size is 35 mu m. The X-rays entering the sensor window are converted directly to electrical charge in the depleted detector material yielding minimum lateral signal spread and maximum image sharpness. The signal charge is collected on the gates of the input field effect transistors of the CMOS signal readout circuits. The analog signal readout is performed by multiplexing in the current mode independent of the signal charge collection enabling multiple readout cycles with negligible dead time and thus imaging with wide dynamic range. Since no intermediate conversion material of X-rays to visible light is needed, the sensor structure is very compact. The analog image signals are guided from the sensor output through a thin cable to signal processing, AD conversio...

  1. Direct oral anticoagulants: analysis of worldwide use and popularity using Google Trends.

    Science.gov (United States)

    Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco; Favaloro, Emmanuel J

    2017-08-01

    Four direct oral anticoagulants (DOACs) have been approved for clinical use by many medicines regulatory agencies around the world. Due to increasing use of these drugs in routine practice, we planned an original study to investigate their worldwide diffusion using a popular Web-search engine. Two electronic searches were performed using Google Trends, the former using the keywords "warfarin" AND "heparin" AND "fondaparinux", and the latter using the keywords "warfarin" AND "dabigatran" AND "rivaroxaban" AND "apixaban" AND "edoxaban", both using the search criterion "prescription drug". No language restriction was applied, and the searches were carried out from the first date available in Google Trends (January 1(st), 2004) to present time (June 1(st), 2017). The median Google Trends score of warfarin (i.e., 86) was consistently higher than that of heparin (54; PGoogle searches for DOACs were performed in North America, central-eastern Europe and Australia. The results of our analysis suggest that the popularity of DOACs is constantly increasing around the world, whereas that of warfarin has exhibited a constant and inexorable decline.

  2. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    Science.gov (United States)

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo.

  3. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

    Science.gov (United States)

    Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

    2017-01-01

    Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r(2) = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r(2) = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

  4. Systematic Treatment Selection (STS): A Review and Future Directions

    Science.gov (United States)

    Nguyen, Tam T.; Bertoni, Matteo; Charvat, Mylea; Gheytanchi, Anahita; Beutler, Larry E.

    2007-01-01

    Systematic Treatment Selection (STS) is a form of technical eclectism that develops and plans treatments using empirically founded principles of psychotherapy. It is a model that provides systematic guidelines for the utilization of different psychotherapeutic strategies based on patient qualities and problem characteristics. Historically, it…

  5. Pattern and phase selection of peritectic reaction during directional solidification

    Institute of Scientific and Technical Information of China (English)

    HUANG; Weidong; (黄卫东); LIN; Xin; (林鑫); WANG; Meng; (王猛); SHEN; Shujuan; (沈淑娟); SU; Yunpeng; (苏云鹏); LIU; Zhenxia; (刘振侠)

    2002-01-01

    Based on the growth competition between different pattern and phases, the pattern and phase selection during peritectic solidification is analysed by applying the maximum interface temperature criterion to the interface response functions calculated from a numerical model for single phase solidification. The theoretical results agree very well with the experimental results published in literature.

  6. DIRECT SELECTION ON LIFE-SPAN IN DROSOPHILA-MELANOGASTER

    NARCIS (Netherlands)

    ZWAAN, B; BIJLSMA, R; HOEKSTRA, RE

    An important issue in the study of the evolution of aging in Drosophila melanogaster is whether decreased early fecundity is inextricably coupled with increased life span in selection experiments on age at reproduction. Here, this problem has been tackled using an experimental design in which

  7. Factors Affecting Patients' Perception On, and Adherence To, Anticoagulant Therapy: Anticipating the Role of Direct Oral Anticoagulants.

    Science.gov (United States)

    Pandya, Ekta Y; Bajorek, Beata

    2017-04-01

    The role of the direct oral anticoagulants (DOACs) in practice has been given extensive consideration recently, albeit largely from the clinician's perspective. However, the effectiveness and safety of using anticoagulants is highly dependent on the patient's ability to manage and take these complex, high-risk medicines. This structured narrative review explores the published literature to identify the factors underpinning patients' non-adherence to anticoagulants in atrial fibrillation (AF), and subsequently contemplates to what extent the DOACs might overcome the known challenges with traditional warfarin therapy. This review comprised a two-tier search of various databases and search platforms (CINAHL, Cochrane, Current Contents Connect, EMBASE, MEDLINE Ovid, EBSCO, PubMed, Google, Google Scholar) to yield 47 articles reporting patients perspectives on, and patients adherence to, anticoagulant therapy. The findings from the literature were synthesised under five interacting dimensions of adherence: therapy-related factors, patient-related factors, condition-related factors, social-economic factors and health system factors. Factors negatively affecting patients' day-to-day lives (especially regular therapeutic drug monitoring, dose adjustments, dietary considerations) predominantly underpin a patient's reluctance to take warfarin therapy, leading to non-adherence. Other patient-related factors underpinning non-adherence include patients' perceptions and knowledge about the purpose of anticoagulation; understanding of the risks and benefits of therapy; socioeconomic status; and expectations of care from health professionals. In considering these findings, it is apparent that the DOACs may overcome some of the barriers to traditional warfarin therapy at least to an extent, particularly the need for regular monitoring, frequent dose adjustment and dietary considerations. However, their high cost, twice-daily dosing and gastrointestinal adverse effects may present

  8. Direct and correlated responses to selection on iridoid glycosides in Plantago lanceolata L.

    NARCIS (Netherlands)

    Marak, H.B.; Biere, A.; Van Damme, J.M.M.

    2000-01-01

    Plantago lanceolata L. (ribwort plantain) produces two costly terpenoid secondary plant compounds, the iridoid glycosides aucubin and catalpol. We performed an artificial selection experiment to investigate direct and correlated responses to selection on the constitutive level of iridoid glycosides

  9. Transition moment directions and selected spectroscopic properties of Ivabradine

    Science.gov (United States)

    Synak, A.; Pikul, P.; Bojarski, P.; Nowakowska, J.; Wiczk, W.; Łukaszewicz, A.; Kubicki, A. A.

    2013-01-01

    Based on the Kawski-Gryczynski method the value of angle β = 38° between absorption and fluorescence transition moments of Ivabradine was determined. Such a high value of β is responsible for low emission anisotropy of Ivabradine in a rigid polyvinyl alcohol matrix and in anhydrous glycerol despite the elongated shape of the fluorophore. Selected steady-state and time-resolved spectroscopic results support the analysis.

  10. Toxoplasma gondii oral infection induces intestinal inflammation and retinochoroiditis in mice genetically selected for immune oral tolerance resistance.

    Directory of Open Access Journals (Sweden)

    Raul Ramos Furtado Dias

    Full Text Available Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS or resistance (TR to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.

  11. Toxoplasma gondii Oral Infection Induces Intestinal Inflammation and Retinochoroiditis in Mice Genetically Selected for Immune Oral Tolerance Resistance

    Science.gov (United States)

    Dias, Raul Ramos Furtado; de Carvalho, Eulógio Carlos Queiroz; Leite, Carla Cristina da Silva; Tedesco, Roberto Carlos; Calabrese, Katia da Silva; Silva, Antonio Carlos; DaMatta, Renato Augusto; de Fatima Sarro-Silva, Maria

    2014-01-01

    Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis. PMID:25437299

  12. Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors

    DEFF Research Database (Denmark)

    Artang, Ramin; Rome, Eric; Nielsen, Jørn Dalsgaard;

    2013-01-01

    . To address these questions, we systematically searched MEDLINE and performed a meta-analysis on randomized trials that compared oral DTIs with warfarin for any indication with end point of MIs after randomization. We furthermore performed a secondary meta-analysis on atrial fibrillation stroke prevention......Dabigatran has been associated with greater risk of myocardial infarction (MI) than warfarin. It is unknown whether the increased risk is unique to dabigatran, an adverse effect shared by other oral direct thrombin inhibitors (DTIs), or the result of a protective effect of warfarin against MI...... trials with alternative anticoagulants compared with warfarin with end point of MIs after randomization. A total of 11 trials (39,357 patients) that compared warfarin to DTIs (dabigatran, ximelagatran, and AZD0837) were identified. In these trials, patients treated with oral DTIs were more likely...

  13. Assessment of the influence of traffic-related particles in urban dust using sequential selective extraction and oral bioaccessibility tests.

    Science.gov (United States)

    Patinha, C; Durães, N; Sousa, P; Dias, A C; Reis, A P; Noack, Y; Ferreira da Silva, E

    2015-08-01

    Urban dust is a heterogeneous mix, where traffic-related particles can combine with soil mineral compounds, forming a unique and site-specific material. These traffic-related particles are usually enriched in potentially harmful elements, enhancing the health risk for population by inhalation or ingestion. Urban dust samples from Estarreja city and traffic-related particles (brake dust and white traffic paint) were studied to understand the relative contribution of the traffic particles in the geochemical behaviour of urban dust and to evaluate the long-term impacts of the metals on an urban environment, as well as the risk to the populations. It was possible to distinguish two groups of urban dust samples according to Cu behaviour: (1) one group with low amounts of fine particles (car brands (with more than 10 years old), composed by coarser wear particles; and (2) another group with greater amounts of fine particles (car brands (with less than 10 years old). The results obtained showed that there is no direct correlation between the geoavailability of metals estimated by sequential selective chemical extraction (SSCE) and the in vitro oral bioaccessibility (UBM) test. Thus, oral bioaccessibility of urban dust is site specific. Geoavailability was greatly dependent on particle size, where the bioaccessibility tended to increase with a reduction in particle diameter. As anthropogenic particles showed high metal concentration and a smaller size than mineral particles, urban dusts are of major concern to the populations' health, since fine particles are easily re-suspended, easily ingested, and show high metal bioaccessibility. In addition, Estarreja is a coastal city often influenced by winds, which favours the re-suspension of small-sized contaminated particles. Even if the risk to the population does not represent an acute case, it should not be overlooked, and this study can serve as baseline study for cities under high traffic influence.

  14. Directionality Theory and the Entropic Principle of Natural Selection

    Directory of Open Access Journals (Sweden)

    Lloyd A. Demetrius

    2014-10-01

    Full Text Available Darwinian fitness describes the capacity of an organism to appropriate resources from the environment and to convert these resources into net-offspring production. Studies of competition between related types indicate that fitness is analytically described by entropy, a statistical measure which is positively correlated with population stability, and describes the number of accessible pathways of energy flow between the individuals in the population. Directionality theory is a mathematical model of the evolutionary process based on the concept evolutionary entropy as the measure of fitness. The theory predicts that the changes which occur as a population evolves from one non-equilibrium steady state to another are described by the following directionality principle–fundamental theorem of evolution: (a an increase in evolutionary entropy when resource composition is diverse, and resource abundance constant; (b a decrease in evolutionary entropy when resource composition is singular, and resource abundance variable. Evolutionary entropy characterizes the dynamics of energy flow between the individual elements in various classes of biological networks: (a where the units are individuals parameterized by age, and their age-specific fecundity and mortality; where the units are metabolites, and the transitions are the biochemical reactions that convert substrates to products; (c where the units are social groups, and the forces are the cooperative and competitive interactions between the individual groups. % This article reviews the analytical basis of the evolutionary entropic principle, and describes applications of directionality theory to the study of evolutionary dynamics in two biological systems; (i social networks–the evolution of cooperation; (ii metabolic networks–the evolution of body size. Statistical thermodynamics is a mathematical model of macroscopic behavior in inanimate matter based on entropy, a statistical measure which

  15. Testing for biases in selection on avian reproductive traits and partitioning direct and indirect selection using quantitative genetic models

    NARCIS (Netherlands)

    Reed, Thomas E; Gienapp, Phillip; Visser, Marcel E

    2016-01-01

    Key life history traits such as breeding time and clutch size are frequently both heritable and under directional selection, yet many studies fail to document micro-evolutionary responses. One general explanation is that selection estimates are biased by the omission of correlated traits that have c

  16. Testing for biases in selection on avian reproductive traits and partitioning direct and indirect selection using quantitative genetic models

    NARCIS (Netherlands)

    Reed, Thomas E; Gienapp, Phillip; Visser, Marcel E

    2016-01-01

    ey life history traits such as breeding time and clutch size are frequently both heritable and under directional selection, yet many studies fail to document micro-evolutionary responses. One general explanation is that selection estimates are biased by the omission of correlated traits that have ca

  17. Ensuring medication adherence with direct oral anticoagulant drugs: lessons from adherence with vitamin K antagonists (VKAs).

    Science.gov (United States)

    Di Minno, Alessandro; Spadarella, Gaia; Tufano, Antonella; Prisco, Domenico; Di Minno, Giovanni

    2014-05-01

    Medication adherence (taking drugs properly) is uncommon among patients on warfarin. Poor adherence to warfarin leads to an increase in adverse medical events, including stroke in atrial fibrillation (AF). Factors related to patients, physicians and the health system account for poor adherence. Direct oral anticoagulants (DOACs) are easier to use than warfarin, with fewer drug and food interactions and no need for routine blood monitoring. A proper use of DOACs may reduce the risk of stroke in AF. However, in clinical settings where no laboratory monitoring is needed, a poor medication adherence is common and may impact clinical outcomes. In the management of chronic disorders, careful knowledge of the individual patient's attitudes and behaviors is a pre-requisite for a successful doctor-patient communication. To increase patient's awareness of the risks and benefits of DOACs and, in turn, increase medication adherence, at each follow-up visit physicians should screen for priorities and motivational problems; check for the lack of understanding and/or knowledge; assess any health system or personal barriers to medication adherence; identify appropriate interventions and provide tailored support to patient needs. Dissemination of guidelines to the health care chain (prescribing physician, general practitioners, caregivers, nurses, pharmacists) further encourages medication adherence. However, the long-term effect of some of these strategies is unknown; one tool may not fit all patients, and the prescribing physician should consider individualization of these aids to ensure medication adherence and persistence (continuing to take drugs properly in long-term treatments) for DOACs in every day practice.

  18. Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures.

    Science.gov (United States)

    Deutsch, David; Boustière, Christian; Ferrari, Emile; Albaladejo, Pierre; Morange, Pierre-Emmanuel; Benamouzig, Robert

    2017-06-01

    The use of direct oral anticoagulants (DOACs) was an important step forward in the management of atrial fibrillation and venous thromboembolism (VTE). The DOACs, anti-IIa for dabigatran and anti-Xa for rivaroxaban, apixaban and edoxaban, all have a rapid onset of action and a short half life. There is no need for routine hemostasis testing for treatment monitoring of a DOAC. Compared with vitamin K antagonists (VKAs), DOACs may increase the risk of gastrointestinal bleeding (relative risk 1.25). Withholding the DOAC treatment, evaluating the time of the last intake and estimating the patient's renal function are the first steps in the management of gastrointestinal bleeding. For patients without impaired renal function, achieving low coagulation takes around 24 h after the last intake of a DOAC. The use of DOAC antagonists will be helpful in controlling bleeding in the most severe and urgent situations. Idarucizumab is available for clinical use for dabigatran and andexanet is currently being reviewed by drug agencies for rivaroxaban, apixaban and edoxaban. It is important to assess the bleeding risk associated with the planned procedure, and the patient's renal function before withholding DOAC therapy for a scheduled intervention. It is mandatory to strengthen the local hemostasis strategies in DOAC-treated patients undergoing a therapeutic endoscopic procedure. Resuming or not resuming anticoagulation with a DOAC after bleeding or a risky procedure depends on the thrombotic and bleeding risk as well as the procedure involved. This discussion should always involve the cardiologist and decisions should be taken by a pluridisciplinary team.

  19. Direction selectivity in the larval zebrafish tectum is mediated by asymmetric inhibition

    Directory of Open Access Journals (Sweden)

    Abhinav eGrama

    2012-09-01

    Full Text Available The extraction of the direction of motion is an important computation performed by many sensory systems and in particular, the mechanism by which direction selective ganglion cells (DS-RGCs in the retina acquire their selective properties, has been studied extensively. However, whether DS-RGCs simply relay this information to downstream areas or whether additional and potentially de-novo processing occurs in these recipient structures is a matter of great interest. Neurons in the larval zebrafish tectum, the largest retino-recipent area in this animal, show direction selective responses to moving visual stimuli but how these properties are acquired is still unknown. In order to study this, we first used two-photon calcium imaging to classify the population responses of tectal cells to bars moving at different speeds and in different directions. Subsequently, we performed in-vivo whole cell electrophysiology on these direction selective tectal neurons and we found that their inhibitory inputs were strongly biased towards the null direction of motion, whereas the excitatory inputs showed little selectivity. In addition, we found that excitatory currents evoked by a stimulus moving in the preferred direction occurred before the inhibitory currents whereas a stimulus moving in the null direction evoked currents in the reverse temporal order. The membrane potential modulations resulting from these currents were enhanced by the spike generation mechanism to generate amplified direction selectivity in the spike output. Thus our results implicate a local inhibitory circuit in generating direction selectivity in tectal neurons.

  20. Discovery and characterization of ACT-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist.

    Science.gov (United States)

    Steiner, Michel A; Gatfield, John; Brisbare-Roch, Catherine; Dietrich, Hendrik; Treiber, Alexander; Jenck, Francois; Boss, Christoph

    2013-06-01

    Stress relief: Orexin neuropeptides regulate arousal and stress processing through orexin receptor type 1 (OXR-1) and 2 (OXR-2) signaling. A selective OXR-1 antagonist, represented by a phenylglycine-amide substituted tetrahydropapaverine derivative (ACT-335827), is described that is orally available, penetrates the brain, and decreases fear, compulsive behaviors and autonomic stress reactions in rats.

  1. 3-Amido-3-aryl-piperidines: A Novel Class of Potent, Selective, and Orally Active GlyT1 Inhibitors.

    Science.gov (United States)

    Pinard, Emmanuel; Alberati, Daniela; Alvarez-Sanchez, Ruben; Brom, Virginie; Burner, Serge; Fischer, Holger; Hauser, Nicole; Kolczewski, Sabine; Lengyel, Judith; Mory, Roland; Saladin, Christian; Schulz-Gasch, Tanja; Stalder, Henri

    2014-04-10

    3-Amido-3-aryl-piperidines were discovered as a novel structural class of GlyT1 inhibitors. The structure-activity relationship, which was developed, led to the identification of highly potent compounds exhibiting excellent selectivity against the GlyT2 isoform, drug-like properties, and in vivo activity after oral administration.

  2. Oral manifestations of selective IgA-deficiency: review and case-report.

    Science.gov (United States)

    Azzi, L; Croveri, F; Vinci, R; Maurino, V; Boggio, A; Mantegazza, D; Farronato, D; Tagliabue, A; Silvestre-Rangil, J; Tettamanti, L

    2017-01-01

    Immunoglobulin A deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA (less than 7 mg/dl) in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations, such as diabetes mellitus, Graves disease and celiac disease. The international literature has not produced any kind of review yet about intra-oral manifestations of selective IgA-deficiency. L.S., a 7-year-old Caucasian girl, was examined at our hospital. After she had undergone a professional dental cleaning, a symmetric, bilateral ulcerative gingivitis developed nearby the upper second primary molars. The gingival ulcers were persistent and did not disappear in the following 3 weeks. In the meantime, the young patient reported the presence of gastrointestinal symptoms. IgA serum level was 4.5 mg/dl, while the other isotypes levels were in the common range. The diagnosis of selective IgA-deficiency was formulated and the girl underwent further examination for the specific IgG autoantibodies in celiac disease, which were not present. Consequently, a full prevention program was planned. This case report emphasizes the role of the paediatric dentist in the early detection of systemic disorder, such as the immunological diseases. The oral cavity often reveals to be the first site of manifestation of important systemic diseases. Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency and is defined as a decrease in serum IgA levels in the presence of normal levels of other immunoglobulin isotypes (1). Serum IgA deficiency was first described in children with ataxia-telangiectasia (2) and has since been identified in other patients, including normal patients. The prevalence of IgA deficiency ranges from 1:223 to 1:1000 in community studies and from 1:400 to 1

  3. The antibiotic neomycin abolishes directional selectivity in rabbit retinal ganglion cells.

    Science.gov (United States)

    Jensen, R J

    1996-12-01

    1. Extracellular recordings from ON/OFF directionally selective ganglion cells in superfused rabbit retinas were made to study the effect of the aminoglycoside antibiotic, neomycin, on the responses of these cells to a moving light stimulus. 2. Neomycin, at 480-800 microM, reversibly abolished the directional selectivity in these ganglion cells by bringing out a response to movement in one ("null") direction that was similar in magnitude to the response to movement in the reverse ("preferred") direction. 3. Gentamicin, streptomycin, and tobramycin were also able to abolish directional selectivity in these ganglion cells but only at concentrations greater than 1000 microM. 4. It is proposed that neomycin abolishes directional selectivity in rabbit retinal ganglion cells by blocking omega-conotoxin MVIIC-sensitive Ca2+ channels in the retina.

  4. Direct Selection of Clostridium acetobutylicum Fermentation Mutants by a Proton Suicide Method

    OpenAIRE

    Cueto, Pablo H.; Méndez, Beatriz S.

    1990-01-01

    Clostridium acetobutylicum ATCC 10132 mutants altered in acetic acid synthesis or in the shift to solventogenesis were directly selected by a proton suicide method after mutagenic treatment, by using bromide and bromate as selective agents. The mutants were characterized according to their solvent and acid production. On the selection plates they differed in colony phenotype from the parent strain.

  5. Charge-transfer-directed radical substitution enables para-selective C-H functionalization

    Science.gov (United States)

    Boursalian, Gregory B.; Ham, Won Seok; Mazzotti, Anthony R.; Ritter, Tobias

    2016-08-01

    Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.

  6. Two-dimensional map of direction selectivity in cortical visual area MT of Cebus monkey

    OpenAIRE

    ANTONIA CINIRA M. DIOGO; Soares, Juliana G. M.; Albright, Thomas D.; RICARDO GATTASS

    2002-01-01

    We studied the spatial organization of direction of motion in visual area MT of the Cebus apella monkey. We used arrays of 6 (700 µm apart) parallel electrodes in penetrations tangential to the cortical layers to record multi-unit responses to moving bars, at 200 µm steps. We determined the direction selectivity at each recording site. The data from single penetrations showed cyclic and gradual changes in the direction selectivity of clusters of cells, intermixed with abrupt 180º discontinuit...

  7. Sensitivity of direct immunofluorescence in oral diseases. Study of 125 cases.

    Science.gov (United States)

    Sano, Susana Mariela; Quarracino, María Cecilia; Aguas, Silvia Cristina; González, Ernestina Jesús; Harada, Laura; Krupitzki, Hugo; Mordoh, Ana

    2008-05-01

    Direct immunofluorescence (DIF) is widely used for the diagnosis of bullous diseases and other autoimmune pathologies such as oral lichen planus. There is no evidence in the literature on how the following variants influence the detection rate of DIF: intraoral site chosen for the biopsy, perilesional locus or distant site from the clinical lesion, number of biopsies and instrument used. to determine if the following variants influenced the sensitivity (detection rate): intraoral site chosen for the biopsy, perilesional or distant site from the clinical lesion, number of biopsies and instrument used (punch or scalpel). A retrospective study was done at the Cátedra de Patología y Clínica Bucodental II at the Facultad de Odontología, Universidad de Buenos Aires; 136 clinical medical histories were revised for the period March 2000 - March 2005 corresponding to patients with clinical diagnosis of OLP and bullous diseases (vulgar pemphigus, bullous pemphigoid and cicatricial pemphigoid). DIF detection rate was 65.8% in patients with OLP, 66.7% in cicatricial pemphigoid patients, in bullous pemphigoid 55.6%, in pemphigus vulgaris 100%, and in those cases in which certain diagnosis could not be obtained, the DIF positivity rate was 45.5% (Pearson chi(2) (4)= 21.5398 Pr= 0.000). There was no statistically significant difference between the different sites of biopsy (Fisher exact test: 0.825). DIF detection rate in perilesional biopsies was 66.1% and in those distant from the site of clinical lesion was 64.7% (Pearson chi(2) v1)= 0.0073 Pr= 0.932. When the number of biopsies were incremented, DIF detection rate also incremented (Pearson chi(2) = 8.7247 Pr= 0.003). The biopsies taken with punch had a higher detection rate than those taken with scalpel (39.1% versus 71.7%) (Pearson chi(2) = 49.0522 Pr= 0.000). While not statistically significant, the tendency outlined in this study indicates there are intraoral regions in which the detection rate of the DIF technique is

  8. Facial nerve paralysis after super-selective intra-arterial chemotherapy for oral cancer.

    Science.gov (United States)

    Sugiyama, S; Iwai, T; Oguri, S; Koizumi, T; Mitsudo, K; Tohnai, I

    2017-02-10

    Facial nerve paralysis (FNP) after super-selective intra-arterial chemotherapy (SSIAC) is a relatively rare local side effect of SSIAC to the maxillary artery (MA) or the middle meningeal artery (MMA). The incidence and prognosis of FNP after SSIAC in 381 patients with oral cancer (133 with catheterization of the MA, 248 without) was investigated retrospectively. Only three patients (two male and one female) had FNP, for an incidence of 0.8%. All patients with FNP had undergone catheterization of the MA, and the incidence of FNP in this group was 2.3% (3/133). One of the three patients with FNP had paralysis of the third branch of the trigeminal nerve. FNP occurred a mean of 8.7 days (range 5-11 days) after initial SSIAC, and the mean total dose of cisplatin was 55.8mg (range 42.5-67.2mg) and of docetaxel was 25.4mg (range 17.0-33.6mg). FNP resolved completely a mean of 12.7 months (range 6-19 months) after onset. Because the administration of anticancer agents via the MA or MMA carries a risk of FNP, this information will be useful when obtaining informed consent from patients before treatment.

  9. The resistance and adaptation of selected oral bacteria to mercury and its impact on their growth.

    Science.gov (United States)

    Lyttle, H A; Bowden, G H

    1993-09-01

    Selected strains of oral Streptococcus and Actinomyces have been tested for their ability to grow in the presence of mercury. Strains were tested for growth on a semi-defined medium with low mercury-binding characteristics. Sensitivities were initially measured on agar plates, and subsequently, selected strains were grown in broth so that the impact of mercury on the growth characteristics could be determined. Streptococci were more resistant to mercury (5 micrograms/mL to 40 micrograms/mL) than Actinomyces (salivarius, S. sobrinus, and one strain of S. mutans, all of which grew on agar with 40 micrograms/mL of mercury. Two other S. mutans strains were more sensitive, being inhibited by 10 and 20 micrograms/mL mercury. The most resistant Actinomyces was A. naeslundii genospecies 1 (ATCC12104), which grew on medium with 30 micrograms/mL mercury; two strains of Actinomyces were completely inhibited by 5 micrograms/mL. Mercury caused increased lag times and reduced cell density in broth cultures. Enrichment cultures of samples of human dental plaque showed that streptococci were the most resistant organisms that could be cultured on the medium and that these strains could adapt to relatively high mercury concentrations. S. oralis and S. mitis biovar 1 were the most resistant organisms isolated from enriched cultures, growing in broth media with 65 micrograms/mL mercury. Mercury was bound to cell walls and cell cytoplasm of streptococci grown in the presence of mercury.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Selecting a comparison group for 5-year oral and pharyngeal cancer survivors: Two methods

    Directory of Open Access Journals (Sweden)

    Logan Henrietta L

    2012-05-01

    Full Text Available Abstract Background To assess potential long-term consequences of cancer treatment, studies that include comparison groups are needed. These comparison groups should be selected in a way that allows the subtle long-range effects of cancer therapy to be detected and distinguishes them from the effects of aging and other risk factors. The purpose of this investigation was to test two methods of recruiting a comparison group for 5-year oral and pharyngeal cancer survivors (peer-nominated and listed sample with emphasis on feasibility and the quality of the match. Methods Participants were drawn from a pool of 5-year survivors treated at a large Southeastern hospital. A peer-nominated sample was solicited from the survivors. A listed sample matched on sex, age, and zip code was purchased. Telephone interviews were conducted by a professional call center. Results The following represent our key findings: The quality of matching between survivors and listed sample was better than that between survivors and peer-nominated group in age and sex. The quality of matching between the two methods on other key variables did not differ except for education, with the peer method providing a better match for the survivors than the listed sample. The yield for the listed sample method was greater than for the peer-nominated method. The cost per completed interview was greater for the peer-nominated method than the listed sample. Conclusion This study not only documents the methodological challenges in selecting a comparison group for studies examining the late effects of cancer treatment among older individuals but also documents challenges in matching groups that potentially have disproportionate levels of comorbidities and at-risk health behaviors.

  11. Protection of mice from oral Candidiasis by heat-killed enterococcus faecalis, possibly through its direct binding to Candida albicans.

    Science.gov (United States)

    Ishijima, Sanae A; Hayama, Kazumi; Ninomiya, Kentaro; Iwasa, Masahiro; Yamazaki, Masatoshi; Abe, Shigeru

    2014-01-01

    To develop a new therapy against oral candidiasis, a commensal microorganism, Enterococcus faecalis was tested for its ability to modulate Candida growth in vitro and its therapeutic activities against a murine model in vivo. Addition of heat-killed E. faecalis strain EF2001 (EF2001) isolated from healthy human feces to the culture of C. albicans strain TIMM1768 inhibited adherence of the latter to a microtiter plate in a dose dependent manner and Candida cells surrounded by EF2001 were increased. To examine the protective activities of EF2001 in vivo, heat-killed EF2001 was applied orally before and after inoculation of Candida to the tongue of mice previously immunosuppressed. Two days after inoculation this inoculation, both the symptom score and CFU from swabbed-tongue were significantly reduced in the EF2001-treated animals. Histological analysis indicated that EF2001 may potentiate the accumulation of polymorphnuclear cells near a Candida-infected region. These results suggest that oral administration of EF2001 has protective activity against oral candidiasis and that the in vivo activity may be reflected by direct interaction between EF2001 and Candida cells in vitro and the potentiation of an immunostimulatory effect of EF2001.

  12. New oral antithrombotics: focus on dabigatran, an oral, reversible direct thrombin inhibitor for the prevention and treatment of venous and arterial thromboembolic disorders

    Directory of Open Access Journals (Sweden)

    Dahl OE

    2012-01-01

    Full Text Available Ola E Dahl1,21Department of Orthopaedics, Innlandet Hospital Trust, Elverum Central Hospital, Elverum, Norway; 2Thrombosis Research Institute, London, UKAbstract: Venous thromboembolism, presenting as deep vein thrombosis or pulmonary embolism, is a major challenge for health care systems. It is the third most common vascular disease after coronary heart disease and stroke, and many hospitalized patients have at least one risk factor. In particular, patients undergoing hip or knee replacement are at risk, with an incidence of asymptomatic deep vein thrombosis of 40%–60% without thromboprophylaxis. Venous thromboembolism is associated with significant mortality and morbidity, with patients being at risk of recurrence, post-thrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Arterial thromboembolism is even more frequent, and atrial fibrillation, the most common embolic source (cardiac arrhythmia, is associated with a five-fold increase in the risk of stroke. Strokes due to atrial fibrillation tend to be more severe and disabling and are more often fatal than strokes due to other causes. Currently, recommended management of both venous and arterial thromboembolism involves the use of anticoagulants such as coumarin and heparin derivatives. These agents are effective, although have characteristics that prevent them from providing optimal anticoagulation and convenience. Hence, new improved oral anticoagulants are being investigated. Dabigatran is a reversible, direct thrombin inhibitor, which is administered as dabigatran etexilate, the oral prodrug. Because it is the first new oral anticoagulant that has been licensed in many countries worldwide for thromboprophylaxis following orthopedic surgery and for stroke prevention in patients with atrial fibrillation, this compound will be the main focus of this review. Dabigatran has been investigated for the treatment of established venous thromboembolism and prevention of

  13. Prevalence of Oral Trichomoniasis in Patients with Periodontitis and Gingivitis Using PCR and Direct Smear

    Directory of Open Access Journals (Sweden)

    A Athari

    2007-09-01

    Full Text Available Background: Trichomonas tenax, a commensal flagellated protozoan, inhabits in human oral cavity. This parasite is cos-mopoli­tan and frequently found in patients with poor oral hygiene and advanced periodontal disease. There is only one pub­lished study that rebound the prevalence of this parasite in Iran. This PCR based study compared the prevalence of oral tricho­moni­asis in patients with oral diseases and a healthy control group.Methods: From May 2005 to April 2006, the subgingival dental plaques of 160 patients with gingivitis or periodontitis and 160 controls who attended to Dental School of Shaheed Beheshti Medical University, Iran were taken and examined by wet mount smear, and Giemsa staining. Likewise, a PCR protocol was developed for specific detection of T.tenax using a pair of prim­ers designed for its 18S rRNA gene. Results: Thirty three (20.6% of patients were PCR positive while 28 (15.5% were diagnosed using wet preparation and Giemsa staining. In the other hand, 2 (1.9% of control group were identified positive by PCR procedure.  The prevalence of oral trichomoniasis in our study (20.6% was compatible with many other published reports which mostly has ranged from 12%-32%.  Conclusion: The study revealed dependence between the frequency of occurrence of T. tenax and the state of periodontitis. The present PCR procedure could provide a simple and rapid detection method of T. tenax in dental plague.

  14. The Role of Language for Thinking and Task Selection in EFL Learners' Oral Collocational Production

    Science.gov (United States)

    Wang, Hung-Chun; Shih, Su-Chin

    2011-01-01

    This study investigated how English as a foreign language (EFL) learners' types of language for thinking and types of oral elicitation tasks influence their lexical collocational errors in speech. Data were collected from 42 English majors in Taiwan using two instruments: (1) 3 oral elicitation tasks and (2) an inner speech questionnaire. The…

  15. A Study of the Management of Patients Taking Novel Oral Antiplatelet or Direct Oral Anticoagulant Medication Undergoing Dental Surgery in a Rural Setting

    Directory of Open Access Journals (Sweden)

    Steven Johnston

    2015-10-01

    Full Text Available Purpose: Novel oral antiplatelet (NOAP (prasugrel and ticagrelor and direct oral anticoagulant drugs (DOAC (dabigatran, rivaroxaban and apixaban have emerged in the last decade. This study was undertaken to determine current approaches taken to the management of patients taking these agents in dental practice in a remote and rural setting. Methods: A small retrospective study was carried out in a small island population that identified patients taking one of the above drugs. All national health service and private dental records were examined to determine the type of treatment carried out and whether drug therapy, treatment plans or actual treatment were modified as a result of NOAP or DOAC therapy. In addition other outcomes such as referral to another service for advice or treatment and any adverse bleeding events were noted. Results: 156 dental encounters for 95 patients taking one of the drugs were identified. Significant events were identified in sixteen encounters and the management of patients taking each drug type differed significantly between cases but no patients returned with troublesome post-operative bleeding. Conclusions: The approaches taken by dental surgeons in Orkney in the management of the NOAPs and DOACs varied and this is likely to be a reflection of the limited literature available.

  16. Direction selectivity is computed by active dendritic integration in retinal ganglion cells.

    Science.gov (United States)

    Sivyer, Benjamin; Williams, Stephen R

    2013-12-01

    Active dendritic integration is thought to enrich the computational power of central neurons. However, a direct role of active dendritic processing in the execution of defined neuronal computations in intact neural networks has not been established. Here we used multi-site electrophysiological recording techniques to demonstrate that active dendritic integration underlies the computation of direction selectivity in rabbit retinal ganglion cells. Direction-selective retinal ganglion cells fire action potentials in response to visual image movement in a preferred direction. Dendritic recordings revealed that preferred-direction moving-light stimuli led to dendritic spike generation in terminal dendrites, which were further integrated and amplified as they spread through the dendritic arbor to the axon to drive action potential output. In contrast, when light bars moved in a null direction, synaptic inhibition vetoed neuronal output by directly inhibiting terminal dendritic spike initiation. Active dendritic integration therefore underlies a physiologically engaged circuit-based computation in the retina.

  17. Impact of oral rehydration and selected public health interventions on reduction of mortality from childhood diarrhoeal diseases in Mexico.

    OpenAIRE

    Gutiérrez, G.; Tapia-Conyer, R.; Guiscafré, H.; Reyes, H; Martínez, H.; Kumate, J.

    1996-01-01

    Reported are the results of an analysis of mortality trends from diarrhoeal diseases among under-5-year-olds in Mexico between 1978 and 1993 in relation to the impact of education, basic sanitation, and selected medical care practices. The study period was divided into three stages; the first pre-dated the widespread application of oral rehydration therapy (ORT); the second, covered the implementation of a nationwide programme promoting ORT; and the third included additional measures, such as...

  18. Impact of oral rehydration and selected public health interventions on reduction of mortality from childhood diarrhoeal diseases in Mexico.

    OpenAIRE

    Gutiérrez, G.; TAPIA-CONYER, R.; Guiscafré, H; Reyes, H; Martínez, H.; Kumate, J

    1996-01-01

    Reported are the results of an analysis of mortality trends from diarrhoeal diseases among under-5-year-olds in Mexico between 1978 and 1993 in relation to the impact of education, basic sanitation, and selected medical care practices. The study period was divided into three stages; the first pre-dated the widespread application of oral rehydration therapy (ORT); the second, covered the implementation of a nationwide programme promoting ORT; and the third included additional measures, such as...

  19. Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy.

    Science.gov (United States)

    Yeoh, Sern Wei

    2016-09-01

    Direct acting antiviral (DAA) regimens containing ritonavir have been developed to treat hepatitis C, with fewer side effects than that by interferon-based regimens. However prescribers must be aware of drug-drug interactions. There are multiple reports of iatrogenic Cushing syndrome (CS) caused by ritonavir, when used to treat human immunodeficiency virus, increasing the bioavailability of exogenous steroids by inhibiting cytochrome p450 enzymes in the liver and gut wall and thus reducing steroid metabolism. We herein report a novel scenario of CS due to interaction between ritonavir for hepatitis C treatment and oral budesonide for autoimmune hepatitis.

  20. Direct identification of propionylcarnitine in propionic acidaemia: biochemical and clinical results of oral carnitine supplementation.

    Science.gov (United States)

    Duran, M; Ketting, D; Beckeringh, T E; Leupold, D; Wadman, S K

    1986-01-01

    Urinary short-chain acylcarnitine in a patient with propionic acidaemia and low levels of free carnitine was found to consist mainly of propionylcarnitine. The compound was isolated by sequential paper and thin layer chromatography and identified by ammonia desorption chemical ionization mass spectrometry. Treatment of the patient with oral carnitine supplements led to a near-normalization of the plasma free carnitine concentrations and an increase in his muscle tone. The propionylcarnitine excretion rose and there was a simultaneous decrease in the methylcitrate output. Carnitine treatment did not prevent the occurrence of an episode of metabolic decompensation.

  1. Direct Slicing Based on Material Performance and Process Parameters for Selective Laser Sintering

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Direct slicing from CAD models to generate sectional contours of thepart to be sintered for Selective Laser Sintering (SLS) may overcome inherent disadvantages of using a Stereo Lithography ( STL ) format. In this paper, a direct slicing procedure is proposed for Selective Laser Sintering based on material performance and process parameters. Slicing thickness depends on the 3 D geometric model,material performance and process parameters. The relationship among material performance, process parameters and the largest slicing thickness is established using analysis of a sintering temperature field. A dynamic linked library is developed to realize direct slicing from a CAD model.

  2. Case selection criteria and a simplified technique for placing and finishing direct composite veneers.

    Science.gov (United States)

    Blank, Jeff T

    2002-09-01

    This article addresses the key obstacles clinicians face when considering direct composite veneers as a treatment option for the cosmetic correction of anterior teeth. These obstacles include case selection, material selection, the best technique to allow the expeditious placement of the veneers, and, ultimately, final esthetics. The best clinical situations for choosing direct composite veneers are identified, and a new microhybrid composite resin system, Esthet-X, which offers a simplified solution to shade matching and polishing, is introduced. A clinical case demonstrates a simplified technique for the placement of stratified, polychromatic direct veneers, and describes a new polishing system that generates a microfill type of shine with modern microhybrids.

  3. Oral Tolerance: A New Tool for the Treatment of Gastrointestinal Inflammatory Disorders and Liver-Directed Gene Therapy

    Directory of Open Access Journals (Sweden)

    Yaron Ilan

    1999-01-01

    Full Text Available Oral tolerance is a method of downregulating an immune response by feeding antigens. The use of oral tolerance toward adenoviruses and colitis-extracted proteins for long term gene therapy and alleviation of experimental colitis, and the mechanisms of tolerance induction are presented. Adenoviruses are efficient vectors in liver-directed gene therapy; however, the antiviral immune response precludes the ability to achieve long term gene expression and prohibits the ability to reinject the recombinant virus. Oral tolerance induction via feeding of viral-extracted proteins prevented the antiadenoviral humoral and cellular immune responses, thus enabling long term gene therapy using these viruses. Moreover, pre-existing immune response to the virus was overcome by tolerance induction, enabling prolonged gene expression in a presensitized host. Inflammatory bowel diseases are immune-mediated disorders where an imbalance between proinflammatory (T helper cell type 1 and anti-inflammatory (T helper cell type 2 cytokines are thought to play a role in the pathogenesis. In the experimental colitis model, the feeding of colitis-extracted proteins downregulated the anticolon immune response. Tolerance induction toward colitis-extracted proteins ameliorated colonic inflammation as shown by decreased diarrhea and reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness and edema. Histological parameters for colitis were markedly improved in tolerized animals. In both models, tolerized animals developed an increase in transforming growth factor-beta, interleukin-4 and interleukin-10, and a decrease in the mRNA of interferon-gamma lymphocytes and serum levels. Adoptive transfer of tolerized lymphocytes enabled the transfer of tolerance toward adenoviruses and colon-extracted proteins. Thus, oral tolerance induces suppressor lymphocytes that mediate immune response downregulation by induction of a shift from a proinflammatory T

  4. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs.

    Science.gov (United States)

    Dahan, Arik; Hoffman, Amnon

    2008-07-02

    As a consequence of modern drug discovery techniques, there has been a consistent increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered medications with sufficient bioavailability. One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based drug delivery system. Unfortunately, current development strategies in the area of lipid based delivery systems are mostly empirical. Hence, there is a need for a simplified in vitro method to guide the selection of a suitable lipidic vehicle composition and to rationalize the delivery system design. To address this need, a dynamic in vitro lipolysis model, which provides a very good simulation of the in vivo lipid digestion process, has been developed over the past few years. This model has been extensively used for in vitro assessment of different lipid based delivery systems, leading to enhanced understanding of the suitability of different lipids and surfactants as a delivery system for a given poorly water soluble drug candidate. A key goal in the development of the dynamic in vitro lipolysis model has been correlating the in vitro data of various drug-lipidic delivery system combinations to the resultant in vivo drug profile. In this paper, we discuss and review the need for this model, its underlying theory, practice and limitations, and the available data accumulated in the literature. Overall, the dynamic in vitro lipolysis model seems to provide highly useful initial guidelines in the development process of oral lipid based drug delivery systems for poorly water soluble drugs, and it predicts phenomena that occur in the pre-enterocyte stages of the intestinal absorption cascade.

  5. Egg baked in product open oral food challenges are safe in selected egg-allergic patients.

    Science.gov (United States)

    Buelow, Becky J; Lee, Carrie; Zafra, Heidi T; Dasgupta, Mahua; Hoffmann, Ray G; Vasudev, Monica

    2014-07-01

    Egg allergy is one of the most common food allergies in children. Most egg-allergic children are able to tolerate egg baked in product (EBP) and will likely outgrow his/her egg allergy. By introducing EBP in the diet of an egg-allergic child, diet can be expanded and family stress can be reduced. Recent evidence suggests that children who tolerate EBP and continue to consume it will have quicker resolution of egg allergy than those who strictly avoid EBP; therefore, we aimed to evaluate the egg-allergic children who underwent EBP oral food challenge (OFC) in our allergy clinic to help define any specific predictors to be used in predicting the outcome of such challenges. We performed a retrospective chart review and 43 egg-allergic patients underwent EBP OFC in our outpatient allergy office from January 2011 to December 2012 were excluded. Nine patients who did not have a prior history of symptomatic egg ingestion. Clinical characteristics and laboratory findings of the remaining 34 patients were all recorded and analyzed. Of the remaining 34 patients, 22 (64.7%) were boys. Average age of first reaction to egg was 12.90 months, with average age at EBP OFC of 71.32 months. The average of the most recent skin-prick test wheal size was 10.10 mm and serum-specific IgE to egg white was 3.21 kU/L. Twenty-eight of the 34 patients (82.4%) passed the EBP OFC. Of the six patients who failed, none required epinephrine. After analysis of all of the clinical characteristics and laboratory findings, no risk factors, such as skin-prick test wheal size, were identified to be associated with an increased risk of failing EBP OFC. EBP OFC is a valuable tool to assess tolerance. As seen in our group of patients, the majority of egg-allergic patients pass EBP OFC. Thus, OFC should be considered as a clinical tool to expand a patient's diet and to improve quality of life as early as possible. Because we were unable to determine any clinical or laboratory predictors helpful to select egg

  6. Selection of lasing direction in single mode semiconductor square ring cavities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin-Woong; Kim, Kyoung-Youm; Moon, Hee-Jong; Hyun, Kyung-Sook, E-mail: kshyun@sejong.ac.kr [Department of Optical Engineering, Sejong University, 98 Kunja-Dong, Kwangjin-K, Seoul 143-747 (Korea, Republic of)

    2016-02-07

    We propose and demonstrate a selection scheme of lasing direction by imposing a loss imbalance structure into the single mode square ring cavity. The control of the traveling direction is realized by introducing a taper-step section in one of the straight waveguides of the square ring cavity. It was shown by semi-analytic calculation that the taper-step section in the cavity provides effective loss imbalance between two travelling directions as the round trip repeats. Various kinds of square cavities were fabricated using InGaAsP/InGaAs multiple quantum well semiconductor materials in order to test the direction selectivity while maintaining the single mode. We also measured the pump power dependent lasing spectra to investigate the maintenance property of the lasing direction. The experimental results demonstrated that the proposed scheme is an efficient means for a unidirectional lasing in a single mode laser.

  7. Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

    LENUS (Irish Health Repository)

    Gong, H

    1990-03-01

    The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

  8. Comparative study on direction selectivity and functional organization of the primary visual cortical cells in monkeys and cats

    Institute of Scientific and Technical Information of China (English)

    寿天德; 周逸峰; 俞洪波

    2000-01-01

    Although the directionally selective cells in many visual cortical areas are organized in columnar manner, the functional organization of direction selectivity of area VI in the monkey still remains unclear. We quantitatively studied the proportion of directionally selective cells, direction selectivity and the functional organization of the striate cortical cells in the monkey and compared those with the cat. The results show that the direction selectivity and directional organization of striate cortical cells in the monkey are significantly weaker than those in the cat, suggesting that the species difference between the two kinds of animal is related to their different anatomic pathways.

  9. Comparative study on direction selectivity and functional organization of the primary visual cortical cells in monkeys and cats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Although the directionally selective cells in many visual cortical areas are organized in columnar manner, the functional organization of direction selectivity of area Vl in the monkey still remains unclear. We quantitatively studied the proportion of directionally selective cells, direction selectivity and the functional organization of the striate cortical cells in the monkey and compared those with the cat. The results show that the direction selectivity and directional organization of striate cortical cells in the monkey are significantly weaker than those in the cat, suggesting that the species difference between the two kinds of animal is related to their different anatomic pathways.

  10. New clinical guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients.

    Science.gov (United States)

    Onoda, Noritaka; Fukagawa, Masafumi; Tominaga, Yoshihiro; Kitaoka, Masafumi; Akizawa, Tadao; Koiwa, Fumihiko; Kakuta, Takatoshi; Kurokawa, Kiyoshi

    2008-08-01

    In 2000, the Japanese Society for Parathyroid Intervention issued the 'Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients'. Since then, the concept of 'selective PEIT' has been well accepted and the number of patients treated by this method in Japan has increased. Recently, it has been reported that the effect of PEIT differs depending on the degree of nodular hyperplasia. Several new drugs have become available since 2000, and active vitamin D and its analogue have also been used for direct injection into the parathyroids. We present the new 'Guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients', a revised version of the 2000 Guidelines. We believe that these new guidelines are useful for selecting direct injection therapy in patients with advanced secondary hyperparathyroidism.

  11. Competitive selection of lactic acid bacteria that persist in the human oral cavity

    NARCIS (Netherlands)

    Snel, J.; Marco, M.L.; Kingma, F.; Noordman, W.M.; Rademaker, J.; Kleerebezem, M.

    2011-01-01

    Lactic acid bacteria (LAB) might offer opportunities as oral probiotics provided candidate strains persist in the mouth. After intake of a mixture of 69 LAB, strains of Lactobacillus fermentum and Lactobacillus salivarius were especially recovered. Coaggregation with other microbes is likely not a p

  12. Oral status indicators DMFT and FS-T : reflections on index selection

    NARCIS (Netherlands)

    Schuller, A A; Holst, D

    2001-01-01

    Oral status in a population has traditionally been described by the DMFT index (decayed, filled, and missing teeth). There seems to be contradicting and confusing evidence in the literature with regard to the usefulness of different indices. Limitations of the DMFT are recognised, and attempts have

  13. Birefringence-Directed Raman Selection Rules in 2D Black Phosphorus Crystals.

    Science.gov (United States)

    Mao, Nannan; Wu, Juanxia; Han, Bowen; Lin, Jingjing; Tong, Lianming; Zhang, Jin

    2016-05-01

    The incident and scattered light engaged in the Raman scattering process of low symmetry crystals always suffer from the birefringence-induced depolarization. Therefore, for anisotropic crystals, the classical Raman selection rules should be corrected by taking the birefringence effect into consideration. The appearance of the 2D anisotropic materials provides an excellent platform to explore the birefringence-directed Raman selection rules, due to its controllable thickness at the nanoscale that greatly simplifies the situation comparing with bulk materials. Herein, a theoretical and experimental investigation on the birefringence-directed Raman selection rules in the anisotropic black phosphorus (BP) crystals is presented. The abnormal angle-dependent polarized Raman scattering of the Ag modes in thin BP crystal, which deviates from the normal Raman selection rules, is successfully interpreted by the theoretical model based on birefringence. It is further confirmed by the examination of different Raman modes using different laser lines and BP samples of different thicknesses.

  14. The effect of breed selection on interpreting human directed cues in the domestic dog

    OpenAIRE

    Winnerhall, Louise

    2014-01-01

    During the course of time, artificial selection has given rise to a great diversity among today's dogs. Humans and dogs have evolved side by side and dogs have come to understand human body language relatively well. This study investigates whether selection pressure and domestication could reveal differences in dogs’ skill to interpret human directional cues, such as distal pointing. In this study, 46 pet dogs were tested from 27 breeds and 6 crossbreeds for performance in the two-way object ...

  15. Evolvability Search: Directly Selecting for Evolvability in order to Study and Produce It

    OpenAIRE

    Mengistu, Henok; Lehman, Joel Anthony; Clune, Jeff

    2016-01-01

    One hallmark of natural organisms is their significant evolvability, i.e.,their increased potential for further evolution. However, reproducing such evolvability in artificial evolution remains a challenge, which both reduces the performance of evolutionary algorithms and inhibits the study of evolvable digital phenotypes. Although some types of selection in evolutionary computation indirectly encourage evolvability, one unexplored possibility is to directly select for evolvability. To do so,...

  16. Mathematical analysis and modeling of motion direction selectivity in the retina.

    Science.gov (United States)

    Escobar, María-José; Pezo, Danilo; Orio, Patricio

    2013-11-01

    Motion detection is one of the most important and primitive computations performed by our visual system. Specifically in the retina, ganglion cells producing motion direction-selective responses have been addressed by different disciplines, such as mathematics, neurophysiology and computational modeling, since the beginnings of vision science. Although a number of studies have analyzed theoretical and mathematical considerations for such responses, a clear picture of the underlying cellular mechanisms is only recently emerging. In general, motion direction selectivity is based on a non-linear asymmetric computation inside a receptive field differentiating cell responses between preferred and null direction stimuli. To what extent can biological findings match these considerations? In this review, we outline theoretical and mathematical studies of motion direction selectivity, aiming to map the properties of the models onto the neural circuitry and synaptic connectivity found in the retina. Additionally, we review several compartmental models that have tried to fill this gap. Finally, we discuss the remaining challenges that computational models will have to tackle in order to fully understand the retinal motion direction-selective circuitry.

  17. Dominance Genetic Variance for Traits Under Directional Selection in Drosophila serrata

    Science.gov (United States)

    Sztepanacz, Jacqueline L.; Blows, Mark W.

    2015-01-01

    In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait–fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. PMID:25783700

  18. Role for Visual Experience in the Development of Direction-Selective Circuits.

    Science.gov (United States)

    Bos, Rémi; Gainer, Christian; Feller, Marla B

    2016-05-23

    Visually guided behavior can depend critically on detecting the direction of object movement. This computation is first performed in the retina where direction is encoded by direction-selective ganglion cells (DSGCs) that respond strongly to an object moving in the preferred direction and weakly to an object moving in the opposite, or null, direction (reviewed in [1]). DSGCs come in multiple types that are classified based on their morphologies, response properties, and targets in the brain. This study focuses on two types-ON and ON-OFF DSGCs. Though animals can sense motion in all directions, the preferred directions of DSGCs in adult retina cluster along distinct directions that we refer to as the cardinal axes. ON DSGCs have three cardinal axes-temporal, ventral, and dorsonasal-while ON-OFF DSGCs have four-nasal, temporal, dorsal, and ventral. How these preferred directions emerge during development is still not understood. Several studies have demonstrated that ON [2] and ON-OFF DSGCs are well tuned at eye-opening, and even a few days prior to eye-opening, in rabbits [3], rats [4], and mice [5-8], suggesting that visual experience is not required to produce direction-selective tuning. However, here we show that at eye-opening the preferred directions of both ON and ON-OFF DSGCs are diffusely distributed and that visual deprivation prevents the preferred directions from clustering along the cardinal axes. Our findings indicate a critical role for visual experience in shaping responses in the retina.

  19. DATA OF CLINICAL PRACTICE AS A TOOL FOR CHOICE OF DIRECT ORAL ANTICOAGULANT

    Directory of Open Access Journals (Sweden)

    D. А. Napalkov

    2017-01-01

    Full Text Available The review actualizes the need to validate data  obtained in randomized clinical trials (RCT by the results of routine clinical practice (RCP. Definitely, both methods have some disadvantages. Only patients with minimal comorbidity and a number of other restrictions are included into the RCT in accordance with strict procedures and treatment protocol. On the contrary, the analysis of the RCP shows that data  bases  of insurance companies and medical records are associated with less exact information about the patients, heterogeneity of comparison groups might be significant, and end points evaluation can be different. At the same time, if the RCT data are confirmed by the key results of the RCP analysis, it is a strong  evidence of the credibility of information, obtained by the both methods. The analysis of various RCP data bases published over the past 2 years shows that, among all new oral anticoagulants, apixaban is associated with the best adherence to treatment and lowest bleeding incidence in patients with non-valvular atrial fibrillation. These results confirm good safety profile of apixaban which was previously demonstrated in ARISTOTLE trial. On the contrary, rivaroxaban was associated with the most frequent bleeding in long-term use in patients with atrial fibrillation.

  20. Direct Visualization of Spatial and Temporal Patterns of Antimicrobial Action within Model Oral Biofilms▿

    Science.gov (United States)

    Takenaka, Shoji; Trivedi, Harsh M.; Corbin, Audrey; Pitts, Betsey; Stewart, Philip S.

    2008-01-01

    A microscopic method for noninvasively visualizing the action of an antimicrobial agent inside a biofilm was developed and applied to describe spatial and temporal patterns of mouthrinse activity on model oral biofilms. Three species biofilms of Streptococcus oralis, Streptococcus gordonii, and Actinomyces naeslundii were grown in glass capillary flow cells. Bacterial cells were stained with the fluorogenic esterase substrate Calcien AM (CAM). Loss of green fluorescence upon exposure to an antimicrobial formulation was subsequently imaged by time-lapse confocal laser scanning microscopy. When an antimicrobial mouthrinse containing chlorhexidine digluconate was administered, a gradual loss of green fluorescence was observed that began at the periphery of cell clusters where they adjoined the flowing bulk fluid and progressed inward over a time period of several minutes. Image analysis was performed to quantify a penetration velocity of 4 μm/min. An enzyme-based antimicrobial formulation led to a gradual, continually slowing loss of fluorescence in a pattern that was qualitatively different from the behavior observed with chlorhexidine. Ethanol at 11.6% had little effect on the biofilm. None of these treatments resulted in the removal of biomass from the biofilm. Most methods to measure or visualize antimicrobial action in biofilms are destructive. Spatial information is important because biofilms are known for their structural and physiological heterogeneity. The CAM staining technique has the potential to provide information about the rate of antimicrobial penetration, the presence of tolerant subpopulations, and the extent of biomass removal effected by a treatment. PMID:18223108

  1. Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jung-Hwan Lee

    Full Text Available The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP-induced radicals on the epidermal growth factor receptor (EGFR, which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

  2. Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Lee, Jung-Hwan; Om, Ji-Yeon; Kim, Yong-Hee; Kim, Kwang-Mahn; Choi, Eun-Ha; Kim, Kyoung-Nam

    2016-01-01

    The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP)-induced radicals on the epidermal growth factor receptor (EGFR), which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

  3. Orientational and directional selectivities of visual neurons in the superior colliculus of the cat

    Institute of Scientific and Technical Information of China (English)

    李兵; 王磊; 王毅; 刁云程

    1996-01-01

    Based on quantitative analyses of the response characteristics of visual neurons in the superior colliculus to moving optical bar stimuli, it is demonstrated for the first time that the visual neurons in superior colliculus of the cat have, to some extent, orientational selectivity. The significance of this selectivity is discussed in reference to its morphological substrate and physiological functions. In addition, both the directional and orientational selectivities in the superior colliculus are relatively weak when compared with those in the primary visual cortex, and the majority of the neurons prefer upward or downward motion in the visual field.

  4. Direct oxidation of methyl radicals in OCM process deduced from correlation of product selectivities

    Institute of Scientific and Technical Information of China (English)

    Zhiming Gao; Yuanyuan Ma

    2010-01-01

    Selectivity of hydrogen in reaction of oxidative coupling of methane(OCM)was evaluated over the MxOy-BaCO3(MxOy: La2O3,Sm2O3,MgO,CaO)catalysts.Correlation of product selectivities was thus discussed.From the correlation of product selectivities,it is revealed that the carbon oxides(CO and CO2)were most probably formed from the direct oxidation of methyl radicals under the conditions adopted in the present work.This is also in accordance with the OCM mechanism proposed in literature.

  5. The recent clinical trials on use of the novel direct oral anticoagulants in patients with venous thromboembolism: a review

    Directory of Open Access Journals (Sweden)

    Gualtiero Palareti

    2014-10-01

    Full Text Available Venous thromboembolism (VTE, encompassing deep vein thrombosis and pulmonary embolism, requires an immediate anticoagulation, that has been carried out so far by administering a parenteral anticoagulant drug (heparin or derivatives overlapped with an oral vitamin K antagonist (VKA, more often warfarin. Several new direct oral anticoagulants (DOACs, with a mechanism of action completely different than VKA, have been developed in recent years. Recent clinical trials have investigated their use in VTE patients showing results at least equal for efficacy and safety, and sometime even better, as the standard anticoagulant treatment. There are differences in the design of the trials. In two cases the involved DOAC was administered immediately after VTE diagnosis as a single drug treatment (rivaroxaban and apixaban, whereas in the other trials (involving dabigatran and edoxaban the DOAC was administered after an initial course of approximately 7 days with heparin or derivatives. Some clinical trials have also investigated the use of DOACs for extended anticoagulant treatment after the acute phase. Aim of this article is to review the results of the currently available clinical trials that have compared the use of DOACs versus the standard of care in patients with VTE.

  6. Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

    Science.gov (United States)

    Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

    2017-07-01

    Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Direct oral anticoagulants in real practice: which doses for which patients. Limitations and bleeding risk compared to vitamin K antagonists

    Directory of Open Access Journals (Sweden)

    Giancarlo Landini

    2013-12-01

    Full Text Available The new oral direct anticoagulants (DOACs could represent a new frontier for management of thromboembolic diseases. However, the new drugs have limitations that need to be considered. Despite the fact that their efficacy and safety profile are at least not inferior to comparators, bleeding risk represents the most feared complication, as for all the antithrombotic drugs. Bleeding risk increases with conditions that interfere with pharmacokinetics, in addition to the risk strictly linked to patients or their co-morbidities. Since all DOACs are excreted from kidneys (even though at different percentages according to the different molecules, renal impairment represents one of the leading causes of DOACs accumulation and bleeding risk. Moderate renal failure is the main condition in which dose adjustment of DOACs could be required, while severe renal impairment represents an absolute contraindication for their use. Renal function must, therefore, be carefully monitored before prescription and during assumption. The older population is at higher bleeding risk, and dose adjustment of DOACs could be required. Although to a lesser degree than oral anticoagulant vitamin K antagonists, DOACs can have drug interactions, especially with P-glycoprotein and cytochrome P3A4 inducers or inhibitors, and these interactions must be taken into account in real practice to avoid accumulation or under dosage. The concomitant use of other drugs, especially antithrombotics, may expose the patients to bleeding risk by reducing the hemostatic properties.

  8. Pharmacological profile of AW-814141, a novel, potent, selective and orally active inhibitor of p38 MAP kinase

    DEFF Research Database (Denmark)

    Chopra, Puneet; Kulkarni, Onkar; Gupta, Shashank

    2010-01-01

    -inflammatory activity of a p38 MAPK inhibitor, AW-814141. AW-814141 inhibited enzymatic activity of recombinant p38-alpha and beta isoforms with IC(50) value of 100nM and 158nM, respectively. AW-814141 also inhibited the release of tumor necrosis factor (TNF)-alpha by lipopolysaccharide (LPS) treated human peripheral...... blood mononuclear cells with an IC(50) value of 212nM and demonstrated selectivity against a panel of few kinases. Oral administration of AW-814141 (10mpk) in LPS-injected mice resulted in a significant reduction in TNF-alpha production in the circulation. In a carrageenan-induced rat paw edema model...

  9. Identification of a novel boronic acid as a potent, selective, and orally active hormone sensitive lipase inhibitor.

    Science.gov (United States)

    Ogiyama, Tomoko; Yamaguchi, Mitsuhiro; Kurikawa, Nobuya; Honzumi, Shoko; Yamamoto, Yuka; Sugiyama, Daisuke; Inoue, Shinichi

    2016-08-15

    Hormone sensitive lipase (HSL) is an attractive therapeutic target of dyslipidemia. We designed and synthesized several compounds as reversible HSL inhibitors with a focus on hydrophobic interactions, which was thought to be effective upon the HSL inhibitory activity. In these efforts, we identified boronated compound 12 showing a potent HSL inhibitory activity with an IC50 value of 7nM and a high selectivity against cholinesterases. Furthermore, compound 12 is the first boron containing HSL inhibitor that has shown an antilipolytic effect in rats after oral administration at 3mg/kg. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Pre-analytical stability of selected benzodiazepines on a polymeric oral fluid sampling device.

    Science.gov (United States)

    Kempf, Jürgen; Wuske, Thomas; Schubert, Rolf; Weinmann, Wolfgang

    2009-04-15

    Oral fluid field tests are designed to provide preliminary results with a high grade of reliability in order to meet analytical and forensic standards. Some test systems additionally offer the possibility of an independent confirmatory analysis of a test sample. The pre-analytical stability of 11 frequently abused benzodiazepines on an oral fluid collecting device (Dräger DCD 5000) has been investigated. The collection device was designed to complement a special mobile testing system (Dräger DrugTest 5000) to be sent to a laboratory for further confirmatory analysis. Blank oral fluid pool was spiked with a mixture of eleven frequently abused benzodiazepines and given onto a collection device. To simulate possible sample shipping, the collection devices were stored in the dark up to 14 days at ambient temperature in a plastic tube. The collection device was simultaneously stored without further treatment after oral fluid collection ('native') and with addition of 950muL of methanol, respectively. At different storage intervals repeat determination was carried out for every sample using a modified version of our standard LC-MS/MS method for the detection of benzodiazepines in serum. Different recoveries of benzodiazepines due to degradation and/or adsorption to the collection device during the 14 days of 'native' storage were found. Major loss of analytes was found for benzodiazepines containing a nitro-group such as flunitrazepam and clonazepam. This could be prevented almost completely by methanolic storage of the collection device after sampling. Therefore, we recommend the centrifugation of the collection device and separation from the polymer unit prior to sample shipping. If this should not be possible, addition of methanol immediately after sample collection can be used to avoid degradation of benzodiazepines during shipment.

  11. Experience-dependent firing rate remapping generates directional selectivity in hippocampal place cells

    Directory of Open Access Journals (Sweden)

    Zaneta eNavratilova

    2012-02-01

    Full Text Available When rodents engage in irregular foraging in an open field environment, hippocampal principal cells exhibit place-specific firing that is statistically independent of the direction of traverse through the place field. When the path is restricted to a track, however, in-field rates differ substantially in opposite directions. Frequently, the representations of the track in the two directions are essentially orthogonal. We show that this directionally selective firing is not hard-wired, but develops through experience-dependent plasticity. During the rats’ first pass in each direction, place fields were highly directionally symmetric, whereas over subsequent laps, the firing rates in the two directions gradually but substantially diverged. We conclude that, even on a restricted track, place cell firing is initially determined by allocentric position, and only later, the within-field firing rates change in response to differential sensory information or behavioral cues in the two directions. In agreement with previous data, place fields near local cues, such as textures on the track, developed less directionality than place fields on a uniform part of the track, possibly because the local cues reduced the net difference in sensory input at a given point. Directionality also developed in an open environment without physical restriction of the animal’s path, when rats learned to run along a specified path. In this case, directionality developed later than on the running track, only after the rats began to run in a stereotyped manner. Although the average population firing rates exhibited little if any change over laps in either direction, the direction-specific firing rates in a given place field were up- or down-regulated with about equal probability and magnitude, which was independent in the two directions, suggesting some form of competitive mechanism (e.g., LTP/LTD acting coherently on the set of synapses conveying external information to

  12. Activity of potent and selective host defense peptide mimetics in mouse models of oral candidiasis.

    Science.gov (United States)

    Ryan, Lisa K; Freeman, Katie B; Masso-Silva, Jorge A; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G; Fatahzadeh, Mahnaz; Scott, Richard W; Diamond, Gill

    2014-07-01

    There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.

  13. ABO blood groups and oral premalignancies: A clinical study in selected Indian population

    Directory of Open Access Journals (Sweden)

    S Bhateja

    2014-01-01

    Full Text Available Background: The ABO blood group antigens are present on the surface of red blood cells and various epithelial cells. As the majority of human cancers are derived from epithelial cells, changes in blood group antigens constitute an important aspect of human cancers. The aim of the study was to establish clinical usefulness of ABO blood group as a predisposing factor in early diagnosis and management of patients with oral precancerous lesions/conditions. Materials and Methods: The study sample consisted of 50 control and 50 oral precancer (25 leukoplakia and 25 Oral Submucous Fibrosis confirmed by histopathologic examination. All samples were subjected to blood group testing and their prevalence was compared by Z-test using STATA version 8. Results: The "A" blood group was prevalent among the precancerous group. Significant differences on prevalences of blood groups were found (P < 0.05 between control versus leukoplakia and OSMF. Interestingly, 24% gutka chewers who had higher number of grades of dysplasia were falling in "A" blood group. Conclusion: Blood group type should be considered along with other risk factors to understand the individual patient′s risk and further studies in larger samples with inclusion of Rh factor is needed to elucidate the relationship with ABO blood group types.

  14. ABO blood groups and oral premalignancies: A clinical study in selected Indian population.

    Science.gov (United States)

    Bhateja, S; Arora, G

    2014-01-01

    Background: The ABO blood group antigens are present on the surface of red blood cells and various epithelial cells. As the majority of human cancers are derived from epithelial cells, changes in blood group antigens constitute an important aspect of human cancers. The aim of the study was to establish clinical usefulness of ABO blood group as a predisposing factor in early diagnosis and management of patients with oral precancerous lesions/conditions. Materials and Methods: The study sample consisted of 50 control and 50 oral precancer (25 leukoplakia and 25 Oral Submucous Fibrosis) confirmed by histopathologic examination. All samples were subjected to blood group testing and their prevalence was compared by Z-test using STATA version 8. Results: The "A" blood group was prevalent among the precancerous group. Significant differences on prevalences of blood groups were found (P blood group. Conclusion: Blood group type should be considered along with other risk factors to understand the individual patient's risk and further studies in larger samples with inclusion of Rh factor is needed to elucidate the relationship with ABO blood group types.

  15. On the selection of words and oral motor responses: evidence of a response-independent fronto-parietal network.

    Science.gov (United States)

    Tremblay, Pascale; Gracco, Vincent L

    2010-01-01

    Several brain areas including the medial and lateral premotor areas, and the prefrontal cortex, are thought to be involved in response selection. It is unclear, however, what the specific contribution of each of these areas is. It is also unclear whether the response selection process operates independent of response modality or whether a number of specialized processes are recruited depending on the behaviour of interest. In the present study, the neural substrates for different response selection modes (volitional and stimulus-driven) were compared, using sparse-sampling functional magnetic resonance imaging, for two different response modalities: words and comparable oral motor gestures. Results demonstrate that response selection relies on a network of prefrontal, premotor and parietal areas, with the pre-supplementary motor area (pre-SMA) at the core of the process. Overall, this network is sensitive to the manner in which responses are selected, despite the absence of a medio-lateral axis, as was suggested by Goldberg (1985). In contrast, this network shows little sensitivity to the modality of the response, suggesting of a domain-general selection process. Theoretical implications of these results are discussed.

  16. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

    Directory of Open Access Journals (Sweden)

    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  17. Direct selective oxygen-assisted acylation of amines driven by metallic silver surfaces: dimethylamine with formaldehyde.

    Science.gov (United States)

    Zhou, Ling; Freyschlag, Cassandra G; Xu, Bingjun; Friend, Cynthia M; Madix, Robert J

    2010-02-07

    Facile, direct acylation of dimethylamine with formaldehyde to N,N-dimethylformamide proceeds with a selectivity approaching 100% at low oxygen concentrations on metallic silver surfaces; the reaction proceeds via nucleophilic attack of adsorbed dimethylamide on formaldehyde with subsequent beta-H elimination from the adsorbed hemiaminal.

  18. Adaptation to real motion reveals direction-selective interactions between real and implied motion processing

    NARCIS (Netherlands)

    Lorteije, J.A.M.; Kenemans, J.L.; Jellema, T.; Lubbe, R.H.J. van der; Lommers, M.W.; Wezel, R.J.A. van

    2007-01-01

    Viewing static pictures of running humans evokes neural activity in the dorsal motion-sensitive cortex. To establish whether this response arises from direction-selective neurons that are also involved in real motion processing, we measured the visually evoked potential to implied motion following a

  19. Adaptation to Real Motion Reveals Direction-selective Interactions between Real and Implied Motion Processing

    NARCIS (Netherlands)

    Lorteije, Jeannette A.M.; Kenemans, Leon; Jellema, Tjeerd; Lubbe, van der Rob H.J.; Lommers, Marjolein W.; Wezel, van Richard J.A.

    2007-01-01

    Viewing static pictures of running humans evokes neural activity in the dorsal motion-sensitive cortex. To establish whether this response arises from direction-selective neurons that are also involved in real motion processing, we measured the visually evoked potential to implied motion following a

  20. Oral bioavailability of arsenic, antimony and a selection of metals in ashes; Oral biotillgaenglighet av arsenik, antimon och ett urval av metaller i askor

    Energy Technology Data Exchange (ETDEWEB)

    Carlsson, Christel; Bendz, David; Jones, Celia

    2008-06-15

    In an earlier study, financed by Varmeforsk, 'Q4-238 Environmental guidelines for reuse of ash in civil engineering applications', the total content of arsenic and lead was shown to determine whether or not reuse of some of the ashes in construction work is feasible. The model used to calculate the guidelines uses the total concentration of metals to evaluate the health risks resulting from exposure to the ashes. The use of total concentration can lead to overly conservative risk assessments if a significant fraction of the total metal content is not bioavailable. Better precision in the risk assessment can be given by the use of the bioavailable fraction of arsenic and lead in the model. As a result, ashes which are rejected on the basis of total metal concentration may be acceptable for use in engineering construction when the assessment is based on the bioavailable fraction. The purpose of the study was to (i) compile information on the oral bioavailability of arsenic, antimony and a selection of metals in ashes and similar materials, and on in vitro methods for determination of oral bioavailability, and (ii) experimentally estimate oral bioavailability of arsenic, antimony and some metals in a selection of ashes by analysis of the gastrointestinal bioaccessibility of these elements. The investigated elements were antimony, arsenic, lead, cadmium, copper, chromium, nickel and zinc. In the literature study performed within the project a number of static and dynamic in vitro methods simulating gastrointestinal processes of contaminants were compiled. The methods include one or several segments, i.e. mouth, stomach and intestine. Among the compiled methods, the RIVM (Rijksinstituut voor volksgesundheid en milieu) in vitro method was used in the experimental part of the project. The advantages with the method was that: the method to a high degree mimicked the human gastrointestinal processes (the method included three segments mouth, stomach, and intestine

  1. Direct and mediated effects of language and cognitive skills on comprehension of oral narrative texts (listening comprehension) for children.

    Science.gov (United States)

    Kim, Young-Suk Grace

    2016-01-01

    We investigated component language and cognitive skills of oral language comprehension of narrative texts (i.e., listening comprehension). Using the construction-integration model of text comprehension as an overarching theoretical framework, we examined direct and mediated relations of foundational cognitive skills (working memory and attention), foundational language skills (vocabulary and grammatical knowledge), and higher-order cognitive skills (inference, theory of mind, and comprehension monitoring) to listening comprehension. A total of 201 first grade children in South Korea participated in the study. Structural equation modeling results showed that listening comprehension is directly predicted by working memory, grammatical knowledge, inference, and theory of mind and is indirectly predicted by attention, vocabulary, and comprehension monitoring. The total effects were .46 for working memory, .07 for attention, .30 for vocabulary, .49 for grammatical knowledge, .31 for inference, .52 for theory of mind, and .18 for comprehension monitoring. These results suggest that multiple language and cognitive skills make contributions to listening comprehension, and their contributions are both direct and indirect. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Diagnostic Accuracy of Image Enhancement in Intra-Oral Direct Digital Radiography in the Assessment of Interproximal Caries

    Directory of Open Access Journals (Sweden)

    Farzad Esmaeili

    2016-07-01

    Full Text Available Background The first commercial system for digital radiography was introduced in 1987, and it has evolved a great deal since then. Currently, it is possible to enhance images in digital radiography. Objectives The aim of this study is to evaluate the diagnostic accuracy of image enhancement in direct digital radiography as it relates to interproximal carries assessment. Materials and Methods Following extraction, 50 human teeth were kept in acidic gel (methyl cellulose + acetate buffer PH = 4.8 for 42 days at 37°C to cause caries before mounting. Direct digital radiography was then taken. Two filters were used: sharpen and emboss. Three radiologists evaluated the images with two weeks interval. The histologic assessments were gold standard. Additionally, SPSS 20 was used to draw an ROC curve and calculate AUC. Cohen’s kappa and interclass correlation coefficient (ICC were used to measure intra- and inter-observer reliability. Results For the emboss filter, sensitivity was 95%, specificity was 100%, and accuracy was 96%. For the sharpen filter, sensitivity was 88%, specificity was 100%, and accuracy was 90%. Also, the AUC for the emboss filter was 0.97, and it was 0.94 for the sharpen filter. Cohen’s simple kappa was in the range of excellent. Conclusions Using these filters in intra-oral direct digital radiography (especially the emboss filter can help some clinicians to increase diagnostic accuracy in the assessment of inter proximal caries of posterior teeth.

  3. Evolution of starvation resistance in Drosophila melanogaster: measurement of direct and correlated responses to artificial selection.

    Science.gov (United States)

    Schwasinger-Schmidt, T E; Kachman, S D; Harshman, L G

    2012-02-01

    Laboratory selection for resistance to starvation has been conducted under relatively controlled conditions to investigate direct and correlated responses to artificial selection. With regard to starvation resistance, there are three physiological routes by which the trait can evolve: resource accumulation, energy conservation and starvation tolerance. A majority of energetic compounds and macromolecules including triglycerides, trehalose and other sugars, and soluble protein increased in abundance as a result of selection. Movement was additionally investigated with selected males moving less than control males and selected females exhibiting a similar response to selection. Results obtained from this study supported two of the possible evolutionary mechanisms for adaptation to starvation: energy compound storage and conservation. If the response to selection is based on an evolutionarily conserved pattern of genetic correlations (elevated lipid, elevated sugars and reduced movement), then the response to selection is medically relevant and the genetic architecture should be investigated in depth. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  4. Charles Darwin's Origin of Species, directional selection, and the evolutionary sciences today.

    Science.gov (United States)

    Kutschera, Ulrich

    2009-11-01

    The book On the Origin of Species, published in November 1859, is an "abstract" without references, compiled by Charles Darwin from a much longer manuscript entitled "Natural Selection." Here, I summarize the five theories that can be extracted from Darwin's monograph, explain the true meaning of the phrase "struggle for life" (i.e., competition and cooperation), and outline Darwin's original concept of natural selection in populations of animals and plants. Since neither Darwin nor Alfred R. Wallace distinguished between stabilizing and directional natural selection, the popular argument that "selection only eliminates but is not creative" is still alive today. However, I document that August Weismann (Die Bedeutung der sexuellen Fortpflanzung für die Selektions-Theorie. Gustav Fischer-Verlag, Jena, 1886) and Ivan Schmalhausen (Factors of evolution. The theory of stabilizing selection. The Blackiston Company, Philadelphia, 1949) provided precise definitions for directional (dynamic) selection in nature and illustrate this "Weismann-Schmalhausen principle" with respect to the evolutionary development of novel phenotypes. Then, the modern (synthetic) theory of biological evolution that is based on the work of Theodosius Dobzhansky (Genetics and the origin of species. Columbia University Press, New York, 1937) and others, and the expanded version of this system of theories, are outlined. Finally, I document that symbiogenesis (i.e., primary endosymbiosis, a process that gave rise to the first eukaryotic cells), ongoing directional natural selection, and the dynamic Earth (plate tectonics, i.e., geological events that both created and destroyed terrestrial and aquatic habitats) were the key processes responsible for the documented macroevolutionary patterns in all five kingdoms of life. Since the evolutionary development of the earliest archaic bacteria more than 3,500 mya, the biosphere of our dynamic planet has been dominated by prokaryotic microbes. Eubacteria

  5. Oral Health Glossary

    Science.gov (United States)

    ... About | Contact InfoBites Quick Reference Learn more Children's Oral Health Mouth Breathing Can Cause Major Health Problems Over ... news feeds delivered directly to your desktop! more... Oral Health Glossary Article Chapters Oral Health Glossary print full ...

  6. Localized direction selective responses in the dendrites of visual interneurons of the fly

    Directory of Open Access Journals (Sweden)

    Tinnefeld Philip

    2010-04-01

    Full Text Available Abstract Background The various tasks of visual systems, including course control, collision avoidance and the detection of small objects, require at the neuronal level the dendritic integration and subsequent processing of many spatially distributed visual motion inputs. While much is known about the pooled output in these systems, as in the medial superior temporal cortex of monkeys or in the lobula plate of the insect visual system, the motion tuning of the elements that provide the input has yet received little attention. In order to visualize the motion tuning of these inputs we examined the dendritic activation patterns of neurons that are selective for the characteristic patterns of wide-field motion, the lobula-plate tangential cells (LPTCs of the blowfly. These neurons are known to sample direction-selective motion information from large parts of the visual field and combine these signals into axonal and dendro-dendritic outputs. Results Fluorescence imaging of intracellular calcium concentration allowed us to take a direct look at the local dendritic activity and the resulting local preferred directions in LPTC dendrites during activation by wide-field motion in different directions. These 'calcium response fields' resembled a retinotopic dendritic map of local preferred directions in the receptive field, the layout of which is a distinguishing feature of different LPTCs. Conclusions Our study reveals how neurons acquire selectivity for distinct visual motion patterns by dendritic integration of the local inputs with different preferred directions. With their spatial layout of directional responses, the dendrites of the LPTCs we investigated thus served as matched filters for wide-field motion patterns.

  7. Direct selective laser sintering of high performance metals: Machine design, process development and process control

    Science.gov (United States)

    Das, Suman

    1998-11-01

    This dissertation describes the development of an advanced manufacturing technology known as Direct Selective Laser Sintering (Direct SLS). Direct SLS is a laser based rapid manufacturing technology that enables production of functional, fully dense, metal and cermet components via the direct, layerwise consolidation of constituent powders. Specifically, this dissertation focuses on a new, hybrid net shape manufacturing technique known as Selective Laser Sintering/Hot Isostatic Pressing (SLS/HIP). The objective of research presented in this dissertation was to establish the fundamental machine technology and processing science to enable direct SLS fabrication of metal components composed of high performance, high temperature metals and alloys. Several processing requirements differentiate direct SLS of metals from SLS of polymers or polymer coated powders. Perhaps the most important distinguishing characteristic is the regime of high temperatures involved in direct SLS of metals. Biasing the temperature of the feedstock powder via radiant preheat prior to and during SLS processing was shown to be beneficial. Preheating the powder significantly influenced the flow and wetting characteristics of the melt. During this work, it was conclusively established that powder cleanliness is of paramount importance for successful layerwise consolidation of metal powders by direct SLS. Sequential trials were conducted to establish optimal bake-out and degas cycles under high vacuum. These cycles agreed well with established practices in the powder metallurgy industry. A study of some of the important transport mechanisms in direct SLS of metals was undertaken to obtain a fundamental understanding of the underlying process physics. This study not only provides an explanation of phenomena observed during SLS processing of a variety of metallic materials but also helps in developing selection schemes for those materials that are most amenable to direct SLS processing. The

  8. Directional, stabilizing, and disruptive trait selection as alternative mechanisms for plant community assembly.

    Science.gov (United States)

    Rolhauser, Andrés G; Pucheta, Eduardo

    2017-03-01

    How plant functional traits (e.g., seed mass) drive species abundance within communities remains an unsolved question. Borrowing concepts from natural selection theory, we propose that trait-abundance relationships can generally correspond to one of three modes of trait selection: directional (a rectilinear relationship, where species at one end of a trait axis are most abundant), stabilizing (an n-shaped relationship), and disruptive (a u-shaped relationship). Stabilizing selection (i.e., the functional convergence of abundant species) would result from positive density-dependent interactions (e.g., facilitation) or due to generalized trade-offs in resource acquisition/use, while disruptive selection (i.e., the divergence of abundant species) would result from negative density-dependent interactions (e.g., competition) or due to environmental heterogeneity. These selection modes can be interpreted as proxies for community-level trait-fitness functions, which establish the degree to which traits are truly "functional". We searched for selection modes in a desert annual-plant community in Argentina (which was divided into winter and summer guilds) to test the hypothesis that the relative importance of disruptive mechanisms (competition, disturbances) decreases with the increase of abiotic stress, a stabilizing agent. Average density was analyzed as a function of eight traits generally linked to resource acquisition and competitive ability (maximum plant height, leaf size, specific leaf area, specific root length), resource retention and stress tolerance (leaf dissection, leaf dry matter content, specific root volume), and regeneration (seed mass) using multiple quadratic-regression models. Trait selection was stabilizing and/or directional when the environment was harshest (winter) and disruptive and/or directional when conditions were milder (summer). Selection patterns differed between guilds for two important traits: plant height and seed mass. These results

  9. A visual method for direct selection of high-producing Pichia pastoris clones

    Directory of Open Access Journals (Sweden)

    Liu Sheng

    2011-03-01

    Full Text Available Abstract Background The methylotrophic yeast, Pichia pastoris, offers the possibility to generate a high amount of recombinant proteins in a fast and easy way to use expression system. Being a single-celled microorganism, P. pastoris is easy to manipulate and grows rapidly on inexpensive media at high cell densities. A simple and direct method for the selection of high-producing clones can dramatically enhance the whole production process along with significant decrease in production costs. Results A visual method for rapid selection of high-producing clones based on mannanase reporter system was developed. The study explained that it was possible to use mannanase activity as a measure of the expression level of the protein of interest. High-producing target protein clones were directly selected based on the size of hydrolysis holes in the selected plate. As an example, the target gene (9elp-hal18 was expressed and purified in Pichia pastoris using this technology. Conclusions A novel methodology is proposed for obtaining the high-producing clones of proteins of interest, based on the mannanase reporter system. This system may be adapted to other microorganisms, such as Saccharomyces cerevisiae for the selection of clones.

  10. Point-of-care coagulation testing for assessment of the pharmacodynamic anticoagulant effect of direct oral anticoagulant.

    Science.gov (United States)

    Mani, Helen; Herth, Natalie; Kasper, Alexander; Wendt, Thomas; Schuettfort, Gundolf; Weil, Yvonne; Pfeilschifter, Waltraud; Linnemann, Birgit; Herrmann, Eva; Lindhoff-Last, Edelgard

    2014-10-01

    This investigation was carried out with already available point-of-care testing (POCT) systems for coagulation parameters to evaluate the qualitative and semiquantitative determination of the time- and concentration-dependent anticoagulant effects of the direct oral anticoagulants rivaroxaban and dabigatran. The whole blood prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT) were determined using the GEM PCL Plus coagulation system. Whole blood PT was also measured on the CoaguCheck XS instrument. In addition, PT and aPTT values were obtained in citrated plasma using the PT reagent Neoplastin Plus and the STA APTT reagent. Drug concentrations of rivaroxaban and dabigatran were determined with a chromogenic anti-Xa assay and the hemoclot assay, which are reported to have good agreement with liquid chromatography coupled with tandem mass spectrometry measurements. POCT was performed in 27 consecutive patients who received rivaroxaban 10, 15, or 20 mg once daily and in 15 patients receiving dabigatran 110 or 150 mg twice daily. Blood samples were collected predose and 2 hours after observed drug intake at steady state. Two hours after observed rivaroxaban administration, the whole blood PT measured on the GEM PCL Plus was prolonged by an average of 64.5% in comparison with predose levels. Less differentiation was observed for rivaroxaban when the PT was measured on the CoaguCheck XS instrument or in plasma (prolongation of 24.1% and 36.8%, respectively). After 2 hours observed dabigatran administration, the whole blood aPTT was comparable with plasma values and was prolonged by 23.5% in comparison with trough values. Significant concentration-dependent prolongations of the activated clotting time were observed to different extents for both direct anticoagulants. Direct oral anticoagulants display variable ex vivo effects on different POCT-assays. POCT for aPTT is sensitive to increased concentrations of dabigatran

  11. Adaptation to real motion reveals direction-selective interactions between real and implied motion processing.

    Science.gov (United States)

    Lorteije, Jeannette A M; Kenemans, J Leon; Jellema, Tjeerd; van der Lubbe, Rob H J; Lommers, Marjolein W; van Wezel, Richard J A

    2007-08-01

    Viewing static pictures of running humans evokes neural activity in the dorsal motion-sensitive cortex. To establish whether this response arises from direction-selective neurons that are also involved in real motion processing, we measured the visually evoked potential to implied motion following adaptation to static or moving random dot patterns. The implied motion response was defined as the difference between evoked potentials to pictures with and without implied motion. Interaction between real and implied motion was found as a modulation of this difference response by the preceding motion adaptation. The amplitude of the implied motion response was significantly reduced after adaptation to motion in the same direction as the implied motion, compared to motion in the opposite direction. At 280 msec after stimulus onset, the average difference in amplitude reduction between opposite and same adapted direction was 0.5 muV on an average implied motion amplitude of 2.0 muV. These results indicate that the response to implied motion arises from direction-selective motion-sensitive neurons. This is consistent with interactions between real and implied motion processing at a neuronal level.

  12. Barriers to oral health across selected European countries and the USA.

    Science.gov (United States)

    Manski, Richard; Moeller, John

    2017-01-12

    In this review we consider oral-health access among older adults within and between the USA and various European countries with regard to possible primary financial and modifiable secondary non-financial factors. For older adults, the likelihood of using dental services has been associated, in the health literature, with a multiplicity of factors. These factors are traditionally classified into predisposing, enabling and need categories, and can be further classified into modifiable and non-modifiable subcategories. This raises the question of which single factor or group of factors has the most influence in keeping older adults from seeking care, and how these influences might differ between the USA and various other (European) countries. As it turns out, there is variation in the magnitude of effects across certain measurable potential barriers, but generally it takes a combination of characteristics associated with non-use to have a substantial impact.

  13. Direct Selective Laser Sintering/Melting of High Density Alumina Powder Layers at Elevated Temperatures

    Science.gov (United States)

    Deckers, J.; Meyers, S.; Kruth, J. P.; Vleugels, J.

    Direct selective laser sintering (SLS) or selective laser melting (SLM) are additive manufacturing techniques that can be used to produce three-dimensional ceramic parts directly, without the need for a sacrificial binder. In this paper, a low laser energy density is applied to SLS/SLM high density powder layers of sub-micrometer alumina at elevated temperatures (up to 800̊C). In order to achieve this, a furnace was designed and built into a commercial SLS machine. This furnace was able to produce a homogeneously heated cylindrical zone with a height of 60 mm and a diameter of 32 mm. After optimizing the layer deposition and laser scanning parameters, two ceramic parts with a density up to 85% and grain sizes as low as 5 μm were successfully produced.

  14. Palladium-tin catalysts for the direct synthesis of H₂O₂ with high selectivity.

    Science.gov (United States)

    Freakley, Simon J; He, Qian; Harrhy, Jonathan H; Lu, Li; Crole, David A; Morgan, David J; Ntainjua, Edwin N; Edwards, Jennifer K; Carley, Albert F; Borisevich, Albina Y; Kiely, Christopher J; Hutchings, Graham J

    2016-02-26

    The direct synthesis of hydrogen peroxide (H2O2) from H2 and O2 represents a potentially atom-efficient alternative to the current industrial indirect process. We show that the addition of tin to palladium catalysts coupled with an appropriate heat treatment cycle switches off the sequential hydrogenation and decomposition reactions, enabling selectivities of >95% toward H2O2. This effect arises from a tin oxide surface layer that encapsulates small Pd-rich particles while leaving larger Pd-Sn alloy particles exposed. We show that this effect is a general feature for oxide-supported Pd catalysts containing an appropriate second metal oxide component, and we set out the design principles for producing high-selectivity Pd-based catalysts for direct H2O2 production that do not contain gold.

  15. Direct and Indirect Evidence of Size-Selective Grazing on Pelagic Bacteria by Freshwater Nanoflagellates

    OpenAIRE

    Šimek, Karel; Chrzanowski, Thomas H.

    1992-01-01

    Size-selective grazing of three heterotrophic nanoflagellates (with cell sizes of 21, 44, and 66 μm3) isolated from Lake Arlington, Texas was examined by using a natural mixture of fluorescence labelled lake bacteria. Sizes of ingested bacteria in food vacuoles were directly measured. Larger bacterial cells were ingested at a frequency much higher than that at which they occurred in the assemblage, indicating preferential flagellate grazing on the larger size classes within the lake bacteriop...

  16. Direct and Indirect Evidence of Size-Selective Grazing on Pelagic Bacteria by Freshwater Nanoflagellates

    OpenAIRE

    Šimek, Karel; Chrzanowski,Thomas H

    1992-01-01

    Size-selective grazing of three heterotrophic nanoflagellates (with cell sizes of 21, 44, and 66 μm3) isolated from Lake Arlington, Texas was examined by using a natural mixture of fluorescence labelled lake bacteria. Sizes of ingested bacteria in food vacuoles were directly measured. Larger bacterial cells were ingested at a frequency much higher than that at which they occurred in the assemblage, indicating preferential flagellate grazing on the larger size classes within the lake bacteriop...

  17. Directional Filter for SAR Images Based on Nonsubsampled Contourlet Transform and Immune Clonal Selection

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Yang; Li-Cheng Jiao; Deng-Feng Li

    2009-01-01

    A directional filter algorithm for intensity synthetic aperture radar (SAR) image based on nonsubsampled contourlet transform (NSCT) and immune clonal selection (ICS) is presented. The proposed filter mainly focuses on exploiting different features of edges and noises by NSCT. Furthermore, ICS strategy is introduced to optimize threshold parameter and amplify parameter adaptively. Numerical experiments on real SAR images show that there are improvements in both visual effects and objective indexes.

  18. In-vitro activity of saponins of bauhinia purpurea, madhuca longifolia, celastrus paniculatus and semecarpus anacardium on selected oral pathogens.

    Science.gov (United States)

    Jyothi, K S; Seshagiri, M

    2012-01-01

    Dental caries, periodontitis and other mucosal diseases are caused by a complex community of microorganisms. This study aimed to investigate the antimicrobial properties of saponins of four important oil yielding medicinal plant extracts on selected oral pathogens that are involved in such diseases. Saponins were extracted from Bauhinia purpurea, Madhuca longifolia, Celastrus paniculatus and Semecarpus anacardium and purified. Antimicrobial properties of these saponins against Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Staphylococcus aureus and Lactobacillus acidophilus were determined using well diffusion method. The minimum inhibitory concentration (MIC) was determined as the lowest concentration of saponins inhibiting bacterial growth after 14 h of incubation at 37°C. The bactericidal activity was evaluated using the viable cell count method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Madhuca longifolia saponin on Streptococcus mutans MTCC 890, Streptococcus mitis and Staphylococcus aureus was 18.3 ± 0.15/34.4 ± 0.24 μg/ml, 19.0 ± 0.05/32.2 ± 0.0 μg/ml and 21.2 ± 0.35/39.0 ± 0.30 μg/ml, respectively and Bauhinia purpurea saponin on Streptococcus mutans MTCC 890, Staphylococcus aureus and Lactobacillus acidophilus was 26.4 ± 0.20/43.0 ± 0.40 μg/ml, 29.0 ± 0.30/39.6 ± 0.12 μg/ml and 20.2 ± 0.05/36.8 ± 0.23 μg/ml, respectively. The strong antimicrobial activity of Madhuca longifolia and Bauhinia purpurea may be due to the presence of complex triterpenoid saponins, oleanane type triterpenoid glycosides or atypical pentacyclic triterpenoid saponin. Hence, these extracted saponins may be used in food and oral products to prevent and control oral diseases.

  19. In-Vitro Activity of Saponins of Bauhinia Purpurea Madhuca Longifolia Celastrus Paniculatus and Semecarpus Anacardium on Selected Oral Pathogens

    Directory of Open Access Journals (Sweden)

    K. S. Jyothi

    2012-01-01

    Full Text Available Objective: Dental caries, periodontitis and other mucosal diseases are caused by a complex community of microorganisms. This study aimed to investigate the antimicrobial properties of saponins of four important oil yielding medicinal plant extracts on selected oral pathogens that are involved in such diseases.Materials and Methods: Saponins were extracted from Bauhinia purpurea, Madhuca longifolia, Celastrus paniculatus and Semecarpus anacardium and purified. Antimicrobial properties of these saponins against Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Staphylococcus aureus and Lactobacillus acidophilus were determined using well diffusion method. The minimum inhibitory concentration (MIC was determined as the lowest concentration of saponins inhibiting bacterial growth after 14 h of incubation at 37°C. The bactericidal activity was evaluated using the viable cell count method.Results: The minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC of Madhuca longifolia saponin on Streptococcus mutans MTCC 890, Streptococcus mitis and Staphylococcus aureus was 18.3 ± 0.15/34.4 ± 0.24 µg/ml, 19.0 ± 0.05/32.2 ± 0.0 µg/ml and 21.2 ± 0.35/39.0 ± 0.30 µg/ml, respectively and Bauhinia purpurea saponin on Streptococcus mutans MTCC 890, Staphylococcus aureus and Lactobacillus acidophilus was 26.4 ± 0.20/43.0 ± 0.40 µg/ml, 29.0 ± 0.30/39.6 ± 0.12 µg/ml and 20.2 ± 0.05/36.8 ± 0.23 µg/ml, respectively.Conclusion: The strong antimicrobial activity of Madhuca longifolia and Bauhinia purpurea may be due to the presence of complex triterpenoid saponins, oleanane type triterpenoid glycosides or atypical pentacyclic triterpenoid saponin. Hence, these extracted saponins may be used in food and oral products to prevent and control oral diseases.

  20. The research of high-directive anisotropic magnetic metamaterial antenna loaded with frequency-selective surface

    Institute of Scientific and Technical Information of China (English)

    Sun Yong-Zhi; Ran Li-Xin; Peng Liang; Wang Wei-Guang; Li Ting; Zhao Xu; Chen Qiu-Lin

    2009-01-01

    This paper uses a Computer Simulation Technology microwave studio to simulate the performance of a new highdirectivity anisotropic magnetic metamaterial antenna loaded with a frequency-selective surface. Frequency-selective surface with cross-dipole element has a great effect on the directivity, radiation pattern, and gain of such an antenna. The experimental results show that frequency-selective surface (FSS) significantly improve the radiation performance of anisotropic magnetic metamaterial antenna. For example, as a single anisotropic magnetic metamaterial antenna, half power beam width is 4 degrees in the H planes, and the gain of this antenna is 19.5dBi at 10GHz, achieving a 2.1 degree increment in half power beam width, and a 7.3dB gain increment by loading with the FSS reflector. The simulating results are consistent with our experimental results.

  1. Library selection and directed evolution approaches to engineering targeted viral vectors.

    Science.gov (United States)

    Jang, Jae-Hyung; Lim, Kwang-il; Schaffer, David V

    2007-10-15

    Gene therapy, to delivery of genetic material to a patient for therapeutic benefit, has significant promise for translating basic knowledge of disease mechanism into biomedical treatments. The clinical development of the field has been slowed, however, by the need for improvements in the properties and capabilities of gene delivery vehicles. Vehicles based on viruses offer the potential for efficient gene delivery, but because viruses did not evolve to serve human therapeutic needs, many of their properties require significant improvement, including their safety, efficiency, and capacity for targeted gene delivery. Since viruses are highly complex biological entities, engineering such properties at the molecular level can be challenging. However, there has been significant progress in developing approaches that mimic the mechanisms by which viruses arose in the first place. In particular, library-based selection, the generation of one diverse genetic library and selection for new properties, and directed evolution, based on the multiple rounds of library generation and selection for iterative improvement of function, have strong potential in engineering novel properties into these complex biomolecular assemblies. This review will discuss progress in the application of peptide display, library selection, and directed evolution technologies toward engineering vectors based on retrovirus, adeno-associated virus, and adenovirus that are capable of targeted delivery to specific cell types. In addition to creating biomedically useful products, these approaches have future potential to yield novel insights into viral structure-function relationships. Copyright 2007 Wiley Periodicals, Inc.

  2. Direction-Selective Circuits Shape Noise to Ensure a Precise Population Code.

    Science.gov (United States)

    Zylberberg, Joel; Cafaro, Jon; Turner, Maxwell H; Shea-Brown, Eric; Rieke, Fred

    2016-01-20

    Neural responses are noisy, and circuit structure can correlate this noise across neurons. Theoretical studies show that noise correlations can have diverse effects on population coding, but these studies rarely explore stimulus dependence of noise correlations. Here, we show that noise correlations in responses of ON-OFF direction-selective retinal ganglion cells are strongly stimulus dependent, and we uncover the circuit mechanisms producing this stimulus dependence. A population model based on these mechanistic studies shows that stimulus-dependent noise correlations improve the encoding of motion direction 2-fold compared to independent noise. This work demonstrates a mechanism by which a neural circuit effectively shapes its signal and noise in concert, minimizing corruption of signal by noise. Finally, we generalize our findings beyond direction coding in the retina and show that stimulus-dependent correlations will generally enhance information coding in populations of diversely tuned neurons.

  3. Market study for direct utilization of geothermal resources by selected sectors of economy

    Energy Technology Data Exchange (ETDEWEB)

    1980-08-01

    A comprehensive analysis is presented of industrial markets potential for direct use of geothermal energy by a total of six industry sectors: food and kindred products; tobacco manufactures; textile mill products; lumber and wood products (except furniture); chemicals and allied products; and leather and leather products. A brief statement is presented regarding sectors of the economy and major manufacturing processes which can readily utilize direct geothermal energy. Previous studies on plant location determinants are summarized and appropriate empirical data provided on plant locations. Location determinants and potential for direct use of geothermal resources are presented. The data was gathered through interviews with 30 senior executives in the six sectors of economy selected for study. Probable locations of plants in geothermal resource areas and recommendations for geothermal resource marketing are presented. Appendix A presents factors which impact on industry location decisions. Appendix B presents industry executives interviewed during the course of this study. (MHR)

  4. Charles Darwin's Origin of Species, directional selection, and the evolutionary sciences today

    Science.gov (United States)

    Kutschera, Ulrich

    2009-11-01

    The book On the Origin of Species, published in November 1859, is an “abstract” without references, compiled by Charles Darwin from a much longer manuscript entitled “Natural Selection.” Here, I summarize the five theories that can be extracted from Darwin’s monograph, explain the true meaning of the phrase “struggle for life” (i.e., competition and cooperation), and outline Darwin’s original concept of natural selection in populations of animals and plants. Since neither Darwin nor Alfred R. Wallace distinguished between stabilizing and directional natural selection, the popular argument that “selection only eliminates but is not creative” is still alive today. However, I document that August Weismann ( Die Bedeutung der sexuellen Fortpflanzung für die Selektions-Theorie. Gustav Fischer-Verlag, Jena, 1886) and Ivan Schmalhausen ( Factors of evolution. The theory of stabilizing selection. The Blackiston Company, Philadelphia, 1949) provided precise definitions for directional (dynamic) selection in nature and illustrate this “Weismann-Schmalhausen principle” with respect to the evolutionary development of novel phenotypes. Then, the modern (synthetic) theory of biological evolution that is based on the work of Theodosius Dobzhansky ( Genetics and the origin of species. Columbia University Press, New York, 1937) and others, and the expanded version of this system of theories, are outlined. Finally, I document that symbiogenesis (i.e., primary endosymbiosis, a process that gave rise to the first eukaryotic cells), ongoing directional natural selection, and the dynamic Earth (plate tectonics, i.e., geological events that both created and destroyed terrestrial and aquatic habitats) were the key processes responsible for the documented macroevolutionary patterns in all five kingdoms of life. Since the evolutionary development of the earliest archaic bacteria more than 3,500 mya, the biosphere of our dynamic planet has been dominated by

  5. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity

    NARCIS (Netherlands)

    Baugh, Mark; Black, Darcey; Westwood, Paul; Kinghorn, Emma; McGregor, Kieran; Bruin, John; Hamilton, William; Dempster, Maureen; Claxton, Christopher; Cai, Jiaqiang; Bennett, Jonathan; Long, Clive; Mckinnon, Heather; Vink, Paul; den Hoed, Leontien; Gorecka, Monika; Vora, Kalpit; Grant, Ethan; Percival, M. David; Boots, A. Mieke H.; van Lierop, Marie-Jose; Boots, Annemieke

    2011-01-01

    The purpose of the study was to examine the potential of inhibition of cathepsin S as a treatment for autoimmune diseases. A highly selective cathepsin S inhibitor, CSI-75, was shown to upregulate levels of the cathepsin S substrate, invariant chain Lip10, in vitro as well as in vivo in C57Bl/6 mice

  6. Oral bioavailability of arsenic, antimony and a selection of metals in ashes; Oral biotillgaenglighet av arsenik, antimon och ett urval av metaller i askor

    Energy Technology Data Exchange (ETDEWEB)

    Carlsson, Christel; Bendz, David; Jones, Celia

    2008-06-15

    In an earlier study, financed by Varmeforsk, 'Q4-238 Environmental guidelines for reuse of ash in civil engineering applications', the total content of arsenic and lead was shown to determine whether or not reuse of some of the ashes in construction work is feasible. The model used to calculate the guidelines uses the total concentration of metals to evaluate the health risks resulting from exposure to the ashes. The use of total concentration can lead to overly conservative risk assessments if a significant fraction of the total metal content is not bioavailable. Better precision in the risk assessment can be given by the use of the bioavailable fraction of arsenic and lead in the model. As a result, ashes which are rejected on the basis of total metal concentration may be acceptable for use in engineering construction when the assessment is based on the bioavailable fraction. The purpose of the study was to (i) compile information on the oral bioavailability of arsenic, antimony and a selection of metals in ashes and similar materials, and on in vitro methods for determination of oral bioavailability, and (ii) experimentally estimate oral bioavailability of arsenic, antimony and some metals in a selection of ashes by analysis of the gastrointestinal bioaccessibility of these elements. The investigated elements were antimony, arsenic, lead, cadmium, copper, chromium, nickel and zinc. In the literature study performed within the project a number of static and dynamic in vitro methods simulating gastrointestinal processes of contaminants were compiled. The methods include one or several segments, i.e. mouth, stomach and intestine. Among the compiled methods, the RIVM (Rijksinstituut voor volksgesundheid en milieu) in vitro method was used in the experimental part of the project. The advantages with the method was that: the method to a high degree mimicked the human gastrointestinal processes (the method included three segments mouth, stomach, and intestine

  7. Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice

    Directory of Open Access Journals (Sweden)

    Bacon Teresa H

    2001-12-01

    Full Text Available Abstract Background Acyclovir (ACV resistant herpes simplex virus (HSV isolates can be readily selected in animal infection models receiving suboptimal ACV treatment, however no comparative studies of the emergence of resistance following suboptimal treatment with valacyclovir (VCV or famciclovir (FCV, the prodrugs of acyclovir and penciclovir, respectively, have been reported. Methods Mice (n = 30 were infected with HSV type 1 or 2 in the ear pinnae and administered oral prodrugs at one fifth a dose previously shown to be effective. To select and amplify drug-resistant HSV, a total of seven consecutive in vivo passages with suboptimal treatment were performed for each virus sample and progeny virus from each passage was characterized by the plaque reduction (PRA and plating efficiency assays (PEA. Results No drug-resistant HSV-2 and only a single drug-resistant HSV-1 variant were identified. Virus recovered from the first three sequential passages of this HSV-1 sample was susceptible by PRA, although the proportion of resistant virus recovered gradually increased upon passage. The resistant HSV-1 phenotype was confirmed by PRA after four sequential passages in mice. Unexpectedly, this in vivo-selected drug-resistant HSV-1 failed to yield an infection completely refractory to treatment in subsequent passages. Conclusions Sub-optimal therapy of immunocompetent mice with either VCV or FCV did not readily select for HSV-mutants resistant to either ACV or PCV, suggesting that selection of resistance with either prodrug remains difficult using this system. Futhermore, this study suggests that the PEA may represent a useful adjunct to the PRA for monitoring alterations in the proportion of drug-resistant virus even when no change in IC50 is apparent.

  8. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.

    Science.gov (United States)

    Basaria, Shehzad; Collins, Lauren; Dillon, E Lichar; Orwoll, Katie; Storer, Thomas W; Miciek, Renee; Ulloor, Jagadish; Zhang, Anqi; Eder, Richard; Zientek, Heather; Gordon, Gilad; Kazmi, Syed; Sheffield-Moore, Melinda; Bhasin, Shalender

    2013-01-01

    Concerns about potential adverse effects of testosterone on prostate have motivated the development of selective androgen receptor modulators that display tissue-selective activation of androgenic signaling. LGD-4033, a novel nonsteroidal, oral selective androgen receptor modulator, binds androgen receptor with high affinity and selectivity. Objectives. To evaluate the safety, tolerability, pharmacokinetics, and effects of ascending doses of LGD-4033 administered daily for 21 days on lean body mass, muscle strength, stair-climbing power, and sex hormones. In this placebo-controlled study, 76 healthy men (21-50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days. Blood counts, chemistries, lipids, prostate-specific antigen, electrocardiogram, hormones, lean and fat mass, and muscle strength were measured during and for 5 weeks after intervention. LGD-4033 was well tolerated. There were no drug-related serious adverse events. Frequency of adverse events was similar between active and placebo groups. Hemoglobin, prostate-specific antigen, aspartate aminotransferase, alanine aminotransferase, or QT intervals did not change significantly at any dose. LGD-4033 had a long elimination half-life and dose-proportional accumulation upon multiple dosing. LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone-binding globulin, high density lipoprotein cholesterol, and triglyceride levels. follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation. LGD-4033 was safe, had favorable pharmacokinetic profile, and increased lean body mass even during this short period without change in prostate-specific antigen. Longer randomized trials should evaluate its efficacy in improving physical function

  9. Direct effects of Facio-Oral Tract Therapy(®) on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia.

    Science.gov (United States)

    Konradi, Jürgen; Lerch, Annekatrin; Cataldo, Marilena; Kerz, Thomas

    2015-01-01

    The aim of this study was to investigate the direct effect of Facio-Oral Tract Therapy(®) on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia. Within a pre-, post-/during and follow-up study design, 19 non-tracheotomised dysphagic patients were included consecutively and treated according to three specific preselected Facio-Oral Tract Therapy stimulation techniques. The primary outcome was the direct effect of the three different Facio-Oral Tract Therapy stimulation techniques on the number of swallows. We found a significant effect of Facio-Oral Tract Therapy on swallowing frequency as compared to baseline with an increase by 65.63% and medium effect size of D = 0.62. No significant difference could be demonstrated when comparing baseline to follow-up. For the first time, this positive therapy effect could be demonstrated on a population of non-tracheotomised patients. Facio-Oral Tract Therapy seems to be an appropriate means for improving effectiveness and safety of swallowing. Since improvement was not long lasting, it appears to be reasonable to apply therapy frequently during the day with the plausible result of minimising the amount of aspirated saliva and thereby reducing the risk of aspiration pneumonia. Further studies may consider choosing a randomised controlled trial design to demonstrate that change in swallow frequency is related to the target intervention only.

  10. Direct effects of Facio-Oral Tract Therapy® on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia

    Directory of Open Access Journals (Sweden)

    Jürgen Konradi

    2015-03-01

    Full Text Available Objectives: The aim of this study was to investigate the direct effect of Facio-Oral Tract Therapy® on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia. Methods: Within a pre-, post-/during and follow-up study design, 19 non-tracheotomised dysphagic patients were included consecutively and treated according to three specific preselected Facio-Oral Tract Therapy stimulation techniques. Results: The primary outcome was the direct effect of the three different Facio-Oral Tract Therapy stimulation techniques on the number of swallows. We found a significant effect of Facio-Oral Tract Therapy on swallowing frequency as compared to baseline with an increase by 65.63% and medium effect size of D = 0.62. No significant difference could be demonstrated when comparing baseline to follow-up. Conclusion: For the first time, this positive therapy effect could be demonstrated on a population of non-tracheotomised patients. Facio-Oral Tract Therapy seems to be an appropriate means for improving effectiveness and safety of swallowing. Since improvement was not long lasting, it appears to be reasonable to apply therapy frequently during the day with the plausible result of minimising the amount of aspirated saliva and thereby reducing the risk of aspiration pneumonia. Further studies may consider choosing a randomised controlled trial design to demonstrate that change in swallow frequency is related to the target intervention only.

  11. Direct oral anticoagulants in atrial fibrillation: can data from randomized clinical trials be safely transferred to the general population? No.

    Science.gov (United States)

    Marietta, Marco

    2015-09-01

    Direct oral anticoagulants (DOAC) represent an innovative and relevant treatment for the prevention of cardiac embolism in patients with atrial fibrillation (AF). Their introduction has been followed by an ample debate on their appropriate use, considering that they can offer an effective treatment for the many patients with AF, which are not taking any effective anticoagulant treatment, even though they have a substantial thromboembolic risk (1). On the other hand, DOAC are much less tested in everyday clinical practice and much more expensive than anti-vitamin k anticoagulants (AVKs). Starting from the quite favorable results of the available randomized controlled trials (RCTs)--showing that DOAC are at least non-inferior to AVK and that may be even better for some outcomes--this article discusses their transferability to the majority of AF patients. In summary, the body of evidence supports the efficacy and safety of DOAC in patients carrying demographic and clinical characteristics similar to subjects included in RCT, but their use in less well-characterized subpopulations requires particular caution, while waiting for more reliable data from the real world.

  12. Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

    Science.gov (United States)

    Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L

    2014-10-01

    Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Silent reading of direct versus indirect speech activates voice-selective areas in the auditory cortex.

    Science.gov (United States)

    Yao, Bo; Belin, Pascal; Scheepers, Christoph

    2011-10-01

    In human communication, direct speech (e.g., Mary said: "I'm hungry") is perceived to be more vivid than indirect speech (e.g., Mary said [that] she was hungry). However, for silent reading, the representational consequences of this distinction are still unclear. Although many of us share the intuition of an "inner voice," particularly during silent reading of direct speech statements in text, there has been little direct empirical confirmation of this experience so far. Combining fMRI with eye tracking in human volunteers, we show that silent reading of direct versus indirect speech engenders differential brain activation in voice-selective areas of the auditory cortex. This suggests that readers are indeed more likely to engage in perceptual simulations (or spontaneous imagery) of the reported speaker's voice when reading direct speech as opposed to meaning-equivalent indirect speech statements as part of a more vivid representation of the former. Our results may be interpreted in line with embodied cognition and form a starting point for more sophisticated interdisciplinary research on the nature of auditory mental simulation during reading.

  14. Impact of low-energy CT imaging on selection of positive oral contrast media concentration.

    Science.gov (United States)

    Patino, Manuel; Murcia, Diana J; Iamurri, Andrea Prochowski; Kambadakone, Avinash R; Hahn, Peter F; Sahani, Dushyant V

    2017-05-01

    To determine to what extent low-energy CT imaging affects attenuation of gastrointestinal tract (GIT) opacified with positive oral contrast media (OCM). Second, to establish optimal OCM concentrations for low-energy diagnostic CT exams. One hundred patients (38 men and 62 women; age 62 ± 11 years; BMI 26 ± 5) with positive OCM-enhanced 120-kVp single-energy CT (SECT), and follow-up 100-kVp acquisitions (group A; n = 50), or 40-70-keV reconstructions from rapid kV switching-single-source dual-energy CT (ssDECT) (group B; n = 50) were included. Luminal attenuation from different GIT segments was compared between exams. Standard dose of three OCM and diluted solutions (75%, 50%, and 25% concentrations) were introduced serially in a gastrointestinal phantom and scanned using SECT (120, 100, and 80 kVp) and DECT (80/140 kVp) acquisitions on a ssDECT scanner. Luminal attenuation was obtained on SECT and DECT images (40-70 keV), and compared to 120-kVp scans with standard OCM concentrations. Luminal attenuation was higher on 100-kVp (328 HU) and on 40-60-keV images (410-924 HU) in comparison to 120-kVp scans (298 HU) in groups A and B (p concentration.

  15. A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists.

    Science.gov (United States)

    Hale, Jeffrey J; Lynch, Christopher L; Neway, William; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark J; Milligan, James A; Shei, Gan-Ju; Parent, Stephen A; Chrebet, Gary; Bergstrom, James; Card, Deborah; Ferrer, Marc; Hodder, Peter; Strulovici, Berta; Rosen, Hugh; Mandala, Suzanne

    2004-12-30

    Moderately potent, selective S1P(1) receptor agonists identified from high-throughput screening have been adapted into lipophilic tails for a class of orally bioavailable amino acid-based S1P(1) agonists represented by 7. Many of the new compounds are potent S1P(1) agonists that select against the S1P(2), S1P(3), and S1P(4) (although not S1P(5)) receptor subtypes. Analogues 18 and 24 are highly orally bioavailable and possess excellent pharmacokinetic profiles in the rat, dog, and rhesus monkey.

  16. Bond selectivity in electron-induced reaction due to directed recoil on an anisotropic substrate

    Science.gov (United States)

    Anggara, Kelvin; Huang, Kai; Leung, Lydie; Chatterjee, Avisek; Cheng, Fang; Polanyi, John C.

    2016-12-01

    Bond-selective reaction is central to heterogeneous catalysis. In heterogeneous catalysis, selectivity is found to depend on the chemical nature and morphology of the substrate. Here, however, we show a high degree of bond selectivity dependent only on adsorbate bond alignment. The system studied is the electron-induced reaction of meta-diiodobenzene physisorbed on Cu(110). Of the adsorbate's C-I bonds, C-I aligned `Along' the copper row dissociates in 99.3% of the cases giving surface reaction, whereas C-I bond aligned `Across' the rows dissociates in only 0.7% of the cases. A two-electronic-state molecular dynamics model attributes reaction to an initial transition to a repulsive state of an Along C-I, followed by directed recoil of C towards a Cu atom of the same row, forming C-Cu. A similar impulse on an Across C-I gives directed C that, moving across rows, does not encounter a Cu atom and hence exhibits markedly less reaction.

  17. Two-dimensional map of direction selectivity in cortical visual area MT of Cebus monkey

    Directory of Open Access Journals (Sweden)

    ANTONIA CINIRA M. DIOGO

    2002-09-01

    Full Text Available We studied the spatial organization of direction of motion in visual area MT of the Cebus apella monkey. We used arrays of 6 (700 µm apart parallel electrodes in penetrations tangential to the cortical layers to record multi-unit responses to moving bars, at 200 µm steps. We determined the direction selectivity at each recording site. The data from single penetrations showed cyclic and gradual changes in the direction selectivity of clusters of cells, intermixed with abrupt 180º discontinuities along the electrode track. In order to obtain maps of direction of motion selectivity, we examined the spatial distribution of direction of motion in MT and we applied a method to determine the location of the centers of radial arrangements of direction selectivity. This tangential organization is characterized by slow continuous changes in direction of motion, interrupted by discontinuities. The changes in direction selectivity are organized radially in a pinwheel fashion and in slabs of linear variation. The pinwheel arrangements have 800-1400 µm in diameter. The size of the radial arrangement is comparable to the point image size in area MT at each eccentricity.Estudamos a organização espacial da seletividade ao sentido do movimento na área visual MT do macaco Cebus apella. Utilizamos um arranjo de 6 eletródios paralelos (separados por 700µm em penetrações tangenciais às camadas corticais para registrar, a cada 200µm, a atividade multi-unitária em resposta a barras em movimento. Determinamos a seletividade ao sentido de movimento em cada sítio de registro. Os dados captados por um único eletródio mostraram uma mudança cíclica e gradual na seletividade ao sentido de movimento dos grupos de neurônios registrados ao longo da trajetória do eletródio, interrompida por mudanças abruptas de 180º ocasionando descontinuidades na seletividade ao sentido do movimento. Para obter mapas de seletividade ao sentido do movimento, examinamos a

  18. RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.

    Science.gov (United States)

    Pankova, Katarina; Borst, Alexander

    Neuronal computation underlying detection of visual motion has been studied for more than a half-century. In Drosophila, direction-selective T4/T5 neurons show supralinear signal amplification in response to stimuli moving in their preferred direction, in agreement with the prediction made by the Hassenstein-Reichardt detector. Nevertheless, the molecular mechanism explaining how the Hassenstein-Reichardt model is implemented in T4/T5 cells has not been identified yet. In the present study, we utilized cell type-specific transcriptome profiling with RNA-seq to obtain a complete gene expression profile of T4/T5 neurons. We analyzed the expression of genes that affect neuronal computational properties and can underlie the molecular implementation of the core features of the Hassenstein-Reichardt model to the dendrites of T4/T5 neurons. Furthermore, we used the acquired RNA-seq data to examine the neurotransmitter system used by T4/T5 neurons. Surprisingly, we observed co-expression of the cholinergic markers and the vesicular GABA transporter in T4/T5 neurons. We verified the previously undetected expression of vesicular GABA transporter in T4/T5 cells using VGAT-LexA knock-in line. The provided gene expression dataset can serve as a useful source for studying the properties of direction-selective T4/T5 neurons on the molecular level.

  19. [Research on direct forming of comminuted fracture surgery orienting model by selective laser melting].

    Science.gov (United States)

    He, Xingrong; Yang, Yongqiang; Wu, Weihui; Wang, Di; Ding, Huanwen; Huang, Weihong

    2010-06-01

    In order to simplify the distal femoral comminuted fracture surgery and improve the accuracy of the parts to be reset, a kind of surgery orienting model for the surgery operation was designed according to the scanning data of computer tomography and the three-dimensional reconstruction image. With the use of DiMetal-280 selective laser melting rapid prototyping system, the surgery orienting model of 316L stainless steel was made through orthogonal experiment for processing parameter optimization. The technology of direct manufacturing of surgery orienting model by selective laser melting was noted to have obvious superiority with high speed, precise profile and good accuracy in size when compared with the conventional one. The model was applied in a real surgical operation for thighbone replacement; it worked well. The successful development of the model provides a new method for the automatic manufacture of customized surgery model, thus building a foundation for more clinical applications in the future.

  20. Method of Recognition of Forms When Trying to Select Street Direction

    Directory of Open Access Journals (Sweden)

    Štefan Novak

    2012-10-01

    Full Text Available Roads are one of the main factors which influence roadtraffic safety. They influence the time of the realisation and thecosts of the transport itself by their technical and exploitationcharacteristics. The right selection of a street will highly affectthe costs of transport that can be reduced, and the speed ofrealisation that can be increased. The paper presents one of themethods of recognition of forms which is later on also tested onan example of selecting the type of the street. The aim of this paperwas to show the possibilities of using the recognition offorms in the traffic and transport system. This way of selectionand classification is needed when it is necesswy to decide fastabout the direction of movement, particularly in special circumstances.

  1. A finite volume alternate direction implicit approach to modeling selective laser melting

    DEFF Research Database (Denmark)

    Hattel, Jesper Henri; Mohanty, Sankhya

    2013-01-01

    is proposed for modeling single-layer and few-layers selective laser melting processes. The ADI technique is implemented and applied for two cases involving constant material properties and non-linear material behavior. The ADI FV method consume less time while having comparable accuracy with respect to 3D...... to accurately simulate the process, are constrained by either the size or scale of the model domain. A second challenging aspect involves the inclusion of non-linear material behavior into the 3D implicit FE models. An alternating direction implicit (ADI) method based on a finite volume (FV) formulation......Over the last decade, several studies have attempted to develop thermal models for analyzing the selective laser melting process with a vision to predict thermal stresses, microstructures and resulting mechanical properties of manufactured products. While a holistic model addressing all involved...

  2. Transcranial direct current stimulation improves ipsilateral selective muscle activation in a frequency dependent manner.

    Directory of Open Access Journals (Sweden)

    Kazumasa Uehara

    Full Text Available Failure to suppress antagonist muscles can lead to movement dysfunction, such as the abnormal muscle synergies often seen in the upper limb after stroke. A neurophysiological surrogate of upper limb synergies, the selectivity ratio (SR, can be determined from the ratio of biceps brachii (BB motor evoked potentials to transcranial magnetic stimulation prior to forearm pronation versus elbow flexion. Surprisingly, cathodal transcranial direct current stimulation (c-TDCS over ipsilateral primary motor cortex (M1 reduces (i.e. improves the SR in healthy adults, and chronic stroke patients. The ability to suppress antagonist muscles may be exacerbated at high movement rates. The aim of the present study was to investigate whether the selective muscle activation of the biceps brachii (BB is dependent on altering frequency demands, and whether the c-tDCS improvement of SR is dependent on task frequency. Seventeen healthy participants performed repetitive isometric elbow flexion and forearm pronation at three rates, before and after c-tDCS or sham delivered to ipsilateral left M1. Ipsilateral c-tDCS improved the SR in a frequency dependent manner by selectively suppressing BB antagonist excitability. Our findings confirm that c-tDCS is an effective tool for improving selective muscle activation, and provide novel evidence for its efficacy at rates of movement where it is most likely to benefit task performance.

  3. Subgenomic Diversity Patterns Caused by Directional Selection in Bread Wheat Gene Pools

    Directory of Open Access Journals (Sweden)

    Kai Voss-Fels

    2015-07-01

    Full Text Available Genetic diversity represents the fundamental key to breeding success, providing the basis for breeders to select varieties with constantly improving yield performance. On the other hand, strong selection during domestication and breeding have eliminated considerable genetic diversity in the breeding pools of major crops, causing erosion of genetic potential for adaptation to emerging challenges like climate change. High-throughput genomic technologies can address this dilemma by providing detailed knowledge to characterize and replenish genetic diversity in breeding programs. In hexaploid bread wheat ( L., the staple food for 35% of the world’s population, bottlenecks during allopolyploidisation followed by strong artificial selection have considerably narrowed diversity to the extent that yields in many regions appear to be unexpectedly stagnating. In this study, we used a 90,000 single nucleotide polymorphism (SNP wheat genotyping array to assay high-frequency, polymorphic SNP markers in 460 accessions representing different phenological diversity groups from Asian, Australian, European, and North American bread wheat breeding materials. Detailed analysis of subgroup diversity at the chromosome and subgenome scale revealed highly distinct patterns of conserved linkage disequilibrium between different gene pools. The data enable identification of genome regions in most need of rejuvenation with novel diversity and provide a high-resolution molecular basis for genomic-assisted introgression of new variation into chromosome segments surrounding directionally selected metaloci conferring important adaptation and quality traits.

  4. Induced defences alter the strength and direction of natural selection on reproductive traits in common milkweed.

    Science.gov (United States)

    Thompson, K A; Cory, K A; Johnson, M T J

    2017-06-01

    Evolutionary biologists have long sought to understand the ecological processes that generate plant reproductive diversity. Recent evidence indicates that constitutive antiherbivore defences can alter natural selection on reproductive traits, but it is unclear whether induced defences will have the same effect and whether reduced foliar damage in defended plants is the cause of this pattern. In a factorial field experiment using common milkweed, Asclepias syriaca L., we induced plant defences using jasmonic acid (JA) and imposed foliar damage using scissors. We found that JA-induced plants experienced selection for more inflorescences that were smaller in size (fewer flowers), whereas control plants only experienced a trend towards selection for larger inflorescences (more flowers); all effects were independent of foliar damage. Our results demonstrate that induced defences can alter both the strength and direction of selection on reproductive traits, and suggest that antiherbivore defences may promote the evolution of plant reproductive diversity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  5. Direct and Indirect Factors Influencing Selection of Birthing Attendants in Gunungsari, West Lombok (NTB

    Directory of Open Access Journals (Sweden)

    Ni Nyoman Aryaniti

    2015-04-01

    Full Text Available Background and purpose: This study aims to determine the direct and indirect factors influencing the selection of birth attendants in Gunungsari subdistrict, West Lombok.Methods: This study was cross-sectional with a purposively selected sample of 27 mothers giving birth assisted by non-health professionals. Samples of those assisted by health professionals were taken by means of proportional systematic random sampling in Gunungsari and Penimbung health centers, respectively 29 of 916 and 14 of 437. Exogenous factors were maternal education levels, attendance to ANC classes, knowledge levels regarding to birthing attendants, maternal attitude, family support, and access to facilities. Birth attendant selection was the endogenousfactor. Data were collected by means of interviews. Data analysis includes descriptive and inferential analysis with path analysis by linear regression.Results: The majority of respondents were 21-25 years old (87.4% , housewives (47.14% had educat ion under high school (65.72% and were married (88.57%. Family support had a direct influence in decision making with a coefficient of 0.534 and 35.54% influence overall. Attendance to ANC classes in addition to family support had anindirect influence with a coefficient of 0.520 and 34.78% influence overall. Family support had a direct influence and the factor of attendance to ANC classes and family support has an indirect effect with the overall effect of 70.32%.Conclusion: The presence of the husband/family was needed in ANC class, through an implementation of schedule agreement.Keywords: family support, ANC class, birth attendants, path analysis, West Lombok

  6. Crossover scaling of wavelength selection in directional solidification of binary alloys.

    Science.gov (United States)

    Greenwood, Michael; Haataja, Mikko; Provatas, And Nikolas

    2004-12-10

    We simulate cellular and dendritic growth in directional solidification in dilute binary alloys using a phase-field model solved with adaptive-mesh refinement. The spacing of primary branches is examined for a wide range of thermal gradients and alloy compositions and is found to undergo a maximum as a function of pulling velocity, in agreement with experimental observations. We demonstrate that wavelength selection is unambiguously described by a nontrivial crossover scaling function from the emergence of cellular growth to the onset of dendritic fingers. This result is further validated using published experimental data, which obeys the same scaling function.

  7. Template-Directed meta-Selective Olefination of Aryl C–H Bonds

    OpenAIRE

    2015-01-01

    Authors: Jinquan Yu ### Abstract The most common bond in many organic compounds is the C–H bond. Hence, it is a great challenge to selectively cleave a particular C–H bond in the presence of multiple ones. One of most widely used approach to this problem is the use of -chelating directing groups (1). However, the insertion of the transition metal is strictly restricted to the ortho-C–H bond through a six- or seven-membered cyclic pre-transition state (TS). Although many strategies ha...

  8. Velocity-selective direct frequency-comb spectroscopy of atomic vapors

    CERN Document Server

    Stalnaker, J E; Rowan, M E; Nguyen, K; Pradhananga, T; Palm, C A; Kimball, D F Jackson

    2015-01-01

    We present an experimental and theoretical investigation of two-photon direct frequency-comb spectroscopy performed through velocity-selective excitation. In particular, we explore the effect of repetition rate on the $\\textrm{5S}_{1/2}\\rightarrow \\textrm{5D}_{3/2, 5/2}$ two-photon transitions excited in a rubidium atomic vapor cell. The transitions occur via step-wise excitation through the $\\textrm{5P}_{1/2, 3/2}$ states by use of the direct output of an optical frequency comb. Experiments were performed with two different frequency combs, one with a repetition rate of $\\approx 925$ MHz and one with a repetition rate of $\\approx 250$ MHz. The experimental spectra are compared to each other and to a theoretical model.

  9. Electrofluidics fabricated by space-selective metallization in glass microfluidic structures using femtosecond laser direct writing.

    Science.gov (United States)

    Xu, Jian; Wu, Dong; Hanada, Yasutaka; Chen, Chi; Wu, Sizhu; Cheng, Ya; Sugioka, Koji; Midorikawa, Katsumi

    2013-12-07

    Space-selective metallization of the inside of glass microfluidic structures using femtosecond laser direct-write ablation followed by electroless plating is demonstrated. Femtosecond laser direct writing followed by thermal treatment and successive chemical etching allows us to fabricate three-dimensional microfluidic structures inside photosensitive glass. Then, femtosecond laser ablation followed by electroless metal plating enables flexible deposition of patterned metal films on desired locations of not only the top and bottom walls but also the sidewalls of fabricated microfluidic structures. A volume writing scheme for femtosecond laser irradiation inducing homogeneous ablation on the sidewalls of microfluidic structures is proposed for sidewall metallization. The developed technique is used to fabricate electrofluidics in which microelectric components are integrated into glass microchannels. The fabricated electrofluidics are applied to control the temperature of liquid samples in the microchannels for the enhancement of chemical reactions and to manipulate the movement of biological samples in the microscale space.

  10. Species-specific wiring for direction selectivity in the mammalian retina.

    Science.gov (United States)

    Ding, Huayu; Smith, Robert G; Poleg-Polsky, Alon; Diamond, Jeffrey S; Briggman, Kevin L

    2016-07-07

    Directionally tuned signalling in starburst amacrine cell (SAC) dendrites lies at the heart of the circuit that detects the direction of moving stimuli in the mammalian retina. The relative contributions of intrinsic cellular properties and network connectivity to SAC direction selectivity remain unclear. Here we present a detailed connectomic reconstruction of SAC circuitry in mouse retina and describe two previously unknown features of synapse distributions along SAC dendrites: input and output synapses are segregated, with inputs restricted to proximal dendrites; and the distribution of inhibitory inputs is fundamentally different from that observed in rabbit retina. An anatomically constrained SAC network model suggests that SAC–SAC wiring differences between mouse and rabbit retina underlie distinct contributions of synaptic inhibition to velocity and contrast tuning and receptive field structure. In particular, the model indicates that mouse connectivity enables SACs to encode lower linear velocities that account for smaller eye diameter, thereby conserving angular velocity tuning. These predictions are confirmed with calcium imaging of mouse SAC dendrites responding to directional stimuli.

  11. COX-2 selective inhibitors: a literature review of analgesic efficacy and safety in oral-maxillofacial surgery.

    Science.gov (United States)

    Cicconetti, Andrea; Bartoli, Adriano; Ripari, Francesca; Ripari, Andrea

    2004-02-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesic agents in surgical outpatients. Major limitations of NSAIDs are their gastrointestinal (GI) adverse events (perforation, ulceration, and bleeding), impairment of hemostatic function, and renal failure (with long-term therapy). A new class of NSAIDs, the COX-2 selective inhibitors (CSIs or Coxibs), have been developed with the aim of reducing the GI adverse events of traditional NSAIDs while maintaining their effective anti-inflammatory and analgesic properties. This is a narrative review of the literature aimed to discuss analgesic efficacy, clinical safety and cost-benefit ratio of CSIs in the treatment of post-oral surgery pain. Relevant drug and clinical studies of analgesic efficacy and safety of CSIs in the management of postoperative dental pain were identified through searches of MEDLINE/PubMed, in peer-reviewed journals of medicine and dentistry. The Food and Drug Administration Web site was searched for data of tolerability. Hand-searching included several dental journals and bibliographies of relevant studies. The last electronic search was conducted in April 2003. Data from well-designed, randomized, controlled trials of CSIs on the management of post-oral surgery pain indicate that these drugs are as well-effective analgesic agents as traditional NSAIDs and offer clinical advantages in terms of GI safety and unimpaired platelet function. CSIs do not offer advantages of renal safety over traditional NSAIDs. Although CSIs display analgesic efficacy similar to that of traditional NSAIDs in the treatment of acute, post-oral surgery pain, there is reasonable evidence that these new drugs are preferable in patients who are at an increased risk of developing serious upper-GI complications, in patients who take aspirin for cardiovascular comorbid conditions, and in those allergic to aspirin. Furthermore, CSIs may be given more safely than NSAIDs in perioperative settings

  12. Potential Effect of Substituting Estimated Glomerular Filtration Rate for Estimated Creatinine Clearance for Dosing of Direct Oral Anticoagulants.

    Science.gov (United States)

    Schwartz, Janice B

    2016-10-01

    To determine the potential effect of substituting glomerular filtration rate (GFR) estimates for renal clearance estimated using the Cockcroft-Gault method (CrCL-CG) to calculate direct oral anticoagulant (DOAC) dosing. Simulation and retrospective data analysis. Community, academic institution, nursing home. Noninstitutionalized individuals aged 19 to 80 from the National Health and Nutrition Examination Survey (NHANES) (2011/12) (n = 4,687) and medically stable research participants aged 25 to 105 (n = 208). Age, height, weight, sex, race, serum creatinine, CrCL-CG, and GFR (according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations). Outcome measures were dosing errors if GFR were to be substituted for CrCL-CG. Renal clearance estimates according to all methods were highly correlated (P < .001), although at lower clearances, substitution of GFR estimates for CrCL-CG resulted in failure to recognize needs for dose reductions of rivaroxaban or edoxaban in 28% of NHANES subjects and 47% to 56% of research subjects. At a CrCL-CG of less than 30 mL/min, GFR estimates missed indicated dosage reductions for dabigatran in 18% to 21% of NHANES subjects and 57% to 86% of research subjects. Age and weight contributed to differences between renal clearance estimates (P < .001), but correction of GFR for body surface area (BSA) did not reduce dosing errors. At a CrCL-CG greater than 95 mL/min, edoxaban is not recommended, and GFR esimates misclassified 24% of NHANES and 39% of research subjects. Correction for BSA reduced misclassification to 7% for NHANES and 14% in research subjects. Substitution of GFR estimates for estimated CrCl can lead to failure to recognize indications for reducing DOAC dose and potentially higher bleeding rates than in randomized trials. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  13. Efficacy and safety of the drugs used to reverse direct oral anticoagulants: a systematic review and meta-analysis.

    Science.gov (United States)

    da Luz, Luis Teodoro; Marchand, Mylene; Nascimento, Bartolomeu; Tien, Homer; Nathens, Avery; Shah, Prakesh

    2017-07-01

    Direct oral anticoagulants (DOACs) are effective and safe for prophylaxis and treatment of thromboembolic phenomena. However, managing DOACs during bleeding emergencies is challenging. A systematic review and meta-analysis was conducted on studies addressing efficacy and safety of the drugs used for reversal of DOACs. Medline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to September 2016. Studies that examined clinical and laboratory effects of drugs used to reverse DOACs were included. Risk of bias was assessed using Newcastle-Ottawa scale and Cochrane Collaboration tool. Primary and secondary outcomes assessed were reversal of clinical bleeding, clotting assays, and safety, respectively. Overall effect estimates were pooled, and clinical and statistical heterogeneity were assessed. Meta-analysis was conducted using random-effects model. Four cohort studies in bleeding patients (n = 230) and eight randomized controlled trials in healthy volunteers (n = 381) were included, both with moderate risk of bias. Reversal of clotting assays in healthy volunteers was frequently reported, demonstrating that prothrombin complex concentrate (PCC) reversed prothrombin time (PT) and endogenous thrombin potential (ETP) substantially. For PT, pooled mean difference was 1.68 seconds (95% confidence interval [CI], -0.33 to 3.70 sec; p < 0.01; I(2)  = 97%). For ETP, pooled mean difference was 2.16 seconds (95% CI, 0.57 to 3.75 sec; p < 0.01; I(2)  =( ) 98%). Andexanet alfa and idarucizumab both reverse clotting assays. No important safety concerns were identified. Clotting assays are partially reversed by PCC in healthy volunteers. Idarucizumab and andexanet alfa have solid laboratory reversal effect and potential to be clinically efficacious and safe. However, clinical evidence is still lacking for all agents. © 2017 AABB.

  14. Direct oral anticoagulants in the secondary prevention of stroke and transient ischemic attack in patients with atrial fibrillation.

    Science.gov (United States)

    Arnao, Valentina; Agnelli, Giancarlo; Paciaroni, Maurizio

    2015-08-01

    In patients with non-valvular atrial fibrillation (NVAF) and history of transient ischemic attack (TIA) or stroke, the rate of vascular events is higher in comparison to patients without history of stroke or TIA. A meta-analysis of direct oral anticoagulants (DOACs) studies, including only patients with history of stroke or TIA, report a significant reduction of 15 % in the rates of composite of stroke and systemic embolism in patients treated with DOACs, compared to those treated with warfarin. Furthermore, a reduction of 14 % for major bleeding, as well as a 56 % reduction for hemorrhagic stroke over a median follow-up of 1.8-2.0 years is reported. The combination of DOACs and antiplatelet agents carries the potential of additive benefits in patients with NVAF and other vascular diseases. However, the rate of major bleeding is higher among patients who receive concomitantly antiplatelet agents, compared to those taking only a single drug category. The risk of major bleeding seems to be higher among patients receiving dual antiplatelet agents, compared to those receiving a single antiplatelet drug. When NVAF is associated with an acute coronary syndrome requiring dual antiplatelet therapy (e.g. coronary angioplasty and stenting), DOACs plus this therapy should be considered. However, this therapy has to be administered for the shortest possible time, according to the patient's haemorrhagic and thrombotic risks, and stent type. When NVAF is associated with carotid stenosis, a single antiplatelet therapy should be considered. Regarding carotid revascularization, it seems preferable to treat these patients with endarterectomy, so to avoid dual antiplatelet therapy, which is generally administered after stenting.

  15. Financial Impact of Direct-Acting Oral Anticoagulants in Medicaid: Budgetary Assessment Based on Number Needed to Treat.

    Science.gov (United States)

    Fairman, Kathleen A; Davis, Lindsay E; Kruse, Courtney R; Sclar, David A

    2017-04-01

    Faced with rising healthcare costs, state Medicaid programs need short-term, easily calculated budgetary estimates for new drugs, accounting for medical cost offsets due to clinical advantages. To estimate the budgetary impact of direct-acting oral anticoagulants (DOACs) compared with warfarin, an older, lower-cost vitamin K antagonist, on 12-month Medicaid expenditures for nonvalvular atrial fibrillation (NVAF) using number needed to treat (NNT). Medicaid utilization files, 2009 through second quarter 2015, were used to estimate OAC cost accounting for generic/brand statutory minimum (13/23%) and assumed maximum (13/50%) manufacturer rebates. NNTs were calculated from clinical trial reports to estimate avoided medical events for a hypothetical population of 500,000 enrollees (approximate NVAF prevalence × Medicaid enrollment) under two DOAC market share scenarios: 2015 actual and 50% increase. Medical service costs were based on published sources. Costs were inflation-adjusted (2015 US$). From 2009-2015, OAC reimbursement per claim increased by 173 and 279% under maximum and minimum rebate scenarios, respectively, while DOAC market share increased from 0 to 21%. Compared with a warfarin-only counterfactual, counts of ischemic strokes, intracranial hemorrhages, and systemic embolisms declined by 36, 280, and 111, respectively; counts of gastrointestinal hemorrhages increased by 794. Avoided events and reduced monitoring, respectively, offset 3-5% and 15-24% of increased drug cost. Net of offsets, DOAC-related cost increases were US$258-US$464 per patient per year (PPPY) in 2015 and US$309-US$579 PPPY after market share increase. Avoided medical events offset a small portion of DOAC-related drug cost increase. NNT-based calculations provide a transparent source of budgetary-impact information for new medications.

  16. A synthetic vision system using directionally selective motion detectors to recognize collision.

    Science.gov (United States)

    Yue, Shigang; Rind, F Claire

    2007-01-01

    Reliably recognizing objects approaching on a collision course is extremely important. A synthetic vision system is proposed to tackle the problem of collision recognition in dynamic environments. The system combines the outputs of four whole-field motion-detecting neurons, each receiving inputs from a network of neurons employing asymmetric lateral inhibition to suppress their responses to one direction of motion. An evolutionary algorithm is then used to adjust the weights between the four motion-detecting neurons to tune the system to detect collisions in two test environments. To do this, a population of agents, each representing a proposed synthetic visual system, either were shown images generated by a mobile Khepera robot navigating in a simplified laboratory environment or were shown images videoed outdoors from a moving vehicle. The agents had to cope with the local environment correctly in order to survive. After 400 generations, the best agent recognized imminent collisions reliably in the familiar environment where it had evolved. However, when the environment was swapped, only the agent evolved to cope in the robotic environment still signaled collision reliably. This study suggests that whole-field direction-selective neurons, with selectivity based on asymmetric lateral inhibition, can be organized into a synthetic vision system, which can then be adapted to play an important role in collision detection in complex dynamic scenes.

  17. A metamaterial absorber with direction-selective and polarisation-insensitive properties

    Institute of Scientific and Technical Information of China (English)

    Gu Chao; Qu Shao-Bo; Pei Zhi-Bin; Xu Zhuo

    2011-01-01

    This paper reports the design of a metamaterial absorber with direction-selective and polarisation-insensitive property. Both theoretical and simulated results reveal that the absorber has a distinct absorption point with direction selectivity at 7.48 GHz, which is related to the resonance of the metamaterial and is not influenced by the polarisation. The retrieved impedance indicates that the impedance of the absorber can be tuned to approximatively match the impedance of the free space on one side and not to match the impedance of the free space on the other side. This design can result in the minimal reflectance, the minimal transmission and the highest absorbance at the absorption frequency. The distribution of the power loss indicates that the absorber is an excellent electromagnetic wave collector: the wave is first trapped and reinforced in certain specific locations, and then mostly consumed. The distribution of the surface current is consistent with the design, the retrieved impedance and the distribution of the power loss. This absorber may have applications in many scientific and technological areas.

  18. A Data Mining-Based Response Model for Target Selection in Direct Marketing

    Directory of Open Access Journals (Sweden)

    Eniafe Festus Ayetiran

    2012-02-01

    Full Text Available Identifying customers who are more likely to respond to new product offers is an important issue in direct marketing. In direct marketing, data mining has been used extensively to identify potential customers for a new product (target selection. Using historical purchase data, a predictive response model with data mining techniques was developed to predict a probability that a customer in Ebedi Microfinance bank will respond to a promotion or an offer. To achieve this purpose, a predictive response model using customers’ historical purchase data was built with data mining techniques. The data were stored in a data warehouse to serve as management decision support system. The response model was built from customers’ historic purchases and demographic dataset.Bayesian algorithm precisely Naïve Bayes algorithm was employed in constructing the classifier system. Both filter and wrapper feature selection techniques were employed in determining inputs to the model.The results obtained shows that Ebedi Microfinance bank can plan effective marketing of their products and services by obtaining a guiding report on the status of their customers which will go a long way in assisting management in saving significant amount of money that could have been spent on wasteful promotional campaigns.

  19. Tenuifolide B from Cinnamomum tenuifolium Stem Selectively Inhibits Proliferation of Oral Cancer Cells via Apoptosis, ROS Generation, Mitochondrial Depolarization, and DNA Damage

    Directory of Open Access Journals (Sweden)

    Chung-Yi Chen

    2016-11-01

    Full Text Available The development of drugs that selectively kill oral cancer cells but are less harmful to normal cells still provide several challenges. In this study, the antioral cancer effects of tenuifolide B (TFB, extracted from the stem of the plant Cinnamomum tenuifolium are evaluated in terms of their effects on cancer cell viability, cell cycle analysis, apoptosis, oxidative stress, and DNA damage. Cell viability of oral cancer cells (Ca9-22 and CAL 27 was found to be significantly inhibited by TFB in a dose-responsive manner in terms of ATP assay, yielding IC50 = 4.67 and 7.05 μM (24 h, but are less lethal to normal oral cells (HGF-1. Dose-responsive increases in subG1 populations as well as the intensities of flow cytometry-based annexin V/propidium iodide (PI analysis and pancaspase activity suggested that apoptosis was inducible by TFB in these two types of oral cancer cells. Pretreatment with the apoptosis inhibitor (Z-VAD-FMK reduced the annexin V intensity of these two TFB-treated oral cancer cells, suggesting that TFB induced apoptosis-mediated cell death to oral cancer cells. Cleaved-poly (ADP-ribose polymerase (PARP and cleaved-caspases 3, 8, and 9 were upregulated in these two TFB-treated oral cancer cells over time but less harmful for normal oral HGF-1 cells. Dose-responsive and time-dependent increases in reactive oxygen species (ROS and decreases in mitochondrial membrane potential (MitoMP in these two TFB-treated oral cancer cells suggest that TFB may generate oxidative stress as measured by flow cytometry. N-acetylcysteine (NAC pretreatment reduced the TFB-induced ROS generation and further validated that ROS was relevant to TFB-induced cell death. Both flow cytometry and Western blotting demonstrated that the DNA double strand marker γH2AX dose-responsively increased in TFB-treated Ca9-22 cells and time-dependently increased in two TFB-treated oral cancer cells. Taken together, we infer that TFB can selectively inhibit cell

  20. Tenuifolide B from Cinnamomum tenuifolium Stem Selectively Inhibits Proliferation of Oral Cancer Cells via Apoptosis, ROS Generation, Mitochondrial Depolarization, and DNA Damage

    Science.gov (United States)

    Chen, Chung-Yi; Yen, Ching-Yu; Wang, Hui-Ru; Yang, Hui-Ping; Tang, Jen-Yang; Huang, Hurng-Wern; Hsu, Shih-Hsien; Chang, Hsueh-Wei

    2016-01-01

    The development of drugs that selectively kill oral cancer cells but are less harmful to normal cells still provide several challenges. In this study, the antioral cancer effects of tenuifolide B (TFB), extracted from the stem of the plant Cinnamomum tenuifolium are evaluated in terms of their effects on cancer cell viability, cell cycle analysis, apoptosis, oxidative stress, and DNA damage. Cell viability of oral cancer cells (Ca9-22 and CAL 27) was found to be significantly inhibited by TFB in a dose-responsive manner in terms of ATP assay, yielding IC50 = 4.67 and 7.05 μM (24 h), but are less lethal to normal oral cells (HGF-1). Dose-responsive increases in subG1 populations as well as the intensities of flow cytometry-based annexin V/propidium iodide (PI) analysis and pancaspase activity suggested that apoptosis was inducible by TFB in these two types of oral cancer cells. Pretreatment with the apoptosis inhibitor (Z-VAD-FMK) reduced the annexin V intensity of these two TFB-treated oral cancer cells, suggesting that TFB induced apoptosis-mediated cell death to oral cancer cells. Cleaved-poly (ADP-ribose) polymerase (PARP) and cleaved-caspases 3, 8, and 9 were upregulated in these two TFB-treated oral cancer cells over time but less harmful for normal oral HGF-1 cells. Dose-responsive and time-dependent increases in reactive oxygen species (ROS) and decreases in mitochondrial membrane potential (MitoMP) in these two TFB-treated oral cancer cells suggest that TFB may generate oxidative stress as measured by flow cytometry. N-acetylcysteine (NAC) pretreatment reduced the TFB-induced ROS generation and further validated that ROS was relevant to TFB-induced cell death. Both flow cytometry and Western blotting demonstrated that the DNA double strand marker γH2AX dose-responsively increased in TFB-treated Ca9-22 cells and time-dependently increased in two TFB-treated oral cancer cells. Taken together, we infer that TFB can selectively inhibit cell proliferation of

  1. A phase I pharmacokinetic and pharmacodynamic study of CHR-3996, an oral class I selective histone deacetylase inhibitor in refractory solid tumors

    NARCIS (Netherlands)

    U. Banerji (Udai); L. van Doorn (Leni); D. Papadatos-Pastos (Dionysis); R.S. Kristeleit (R.); P.M. Debnam (Phillip); A.R. Tall (Alan); A. Stewart (Alison); P. Raynaud (Philippe); J.M. Garrett; M. Toal (Martin); L. Hooftman (Leon); J.S. de Bono (Johann); J. Verweij (Jaap); F.A.L.M. Eskens (Ferry)

    2012-01-01

    textabstractPurpose: This clinical trial investigated the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profile of CHR-3996, a selective class I histone deacetylase inhibitor. Patients and Methods: CHR-3996 was administered orally once a day. This phase I trial used a 3+3

  2. Potent, selective, and orally efficacious antagonists of melanin-concentrating hormone receptor 1.

    Science.gov (United States)

    Tavares, Francis X; Al-Barazanji, Kamal A; Bigham, Eric C; Bishop, Michael J; Britt, Christy S; Carlton, David L; Feldman, Paul L; Goetz, Aaron S; Grizzle, Mary K; Guo, Yu C; Handlon, Anthony L; Hertzog, Donald L; Ignar, Diane M; Lang, Daniel G; Ott, Ronda J; Peat, Andrew J; Zhou, Hui-Qiang

    2006-11-30

    The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists. In general, a good correlation was observed between pKas and activity in the right-hand side of the template, with Asp123 playing an important role in the enhancement of binding affinity. A representative example when evaluated chronically in diet-induced obese mice resulted in good weight loss effects. These antagonists provide a viable lead series in the discovery of new therapies for the treatment of obesity.

  3. Adapting to a Changing Environment: Modeling the Interaction of Directional Selection and Plasticity.

    Science.gov (United States)

    Nunney, Leonard

    2016-01-01

    Human-induced habitat loss and fragmentation constrains the range of many species, making them unable to respond to climate change by moving. For such species to avoid extinction, they must respond with some combination of phenotypic plasticity and genetic adaptation. Haldane's "cost of natural selection" limits the rate of adaptation, but, although modeling has shown that in very large populations long-term adaptation can be maintained at rates substantially faster than Haldane's suggested limit, maintaining large populations is often an impossibility, so phenotypic plasticity may be crucial in enhancing the long-term survival of small populations. The potential importance of plasticity is in "buying time" for populations subject to directional environmental change: if genotypes can encompass a greater environmental range, then populations can maintain high fitness for a longer period of time. Alternatively, plasticity could be detrimental by lessening the effectiveness of natural selection in promoting genetic adaptation. Here, I modeled a directionally changing environment in which a genotype's adaptive phenotypic plasticity is centered around the environment where its fitness is highest. Plasticity broadens environmental tolerance and, provided it is not too costly, is favored by natural selection. However, a paradoxical result of the individually advantageous spread of plasticity is that, unless the adaptive trait is determined by very few loci, the long-term extinction risk of a population increases. This effect reflects a conflict between the short-term individual benefit of plasticity and a long-term detriment to population persistence, adding to the multiple threats facing small populations under conditions of climate change.

  4. Bipartite functions of the CREB co-activators selectively direct alternative splicing or transcriptional activation.

    Science.gov (United States)

    Amelio, Antonio L; Caputi, Massimo; Conkright, Michael D

    2009-09-16

    The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co-activators, independently direct either pre-mRNA splice-site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co-activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre-mRNA splicing or transcriptional activation. Interestingly, the CRTC1-MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice-site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co-activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity.

  5. Molecular template-directed synthesis of microporous polymer networks for highly selective CO2 capture.

    Science.gov (United States)

    Shi, Yao-Qi; Zhu, Jing; Liu, Xiao-Qin; Geng, Jian-Cheng; Sun, Lin-Bing

    2014-11-26

    Porous polymer networks have great potential in various applications including carbon capture. However, complex monomers and/or expensive catalysts are commonly used for their synthesis, which makes the process complicated, costly, and hard to scale up. Herein, we develop a molecular template strategy to fabricate new porous polymer networks by a simple nucleophilic substitution reaction of two low-cost monomers (i.e., chloromethylbenzene and ethylene diamine). The polymerization reactions can take place under mild conditions in the absence of any catalysts. The resultant materials are interconnected with secondary amines and show well-defined micropores due to the structure-directing role of solvent molecules. These properties make our materials highly efficient for selective CO2 capture, and unusually high CO2/N2 and CO2/CH4 selectivities are obtained. Furthermore, the adsorbents can be completely regenerated under mild conditions. Our materials may provide promising candidates for selective capture of CO2 from mixtures such as flue gas and natural gas.

  6. Acoustic noise alters selective attention processes as indicated by direct current (DC) brain potential changes.

    Science.gov (United States)

    Trimmel, Karin; Schätzer, Julia; Trimmel, Michael

    2014-09-26

    Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information) versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes). This study investigated brain direct current (DC) potential shifts-which are discussed to represent different states of cortical activation-of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest-besides some limitations-that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested "attention shift". Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

  7. Acoustic Noise Alters Selective Attention Processes as Indicated by Direct Current (DC Brain Potential Changes

    Directory of Open Access Journals (Sweden)

    Karin Trimmel

    2014-09-01

    Full Text Available Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes. This study investigated brain direct current (DC potential shifts—which are discussed to represent different states of cortical activation—of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest—besides some limitations—that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested “attention shift”. Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

  8. Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives

    Energy Technology Data Exchange (ETDEWEB)

    Kloosterboer, H.J.; Vonk-Noordegraaf, C.A.; Turpijn, E.W.

    1988-09-01

    The relative binding affinities (RBAs) of four progestational compounds (norethisterone, levonorgestrel, 3-keto-desogestrel and gestodene) for the human progesterone and androgen receptors were measured in MCF-7 cytosol and intact MCF-7 cells. For the binding to the progesterone receptor, both Org 2058 and Org 3236 (or 3-keto-desogestrel) were used as labelled ligands. The following ranking (low to high) for the RBA of the nuclear (intact cells) progesterone receptor irrespective of the ligand used is found: norethisterone much less than levonorgestrel less than 3-keto-destogestrel less than gestodene. The difference between the various progestagens is significant with the exception of that between 3-keto-desogestrel and gestodene, when Org 2058 is used as ligand. For the cytosolic progesterone receptor, the same order is found with the exception that similar RBAs are found for gestodene and 3-keto-desogestrel. The four progestagens clearly differ with respect to binding to the androgen receptor using dihydrotestosterone as labelled ligand in intact cells; the ranking (low to high) is: norethisterone less than 3 keto-desogestrel less than levonorgestrel and gestodene. The difference between 3-keto-desogestrel and levonorgestrel or gestodene is significant. The selectivity indices (ratio of the mean RBA for the progesterone receptor to that of androgen receptor) in intact cells are significantly higher for 3-keto-desogestrel and gestodene than for levonorgestrel and norethisterone. From these results we conclude that the introduction of the 18-methyl in norethisterone (levonorgestel) increases both the binding to the progesterone and androgen receptors.

  9. Higher-resolution selective metallization on alumina substrate by laser direct writing and electroless plating

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Ming; Liu, Jianguo, E-mail: liujg@mail.hust.edu.cn; Wang, Suhuan; Ai, Jun; Zeng, Xiaoyan

    2016-03-15

    Graphical abstract: - Highlights: • Mechanisms of laser direct writing and electroless plating were studied. • Active seeds in laser-irradiated zone and laser-affected zone were found to be different. • A special chemical cleaning method with aqua regia was taken. • Higher-resolution copper patterns on alumina ceramic were obtained conveniently. - Abstract: How to fabricate conductive patterns on ceramic boards with higher resolution is a challenge in the past years. The fabrication of copper patterns on alumina substrate by laser direct writing and electroless copper plating is a low cost and high efficiency method. Nevertheless, the lower resolution limits its further industrial applications in many fields. In this report, the mechanisms of laser direct writing and electroless copper plating were studied. The results indicated that as the decomposed products of precursor PdCl{sub 2} have different chemical states respectively in laser-irradiated zone (LIZ) and laser-affected zone (LAZ). This phenomenon was utilized and a special chemical cleaning method with aqua regia solution was taken to selectively remove the metallic Pd in LAZ, while kept the PdO in LIZ as the only active seeds. As a result, the resolution of subsequent copper patterns was improved significantly. This technique has a great significance to develop the microelectronics devices.

  10. Direct synthesis of hydrogen peroxide using in-situ selective layer

    Science.gov (United States)

    Makertihartha, I. G. B. N.; Dharmawijaya, P. T.; Zunita, M.; Wenten, I. G.

    2017-05-01

    Hydrogen peroxide is used in broad range of application such as oxidation, bleaching, and wastewater treatment. Conventionally, hydrogen peroxide is synthesized using reduction oxidation cycle of anthraquinones from hydrogen and oxygen. This process is rather complex and requires considerable amount of energy. Direct synthesis of hydrogen peroxide is one attractive approach to said problems. However, activity and selectivity is the main problem of direct synthesis since the reactants form explosive mixture. Dilution of gasses is commonly used to solve said problem but limit the amount of reactants in the liquid solvent. Membrane reactor can separate pure reactant gases and also constantly feed them over the length of reaction channel. Pd-Ag alloy membrane can be used both as a catalyst and hydrogen dosage. There are some studies that investigate the use of Pd based membrane reactor but still no commercial application. This paper will bring basic concept of Pd based membrane reactor for direct synthesis of hydrogen peroxide. Special attention will be given to current hurdles and their possible solutions that lead to facile production of hydrogen peroxide. Furthermore, recent trends towards utilization of micro reactor will also be discussed.

  11. The impacts of a pharmacist-managed outpatient clinic and chemotherapy-directed electronic order sets for monitoring oral chemotherapy.

    Science.gov (United States)

    Battis, Brandon; Clifford, Linda; Huq, Mostaqul; Pejoro, Edrick; Mambourg, Scott

    2016-10-12

    Patients treated with oral chemotherapy appear to have less contact with the treating providers. As a result, safety, adherence, medication therapy monitoring, and timely follow-up may be compromised. The trend of treating cancer with oral chemotherapy agents is on the rise. However, standard clinical guidance is still lacking for prescribing, monitoring, patient education, and follow-up of patients on oral chemotherapy across the healthcare settings. The purpose of this project is to establish an oral chemotherapy monitoring clinic, to create drug and lab specific provider order sets for prescribing and lab monitoring, and ultimately to ensure safe and effective treatment of the veterans we serve. A collaborative agreement was reached among oncology pharmacists, a pharmacy resident, two oncologists, and a physician assistant to establish a pharmacist-managed oral chemotherapy monitoring clinic at the VA Sierra Nevada Healthcare System. Drug-specific electronic order sets for prescribing and lab monitoring were created for initiating new drug therapy and prescription renewal. The order sets were created to be provider-centric, minimizing clicks needed to order necessary medications and lab monitoring. A standard progress note template was developed for documenting interventions made by the clinic. Patients new to an oral chemotherapy regimen were first counseled by an oncology pharmacist. The patients were then enrolled into the oral chemotherapy monitoring clinic for subsequent follow up and pharmacist interventions. Further, patients lacking monitoring or missing provider appointments were captured through a Clinical Dashboard developed by the US Department of Veterans Affairs (VA) Regional Office (VISN21) using SQL Server Reporting Services. Between September 2014 and April 2015, a total of 68 patients on different oral chemotherapy agents were enrolled into the clinic. Out of the 68 patients enrolled into the oral chemotherapy monitoring clinic, 31 patients (45

  12. Neural network models for spatial data mining, map production, and cortical direction selectivity

    Science.gov (United States)

    Parsons, Olga

    A family of ARTMAP neural networks for incremental supervised learning has been developed over the last decade. The Sensor Exploitation Group of MIT Lincoln Laboratory (LL) has incorporated an early version of this network as the recognition engine of a hierarchical system for fusion and data mining of multiple registered geospatial images. The LL system has been successfully fielded, but it is limited to target vs. non-target identifications and does not produce whole maps. This dissertation expands the capabilities of the LL system so that it learns to identify arbitrarily many target classes at once and can thus produce a whole map. This new spatial data mining system is designed particularly to cope with the highly skewed class distributions of typical mapping problems. Specification of a consistent procedure and a benchmark testbed has permitted the evaluation of candidate recognition networks as well as pre- and post-processing and feature extraction options. The resulting default ARTMAP network and mapping methodology set a standard for a variety of related mapping problems and application domains. The second part of the dissertation investigates the development of cortical direction selectivity. The possible role of visual experience and oculomotor behavior in the maturation of cells in the primary visual cortex is studied. The responses of neurons in the thalamus and cortex of the cat are modeled when natural scenes are scanned by several types of eye movements. Inspired by the Hebbian-like synaptic plasticity, which is based upon correlations between cell activations, the second-order statistical structure of thalamo-cortical activity is examined. In the simulations, patterns of neural activity that lead to a correct refinement of cell responses are observed during visual fixation, when small ocular movements occur, but are not observed in the presence of large saccades. Simulations also replicate experiments in which kittens are reared under stroboscopic

  13. Impact of oral rehydration and selected public health interventions on reduction of mortality from childhood diarrhoeal diseases in Mexico.

    Science.gov (United States)

    Gutiérrez, G; Tapia-Conyer, R; Guiscafré, H; Reyes, H; Martínez, H; Kumate, J

    1996-01-01

    Reported are the results of an analysis of mortality trends from diarrhoeal diseases among under-5-year-olds in Mexico between 1978 and 1993 in relation to the impact of education, basic sanitation, and selected medical care practices. The study period was divided into three stages; the first pre-dated the widespread application of oral rehydration therapy (ORT); the second, covered the implementation of a nationwide programme promoting ORT; and the third included additional measures, such as immunization and improvements in basic sanitation. Mortality rates decreased progressively, at an average of 1.8% per year in the first stage, 6.4% in the second, and 17.8% in the third. The importance of literacy campaigns for women and the promotion of ORT was confirmed. Both of these measures reduced mortality; however, a greater reduction resulted from a massive immunization campaign against measles and improvements in sanitation (expansion of the drainage and piped water systems, improved water chlorination procedure, and effective prohibition of the use of sanitary sewage for vegetable irrigation).

  14. Direct manufacturing of Cu-based alloy parts by selective laser melting

    Institute of Scientific and Technical Information of China (English)

    Weihui Wu; Yongqiang Yang; Yanlu Huang

    2007-01-01

    The frequent defects of the metal parts, such as non-fully melting, thermal strain, and balling, which are produced by selective laser melting (SLM) that is a novel method of one-step manufacturing, are analyzed theoretically and experimentally. The processing parameters significantly affect the quality of the final parts, and simultaneously, the appropriate laser mode and the special scanning strategy assure a satisfying quality of the final parts. The SLM experiment is carried out using Cu-based powder. The metal part is divided into several scanned regions, each of which is scanned twice at the cross direction with different scanning speeds. The microstructure is analyzed on microscope. The results show that the part is metallurgically bonded entity with a relative density of 95%, and the microstructure is composed of equiaxial crystal and dendritic crystal whose distributions are mainly decided by the scanning strategy.

  15. Appropriate microwave frequency selection for biasing superconducting hot electron bolometers as terahertz direct detectors

    Science.gov (United States)

    Jiang, S. L.; Li, X. F.; Jia, X. Q.; Kang, L.; Jin, B. B.; Xu, W. W.; Chen, J.; Wu, P. H.

    2017-04-01

    Terahertz (THz) direct detectors based on superconducting niobium nitride (NbN) hot electron bolometers (HEBs) and biased by a simple microwave (MW) source have been studied. The frequency and power of the MW are selected by measuring the MW responses of the current–voltage (I–V) curves and resistance–temperature (R–T) curves of the NbN HEBs. The non-uniform absorption theory is used to explain the current jumps in the I–V curves and the resistance jumps in the R–T curves. Compared to the thermal biasing, the MW biasing method can improve the sensitivity, make the readout system much easier and consumes less liquid helium, which is important for long lasting experiments. The noise equivalent power (NEP) of 1.6 pW Hz‑1/2 and the response time of 86 ps are obtained for the detectors working at 4.2 K and 0.65 THz.

  16. Artificial selection on chill-coma recovery time in Drosophila melanogaster: Direct and correlated responses to selection.

    Science.gov (United States)

    Gerken, Alison R; Mackay, Trudy F C; Morgan, Theodore J

    2016-07-01

    Artificial selection can be used to create populations with extreme phenotypic responses to environmental stressors. When artificial selection is applied to a single component of a stress response, this selection may result in correlated responses in other stress responses, a phenomenon called cross-tolerance, which is ultimately controlled by the genetic correlations among traits. We selected for extreme responses to cold tolerance by selecting for chill-coma recovery time from a single temperate population of Drosophila melanogaster. Chill-coma recovery time is a common metric of low, but non-lethal, cold temperature tolerance. Replicated divergent artificial selection was applied to a genetically variable base population for 31 generations, resulting in two cold resistant, two cold susceptible, and two unselected control lines. To quantify the relationship between selection on chill-coma recovery and other metrics of thermal performance, we also measured survivorship after acute cold exposure, survivorship after chronic cold exposure, survivorship after cold exposure following a pre-treatment period (rapid cold hardening), starvation tolerance, and heat tolerance. We find that chill-coma recovery time is heritable within this population and that there is an asymmetric response to increased and decreased chill-coma recovery time. Surprisingly, we found no cross-tolerances between selection on chill-coma recovery time and the other environmental stress response traits. These results suggest that although artificial selection has dramatically altered chill-coma recovery time, the correlated response to selection on other stress response phenotypes has been negligible. The lack of a correlated response suggests that chill-coma recovery time in these selection lines is likely genetically independent from measures of cold survivorship tested here.

  17. Scaffolding advice on task selection: A safe path toward self-directed learning in on-demand education.

    NARCIS (Netherlands)

    Kicken, Wendy; Brand-Gruwel, Saskia; Van Merriënboer, Jeroen

    2008-01-01

    Kicken, W., Brand-Gruwel, S., & Van Merrienboer, J. J. G. (2008). Scaffolding advice on task selection: A safe path toward self-directed learning in on-demand education. Journal of Vocational Education and Training, 60, 223-239.

  18. Scaffolding advice on task selection: A safe path toward self-directed learning in on-demand education.

    NARCIS (Netherlands)

    Kicken, Wendy; Brand-Gruwel, Saskia; Van Merriënboer, Jeroen

    2008-01-01

    Kicken, W., Brand-Gruwel, S., & Van Merrienboer, J. J. G. (2008). Scaffolding advice on task selection: A safe path toward self-directed learning in on-demand education. Journal of Vocational Education and Training, 60, 223-239.

  19. Global stabilities, selection of steady cellular growth, and origin of side branches in directional solidification.

    Science.gov (United States)

    Xu, Jian-Jun; Chen, Yong-Qiang

    2011-06-01

    The present paper investigates the global instability mechanisms of arrayed-cellular growth with asymptotic approach. We find that the system of directional solidification involves two types of global instability mechanisms: the low-frequency instability and the global oscillatory instability, which are profoundly similar to that found in the system of viscous fingering and free dendritic growth. Based on these global instabilities, the neutral mode selection principle for the limiting state of growth is proposed; the origin and essence of side branching on the interface are elucidated with the so-called global trapped wave mechanism, which involves the interfacial wave reflection and amplification along the interface. It is demonstrated that side branching is self-sustaining and can persist without continuously applying the external noise; the effect of the anisotropy of interfacial energy is not essential for the selection of steady cellular growth and for the origin and formation of side branching at the interface. The comparisons of theoretical results are made with the most recent experimental works and the numerical simulations which show very good quantitative agreement.

  20. A membraneless alkaline direct liquid fuel cell (DLFC) platform developed with a catalyst-selective strategy

    Science.gov (United States)

    Yu, Xingwen; Pascual, Emilio J.; Wauson, Joshua C.; Manthiram, Arumugam

    2016-11-01

    With a logical management of the catalyst selectivity, we present a scalable, membraneless alkaline direct liquid fuel cell (DLFC) platform. The uniqueness of this innovation is that the inexpensive (non-platinum) cathode catalysts, based on strongly coupled transition-metal-oxide nanocrystals and nano-structured carbon materials (e. g., NiCo2O4 nano-particles on a nitrogen-doped graphene and MnNiCoO4 nano-particles on a nitrogen-doped multi-wall carbon nanotube), exhibit high activity for the oxygen reduction reaction (ORR) but without activity for the anode fuel oxidation reaction (FOR). Therefore, operation of the DLFCs allows the anode fuel to freely enter the cathode. This strategy avoids the reliance on expensive or difficult-to-develop cation- or anion-exchange membranes and circumvents the scalability concerns of the conventional membraneless DLFCs that are operated under a laminar-flow principle. With proper catalyst selectivity, a variety of organic liquids can be used as anode fuels. The high power density delivered by the membraneless DLFCs with inexpensive components and safe fuels can enable the development of not only small-scale portable power sources but also large-scale energy generation systems for transportation and stationary storage.

  1. A selective working memory impairment after transcranial direct current stimulation to the right parietal lobe.

    Science.gov (United States)

    Berryhill, Marian E; Wencil, Elaine B; Branch Coslett, H; Olson, Ingrid R

    2010-08-02

    The role of the posterior parietal cortex in working memory (WM) is poorly understood. We previously found that patients with parietal lobe damage exhibited a selective WM impairment on recognition but not recall tasks. We hypothesized that this dissociation reflected strategic differences in the utilization of attention. One concern was that these findings, and our subsequent interpretation, would not generalize to normal populations because of the patients' older age, progressive disease processes, and/or possible brain reorganization following injury. To test whether our findings extended to a normal population we applied transcranial direct current stimulation (tDCS) to right inferior parietal cortex. tDCS is a technique by which low electric current applied to the scalp modulates the resting potentials of underlying neural populations and can be used to test structure-function relationships. Eleven normal young adults received cathodal, anodal, or sham stimulation over right inferior posterior parietal cortex and then performed separate blocks of an object WM task probed by recall or recognition. The results showed that cathodal stimulation selectively impaired WM on recognition trials. These data replicate and extend our previous findings of preserved WM recall and impaired WM recognition in patients with parietal lobe lesions. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  2. The Composition Effect of Macroeconomic Factors on Foreign Direct Investment in Selected SAARC Countries

    Directory of Open Access Journals (Sweden)

    Mehwish MALIK

    2014-06-01

    Full Text Available The objective of the study is to investigate the most promising economic variables i.e., foreign direct investment (FDI, exports and financial development on economic growth in selected South Asian Association of Regional Co-corporation (SAARC countries. In addition, this study argued that whether FDI, Exports and financial development fosters or hinder economic growth in SAARC countries, for this purpose, panel data set of selected five SAARC countries namely, Bangladesh, India, Nepal, Pakistan and Srilanka considered for empirical consideration over a period of 1975 to 2011. By using two-stage least square (2SLSL technique, empirical evidence on the effects of FDI, exports and financial development on economic growth is mix in terms of apriori expectations. In case of Bangladesh, exports and broad money supply (M2 is the positive and significant contributor to increase economic growth, whereas, M2 increases India’s GDP. FDI is the only significant contributor to increase Pakistan’s economic growth. In case of Nepal and Srilanka, broad money supply increases economic growth, whereas, due to high dependency on imports, exports could not considerably increases economic growth in those regions.

  3. Design and direct manufacture of non-assembly abacus by Selective Laser Melting

    Science.gov (United States)

    Song, Changhui; Yang, Yongqiang; Xiao, Zefeng; Wang, Di; Liu, Yang; Liu, Ruicheng

    2014-12-01

    Selective Laser Melting (SLM), as an additive manufacturing technology, can directly manufacture desired functional metal parts. With the ability to freeform manufacture, SLM has had breakthroughs on design and manufacture compared with traditional methods. SLM apparatus in Dimetal series, DiMetal-100 developed by SCUT research group, has been used to study non-assembly mechanism. Taking copper cash abacus and collapsible abacus as examples, this article had studied the design rules and the key points to manufacture the non-assembly mechanism based on the SLM. An investigation into the capability of SLM technology, such as the geometric features resolution, critical incline angle, provided theoretical basis for designing the clearance of the joint and manufacturing direction of non-assembly mechanism. Then, the experiment of manufacturing copper cash abacus and collapsible abacus were conducted. The results proved that non-assembly mechanism can be well manufactured by SLM. This study provides basis for designing and manufacturing of creative non-assembly mechanism based on SLM technique.

  4. Targeted strategies directed at the molecular defect: Toward precision medicine for select primary immunodeficiency disorders.

    Science.gov (United States)

    Notarangelo, Luigi D; Fleisher, Thomas A

    2017-03-01

    Primary immunodeficiency disorders (PIDs) represent a range of genetically determined diseases that typically have increased susceptibility to infections and in many cases also have evidence of immune dysregulation that often presents as autoimmunity. Most recently, the concept of gain-of-function mutations associated with PIDs has become well recognized and adds a new dimension to the understanding of this group of disorders, moving beyond the more commonly seen loss-of-function mutations. The rapidly expanding genetic defects that have been identified in patients with previously uncharacterized PIDs has opened up the potential for targeted therapy directed at the specific disease-causing abnormality. This has been driven by linking PID-specific genetic defects to the associated unique abnormalities in cellular signaling pathways amenable to directed therapies. These include agents that either block overactive or enhance underresponsive cellular pathways. Selected primary immunodeficiencies were chosen, the genetic defects of which have been recently characterized and are amenable to targeted therapy, as a reflection of the power of precision medicine. Published by Elsevier Inc.

  5. Exploring new concepts in directional solidification by electron beam melting and selective laser melting

    Science.gov (United States)

    Martinez, Edwin

    Unlike more conventional directional solidification, electron and laser-beam melting technologies involve building 3D components through layer-by-layer melt/solidification thermal cycling which creates novel, directional microstructural architectures. In this study we compared various the columnar microstructures of various components manufactured by EBM and SLM; image composite observations of columnar microstructural architectures in Cu, Co-29-Cr-6Mo-0.2C alloy, Ni-22Cr-9Mo-4Nb (alloy 625) fabricated by electron beam melting (EBM), and Ni-19Cr-19Fe-5Nb-1Al (alloy 718) by selective laser melting (SLM) as well as stainless steel 17-4 PH (SLM). Cu produced discontinuous columns of Cu2O precipitates while the Co-base alloy exhibited similar columns of Cr 23C6 precipitates. The alloy 625 produced columns of Ni 3Nb (Upsilon"-bct) precipitates. All of the EBM-produced columnar microstructure arrays were spaced ˜2 microm. In contrast, the SLM fabricated alloy 718 contained columnar microstructural arrays of Ni3 Nb (Upsilon") spaced ˜ 0.8microm, the 17-4 PH stainless steel produced martensitic structures dependent on the gas used for manufacturing. The manufactured components were observed by optical microscopy, SEM, XRD and by TEM in order to understand the microstructural development.

  6. Late emergence of the vibrissa direction selectivity map in the rat barrel cortex.

    Science.gov (United States)

    Kremer, Yves; Léger, Jean-François; Goodman, Dan; Brette, Romain; Bourdieu, Laurent

    2011-07-20

    In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topographical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for vibrissa identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intrabarrel map for vibrissa movement direction using in vivo two-photon imaging. We discovered that the emergence of a direction map in rat barrel cortex occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel-like form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intracortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.

  7. Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy

    Science.gov (United States)

    Bedford, J. L.; Webb, S.

    2007-01-01

    Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.

  8. Oral Cancer Exam

    Medline Plus

    Full Text Available ... See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities Diabetes Heart Disease HIV/AIDS See ... this brochure includes information on symptoms, diagnosis, and treatment of oral cancer, along with definitions of selected ...

  9. Oral Cancer Exam

    Medline Plus

    Full Text Available ... diagnosis, and treatment of oral cancer, along with definitions of selected medical terms and resource information. Oral ... of Dental and Craniofacial Research National Institutes of Health Bethesda, MD 20892-2190 301-496-4261 NIH… ...

  10. Oral Cancer Exam

    Medline Plus

    Full Text Available ... See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities Diabetes Heart Disease HIV/AIDS See ... this brochure includes information on symptoms, diagnosis, and treatment of oral cancer, along with definitions of selected ...

  11. Oral Cancer Exam

    Medline Plus

    Full Text Available ... and College Students Recent College Graduates Dental and Medical Students See All Careers & Training Opportunities Job Openings ... of oral cancer, along with definitions of selected medical terms and resource information. Oral Cancer A fact ...

  12. Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: a case report and a review of the French National Pharmacovigilance Database.

    Science.gov (United States)

    Liabeuf, Sophie; Gras, Valérie; Moragny, Julien; Laroche, Marie-Laure; Andrejak, Michel

    2014-01-01

    To report a series of cases of ulceration of the oral mucosa linked to direct contact with ferrous sulfate in elderly patients. The first case report concerns the occurrence of widespread oral ulceration in an 87-year-old woman with Alzheimer's disease. The ulceration extended from the side of the tongue to the floor of the mouth. No clear explanation was found and various local treatments were ineffective. Once it was realized that the ferrous sulfate tablets (given as an iron supplement) were crushed prior to administration (due to the patient's deglutition disorder), withdrawal of this treatment led to rapid resolution of the ulceration. Nine other cases of oral ulcerations associated with ferrous sulfate were identified in the French National Pharmacovigilance Database. All but one of the patients were over 80 years of age and the youngest patient (a 54-year-old) had dysphagia associated with facial paralysis. Only two other reports of oral ulceration due to ferrous sulfate have been published to date. Mucosal toxicity of ferrous sulfate (which is probably related to oxidative stress) has previously been reported for the hypopharynx, the esophageal lumen, and (after inhalation of a tablet) the tracheobronchial tree. The mucosal toxicity of ferrous sulfate must be taken into account when deglutition disorders are present (as in elderly patients) and appropriate pharmaceutical formulations (such as syrups) should be administered to at-risk patients. The use of iron salts other than ferrous sulfate could be considered.

  13. Direct and correlated responses to individual selection for large adult weight in the edible snail Helix aspersa Muller.

    Science.gov (United States)

    Dupont-Nivet, M; Mallard, J; Bonnet, J C; Blanc, J M

    2000-06-15

    A selection experiment for large adult weight based on individual performance was conducted for three generations in Helix aspersa aspersa. A second line was kept as an unselected control line. Direct response measured as deviation from the control line was 3.55 g after three generations of artificial selection, which averaged 13%. Realized heritability was 0.38 +/- 0.04. Correlated responses to selection showed a significant increase in weight after hibernation, mean egg weight and mean weight of newly-hatched snails with selection. For adult age, egg number, and hatching rate, no significant change correlated to selection was found, but this is to be confirmed.

  14. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model.

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-01-01

    Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells.

  15. Evaluation of an immunochromatographic assay for direct identification of thermostable direct hemolysin-producing Vibrio parahaemolyticus colonies on selective agar plates.

    Science.gov (United States)

    Kawatsu, Kentaro; Sakata, Junko; Yonekita, Taro; Kumeda, Yuko

    2015-12-01

    We evaluated the utility of an immunochromatographic assay (NH IC TDH) in identifying thermostable direct hemolysin (TDH)-producing Vibrio parahaemolyticus colonies on selective agar plates. The sensitivity of the NH IC TDH assay was 100% (189 samples) and its specificity was 100% (41 samples) compared with the presence of tdh.

  16. [Selective induction of dog esophageal carcinomas by the restricted oral administration of N-ethyl-N-'-nitro-N-nitrosoguanidine with a projecting spout].

    Science.gov (United States)

    Tsukahara, Y; Fujita, M; Ohmichi, M; Ishii, T; Taguchi, T

    1989-08-01

    In order to establish an effective method to induce selectively experimental dog esophageal carcinoma, we compared the restricted oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) with projecting spout with the ad libitum oral administration of it. Five dogs were given a solution of ENNG at a concentration of 50mg/l with restricted oral administration with projecting spout for 52 weeks. In all of them, elevated type of esophageal lesions were endoscopically observed soon after the cessation of the ENNG administration. Histological examination revealed that besides the multiple squamous cell carcinomas of the esophagus, various degrees of dysplasias were seen. Two dogs had metastasizes to the regional lymph nodes and one dog had metastatic lesions in the lung. Gastric carcinomas were also seen in four dogs. Another five dogs were given ad libitum the same concentration of ENNG solution. Gastric carcinomas were induced in four dogs, but esophageal carcinomas were seen in small lesions in two dogs. The restricted oral administration of ENNG with projecting spout is a reliable method for the selective induction of esophageal carcinoma in dog.

  17. Marked Increase in PROP Taste Responsiveness Following Oral Supplementation with Selected Salivary Proteins or Their Related Free Amino Acids

    Science.gov (United States)

    Melis, Melania; Aragoni, Maria Carla; Arca, Massimiliano; Cabras, Tiziana; Caltagirone, Claudia; Castagnola, Massimo; Crnjar, Roberto; Messana, Irene; Tepper, Beverly J.; Barbarossa, Iole Tomassini

    2013-01-01

    The genetic predisposition to taste 6-n-propylthiouracil (PROP) varies among individuals and is associated with salivary levels of Ps-1 and II-2 peptides, belonging to the basic proline-rich protein family (bPRP). We evaluated the role of these proteins and free amino acids that selectively interact with the PROP molecule, in modulating bitter taste responsiveness. Subjects were classified by their PROP taster status based on ratings of perceived taste intensity for PROP and NaCl solutions. Quantitative and qualitative determinations of Ps-1 and II-2 proteins in unstimulated saliva were performed by HPLC-ESI-MS analysis. Subjects rated PROP bitterness after supplementation with Ps-1 and II-2, and two amino acids (L-Arg and L-Lys) whose interaction with PROP was demonstrated by 1H-NMR spectroscopy. ANOVA showed that salivary levels of II-2 and Ps-1 proteins were higher in unstimulated saliva of PROP super-tasters and medium tasters than in non-tasters. Supplementation of Ps-1 protein in individuals lacking it in saliva enhanced their PROP bitter taste responsiveness, and this effect was specific to the non-taster group.1H-NMR results showed that the interaction between PROP and L-Arg is stronger than that involving L-Lys, and taste experiments confirmed that oral supplementation with these two amino acids increased PROP bitterness intensity, more for L-Arg than for L-Lys. These data suggest that Ps-1 protein facilitates PROP bitter taste perception and identifies a role for free L-Arg and L-Lys in PROP tasting. PMID:23555788

  18. Selective theta-synchronization of choice-relevant information subserves goal-directed behavior

    Directory of Open Access Journals (Sweden)

    Thilo eWomelsdorf

    2010-11-01

    Full Text Available Theta activity reflects a state of rhythmic modulation of excitability at the level of single neuron membranes, within local neuronal groups and between distant nodes of a neuronal network. A wealth of evidence has shown that during theta states distant neuronal groups synchronize, forming networks of spatially confined neuronal clusters at specific time periods during task performance. Here, we show that a functional commonality of networks engaging in theta rhythmic states is that they emerge around decision points, reflecting rhythmic synchronization of choice-relevant information. Decision points characterize a point in time shortly before a subject chooses to select one action over another, i.e. when automatic behavior is terminated and the organism reactivates multiple sources of information to evaluate the evidence for available choices. As such, decision processes require the coordinated retrieval of choice-relevant information including (i the retrieval of stimulus evaluations (stim.-reward associations and reward expectancies about future outcomes, (ii the retrieval of past and prospective memories (e.g. stim.-stim. associations, (iii the reactivation of contextual task rule representations (e.g. stim.-response mappings, along with (iv an ongoing assessment of sensory evidence. An increasing number of studies reveal that retrieval of these multiple types of information proceeds within few theta cycles through synchronized spiking activity across limbic, striatal and cortical processing nodes. The outlined evidence suggests that evolving spatially and temporally specific theta synchronization could serve as the critical correlate underlying the selection of a choice during goal-directed behavior.

  19. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    Science.gov (United States)

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps.

  20. Template-directed ligation of tethered mononucleotides by t4 DNA ligase for kinase ribozyme selection.

    Directory of Open Access Journals (Sweden)

    David G Nickens

    used as the tethered nucleotide. CONCLUSIONS/SIGNIFICANCE: Our results reveal a novel activity for T4 DNA ligase (template-directed ligation of a tethered mononucleotide and establish this partition scheme as being suitable for the selection of ribozymes that phosphorylate mononucleoside substrates.

  1. Biocontrol bacteria selected by a direct plant protection strategy against avocado white root rot show antagonism as a prevalent trait.

    Science.gov (United States)

    González-Sánchez, M Á; Pérez-Jiménez, R M; Pliego, C; Ramos, C; de Vicente, A; Cazorla, F M

    2010-07-01

    This study was undertaken to study bacterial strains obtained directly for their efficient direct control of the avocado white root rot, thus avoiding prescreening by any other possible mechanism of biocontrol which could bias the selection. A collection of 330 bacterial isolates was obtained from the roots and soil of healthy avocado trees. One hundred and forty-three representative bacterial isolates were tested in an avocado/Rosellinia test system, resulting in 22 presumptive protective strains, all of them identified mainly as Pseudomonas and Bacillus species. These 22 candidate strains were screened in a more accurate biocontrol trial, confirming protection of some strains (4 out of the 22). Analyses of the potential bacterial traits involved in the biocontrol activity suggest that different traits could act jointly in the final biocontrol response, but any of these traits were neither sufficient nor generalized for all the active bacteria. All the protective strains selected were antagonistic against some fungal root pathogens. Diverse bacteria with biocontrol activity could be obtained by a direct plant protection strategy of selection. All the biocontrol strains finally selected in this work were antagonistic, showing that antagonism is a prevalent trait in the biocontrol bacteria selected by a direct plant protection strategy. This is the first report on the isolation of biocontrol bacterial strains using direct plant protection strategy in the system avocado/Rosellinia. Characterization of selected biocontrol bacterial strains obtained by a direct plant protection strategy showed that antagonism is a prevalent trait in the selected strains in this experimental system. This suggests that antagonism could be used as useful strategy to select biocontrol strains. © 2009 The Authors. Journal compilation © 2009 The Society for Applied Microbiology.

  2. Detection and measurement of oral malodor in chronic periodontitis patients and its correlation with levels of select oral anaerobes in subgingival plaque

    Directory of Open Access Journals (Sweden)

    H S Grover

    2015-01-01

    Full Text Available Introduction: Oral malodor is generally ascribable to oral microbial putrefaction generating malodorous volatile sulfur compounds. The aim of the present study is to correlate organoleptic recordings with a small handheld portable volatile sulfide monitor and periodontal clinical parameters and correlate the levels of halitosis causing bacteria in plaque between baseline, 1-week, and 1-month. Materials and Methods: A total of 20 systemically healthy subjects with self-reported halitosis were subjected to organoleptic examination and FitScan®. Subgingival plaque samples for anaerobic culturing were harvested followed by an assessment of plaque index (PI, gingival bleeding index (GBI, and pocket probing depth. Data derived were subjected to statistical analysis using Wilcoxon signed rank test and Spearman's rank test (P < 0.05. Results: No correlation was seen between organoleptic measurements and portable volatile sulfide monitor at any time interval. There was a statistically significant (P < 0.05 correlation between the scores of PI, gingival index, GBI, and myeloproliferative disease with organoleptic readings at all-time intervals. Anaerobic culture has shown to identify Fusobacterium species, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia. However, no correlation could be established in between total microbial load with organoleptic and FitScan®reading at any time interval (P < 0.05. Conclusion: Significant correlation could be established between organoleptic readings and periodontal parameters.

  3. Type of oral solid medication packaging and medication preparation time in nursing homes: A direct observation study.

    Science.gov (United States)

    Cready, C M; Hudson, C; Dreyer, K

    2017-06-05

    Medication administration is a substantial portion of the workday in nursing homes, with the medication preparation step being the most time-consuming. However, little is known about how medication preparation time is affected by the type of packaging used for oral solid medications (ie, tablets/capsules). We examined the effects of two types of packaging. As fewer steps are associated with strip packaging compared to bingo card packaging, we hypothesized that the increase in medication preparation seconds per resident with each additional oral solid medication would be smaller when strip packaging was used. A total of 430 medication preparations conducted by eight nurses during the regularly scheduled morning medication administration period in two nursing homes-using strip packaging and bingo card packaging, respectively-were observed. Each medication preparation observation was matched to its corresponding medication administration record and observations averaged across resident. Using the resident sample (N=149), we estimated three regression models (adjusting the standard errors for the clustering of resident by nurse). The first model regressed medication preparation seconds on the number of oral solid medications. The second model added the type of packaging used and the control variables (type of unit [long-term care, post-acute care], the number of one-half pills and the dosage form diversity in the preparation). To test our hypothesis, the third model added an interaction term between the number of oral solid medications and the type of packaging used. As hypothesized, all else equal, the number of oral solid medications tended to increase medication preparation time per resident in both nursing homes, but the increase was smaller in the strip packaging nursing home (Phome increased medication preparation by an average of 13 seconds (b=13.077), whereas each oral solid medication administered in the strip packaging nursing home increased medication

  4. Economic valuation of selected direct and indirect use values of the Makgadikgadi wetland system, Botswana

    Science.gov (United States)

    Setlhogile, Tshepo; Arntzen, Jaap; Mabiza, Collin; Mano, Reneth

    Economic valuation of wetlands aims to investigate public preferences for changes in the state of the wetland and the natural resources it constitutes in monetary terms. It provides a means of quantifying the direct and indirect benefits that people derive from wetlands. In addition, it informs management planning and practice about resource options, optimal allocation and also provides information for conservation of the resource. The Makgadikgadi wetland is a unique system that mostly consists of dry pans during most of the year. This study aimed at estimating the value of groundwater recharge and community-based natural resource management (CBNRM) activities within the Makgadikgadi wetland and how these goods and services contribute to the local and national economy. The study used the Total Economic Valuation approach, which considers both the direct and indirect use values of the resource. In essence, the study concentrated on one direct use value (use of resources through CBNRM) and one indirect use value (groundwater recharge). With regard to CBNRM, three community-based organisations (CBOs) were selected for the study and static and dynamic cost-benefit models for these CBOs were developed. The groundwater recharge value was largely determined through desktop review and interviews with stakeholders. The results indicate a small positive contribution of CBOs towards the economy of Botswana and a high potential for communities to derive substantial benefits from the projects because currently benefits realised by communities are limited. CBOs involved in joint venture partnerships with tourism and hunting enterprises benefit more from utilising the wetland’s resources. Groundwater recharge often occurs in areas away from the physical location of the wetland and may not be easily attributable to the wetland. However, the study assessed the value taking into consideration the various sectors which rely on the groundwater resource. The groundwater recharge

  5. Promotional Model: A New Direction for National Program in Immunization (NPI) and Oral Rehydration Therapy (ORT) in Nigeria

    OpenAIRE

    P.EKERETE, Paulinus

    2000-01-01

    The National Program on Immunization (NPI), formerly known as the Expanded Program on Immunization (EPI) and Oral Rehydration Therapy (ORT), were relaunched in1984 after the problems of vaccine supply have been corrected. The NPI aimed to protect children against six childhood killer disease and ORT, to remedy dehydration. In order to achieve these objectives, Partner-in-Health strategy was set up to educate, convince and motivate mothers, pregnant women and community to accept the programme....

  6. Direct Synthesis and Size Selection of Ferromagnetic FePt Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Wellons, M.S. [Vanderbilt University; MorrisIII, William H [Vanderbilt University; Gai, Zheng [ORNL; Shen, Jian [ORNL; Bentley, James [ORNL; Wittig, J. E. [Vanderbilt University; Lukehart, C.M. [Vanderbilt University

    2007-01-01

    A one-step synthesis of L10 FePt nanoparticles ca. 17.0 nm in diameter by reductive decomposition of the single-source precursor, FePt(CO)4dppmBr2, on a water-soluble support (Na2CO3) is demonstrated. Direct conversion of a FePt(CO)4dppmBr2/Na2CO3 composite to a L10 FePt/Na2CO3 nanocomposite occurs at 600 C under getter gas with metal-ion reduction and minimal nanoparticle coalescence. Triturating the resulting nanocomposite with water simultaneously dissolves the sodium carbonate solid support and precipitates the formed fct FePt nanoparticles. As-prepared FePt nanoparticles are ferromagnetic and exhibit coercivities of 14.5 kOe at 300 K and 21.8 kOe at 5 K. When capped by functionalized methoxypoly(ethylene glycol) surfactant molecules, as-prepared, polydisperse ferromagnetic FePt nanoparticles can be dispersed and size-selected by fractional precipitation.

  7. To get the grasp: seven-month-olds encode and selectively reproduce goal-directed grasping.

    Science.gov (United States)

    Thoermer, Claudia; Woodward, Amanda; Sodian, Beate; Perst, Hannah; Kristen, Susanne

    2013-10-01

    Infants need to analyze human behavior in terms of goal-directed actions in order to form expectations about agents' rationality. There is converging evidence for goal encoding during the first year of life from looking time as well as social learning paradigms using imitation procedures. However, conceptual interpretations of these abilities are challenged by low-level motor resonance accounts that propose task-specific lower level sensorimotor associations underlying looking time tasks rather than abstract conceptual knowledge. To test the differential predictions derived from the two accounts, we investigated within-child consistency of performance on different, but conceptually related, tasks requiring goal encoding. This study presented seven-month-old infants with a looking time task and an imitation task, both testing their ability to encode an action goal based on a reaching action, as well as a working memory task to control for the influence of general cognitive capacity. Results showed inter task convergence to be independent of working memory: infants who spent more time looking at goal change events in the looking time task were more likely to selectively reproduce the goal in the imitation task when the model had performed an intentional grasping action rather than a back-of-hand object contact. These findings support the view that low-level motor resonance mechanisms are not sufficient to explain the capacities of action understanding in infants.

  8. Direct and indirect evidence of size-selective grazing on pelagic bacteria by freshwater nanoflagellates.

    Science.gov (United States)

    Simek, K; Chrzanowski, T H

    1992-11-01

    Size-selective grazing of three heterotrophic nanoflagellates (with cell sizes of 21, 44, and 66 mum) isolated from Lake Arlington, Texas was examined by using a natural mixture of fluorescence labelled lake bacteria. Sizes of ingested bacteria in food vacuoles were directly measured. Larger bacterial cells were ingested at a frequency much higher than that at which they occurred in the assemblage, indicating preferential flagellate grazing on the larger size classes within the lake bacterioplankton. Water samples were collected biweekly from June through September, 1989, fractionated by filtration, and incubated for 40 h at in situ temperatures. The average bacterial size was always larger in water which was passed through 1-mum-pore-size filters (1-mum-filtered water) (which was predator free) than in 5-mum-filtered water (which contained flagellates only) or in unfiltered water (in which all bacterivores were present). The increase of bacterial-cell size in 1-mum-filtered water was caused by a shift in the size structure of the bacterioplankton population. Larger cells became more abundant in the absence of flagellate grazing.

  9. Repeated Thermal Stress, Shading, and Directional Selection in the Florida Reef Tract

    Directory of Open Access Journals (Sweden)

    Robert van Woesik

    2017-06-01

    Full Text Available Over the last three decades reef corals have been subjected to an unprecedented frequency and intensity of thermal-stress events, which have led to extensive coral bleaching, disease, and mortality. Over the next century, the climate is predicted to drive sea-surface temperatures to even higher levels, consequently increasing the risk of mass bleaching and disease outbreaks. Yet, there is considerable temporal and spatial variation in coral bleaching and in disease prevalence. Using data collected from 2,398 sites along the Florida reef tract from 2005 to 2015, this study examined the temporal and spatial patterns of coral bleaching and disease in relation to coral-colony size, depth, temperature, and chlorophyll-a concentrations. The results show that coral bleaching was most prevalent during the warmest years in 2014 and 2015, and disease was also most prevalent in 2010, 2014, and 2015. Although the majority of the corals surveyed were found in habitats with low chlorophyll-a concentrations, and high irradiance, these same habitats showed the highest prevalence of coral bleaching and disease outbreaks during thermal-stress events. These results suggest that directional selection in a warming ocean may favor corals able to tolerate inshore, shaded environments with high turbidity and productivity.

  10. Direct injection HPLC method for the determination of selected benzodiazepines in plasma using a Hisep column.

    Science.gov (United States)

    Pistos, C; Stewart, James T

    2003-12-04

    A direct plasma injection HPLC method has been developed for the determination of selected benzodiazepines (nitrazepam, clobazam, oxazepam, lorazepam). The method uses an analytical hydrophobic shielded phase (Hisep) column equipped with a Hisep guard column, are easy to perform and requires 20 ul of a filtered plasma sample. The chromatographic run time is less than 15 min using a mobile phase of 15:85 v/v acetonitrile-0.18 M ammonium acetate pH 2.5. The method is good for 175 injections before replacement of the guard column. The method was linear in the range 0.5-18 ug ml(-1) (r>0.99, n=6) for the analytes with R.S.D. less than 10.82%. Interday and intraday variability were found to be less than 14%. The limits of detection and quantitation were 0.16 (s/n>3) and 0.5 ug ml(-1) (s/n>10), respectively, for each of the four benzodiazepines.

  11. Tuberculosis Diagnosis and Multidrug Resistance Testing by Direct Sputum Culture in Selective Broth without Decontamination or Centrifugation ▿ †

    Science.gov (United States)

    Grandjean, Louis; Martin, Laura; Gilman, Robert H.; Valencia, Teresa; Herrera, Beatriz; Quino, Willi; Ramos, Eric; Rivero, Maribel; Montoya, Rosario; Escombe, A. Roderick; Coleman, David; Mitchison, Denis; Evans, Carlton A.

    2008-01-01

    Tuberculosis culture usually requires sputum decontamination and centrifugation to prevent cultures from being overgrown by contaminating bacteria and fungi. However, decontamination destroys many tuberculous bacilli, and centrifugation often is not possible in resource-poor settings. We therefore assessed the performance of Mycobacterium tuberculosis culture with unprocessed samples plated directly by using tuberculosis-selective media and compared this procedure to conventional culture using centrifuge decontamination. Quadruplicate aliquots of strain H37RV were cultured in 7H9 broth with and without selective antimicrobials and after centrifuge decontamination. The subsequent comparison was made with 715 sputum samples. Split paired sputum samples were cultured conventionally with centrifuge decontamination and by direct culture in tuberculosis-selective media containing antibiotics. Centrifuge decontamination reduced tuberculosis H37RV colonies by 78% (P < 0.001), whereas direct culture in tuberculosis-selective media had no inhibitory effect. Similarly, in sputum cultures that were not overgrown by contaminants, conventional culture yielded fewer tuberculosis colonies than direct culture (P < 0.001). However, the sensitivity of conventional culture was greater than that of direct culture, because samples were less affected by contamination. Thus, of the 340 sputum samples that were tuberculosis culture positive, conventional culture detected 97%, whereas direct culture detected 81% (P < 0.001). Conventional and direct cultures both took a median of 8.0 days to diagnose tuberculosis (P = 0.8). In those direct cultures that detected drug resistance or susceptibility, there was a 97% agreement with the results of conventional culture (Kappa agreement statistic, 0.84; P < 0.001). Direct culture is a simple, low-technology, and rapid technique for diagnosing tuberculosis and determining drug susceptibility. Compared to that of conventional culture, direct culture

  12. Tuberculosis diagnosis and multidrug resistance testing by direct sputum culture in selective broth without decontamination or centrifugation.

    Science.gov (United States)

    Grandjean, Louis; Martin, Laura; Gilman, Robert H; Valencia, Teresa; Herrera, Beatriz; Quino, Willi; Ramos, Eric; Rivero, Maribel; Montoya, Rosario; Escombe, A Roderick; Coleman, David; Mitchison, Denis; Evans, Carlton A

    2008-07-01

    Tuberculosis culture usually requires sputum decontamination and centrifugation to prevent cultures from being overgrown by contaminating bacteria and fungi. However, decontamination destroys many tuberculous bacilli, and centrifugation often is not possible in resource-poor settings. We therefore assessed the performance of Mycobacterium tuberculosis culture with unprocessed samples plated directly by using tuberculosis-selective media and compared this procedure to conventional culture using centrifuge decontamination. Quadruplicate aliquots of strain H37RV were cultured in 7H9 broth with and without selective antimicrobials and after centrifuge decontamination. The subsequent comparison was made with 715 sputum samples. Split paired sputum samples were cultured conventionally with centrifuge decontamination and by direct culture in tuberculosis-selective media containing antibiotics. Centrifuge decontamination reduced tuberculosis H37RV colonies by 78% (P < 0.001), whereas direct culture in tuberculosis-selective media had no inhibitory effect. Similarly, in sputum cultures that were not overgrown by contaminants, conventional culture yielded fewer tuberculosis colonies than direct culture (P < 0.001). However, the sensitivity of conventional culture was greater than that of direct culture, because samples were less affected by contamination. Thus, of the 340 sputum samples that were tuberculosis culture positive, conventional culture detected 97%, whereas direct culture detected 81% (P < 0.001). Conventional and direct cultures both took a median of 8.0 days to diagnose tuberculosis (P = 0.8). In those direct cultures that detected drug resistance or susceptibility, there was a 97% agreement with the results of conventional culture (Kappa agreement statistic, 0.84; P < 0.001). Direct culture is a simple, low-technology, and rapid technique for diagnosing tuberculosis and determining drug susceptibility. Compared to that of conventional culture, direct culture

  13. Transforming growth factor-β-1 polymorphisms are infrequent but exist at selected loci in oral submucous fibrosis

    Directory of Open Access Journals (Sweden)

    Rajendran R

    2010-01-01

    Full Text Available Background : Oral submucous fibrosis (OSF may be considered a collagen metabolic disorder resulting from areca-nut alkaloid exposure and individual variation in collagen metabolism. Due to the complexity of OSF pathogenesis, it is important to elucidate independent and interactive effects of polymorphisms of collagen-related genes on OSF risk. Materials and Methods : This study is focused on seven polymorphisms (SNPs of transforming growth factor-beta-1 (TGF-beta-1 gene in patients with oral submucous fibrosis (OSF, belonging to south Indian ethnic extraction. The mean age at presentation was 43.9 years, range 23-72 years (n=50, M:F ratio, 2.6:1. DNA samples from 50 subjects of the same ethnic group and comparable demographic features who have had practiced the habit of areca-chewing of almost equal duration, but remained free of disease constituted the controls. All DNA samples were collected progressively and purified from peripheral blood employing standard protocols and tested for SNPs. They included two polymorphisms in the promoter region (C-509T and G-800A, three polymorphisms in exon-1 (Arg25Pro(G915C, Leu10Pro(T869C, Glu47Gly(A979G and two in 5 ¢UTR regions (C→T(rs13306708 and G→A (rs9282871. The extracted DNA samples along with the primers underwent PCR amplification and the genotypic and allelic frequencies were calculated. All calculations were performed using the SPSS software. The PCR products were purified and subsequently sequenced using Flour S™ multi-imager system (Biorad. The sequenced data were analyzed using the BioEdit sequence analysis software. Results : Out of the seven polymorphisms analyzed, six such as two in the promoter region, three in exon-1 and one in 5¢UTR were found to have a " P" value above 0.05 and hence were not significant. The C→T transition (rs13306708 in the 5¢UTR region recorded a " P" value of 0.03 on comparison and hence was found to be significant. The allelic frequencies for this C

  14. Chemically selective polymer substrate based direct isotope dilution alpha spectrometry of Pu.

    Science.gov (United States)

    Paul, Sumana; Pandey, Ashok K; Shah, R V; Aggarwal, S K

    2015-06-01

    Quantification of actinides in the complex environmental, biological, process and waste streams samples requires multiple steps like selective preconcentration and matrix elimination, solid source preparations generally by evaporation or electrodeposition, and finally alpha spectrometry. To minimize the sample manipulation steps, a membrane based isotope dilution alpha spectrometry method was developed for the determination of plutonium concentrations in the complex aqueous solutions. The advantages of this method are that it is Pu(IV) selective at 3M HNO3, high preconcentration factor can be achieved, and obviates the need of solid source preparation. For this, a thin phosphate-sulfate bifunctional polymer layer was anchored on the surface of microporous poly(ethersulfone) membrane by UV induced surface grafting. The thickness of the bifunctional layer on one surface of the poly(ethersulfone) membrane was optimized. The thickness, physical and chemical structures of the bifunctional layer were studied by secondary ionization mass spectrometry (SIMS), scanning electron microscopy (SEM) and SEM-EDS (energy-dispersive spectroscopy). The optimized membrane was used for preconcentration of Pu(IV) from aqueous solutions having 3-4M HNO3, followed by direct quantification of the preconcentrated Pu(IV) by isotope dilution alpha spectrometry using (238)Pu spike. The chemical recovery efficiency of Pu(IV) was found to be 86±3% below Pu(IV) loading capacity (1.08 μg in 2×1 cm(2)) of the membrane sample. The experiments with single representative actinides indicated that Am(III) did not sorb to significant extent (7%) but U(VI) sorbed with 78±3% efficiency from the solutions having 3M HNO3 concentration. However, Pu(IV) chemical recovery in the membrane remained unaffected from the solution containing 1:1000 wt. proportion of Pu(IV) to U(VI). Pu concentrations in the (U, Pu)C samples and in the irradiated fuel dissolver solutions were determined. The results thus obtained

  15. Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms.

    Science.gov (United States)

    Hermann, Robert; Mungo, Julius; Cnota, Peter Jürgen; Ziegler, Dan

    2014-01-01

    The present study aimed to examine the enantiomer-selective pharmacokinetics (PK), relative bioavailability (Frel), and sex effects of various oral dosage forms of racemic alpha-lipoic acid (ALA). In an open-label, randomized, four-period, four-sequence crossover study, 24 healthy adult subjects (12 males and 12 females) received single doses of 600 mg of ALA in fasted state at four different occasions as follows: three 200 mg tablets (T 200); two 300 mg tablets (T 300); one 600 mg tablet (T 600); and a racemic ALA solution (OS). All tablet formulations (Thioctacid HR) were considered test treatments, while the OS (Thioctacid, 600 T) served as the reference treatment. Serial blood samples were collected over 8 hours postdose to quantify R-(+)- and S-(-)-ALA enantiomer plasma concentrations for the PK evaluation. The maximum observed plasma concentration (Cmax) and total exposure (area under the curve [AUC]0-t) were compared between treatments by analysis of variance. Weight-normalized Cmax and the AUC data of male and female study subjects were applied to examine the presence of sex effects. All treatments displayed rapid absorption of both enantiomers with median time to maximum concentration (tmax) values ranging from 0.33-0.5 hours. The Frel of all tablet formulations was comparable, with R-(+)-enantiomer Cmax test/reference ratios ranging from 36% (T 600) to 43% (T 200), and R-(+)-enantiomer AUC test/reference ratios ranging from 64% (T 600) to 79% (T 300), indicating a favorable Frel of all tablet formulations, especially in terms of the total extent of absorption (AUC). An examination of weight-normalized female/male Cmax and AUC sex ratios for both ALA enantiomers indicated the absence of a significant sex effect for Cmax, as well as 20%-26% and 25%-32% higher R-(+)- and S-(-)-ALA enantiomer AUC outcomes in females when compared to males. The observed modest sex effect was comparable for both ALA enantiomers and across all formulations, and it did not appear

  16. Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms

    Directory of Open Access Journals (Sweden)

    Hermann R

    2014-11-01

    Full Text Available Robert Hermann,1 Julius Mungo,2 Peter Jürgen Cnota,2 Dan Ziegler3 1Clinical Research Appliance (cr appliance, Gelnhausen, Germany; 2MEDA Pharma GmbH & Co KG, Bad Homburg, Germany; 3Institute for Clinical Diabetology, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany Abstract: The present study aimed to examine the enantiomer-selective pharmacokinetics (PK, relative bioavailability (Frel, and sex effects of various oral dosage forms of racemic alpha-lipoic acid (ALA. In an open-label, randomized, four-period, four-sequence crossover study, 24 healthy adult subjects (12 males and 12 females received single doses of 600 mg of ALA in fasted state at four different occasions as follows: three 200 mg tablets (T 200; two 300 mg tablets (T 300; one 600 mg tablet (T 600; and a racemic ALA solution (OS. All tablet formulations (Thioctacid HR were considered test treatments, while the OS (Thioctacid, 600 T served as the reference treatment. Serial blood samples were collected over 8 hours postdose to quantify R-(+- and S-(–-ALA enantiomer plasma concentrations for the PK evaluation. The maximum observed plasma concentration (Cmax and total exposure (area under the curve [AUC]0–t were compared between treatments by analysis of variance. Weight-normalized Cmax and the AUC data of male and female study subjects were applied to examine the presence of sex effects. All treatments displayed rapid absorption of both enantiomers with median time to maximum concentration (tmax values ranging from 0.33–0.5 hours. The Frel of all tablet formulations was comparable, with R-(+-enantiomer Cmax test/reference ratios ranging from 36% (T 600 to 43% (T 200, and R-(+-enantiomer AUC test/reference ratios ranging from 64% (T 600 to 79% (T 300, indicating a favorable Frel of all tablet formulations, especially in terms of the total extent of absorption (AUC. An examination of weight-normalized female/male Cmax and AUC sex ratios for both ALA

  17. Evaluation of selected oral cavity microbiota--risk factors of management complications in patients with masticatory system disorders.

    Science.gov (United States)

    Zawadzki, Paweł J; Perkowski, Konrad; Starościak, Bohdan; Dybicz, Monika; Baltaza, Wanda; Pionkowski, Krzysztof; Chomicz, Lidia

    2016-01-01

    The retrospective analysis of data on oral cavity clinical status in relation to microbiota species composition is presented. The research regards patients of different age, with and without congenital malformation, pretreatment assessed for occurrence of pathological changes in the masticatory system. Samples of the swabs collected from each patient (from dental plaque, periodontium and dental pockets) were used for identification of oral protozoans in wet slides and stained preparations; additionally, transmission electron microscope examination was performed. The material was used for in vitro cultures to identify bacteria strains. Clinically, intensity of tissue deteriorations was higher in patients with a congenital disease. Alive Trichomonas tenax and Entamoeba gingivalis, species with confirmed pathogenic impact on oral cavity and neighboring structures, were detected with higher prevalence in older patients. Enterococci, Staphylococcus aureus, various Enterobacteriaceae were more frequently detected in patients with somatic and mental retardations; in mouths of those patients, Klebsiella pneumonia and Pseudomonas aeruginosa opportunistic strains occurred. Masticatory system abnormalities favor colonization of oral cavity by exogenous species and dissemination of infections, especially dangerous for patients with congenital diseases. Oral microbiota assessment and preventive measures may be helpful to avoid subsequent peri-surgery complications.

  18. Oral sex, oral health and orogenital infections

    Directory of Open Access Journals (Sweden)

    Saini Rajiv

    2010-01-01

    Full Text Available Oral sex is commonly practiced by sexually active male-female and same-gender couples of various ages, including adolescents. The various type of oral sex practices are fellatio, cunnilingus and analingus. Oral sex is infrequently examined in research on adolescents; oral sex can transmit oral, respiratory, and genital pathogens. Oral health has a direct impact on the transmission of infection; a cut in your mouth, bleeding gums, lip sores or broken skin increases chances of infection. Although oral sex is considered a low risk activity, it is important to use protection and safer sex precautions. There are various methods of preventing infection during oral sex such as physical barriers, health and medical issues, ethical issues and oral hygiene and dental issues. The lesions or unhealthy periodontal status of oral cavity accelerates the phenomenon of transmission of infections into the circulation. Thus consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex.

  19. Imaging in oral cancers

    Directory of Open Access Journals (Sweden)

    Supreeta Arya

    2012-01-01

    Full Text Available Oral cavity squamous cell cancers form a significant percentage of the cancers seen in India. While clinical examination allows direct visualization, it cannot evaluate deep extension of disease. Cross-sectional imaging has become the cornerstone in the pretreatment evaluation of these cancers and provides accurate information about the extent and depth of disease that can help decide the appropriate management strategy and indicate prognosis. Early cancers are treated with a single modality, either surgery or radiotherapy while advanced cancers are offered a combination of surgery, radiotherapy and chemotherapy. Imaging can decide resectability, help plan the precise extent of resection, and indicate whether organ conservation therapy should be offered. Quality of life issues necessitate preservation of form and function and pretreatment imaging helps plan appropriate reconstruction and counsel patients regarding lifestyle changes. Oral cavity has several subsites and the focus of the review is squamous cancers of the gingivobuccal region, oral tongue and retromolar trigone as these are most frequently encountered in the subcontinent. References for this review were identified by searching Medline and PubMed databases. Only articles published in English language literature were selected. This review aims to familiarize the radiologist with the relevant anatomy of the oral cavity, discuss the specific issues that influence prognosis and management at the above subsites, the optimal imaging methods, the role of imaging in accurately staging these cancers and in influencing management. A checklist for reporting will emphasize the information to be conveyed by the radiologist.

  20. Evolution of the additive genetic variance–covariance matrix under continuous directional selection on a complex behavioural phenotype

    Science.gov (United States)

    Careau, Vincent; Wolak, Matthew E.; Carter, Patrick A.; Garland, Theodore

    2015-01-01

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance–covariance matrix (G). Yet knowledge of G in a population experiencing new or altered selection is not sufficient to predict selection response because G itself evolves in ways that are poorly understood. We experimentally evaluated changes in G when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. PMID:26582016

  1. Evolution of the additive genetic variance-covariance matrix under continuous directional selection on a complex behavioural phenotype.

    Science.gov (United States)

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2015-11-22

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance-covariance matrix ( G: ). Yet knowledge of G: in a population experiencing new or altered selection is not sufficient to predict selection response because G: itself evolves in ways that are poorly understood. We experimentally evaluated changes in G: when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G: induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G: induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G: and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. © 2015 The Author(s).

  2. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Shannon D Shields

    Full Text Available Cerebellar symptoms significantly diminish quality of life in patients with multiple sclerosis (MS. We previously showed that sodium channel Nav1.8, although normally restricted to peripheral somatosensory neurons, is upregulated in the cerebellum in MS, and that Nav1.8 expression is linked to ataxia and MS-like symptoms in mice. Furthermore, intracerebroventricular administration of the Nav1.8 blocker A-803467 temporarily reversed electrophysiological and behavioral manifestations of disease in a mouse MS model; unfortunately A-803467 is not orally bioavailable, diminishing the potential for translation to human patients. In the present study, we assessed the effect of per os (p.o. dosing of a new orally bioavailable Nav1.8-selective blocker, PF-01247324, in transgenic mice expressing Nav1.8 in Purkinje neurons, and in wildtype mice in the experimental autoimmune encephalomyelitis (EAE model. PF-01247324 was administered by oral gavage at 1000 mg/kg; control groups received an equal volume of vehicle. Behavioral assays of motor coordination, grip strength, and ataxia were performed. We observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle. These preclinical proof-of-concept data suggest that PF-01247324, its derivatives, or other Nav1.8-selective blockers merit further study for providing symptomatic therapy for cerebellar dysfunction in MS and related disorders.

  3. Evolution of Grain Selection in Spiral Selector during Directional Solidification of Nickel-base Superalloys

    Institute of Scientific and Technical Information of China (English)

    Xiangbin Meng; Jinguo Li; Tao Jin; Xiaofeng Sun; Changbo Sun; Zhuangqi Hu

    2011-01-01

    The process of grain selection in the spiral selector was investigated by both a ProCAST simulation based on a cellular automaton finite element (CAFE) model and experimental confirmation. The results show that the height of starter block, the spiral diameter and initial angle play an important role in grain selection. The dimension of selector should be maintained in a stable range to optimize the grain orientation and select a single crystal efficiently. A selector which can efficiently select a single crystal had been successfully designed. Grain orientation fluctuation in the spiral part was also studied by means of the variation of thermal condition.

  4. Oral Steroids for Dermatitis.

    Science.gov (United States)

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment.

  5. Selections from the ABC 2015 Annual Conference, Seattle, Washington: Pitching Fish and Innovative Oral and Written Business Communication Assignments

    Science.gov (United States)

    Whalen, D. Joel, Ed.

    2016-01-01

    This article, the first of a two-part series, presents teaching 10 innovations from the 2015 Association for Business Communication's 80th annual conference. The creative new assignments offered here include building listening skills by journaling, oral interpretation, positive message framing, storytelling, delivering bad news, persuasive…

  6. Selected aspects of the oral environment in cleft palate patients – a problem evidently beyond dentists’ scope

    Directory of Open Access Journals (Sweden)

    Joanna AntoszewskaABCD

    2010-12-01

    Full Text Available Introduction:The oral cavity is a specialized ecosystem composed of dentition and mucosa exposed to the effects of saliva and gingival liquid. Its structure provides advantageous conditions for various microorganisms, both aerobic streptococci and anaerobic bacilli. The dynamic balance of the oral cavity ecosystem can be threatened by various factors. Lip and palatal clefts are the most frequent disorders in embryonic facial development. The aim of the study was to evaluate whether Streptococcus mutans and Lactobacillus acidophilus and oral cavity hygiene in patients with cleft palate treated orthodontically are significantly different compared with patients without these congenital malformations.Material/Methods:The study group consisted of 200 patients aged 6–21 who were divided into two groups depending on the presence of cleft palate and treatment method. Group C (control consisted of 50 orthodontically untreated patients with occlusal dental defects. The performed studies consisted of 2 parts: the clinical-laboratory part and statistical analysis.Clinical-laboratory partResults:High bacteria levels of Streptococcus mutans and Lactobacillus acidophilus in saliva of patients were comparably frequent between groups, but there were statistically significant differences in inter-group comparisons.Conclusions:As the orthodontic treatment changes the oral environment, control of proper hygienic behavior is an essential element of health education. Introduction of preventive programs is also very important.

  7. Selections from the ABC 2015 Annual Conference, Seattle, Washington: Pitching Fish and Innovative Oral and Written Business Communication Assignments

    Science.gov (United States)

    Whalen, D. Joel, Ed.

    2016-01-01

    This article, the first of a two-part series, presents teaching 10 innovations from the 2015 Association for Business Communication's 80th annual conference. The creative new assignments offered here include building listening skills by journaling, oral interpretation, positive message framing, storytelling, delivering bad news, persuasive…

  8. A genome-wide scan for signatures of directional selection in domesticated pigs

    NARCIS (Netherlands)

    Moon, S.; Kim, T.H.; Lee, K.T.; Kwak, W.; Lee, T.; Lee, S.W.; Kim, M.J.; Cho, K.; Kim, N.; Chung, W.H.; Sung, S.; Park, T.; Cho, S.; Groenen, M.A.M.; Nielsen, R.; Kim, Y.; Kim, H.

    2015-01-01

    Background: Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication. Results: Who

  9. Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: a case report and a review of the French National Pharmacovigilance Database

    Directory of Open Access Journals (Sweden)

    Liabeuf S

    2014-04-01

    Full Text Available Sophie Liabeuf,1–3 Valérie Gras,1 Julien Moragny,1 Marie-Laure Laroche,4 Michel Andrejak1,3On behalf of the French National Network of Pharmacovigilance Centers1Regional Pharmacovigilance Center, Division of Clinical Pharmacology, Amiens University Medical Center and Jules Verne University of Picardy, Amiens, France; 2Clinical Research Centre, Clinical Pharmacology Division, Amiens University Medical Center and the Jules Verne University of Picardy, Amiens, France; 3INSERM U1088, Amiens, France; 4Regional Pharmacovigilance Center, Department of Pharmacology, Toxicology and Pharmacovigilance, Limoges University Medical Center, Limoges, FranceObjective: To report a series of cases of ulceration of the oral mucosa linked to direct contact with ferrous sulfate in elderly patients.Case summary: The first case report concerns the occurrence of widespread oral ulceration in an 87-year-old woman with Alzheimer’s disease. The ulceration extended from the side of the tongue to the floor of the mouth. No clear explanation was found and various local treatments were ineffective. Once it was realized that the ferrous sulfate tablets (given as an iron supplement were crushed prior to administration (due to the patient’s deglutition disorder, withdrawal of this treatment led to rapid resolution of the ulceration. Nine other cases of oral ulcerations associated with ferrous sulfate were identified in the French National Pharmacovigilance Database. All but one of the patients were over 80 years of age and the youngest patient (a 54-year-old had dysphagia associated with facial paralysis.Discussion: Only two other reports of oral ulceration due to ferrous sulfate have been published to date. Mucosal toxicity of ferrous sulfate (which is probably related to oxidative stress has previously been reported for the hypopharynx, the esophageal lumen, and (after inhalation of a tablet the tracheobronchial tree.Conclusion: The mucosal toxicity of ferrous

  10. tBuLi-Mediated One-Pot Direct Highly Selective Cross-Coupling of Two Distinct Aryl Bromides

    NARCIS (Netherlands)

    Vila, Carlos; Cembellin, Sara; Hornillos, Valentin; Giannerini, Massimo; Fananas-Mastral, Martin; Feringa, Ben L.

    2015-01-01

    A Pd-catalyzed direct cross-coupling of two distinct aryl bromides mediated by tBuLi is described. The use of [Pd-PEPPSI-IPr] or [Pd-PEPPSI-IPent] as catalyst allows for the efficient one-pot synthesis of unsymmetrical biaryls at room temperature. The key for this selective cross-coupling is the use

  11. Using aspen for artist stretcher frames: adding value through quality service, direct marketing, and careful material selection

    Science.gov (United States)

    Chris. Polson

    2001-01-01

    Aspen wood, when carefully selected and kiln dried, makes excellent stock for artist stretcher frames. Direct marketing techniques including the Internet and word of mouth give access to national markets, providing a more diverse and stable customer base for operations from a rural area. High-quality service, as shown by product performance and rapid order fulfillment...

  12. Using the Self-Directed Search in Research: Selecting a Representative Pool of Items to Measure Vocational Interests

    Science.gov (United States)

    Poitras, Sarah-Caroline; Guay, Frederic; Ratelle, Catherine F.

    2012-01-01

    Using Item Response Theory (IRT) and Confirmatory Factor Analysis (CFA), the goal of this study was to select a reduced pool of items from the French Canadian version of the Self-Directed Search--Activities Section (Holland, Fritzsche, & Powell, 1994). Two studies were conducted. Results of Study 1, involving 727 French Canadian students,…

  13. Using the Self-Directed Search in Research: Selecting a Representative Pool of Items to Measure Vocational Interests

    Science.gov (United States)

    Poitras, Sarah-Caroline; Guay, Frederic; Ratelle, Catherine F.

    2012-01-01

    Using Item Response Theory (IRT) and Confirmatory Factor Analysis (CFA), the goal of this study was to select a reduced pool of items from the French Canadian version of the Self-Directed Search--Activities Section (Holland, Fritzsche, & Powell, 1994). Two studies were conducted. Results of Study 1, involving 727 French Canadian students,…

  14. Strategies for Selecting Routes through Real-World Environments: Relative Topography, Initial Route Straightness, and Cardinal Direction.

    Directory of Open Access Journals (Sweden)

    Tad T Brunyé

    Full Text Available Previous research has demonstrated that route planners use several reliable strategies for selecting between alternate routes. Strategies include selecting straight rather than winding routes leaving an origin, selecting generally south- rather than north-going routes, and selecting routes that avoid traversal of complex topography. The contribution of this paper is characterizing the relative influence and potential interactions of these strategies. We also examine whether individual differences would predict any strategy reliance. Results showed evidence for independent and additive influences of all three strategies, with a strong influence of topography and initial segment straightness, and relatively weak influence of cardinal direction. Additively, routes were also disproportionately selected when they traversed relatively flat regions, had relatively straight initial segments, and went generally south rather than north. Two individual differences, extraversion and sense of direction, predicted the extent of some effects. Under real-world conditions navigators indeed consider a route's initial straightness, cardinal direction, and topography, but these cues differ in relative influence and vary in their application across individuals.

  15. Three-dimensional motion aftereffects reveal distinct direction-selective mechanisms for binocular processing of motion through depth

    Science.gov (United States)

    Czuba, Thaddeus B.; Rokers, Bas; Guillet, Kyle; Huk, Alexander C.; Cormack, Lawrence K.

    2013-01-01

    Motion aftereffects are historically considered evidence for neuronal populations tuned to specific directions of motion. Despite a wealth of motion aftereffect studies investigating 2D (frontoparallel) motion mechanisms, there is a remarkable dearth of psychophysical evidence for neuronal populations selective for the direction of motion through depth (i.e., tuned to 3D motion). We compared the effects of prolonged viewing of unidirectional motion under dichoptic and monocular conditions and found large 3D motion aftereffects that could not be explained by simple inheritance of 2D monocular aftereffects. These results (1) demonstrate the existence of neurons tuned to 3D motion as distinct from monocular 2D mechanisms, (2) show that distinct 3D direction selectivity arises from both interocular velocity differences and changing disparities over time, and (3) provide a straightforward psychophysical tool for further probing 3D motion mechanisms. PMID:21945967

  16. Effect of directional selection for body size on fluctuating asymmetry in certain morphological traits in Drosophila ananassae

    Indian Academy of Sciences (India)

    C Vishalakshi; B N Singh

    2009-06-01

    Variation in the subtle differences between the right and left sides of bilateral characters or fluctuating asymmetry (FA) has been considered as an indicator of an organism’s ability to cope with genetic and environmental stresses during development. However, due to inconsistency in the results of empirical studies, the relationship between FA and stress has been the subject of intense debate. In this study, we investigated whether stress caused by artificial bidirectional selection for body size has any effect on the levels of FA of different morphological traits in Drosophila ananassae. The realised heritability (h2) was higher in low-line females and high-line males, which suggests an asymmetrical response to selection for body size. Further, the levels of FA were compared across 10 generations of selection in different selection lines in both sexes for sternopleural bristle number, wing length, wing-to-thorax ratio, sex combtooth number and ovariole number. The levels of FA differed significantly among generations and selection lines but did not change markedly with directional selection. However, the levels of FA were higher in the G10 generation (at the end of selection) than G0 (at the start of selection) but lower than the G5 generation in different selection lines, suggesting that the levels of FA are not affected by the inbreeding generated during the course of selection. Also, the levels of FA in the hybrids of high and low lines were significantly lower than the parental selection lines, suggesting that FA is influenced by hybridisation. These results are discussed in the framework of the literature available on FA and its relationship with stress.

  17. Detecting consistent patterns of directional adaptation using differential selection codon models.

    Science.gov (United States)

    Parto, Sahar; Lartillot, Nicolas

    2017-06-23

    Phylogenetic codon models are often used to characterize the selective regimes acting on protein-coding sequences. Recent methodological developments have led to models explicitly accounting for the interplay between mutation and selection, by modeling the amino acid fitness landscape along the sequence. However, thus far, most of these models have assumed that the fitness landscape is constant over time. Fluctuations of the fitness landscape may often be random or depend on complex and unknown factors. However, some organisms may be subject to systematic changes in selective pressure, resulting in reproducible molecular adaptations across independent lineages subject to similar conditions. Here, we introduce a codon-based differential selection model, which aims to detect and quantify the fine-grained consistent patterns of adaptation at the protein-coding level, as a function of external conditions experienced by the organism under investigation. The model parameterizes the global mutational pressure, as well as the site- and condition-specific amino acid selective preferences. This phylogenetic model is implemented in a Bayesian MCMC framework. After validation with simulations, we applied our method to a dataset of HIV sequences from patients with known HLA genetic background. Our differential selection model detects and characterizes differentially selected coding positions specifically associated with two different HLA alleles. Our differential selection model is able to identify consistent molecular adaptations as a function of repeated changes in the environment of the organism. These models can be applied to many other problems, ranging from viral adaptation to evolution of life-history strategies in plants or animals.

  18. Site-selective C-H arylation of primary aliphatic amines enabled by a catalytic transient directing group

    Science.gov (United States)

    Liu, Yongbing; Ge, Haibo

    2017-01-01

    Transition-metal-catalysed direct C-H bond functionalization of aliphatic amines is of great importance in organic and medicinal chemistry research. Several methods have been developed for the direct sp3 C-H functionalization of secondary and tertiary aliphatic amines, but site-selective functionalization of primary aliphatic amines in remote positions remains a challenge. Here, we report the direct, highly site-selective γ-arylation of primary alkylamines via a palladium-catalysed C-H bond functionalization process on unactivated sp3 carbons. Using glyoxylic acid as an inexpensive, catalytic and transient directing group, a wide array of γ-arylated primary alkylamines were prepared without any protection or deprotection steps. This approach provides straightforward access to important structural motifs in organic and medicinal chemistry without the need for pre-functionalized substrates or stoichiometric directing groups and is demonstrated here in the synthesis of analogues of the immunomodulatory drug fingolimod directly from commercially available 2-amino-2-propylpropane-1,3-diol.

  19. Feasibility of direct utilization of selected geothermal water for aquaculture of macrobrachium rosenbergii. Technical report

    Energy Technology Data Exchange (ETDEWEB)

    Spinosa, C.

    1984-05-01

    The feasibility was tested of direct utilization of geothermal water for the aquaculture of Malaysian freshwater prawns (Macrobrachium rosenbergii). A problem with using geothermal water for aquaculture is the chemical composition of the water with high flouride levels being a particular problem. Results show that (1) some geothermal water in Idaho can be used directly for the aquaculture of Macrobrachium rosenbergii, (2) high flouride levels cannot be directly correlated with high mortality rates and (3) low flouride levels do not correlate with high growth rates.

  20. Rapid selective metal patterning on polydimethylsiloxane (PDMS) fabricated by capillarity-assisted laser direct write

    KAUST Repository

    Lee, Ming-Tsang

    2011-08-12

    In this study we demonstrate a novel approach for the rapid fabricating micro scale metal (silver) patterning directly on a polydimethylsiloxane (PDMS) substrate. Silver nanoparticles were sintered on PDMS to form conductive metal films using laser direct write (LDW) technology. To achieve good metal film quality, a capillarity-assisted laser direct writing (CALDW) of nanoparticle suspensions on a low surface energy material (PDMS) was utilized. Experimental results showed controllable electrical conductivities and good film properties of the sintered silver patterns. This study reveals an advanced method of metal patterning on PDMS, and proposes a new research application of LDW in a nanoparticle colloidal environment. © 2011 IOP Publishing Ltd.

  1. Rapid selective metal patterning on polydimethylsiloxane (PDMS) fabricated by capillarity-assisted laser direct write

    Science.gov (United States)

    Lee, Ming-Tsang; Lee, Daeho; Sherry, Alexander; Grigoropoulos, Costas P.

    2011-09-01

    In this study we demonstrate a novel approach for the rapid fabricating micro scale metal (silver) patterning directly on a polydimethylsiloxane (PDMS) substrate. Silver nanoparticles were sintered on PDMS to form conductive metal films using laser direct write (LDW) technology. To achieve good metal film quality, a capillarity-assisted laser direct writing (CALDW) of nanoparticle suspensions on a low surface energy material (PDMS) was utilized. Experimental results showed controllable electrical conductivities and good film properties of the sintered silver patterns. This study reveals an advanced method of metal patterning on PDMS, and proposes a new research application of LDW in a nanoparticle colloidal environment.

  2. Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC and miltefosine in a mouse model of L. major cutaneous leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Anny Fortin

    2014-09-01

    Full Text Available Cutaneous leishmaniasis (CL represents a range of skin diseases caused by infection with Leishmania parasites and associated with tissue inflammation and skin ulceration. CL is clinically widespread in both the Old and New World but lacks treatments that are well tolerated, effective and inexpensive. Oleylphosphocholine (OlPC is a new orally bioavailable drug of the alkylphosphocholine family with potent antileishmanial activity against a broad range of Leishmania species/strains.The potential of OlPC against Old World CL was evaluated in a mouse model of Leishmania (L. major infection in BALB/c mice. Initial dose-response experiments showed that an oral daily dose of 40 mg/kg of OlPC was needed to impact time to cure and lesion sizes. This dose was then used to directly compare the efficacy of OlPC to the efficacy of the antileishmanial drugs miltefosine (40 mg/kg/day, fluconazole (160 mg/kg/day and amphotericin B (25 mg/kg/day. OlPC, miltefosine and fluconazole were given orally for 21 days while amphotericin B was administered intraperitoneally for 10 days. Ulcer sizes and animal weights were followed up on a weekly basis and parasitemia was determined by means of a real-time in vivo imaging system which detects luminescence emitted from luciferase-expressing infecting L. major parasites. Amphotericin B and OlPC showed excellent efficacy against L. major lesions in terms of reduction of parasitic loads and by inducing complete healing of established lesions. In contrast, treatment with miltefosine did not significantly affect parasitemia and lesion sizes, while fluconazole was completely ineffective at the dose regimen tested.Given the data showing the outstanding efficacy and tolerability of OlPC, our results suggest that OlPC is a promising new drug candidate to improve and simplify current clinical management of L. major CL.

  3. Direct Comparison of the Efficacy and Safety of Oral Treatments with Oleylphosphocholine (OlPC) and Miltefosine in a Mouse Model of L. major Cutaneous Leishmaniasis

    Science.gov (United States)

    Fortin, Anny; Caridha, Diana P.; Leed, Susan; Ngundam, Franklyn; Sena, Jenell; Bosschaerts, Tom; Parriott, Sandi; Hickman, Mark R.; Hudson, Thomas H.; Grogl, Max

    2014-01-01

    Background Cutaneous leishmaniasis (CL) represents a range of skin diseases caused by infection with Leishmania parasites and associated with tissue inflammation and skin ulceration. CL is clinically widespread in both the Old and New World but lacks treatments that are well tolerated, effective and inexpensive. Oleylphosphocholine (OlPC) is a new orally bioavailable drug of the alkylphosphocholine family with potent antileishmanial activity against a broad range of Leishmania species/strains. Methodology/principal findings The potential of OlPC against Old World CL was evaluated in a mouse model of Leishmania (L.) major infection in BALB/c mice. Initial dose-response experiments showed that an oral daily dose of 40 mg/kg of OlPC was needed to impact time to cure and lesion sizes. This dose was then used to directly compare the efficacy of OlPC to the efficacy of the antileishmanial drugs miltefosine (40 mg/kg/day), fluconazole (160 mg/kg/day) and amphotericin B (25 mg/kg/day). OlPC, miltefosine and fluconazole were given orally for 21 days while amphotericin B was administered intraperitoneally for 10 days. Ulcer sizes and animal weights were followed up on a weekly basis and parasitemia was determined by means of a real-time in vivo imaging system which detects luminescence emitted from luciferase-expressing infecting L. major parasites. Amphotericin B and OlPC showed excellent efficacy against L. major lesions in terms of reduction of parasitic loads and by inducing complete healing of established lesions. In contrast, treatment with miltefosine did not significantly affect parasitemia and lesion sizes, while fluconazole was completely ineffective at the dose regimen tested. Conclusions/Significance Given the data showing the outstanding efficacy and tolerability of OlPC, our results suggest that OlPC is a promising new drug candidate to improve and simplify current clinical management of L. major CL. PMID:25210745

  4. The selection rules of high harmonic generation: roles of projections of molecules and dynamical directivities of laser fields

    CERN Document Server

    Liu, Xi; Li, Liang; Li, Yang; Zhang, Qingbin; Lan, Pengfei; Lu, Peixiang

    2016-01-01

    The selection rules of high harmonic generation (HHG) are investigated using three-dimensional time-dependent density functional theory (TDDFT). From the harmonic spectra obtained with various real molecules and different forms of laser fields, several factors that contribute to selection rules are revealed. Extending the targets to stereoscopic molecules, it is shown that the allowed harmonics are dependent on the symmetries of the projections of molecules. Moreover, it is found that the dynamical directivities of the laser fields play an important role on the selection rules. Our study presents a more general form of selection rules, which can be extended to the HHG for more complex molecules and various forms of laser fields.

  5. High efficiency direct thermal to electric energy conversion from radioisotope decay using selective emitters and spectrally tuned solar cells

    Science.gov (United States)

    Chubb, Donald L.; Flood, Dennis J.; Lowe, Roland A.

    1993-01-01

    Thermophotovoltaic (TPV) systems are attractive possibilities for direct thermal-to-electric energy conversion, but have typically required the use of black body radiators operating at high temperatures. Recent advances in both the understanding and performance of solid rare-earth oxide selective emitters make possible the use of TPV at temperatures as low as 1200K. Both selective emitter and filter system TPV systems are feasible. However, requirements on the filter system are severe in order to attain high efficiency. A thin-film of a rare-earth oxide is one method for producing an efficient, rugged selective emitter. An efficiency of 0.14 and power density of 9.2 W/KG at 1200K is calculated for a hypothetical thin-film neodymia (Nd2O3) selective emitter TPV system that uses radioisotope decay as the thermal energy source.

  6. In vitro antiplaque activity of octenidine dihydrochloride (WIN 41464-2) against preformed plaques of selected oral plaque-forming microorganisms.

    Science.gov (United States)

    Slee, A M; O'Connor, J R

    1983-01-01

    The antibacterial activity of octenidine dihydrochloride (WIN 41464-2) against intact preformed in vitro plaques of four indigenous oral plaque-forming microorganisms, Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus, and Actinomyces naeslundii, was studied. Both absolute (plaque bactericidal index) and relative (chlorhexidine coefficient) indices of antiplaque efficacy were established. Octenidine dihydrochloride compared favorably with chlorhexidine digluconate with respect to overall antiplaque potency in this in vitro plaque bactericidal model. These data indicate that prudent selection of treatment concentration and duration and frequency of exposure should provide an effective means to aid in controlling dental caries and Actinomyces-associated disease in vivo. PMID:6847170

  7. A selective androgen receptor modulator enhances male-directed sexual preference, proceptive behavior, and lordosis behavior in sexually experienced, but not sexually naive, female rats.

    Science.gov (United States)

    Kudwa, A E; López, F J; McGivern, R F; Handa, R J

    2010-06-01

    Androgens influence many aspects of reproductive behavior, including sexual preference of females for males. In oophorectomized women with sexual desire disorder, testosterone patches improve libido, but their use is limited because of adverse side effects. Selective androgen receptor modulators offer an improved safety profile for both sexes: enhancing libido and muscle and bone growth in a manner similar to steroidal androgens but with fewer adverse effects, such as hirsutism, acne, and prostate growth. The current study investigated the action of a novel selective androgen receptor modulator (LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one]) on male-directed sexual preference, proceptivity, and lordosis behavior of female rats. LGD-3303 is a nonsteroidal, nonaromatizable, highly selective ligand for the androgen receptor and effectively crosses the blood-brain barrier. Gonadectomized female rats were treated with LGD-3303 (3-30 mg/kg) or vehicle by daily oral gavage. Results showed that LGD-3303 treatment enhanced sexual preference of females for males but only if females had previous sexual experience. This occurred after 1 or 7 d of treatment. In contrast, preference for males was inhibited by LGD-3303 treatments of sexually naive females. The LGD-3303 increase in male preference was blocked by pretreatment with the androgen receptor antagonist flutamide. LGD-3303 treatment increased lordosis and proceptivity behaviors in ovariectomized females primed with suboptimal doses of estradiol benzoate plus progesterone. These data support the concept that LGD-3303 can stimulate aspects of female sexual behavior and may serve as a potential therapeutic for women with sexual desire disorders.

  8. History-dependent Selection of Primary Dendritic Spacing in Directionally Solidified Alloy

    Institute of Scientific and Technical Information of China (English)

    Linlin WANG; Xin LIN; Guolu DING; Lilin WANG; Weidong HUANG

    2007-01-01

    Directional solidification experiments were carried out for succinonitrile-1.0 wt pct acetone alloy with the orientation of dendritic arrays being not parallel to the direction of the temperature gradient. Experimental results show that there exists an allowable range of primary dendritic spacing under a given growth condition.The average primary spacing depends not only on the current growth conditions but also on the way by which the conditions were achieved. The upper limit of the allowable range becomes smaller in comparison with that with direction of dendrite arrays parallel to the direction of the temperature gradient, which means that the history-dependence of dendritic growth is weaker under this condition. The lower limit obtained is compared with a self-consistent model, which shows a good agreement with experimental results.

  9. Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study.

    Science.gov (United States)

    Javed, Ibrahim; Hussain, Syed Zajif; Shahzad, Atif; Khan, Jahanzeb Muhammad; Ur-Rehman, Habib; Rehman, Mubashar; Usman, Faisal; Razi, Muhammad Tahir; Shah, Muhammad Raza; Hussain, Irshad

    2016-05-01

    We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site.

  10. Direct and correlated effects of selection on flight after exposure to thermal stress in Drosophila melanogaster.

    Science.gov (United States)

    Krebs, Robert A; Thompson, Kimberly A

    2006-01-01

    To demonstrate how insects may adapt to ecologically relevant levels of heat stress, we performed artificial selection on the ability of Drosophila melanogaster to fly after an exposure to a high but non-lethal thermal stress. Both tolerance and intolerance to heat stress arose very quickly, as only a few generations of selection were necessary to cause significant separation between high and low lines for heat tolerance. Estimates of heritability based on the lines artificially selected for increased flight ability ranged from 0.024 to 0.052, while estimates of heritability based on the lines selected for the inability to fly after heat stress varied between 0.035 and 0.091. Reciprocal F1 crosses among these lines revealed strong additive effects of one or more autosomes and a weaker X-chromosome effect. This variation apparently affected flight specifically; neither survival to a more extreme stress nor knockdown by high temperature changed between lines selected for high and low heat tolerance as measured by flight ability. As the well-studied heat-shock response is associated with heat tolerance as measured by survival and knockdown, the aspects of the stress physiology that actually affect flight ability remains unknown.

  11. Output of continuous directed selection aimed at short stem development in Winter Rye (Secale cereale L.

    Directory of Open Access Journals (Sweden)

    В. В. Скорик

    2013-05-01

    Full Text Available The article provides progress report on the barley of F3к-10029/Saratovske 4 height decreasing throughout 1974 to 2012 by way of selecting plants of the shortest stem. 38 years of selecting the shortest stem genotypes cut down plant height by 5,7 times at the background of dominant Hl gene expression. Average plant height during 38 breeding cycles was descending by 2,69 cm, but this was not an even trend. New creative donor for ultimate short stem characteristic, Gnome 3, has been developed, with Hl-3Hl-3alleles designation. Relative impact on the efficacy of minus-selection by the plant height of the selection differential (38,00% and inheritance coefficient in its narrow sense (14,56% is established. Efficiency of the selection is realized with the decrease of winter rye height plants by 72,08% as expected by the relative breeding forecast. Analyzes is completed for 11 genetic and statistical clusters of average utilitarian characteristics of Gnome 3 ultra short stem rye over the period from 1974 to 2012.

  12. Liquid chromatography tandem mass spectrometry determination of selected synthetic cathinones and two piperazines in oral fluid. Cross reactivity study with an on-site immunoassay device.

    Science.gov (United States)

    de Castro, Ana; Lendoiro, Elena; Fernández-Vega, Hadriana; Steinmeyer, Stefan; López-Rivadulla, Manuel; Cruz, Angelines

    2014-12-29

    Since the past few years, several synthetic cathinones and piperazines have been introduced into the drug market to substitute illegal stimulant drugs such as amphetamine and derivatives or cocaine due to their unregulated situation. These emerging drugs are not usually included in routine toxicological analysis. We developed and validated a LC-MS/MS method for the determination of methedrone, methylone, mephedrone, 3,4-methylenedioxypyrovalerone (MDPV), fluoromethcathinone, fluoromethamphetamine, 1-(3-chlorophenyl)piperazine (mCPP) and 3-trifluoromethylphenylpiperazine (TFMPP) in oral fluid. Sample extraction was performed using Strata X cartridges. Chromatographic separation was achieved in 10min using an Atlantis(®) T3 column (100mm×2.1mm, 3μm), and formic acid 0.1% and acetonitrile as mobile phase. The method was satisfactorily validated, including selectivity, linearity (0.2-0.5 to 200ng/mL), limits of detection (0.025-0.1ng/mL) and quantification (0.2-0.5ng/mL), imprecision and accuracy in neat oral fluid (%CV=0.0-12.7% and 84.8-103.6% of target concentration, respectively) and in oral fluid mixed with Quantisal™ buffer (%CV=7.2-10.3% and 80.2-106.5% of target concentration, respectively), matrix effect in neat oral fluid (-11.6 to 399.7%) and in oral fluid with Quantisal™ buffer (-69.9 to 131.2%), extraction recovery (87.9-134.3%) and recovery from the Quantisal™ (79.6-107.7%), dilution integrity (75-99% of target concentration) and stability at different conditions (-14.8 to 30.8% loss). In addition, cross reactivity produced by the studied synthetic cathinones in oral fluid using the Dräger DrugTest 5000 was assessed. All the analytes produced a methamphetamine positive result at high concentrations (100 or 10μg/mL), and fluoromethamphetamine also at low concentration (0.075μg/mL).

  13. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs).

    Science.gov (United States)

    van Gorp, Rick H; Schurgers, Leon J

    2015-11-17

    Vitamin K-antagonists (VKA) are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC) drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs). As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

  14. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs Versus Direct Oral Anticoagulants (DOACs

    Directory of Open Access Journals (Sweden)

    Rick H. van Gorp

    2015-11-01

    Full Text Available Vitamin K-antagonists (VKA are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs. As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

  15. Informative Gene Selection and Direct Classification of Tumor Based on Chi-Square Test of Pairwise Gene Interactions

    Directory of Open Access Journals (Sweden)

    Hongyan Zhang

    2014-01-01

    Full Text Available In efforts to discover disease mechanisms and improve clinical diagnosis of tumors, it is useful to mine profiles for informative genes with definite biological meanings and to build robust classifiers with high precision. In this study, we developed a new method for tumor-gene selection, the Chi-square test-based integrated rank gene and direct classifier (χ2-IRG-DC. First, we obtained the weighted integrated rank of gene importance from chi-square tests of single and pairwise gene interactions. Then, we sequentially introduced the ranked genes and removed redundant genes by using leave-one-out cross-validation of the chi-square test-based Direct Classifier (χ2-DC within the training set to obtain informative genes. Finally, we determined the accuracy of independent test data by utilizing the genes obtained above with χ2-DC. Furthermore, we analyzed the robustness of χ2-IRG-DC by comparing the generalization performance of different models, the efficiency of different feature-selection methods, and the accuracy of different classifiers. An independent test of ten multiclass tumor gene-expression datasets showed that χ2-IRG-DC could efficiently control overfitting and had higher generalization performance. The informative genes selected by χ2-IRG-DC could dramatically improve the independent test precision of other classifiers; meanwhile, the informative genes selected by other feature selection methods also had good performance in χ2-DC.

  16. Phosphine-directed C-H borylation reactions: facile and selective access to ambiphilic phosphine boronate esters.

    Science.gov (United States)

    Crawford, Kristina M; Ramseyer, Timothy R; Daley, Christopher J A; Clark, Timothy B

    2014-07-14

    Ambiphilic ligands have received considerable attention over the last two decades due to their unique reactivity as organocatalysts and ligands. The iridium-catalyzed C-H borylation of phosphines is described in which the phosphine is used as a directing group to provide selective formation of arylboronate esters with unique scaffolds of ambiphilic compounds. A variety of aryl and benzylic phosphines were subjected to the reaction conditions, selectively providing stable, isolable boronate esters upon protection of the phosphine as the borane complex. After purification, the phosphine-substituted boronate esters could be deprotected and isolated in pure form.

  17. Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report

    Science.gov (United States)

    Misaka, Kenji; Kishimoto, Takashi; Kawahigashi, Yuji; Sata, Michio; Nagao, Yumiko

    2016-01-01

    Hepatitis C virus (HCV) is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP) is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA) are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN)-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients. PMID:27920651

  18. Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report

    Directory of Open Access Journals (Sweden)

    Kenji Misaka

    2016-10-01

    Full Text Available Hepatitis C virus (HCV is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients.

  19. Exact and Direct Modeling Technique for Rotor-Bearing Systems with Arbitrary Selected Degrees-of-Freedom

    Directory of Open Access Journals (Sweden)

    Shilin Chen

    1994-01-01

    Full Text Available An exact and direct modeling technique is proposed for modeling of rotor-bearing systems with arbitrary selected degrees-of-freedom. This technique is based on the combination of the transfer and dynamic stiffness matrices. The technique differs from the usual combination methods in that the global dynamic stiffness matrix for the system or the subsystem is obtained directly by rearranging the corresponding global transfer matrix. Therefore, the dimension of the global dynamic stiffness matrix is independent of the number of the elements or the substructures. In order to show the simplicity and efficiency of the method, two numerical examples are given.

  20. Highly selective methodology for the direct conversion of aromatic aldehydes to glycol monoesters.

    Science.gov (United States)

    Sharghi, Hashem; Sarvari, Mona Hosseini

    2003-05-16

    Al(2)O(3)/MeSO(3)H (AMA) was found to be an extremely efficient reagent for the conversion of aromatic aldehydes and diols to glycol monoesters. The remarkable selectivity achieved with this reagent is an attractive feature of the present method.

  1. a simple k-map based variable selection scheme in the direct ...

    African Journals Online (AJOL)

    Dr Obe

    The procedure is based on the fact that if 2. X minterms (where x = 1, ... approach [3, 4, 5]. What has hindered ... selection scheme for solving the problem of partitioning the ... proposed k-map based variable partition criterion can be sumarised ...

  2. On dynamic selection of households for direct marketing based on Markov chain models with memory

    NARCIS (Netherlands)

    Otter, Pieter W.

    2007-01-01

    A simple, dynamic selection procedure is proposed, based on conditional, expected profits using Markov chain models with memory. The method is easy to apply, only frequencies and mean values have to be calculated or estimated. The method is empirically illustrated using a data set from a charitable

  3. Template-Directed Self-Assembly of Alkanethiol Monolayers: Selective Growth on Preexisting Monolayer Edges

    NARCIS (Netherlands)

    Sharpe, Ruben B.A.; Burdinski, Dirk; Huskens, Jurriaan; Zandvliet, Harold J.W.; Reinhoudt, David N.; Poelsema, Bene

    2007-01-01

    Self-assembled monolayers were investigated for their suitability as two-dimensional scaffolds for the selective growth of alkanethiol edge structures. Heterostructures with chemical contrast could be grown, whose dimensions were governed by both the initial pattern sizes and the process time. n-Oct

  4. Future Directions in Personality, Occupational and Medical Selection: Myths, Misunderstandings, Measurement, and Suggestions

    Science.gov (United States)

    Ferguson, Eamonn; Lievens, Filip

    2017-01-01

    This paper has two objectives: (1) presenting recent advances in personality theory whereby personality traits are conceptualized within a framework that focuses on the dynamic interactions of behaviour, biology, context, and states, and (2) discussing the implications of these developments for measurement and medical selection. We start by…

  5. Asymmetry in infants’ selective attention to facial features during visual processing of infant-directed speech

    Directory of Open Access Journals (Sweden)

    Nicholas A Smith

    2013-09-01

    Full Text Available Two experiments used eye tracking to examine how infant and adult observers distribute their eye gaze on videos of a mother producing infant- and adult-directed speech. Both groups showed greater attention to the eyes than to the nose and mouth, as well as an asymmetrical focus on the talker’s right eye for infant-directed speech stimuli. Observers continued to look more at the talker’s apparent right eye when the video stimuli were mirror flipped, suggesting that the asymmetry reflects a perceptual processing bias rather than a stimulus artifact, which may be related to cerebral lateralization of emotion processing.

  6. Direct Transaortic TEVAR: An Alternative Option for Selected Patients With Unsuitable Peripheral Access.

    Science.gov (United States)

    Botta, Luca; Bruschi, Giuseppe; Fratto, Pasquale; Margari, Vito; Solcia, Marco; Borgia, Francesco; Rampoldi, Antonio; Russo, Claudio Francesco

    2016-08-01

    Thoracic endovascular aortic repair (TEVAR) is effectively executed in patients with arch or descending aortic diseases. Peripheral access sites are preferably used as standard gates for TEVAR. Feasibility of a peripheral approach might need an intraoperative evaluation and alternative routes should have been carefully assessed. In this article, we report 2 successful cases of direct transaortic TEVAR, where stent grafts were directly introduced into the native ascending aorta without external conduits. A satisfactory result and the absence of aortic-related complications were observed at 2 and 5 years' follow-up, respectively.

  7. Molecular image-directed biopsies: improving clinical biopsy selection in patients with multiple tumors

    Science.gov (United States)

    Harmon, Stephanie A.; Tuite, Michael J.; Jeraj, Robert

    2016-10-01

    Site selection for image-guided biopsies in patients with multiple lesions is typically based on clinical feasibility and physician preference. This study outlines the development of a selection algorithm that, in addition to clinical requirements, incorporates quantitative imaging data for automatic identification of candidate lesions for biopsy. The algorithm is designed to rank potential targets by maximizing a lesion-specific score, incorporating various criteria separated into two categories: (1) physician-feasibility category including physician-preferred lesion location and absolute volume scores, and (2) imaging-based category including various modality and application-specific metrics. This platform was benchmarked in two clinical scenarios, a pre-treatment setting and response-based setting using imaging from metastatic prostate cancer patients with high disease burden (multiple lesions) undergoing conventional treatment and receiving whole-body [18F]NaF PET/CT scans pre- and mid-treatment. Targeting of metastatic lesions was robust to different weighting ratios and candidacy for biopsy was physician confirmed. Lesion ranked as top targets for biopsy remained so for all patients in pre-treatment and post-treatment biopsy selection after sensitivity testing was completed for physician-biased or imaging-biased scenarios. After identifying candidates, biopsy feasibility was evaluated by a physician and confirmed for 90% (32/36) of high-ranking lesions, of which all top choices were confirmed. The remaining cases represented lesions with high anatomical difficulty for targeting, such as proximity to sciatic nerve. This newly developed selection method was successfully used to quantitatively identify candidate lesions for biopsies in patients with multiple lesions. In a prospective study, we were able to successfully plan, develop, and implement this technique for the selection of a pre-treatment biopsy location.

  8. Effects of combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin on fulminant pseudomembranous colitis with septic shock.

    Science.gov (United States)

    Kimura, Yoshihide; Sato, Koichi; Tokuda, Hiroshi; Nakamura, Naka; Dohi, Yasuaki; Orito, Etsuro; Mizokami, Masashi

    2007-03-01

    We report 2 cases of fulminant pseudomembranous colitis with septic shock. The first case showed few symptoms, whereas the second case showed recurrence. Both cases rapidly developed shock and blood pressure was uncontrollable except with the use of pressor agents. Direct hemoperfusion using polymyxin B-immobilized fiber, which was previously demonstrated to have excellent therapeutic effects for the treatment of hypotension in septic shock by removing circulating lipopolysaccharide and oral vancomycin dramatically improved both cases' clinical status and decreased their APACHE II scores (from 18 to 8 and from 16 to 9 points, respectively). Therefore, we suggest that direct hemoperfusion using polymyxin B-immobilized fiber improved hypotension-correcting cytokine balance with adsorption of endogenous cannabinoids in serum. Although colectomy is often performed to treat fulminant pseudomembranous colitis with septic shock, direct hemoperfusion can be easily performed with little risk to the patient. These cases strongly indicated that our combination therapy provides an important treatment for fulminant pseudomembranous colitis with septic shock.

  9. Design, synthesis, and pharmacological evaluation of N-acylhydrazones and novel conformationally constrained compounds as selective and potent orally active phosphodiesterase-4 inhibitors.

    Science.gov (United States)

    Kümmerle, Arthur E; Schmitt, Martine; Cardozo, Suzana V S; Lugnier, Claire; Villa, Pascal; Lopes, Alexandra B; Romeiro, Nelilma C; Justiniano, Hélène; Martins, Marco A; Fraga, Carlos A M; Bourguignon, Jean-Jacques; Barreiro, Eliezer J

    2012-09-13

    Among a small series of tested N-acylhydrazones (NAHs), the compound 8a was selected as a selective submicromolar phosphodiesterase-4 (PDE4) inhibitor associated with anti-TNF-α properties measured both in vitro and in vivo. The recognition pattern of compound 8a was elucidated through molecular modeling studies based on the knowledge of the 3D-structure of zardaverine, a PDE4 inhibitor resembling the structure of 8a, cocrystallized with the PDE4. Based on further conformational analysis dealing with N-methyl-NAHs, a quinazoline derivative (19) was designed as a conformationally constrained NAH analogue and showed similar in vitro pharmacological profile, compared with 8a. In addition 19 was found active when tested orally in LPS-evoked airway hyperreactivity and fully confirmed the working hypothesis supporting this work.

  10. Investigation of selective realignment of the preferred magnetic direction in spin-valve layer stacks using laser radiation

    Energy Technology Data Exchange (ETDEWEB)

    Berthold, Isabel, E-mail: iberthol@hs-mittweida.de [Laserinstitut der Hochschule Mittweida, Hochschule Mittweida, Technikumplatz 17, 09648 Mittweida (Germany); Müller, Mathias; Klötzer, Sascha; Ebert, Robby [Laserinstitut der Hochschule Mittweida, Hochschule Mittweida, Technikumplatz 17, 09648 Mittweida (Germany); Thomas, Senoy; Matthes, Patrick; Albrecht, Manfred [Institute of Physics, Chemnitz University of Technology, 09107 Chemnitz (Germany); Exner, Horst [Laserinstitut der Hochschule Mittweida, Hochschule Mittweida, Technikumplatz 17, 09648 Mittweida (Germany)

    2014-05-01

    Selective realignment of the preferred magnetization direction in a laser micro structured GMR spin-valve layer system (Ni{sub 81}Fe{sub 19}/Co{sub 90}Fe{sub 10}/Cu/Co{sub 90}Fe{sub 10}/IrMn/Ni{sub 81}Fe{sub 19}) with a total film thickness of 23 nm was studied. For this, patterns of isolated microstructures (500 μm × 200 μm) were fabricated by laser ablation. These micropatterns were annealed using laser irradiation at a temperature above the IrMn Néel temperature. During laser annealing, the sample was subjected to an external magnetic field in order to selectively realign the magnetic direction of the reference layer. Two different laser assisted annealing techniques were investigated applying either continuous or pulsed laser systems. After laser annealing, the magnetic properties of the micropatterns were investigated using a magnetic microsensor and magneto optical Kerr effect set up.

  11. Mould Design and Material selection for Film Insert Moulding of Direct Methanol Fuel Cell Packaging

    DEFF Research Database (Denmark)

    Wöhner, Timo; Senkbeil, S.; Olesen, T. L.

    2015-01-01

    This paper presents the mould design for an injection moulding (IM) process for the production of a methanol container for the use in small, passive Direct Methanol Fuel Cell (DMFC) systems, which are intended to be used in behind-the-ear hearing aid systems. One of the crucial properties...

  12. Selective synthesis of thiodiglycol dicarboxylic acid esters via -TsOH/C-catalysed direct esterification

    Indian Academy of Sciences (India)

    Dahong Jiang; Min Huang

    2012-09-01

    The esterification of thiodiglycol and long alkyl-chain carboxylic acids is reported. Reaction of thiodiglycol with carboxylic acid via -TsOH/C-catalysed direct esterification afforded thiodiglycol dicarboxylic acid esters in good yields and chemoselectivity. The use of immobilized -TsOH on activated carbon as catalyst is crucial for the transformation.

  13. Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension.

    Science.gov (United States)

    Zhu, Gui-Dong; Gandhi, Viraj B; Gong, Jianchun; Thomas, Sheela; Woods, Keith W; Song, Xiaohong; Li, Tongmei; Diebold, R Bruce; Luo, Yan; Liu, Xuesong; Guan, Ran; Klinghofer, Vered; Johnson, Eric F; Bouska, Jennifer; Olson, Amanda; Marsh, Kennan C; Stoll, Vincent S; Mamo, Mulugeta; Polakowski, James; Campbell, Thomas J; Martin, Ruth L; Gintant, Gary A; Penning, Thomas D; Li, Qun; Rosenberg, Saul H; Giranda, Vincent L

    2007-06-28

    Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency. A novel and efficient synthetic route toward diversely substituted phenyl derivatives of 7 was developed utilizing a copper-mediated aziridine ring-opening reaction as the key step. To improve the selectivity of these Akt inhibitors over other protein kinases, a nitrogen atom was incorporated into selected phenyl analogues of 7 at the C-6 position of the methyl indazole scaffold. These modifications resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed.

  14. 78 FR 63464 - William D. Ford Federal Direct Loan Program Repayment Plan Selection Form; Extension of Public...

    Science.gov (United States)

    2013-10-24

    ...On October 3, 2013 the U.S. Department of Education published a 30-day comment period notice in the Federal Register (Page 61347, Column 2) seeking public comment for an information collection entitled, ``William D. Ford Federal Direct Loan Program Repayment Plan Selection Form''. ED is extending the comment period to November 18, 2013 due to the public's inability to access the collection at......

  15. Future directions in leadership - implications for the selection and development of senior leaders

    OpenAIRE

    Wallace, Anthony G.

    2003-01-01

    Approved for public release; distribution is unlimited This thesis examines contemporary ideas on leadership with special emphasis on how these concepts affect the development and selection of senior leaders. Leadership is a complex discipline and is described and analyzed through different leadership theories and models. Ongoing leadership research is promoting more integrative leadership constructs. Common features of effective leadership are present in the different models, as well as c...

  16. An improvement direction for filter selection techniques using information theory measures and quadratic optimization

    Directory of Open Access Journals (Sweden)

    Waad Bouaguel

    2012-08-01

    Full Text Available Filter selection techniques are known for their simplicity and efficiency. However this kind of methods doesn’t take into consideration the features inter-redundancy. Consequently the un-removed redundant features remain in the final classification model, giving lower generalization performance. In this paper we propose to use a mathematical optimization method that reduces inter-features redundancy and maximize relevance between each feature and the target variable.

  17. Future directions in leadership - implications for the selection and development of senior leaders

    OpenAIRE

    Wallace, Anthony G.

    2003-01-01

    Approved for public release; distribution is unlimited This thesis examines contemporary ideas on leadership with special emphasis on how these concepts affect the development and selection of senior leaders. Leadership is a complex discipline and is described and analyzed through different leadership theories and models. Ongoing leadership research is promoting more integrative leadership constructs. Common features of effective leadership are present in the different models, as well as c...

  18. Cellular Spacing Selection During the Directional Solidification of Binary Alloys. A Numerical Approach

    Science.gov (United States)

    Catalina, Adrian V.; Sen, S.; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    The evolution of cellular solid/liquid interfaces from an initially unstable planar front was studied by means of a two-dimensional computer simulation. The developed numerical model makes use of an interface tracking procedure and has the capability to describe the dynamics of the interface morphology based on local changes of the thermodynamic conditions. The fundamental physics of this formulation was validated against experimental microgravity results and the predictions of the analytical linear stability theory. The performed simulations revealed that in certain conditions, based on a competitive growth mechanism, an interface could become unstable to random perturbations of infinitesimal amplitude even at wavelengths smaller than the neutral wavelength, lambda(sub c), predicted by the linear stability theory. Furthermore, two main stages of spacing selection have been identified. In the first stage, at low perturbations amplitude, the selection mechanism is driven by the maximum growth rate of instabilities while in the second stage the selection is influenced by nonlinear phenomena caused by the interactions between the neighboring cells. Comparison of these predictions with other existing theories of pattern formation and experimental results will be discussed.

  19. Taiwanin C selectively inhibits arecoline and 4-NQO-induced oral cancer cell proliferation via ERK1/2 inactivation.

    Science.gov (United States)

    Lin, Kuan-Ho; Shibu, Marthandam Asokan; Kuo, Yueh-Hsiung; Chen, Yueh-Chiu; Hsu, Hsi-Hsien; Bau, Da-Tian; Chen, Ming-Cheng; Tu, Chuan-Chou; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2017-01-01

    Arecoline, the most abundant alkaloid in betel nut is known to promote abnormal proliferation of epithelial cells by enhancing epidermal growth factor receptor (EGFR) activation and cyclooxygenase-2 (COX2) expression. Taiwanin C, a naturally occurring lignan extracted from Taiwania cryptomerioides, has been found to be a potential inhibitor of COX2 expression. Based on the MTT assay results, taiwanin C was found to be effective in inhibiting the tumorous T28 cell than the non-tumorous N28 cells. The modulations in the expression of relevant proteins were determined to understand the mechanism induced by taiwanin C to inhibit T28 cell proliferation. The levels of activated EGFR and COX2 were found to be abnormally high in the T28 oral cancer cells. However, taiwanin C was found to inhibit the activation of EGFR and regulated other related downstream proteins and thereby inhibited the T28 cell proliferation. In conclusion the results indicate that taiwanin C suppresses COX2-EGFR and enhances P27 pathways to suppress arecoline induced oral cancer cell proliferation via ERK1/2 inactivation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 62-69, 2017. © 2015 Wiley Periodicals, Inc.

  20. Twenty years of artificial directional selection have shaped the genome of the Italian Large White pig breed.

    Science.gov (United States)

    Schiavo, G; Galimberti, G; Calò, D G; Samorè, A B; Bertolini, F; Russo, V; Gallo, M; Buttazzoni, L; Fontanesi, L

    2016-04-01

    In this study, we investigated at the genome-wide level if 20 years of artificial directional selection based on boar genetic evaluation obtained with a classical BLUP animal model shaped the genome of the Italian Large White pig breed. The most influential boars of this breed (n = 192), born from 1992 (the beginning of the selection program of this breed) to 2012, with an estimated breeding value reliability of >0.85, were genotyped with the Illumina Porcine SNP60 BeadChip. After grouping the boars in eight classes according to their year of birth, filtered single nucleotide polymorphisms (SNPs) were used to evaluate the effects of time on genotype frequency changes using multinomial logistic regression models. Of these markers, 493 had a PBonferroni  genome. The largest proportion of the 493 SNPs was on porcine chromosome (SSC) 7, SSC2, SSC8 and SSC18 for a total of 204 haploblocks. Functional annotations of genomic regions, including the 493 shifted SNPs, reported a few Gene Ontology terms that might underly the biological processes that contributed to increase performances of the pigs over the 20 years of the selection program. The obtained results indicated that the genome of the Italian Large White pigs was shaped by a directional selection program derived by the application of methodologies assuming the infinitesimal model that captured a continuous trend of allele frequency changes in the boar population.

  1. Oral steroid contraception.

    Science.gov (United States)

    Sech, Laura A; Mishell, Daniel R

    2015-11-01

    Oral steroid contraception is a popular method of family planning worldwide. Over the past several decades, this method of contraception has changed significantly by decreasing the estrogen dose, changing the progestin component, and reducing the hormone free interval. Despite the popularity of oral steroid contraception, there has been much criticism regarding the associated risks of venous thromboembolism and stroke. Despite these established, yet uncommon risks, oral steroid contraception has many important health benefits. This review highlights the available formulations of oral contraceptives along with their evidence-based associated risks and benefits. Highlights regarding future directions for development of novel oral contraceptives are also addressed.

  2. Direct Patterning of Colloidal Quantum-Dot Thin Films for Enhanced and Spectrally Selective Out-Coupling of Emission

    Science.gov (United States)

    2017-01-01

    We report on a template-stripping method for the direct surface patterning of colloidal quantum-dot thin films to produce highly luminescent structures with feature sizes less than 100 nm. Through the careful design of high quality bull’s-eye gratings we can produce strong directional beaming (10° divergence) with up to 6-fold out-coupling enhancement of spontaneous emission in the surface-normal direction. A transition to narrow single-mode lasing is observed in these same structures at thresholds as low as 120 μJ/cm2. In addition, we demonstrate that these structures can be fabricated on flexible substrates. Finally, making use of the size-tunable character of colloidal quantum dots, we demonstrate spectrally selective out-coupling of light from mixed quantum-dot films. Our results provide a straightforward route toward significantly improved optical properties of colloidal quantum-dot assemblies.

  3. Identification and characterisation of novel SNP markers in Atlantic cod: Evidence for directional selection

    Directory of Open Access Journals (Sweden)

    Fjalestad Kjersti T

    2008-02-01

    Full Text Available Abstract Background The Atlantic cod (Gadus morhua is a groundfish of great economic value in fisheries and an emerging species in aquaculture. Genetic markers are needed to identify wild stocks in order to ensure sustainable management, and for marker-assisted selection and pedigree determination in aquaculture. Here, we report on the development and evaluation of a large number of Single Nucleotide Polymorphism (SNP markers from the alignment of Expressed Sequence Tag (EST sequences in Atlantic cod. We also present basic population parameters of the SNPs in samples of North-East Arctic cod and Norwegian coastal cod obtained from three different localities, and test for SNPs that may have been targeted by natural selection. Results A total of 17,056 EST sequences were used to find 724 putative SNPs, from which 318 segregating SNPs were isolated. The SNPs were tested on Atlantic cod from four different sites, comprising both North-East Arctic cod (NEAC and Norwegian coastal cod (NCC. The average heterozygosity of the SNPs was 0.25 and the average minor allele frequency was 0.18. FST values were highly variable, with the majority of SNPs displaying very little differentiation while others had FST values as high as 0.83. The FST values of 29 SNPs were found to be larger than expected under a strictly neutral model, suggesting that these loci are, or have been, influenced by natural selection. For the majority of these outlier SNPs, allele frequencies in a northern sample of NCC were intermediate between allele frequencies in a southern sample of NCC and a sample of NEAC, indicating a cline in allele frequencies similar to that found at the Pantophysin I locus. Conclusion The SNP markers presented here are powerful tools for future genetics work related to management and aquaculture. In particular, some SNPs exhibiting high levels of population divergence have potential to significantly enhance studies on the population structure of Atlantic cod.

  4. Selective oxygenation of alkynes: a direct approach to diketones and vinyl acetate.

    Science.gov (United States)

    Xia, Xiao-Feng; Gu, Zhen; Liu, Wentao; Wang, Ningning; Wang, Haijun; Xia, Yongmei; Gao, Haiyan; Liu, Xiang

    2014-12-28

    Arylalkynes can be converted into α-diketones with the use of a copper catalyst, and also be transformed into vinyl acetates under metal-free conditions, both in the presence of PhI(OAc)2 as an oxidant at room temperature. A series of substituted α-diketones were prepared in moderate to good yields. A variety of vinyl halides could be regio- and stereo-selectively synthesized under mild conditions, and I, Br and Cl could be all easily embedded into the alkynes.

  5. Direct use values of selected vegetation resources in the Okavango delta wetland

    Directory of Open Access Journals (Sweden)

    G Mmopelwa

    2011-08-01

    Full Text Available The economic benefits generated by wetlands and the costs associated with their degradation or loss are frequently overlooked. This often leads to decisions that stimulate wetland conversion and degradation.  An important step towards correcting this situation and countering this neglect is to establish the true values of a wetland’s ecosystem goods and services.  This study attempts to estimate the direct use values of native plants, such as palm leaves for basketry, grass for thatching, fuelwood, edible fruits and plant parts used by three villages adjacent to the Okavango Delta during the 2003 calendar year.  Other sources of ecosystem goods and services, such as fishing, floodplain farming and tourism, were not considered in this study.  The average annual value per household of these harvested resources is generally higher than that of similar resources found in other southern African wetlands, owing to higher consumption rates. The overall total direct use value of plant resources, including household income contributions “in kind”, was estimated at US$1 434 per household for 2003 (or US$43.41/ha. This value is almost equal to the average household financial income of US$1 416/year. The net present value of the overall benefit from the direct use of the vegetative resources is estimated at US$101.9 million. This clearly indicates the value of the use of natural resources and their contribution to livelihoods and quality of life.  This value is so significant that economic development planners ought to incorporate it into development planning. They should not conceive infrastructure development that would jeopardise the communities’ access to these natural resources without any well-developed mitigation strategy.

  6. Direct determination of triamterene by potentiometry using a coated wire selective electrode.

    Science.gov (United States)

    Arvand, M; Mousavi, M F; Zanjanchi, M A; Shamsipur, M

    2003-12-04

    A coated wire triamterene-selective electrode based on the incorporation of a triamterene-tetraphenylborate ion-pair in a poly(vinylchloride) coating membrane was constructed. The influence of membrane composition, temperature, pH of the test solution, and foreign ions on the electrode performance were investigated. The electrode showed a Nernstian response over a triamterene concentration range from 1.0 x 10(-6) to 3.5 x 10(-2) M, at 25 degrees C, and was found to be very selective, precise, and usable within the pH range 4.5-7.5. The standard electrode potentials, E degrees, were determined at 15, 20, 25, 30, 35, 40 and 45 degrees C and used to calculate the isothermal temperature coefficient (dE degrees /dt) of the electrode. Temperatures higher than 45 degrees C seriously affected the electrode performance. The electrode was successfully applied to the potentiometric determination of triamterene hydrochloride both in pure solutions and in pharmaceutical preparations.

  7. Future directions in personality, occupational and medical selection: myths, misunderstandings, measurement, and suggestions.

    Science.gov (United States)

    Ferguson, Eamonn; Lievens, Filip

    2017-02-20

    This paper has two objectives: (1) presenting recent advances in personality theory whereby personality traits are conceptualized within a framework that focuses on the dynamic interactions of behaviour, biology, context, and states, and (2) discussing the implications of these developments for measurement and medical selection. We start by presenting evidence that traits are no longer regarded as stable deterministic predictors of behaviour. Instead, traits are found to change across generations, the life span, and in response to environmental contingencies. Thus, there is an urgent need to explore how traits change as function of medical education. Second, drawing on recent theory and research (behavioural reaction norms and the density distribution model) we highlight evidence to show how the expression of trait relevant behaviour is dependent on context, and is distributed with an average (typical behaviour or personality) and a variance (plasticity or adaptability), with traditional personality measure associated with typical responding. Third, we demystify that some traits are better than others showing that so-called "good" traits have a dark-side. Fourth, we show how these developments impact on how personality might be assessed, thereby presenting recent evidence on the use of contextualized personality measures, situational judgment tests, other reports, and implicit measures. Throughout the paper, we outline the key implications of these developments for medical selection practices.

  8. Development of goal-directed action selection guided by intrinsic motivations: an experiment with children.

    Science.gov (United States)

    Taffoni, Fabrizio; Tamilia, Eleonora; Focaroli, Valentina; Formica, Domenico; Ricci, Luca; Di Pino, Giovanni; Baldassarre, Gianluca; Mirolli, Marco; Guglielmelli, Eugenio; Keller, Flavio

    2014-07-01

    Action selection is extremely important, particularly when the accomplishment of competitive tasks may require access to limited motor resources. The spontaneous exploration of the world plays a fundamental role in the development of this capacity, providing subjects with an increasingly diverse set of opportunities to acquire, practice and refine the understanding of action-outcome connection. The computational modeling literature proposed a number of specific mechanisms for autonomous agents to discover and target interesting outcomes: intrinsic motivations hold a central importance among those mechanisms. Unfortunately, the study of the acquisition of action-outcome relation was mostly carried out with experiments involving extrinsic tasks, either based on rewards or on predefined task goals. This work presents a new experimental paradigm to study the effect of intrinsic motivation on action-outcome relation learning and action selection during free exploration of the world. Three- and four-year-old children were observed during the free exploration of a new toy: half of them were allowed to develop the knowledge concerning its functioning; the other half were not allowed to learn anything. The knowledge acquired during the free exploration of the toy was subsequently assessed and compared.

  9. Highly oil-producing microalgae selected through directed-evolution on a microfludic chip

    Science.gov (United States)

    Mestler, Troy; Estevez-Torres, Andre; Lambert, Guillaume; Austin, Robert H.

    2009-03-01

    Some species of photosynthetic microalgae produce signi?cant amounts of oil which can be easily converted to diesel fuel. However, as it stands today, biodiesel is signi?cantly more expensive than fossil fuels. We wish to improve the oil yield and production rate of a single species of microalgae through directed evolution. We propose to utilize our microfabication technology to create microhabitats to control the nutrient environment of the species, monitor oil production through Raman Spectroscopy, and punish colonies of algae which have low oil yield. We believe this process will produce a mutant species with a high oil yield.

  10. Direct laser cladding of stellite coatings and selection of process parameters

    Science.gov (United States)

    Jendrzejewski, Rafal; Sliwinski, Gerard; Conde, Ana; Navas, Carmen; de Damborenea, Juan J.

    2005-03-01

    The direct laser cladding technique is applied for preparation of Co-based stellite SF6 protective coatings on the chromium steel base of a composition designed for the steam turbine blades. The cw 1.5 kW CO2 laser stand equipped with the multi-stream nozzle characterized by a powder feeding coaxial with the laser beam is used. It is observed that the increase of the base preheating temperature and the average temperature of the coating reduces the cracking susceptibility of the laser clads. This is accompanied by the decrease of the corrosion and wear resistances.

  11. Mould Design and Material selection for Film Insert Moulding of Direct Methanol Fuel Cell Packaging

    DEFF Research Database (Denmark)

    Wöhner, Timo; Senkbeil, S.; Olesen, T. L.;

    2015-01-01

    of this container is to enable venting of CO2, which is produced during the use of the DMFC system. This attribute is realized by a functional film insert in the form of a microporous, oleophobic membrane, which covers a venting hole in the injection moulded part of the container. The mould was designed to allow......This paper presents the mould design for an injection moulding (IM) process for the production of a methanol container for the use in small, passive Direct Methanol Fuel Cell (DMFC) systems, which are intended to be used in behind-the-ear hearing aid systems. One of the crucial properties...

  12. Direct Fluorescent Detection of Blood Potassium by Ion-Selective Formation of Intermolecular G-Quadruplex and Ligand Binding.

    Science.gov (United States)

    Yang, Le; Qing, Zhihe; Liu, Changhui; Tang, Qiao; Li, Jishan; Yang, Sheng; Zheng, Jing; Yang, Ronghua; Tan, Weihong

    2016-09-20

    G-quadruplex analogues have been widely used as molecular tools for detection of potassium ion (K(+)). However, interference from a higher concentration of sodium ion (Na(+)), enzymatic degradation of the oligonucleotide, and background absorption and fluorescence of blood samples have all limited the use of G-quadruplex for direct detection of K(+) in blood samples. Here, we reported, for the first time, an intermolecular G-quadruplex-based assay capable of direct fluorescent detection of blood K(+). Increased stringency of intermolecular G-quadruplex formation based on our screened G-rich oligonucleotide (5'-TGAGGGA GGGG-3') provided the necessary selectivity for K(+) against Na(+) at physiological ion level. To increase long-term stability of oligonucleotide in blood, the screened oligonucleotide was modified with an inverted thymine nucleotide whose 3'-terminus was connected to the 3'-terminus of the upstream nucleotide, acting as a blocking group to greatly improve antinuclease stability. Lastly, to avoid interference from background absorption and autofluorescence of blood, a G-quadruplex-binding, two-photon-excited ligand, EBMVC-B, was synthesized and chosen as the fluorescence reporter. Thus, based on selective K(+) ion-induced formation of intermolecular G-quadruplex and EBMVC-B binding, this approach could linearly respond to K(+) from 0.5 to 10 mM, which matches quite well with the physiologically relevant concentration of blood K(+). Moreover, the system was highly selective for K(+) against other metal ions, including Na(+), Ca(2+), Mg(2+), Zn(2+) common in blood. The practical application was demonstrated by direct detection of K(+) from real blood samples by two-photon fluorescence technology. To the best of our knowledge, this is the first attempt to exploit molecular G-quadruplex-based fluorescent sensing for direct assay of blood target. As such, we expect that it will promote the design and practical application of similar DNA-based sensors in

  13. ARQ 092, an orally-available, selective AKT inhibitor, attenuates neutrophil-platelet interactions in sickle cell disease.

    Science.gov (United States)

    Kim, Kyungho; Li, Jing; Barazia, Andrew; Tseng, Alan; Youn, Seock-Won; Abbadessa, Giovanni; Yu, Yi; Schwartz, Brian; Andrews, Robert K; Gordeuk, Victor R; Cho, Jaehyung

    2017-02-01

    Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target in thrombo-inflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets. Treatment of isolated platelets and neutrophils with ARQ 092 inhibited heterotypic cell-cell aggregation under shear conditions. Intravital microscopic studies demonstrated that short-term oral administration of ARQ 092 or hydroxyurea, a major therapy for sickle cell disease, diminishes heterotypic cell-cell interactions in venules of sickle cell disease mice challenged with tumor necrosis factor-α. Co-administration of hydroxyurea and ARQ 092 further reduced the adhesive function of neutrophils in venules and neutrophil transmigration into alveoli, inhibited expression of E-selectin and intercellular adhesion molecule-1 in cremaster vessels, and improved survival in these mice. Ex vivo studies in sickle cell disease mice suggested that co-administration of hydroxyurea and ARQ 092 efficiently blocks neutrophil and platelet activation and that the beneficial effect of hydroxyurea results from nitric oxide production. Our results provide important evidence that ARQ 092 could be a novel drug for the prevention and treatment of acute vaso-occlusive complications in patients with sickle cell disease.

  14. ARQ 092, an orally-available, selective AKT inhibitor, attenuates neutrophil-platelet interactions in sickle cell disease

    Science.gov (United States)

    Kim, Kyungho; Li, Jing; Barazia, Andrew; Tseng, Alan; Youn, Seock-Won; Abbadessa, Giovanni; Yu, Yi; Schwartz, Brian; Andrews, Robert K.; Gordeuk, Victor R.; Cho, Jaehyung

    2017-01-01

    Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target in thrombo-inflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50–500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets. Treatment of isolated platelets and neutrophils with ARQ 092 inhibited heterotypic cell-cell aggregation under shear conditions. Intravital microscopic studies demonstrated that short-term oral administration of ARQ 092 or hydroxyurea, a major therapy for sickle cell disease, diminishes heterotypic cell-cell interactions in venules of sickle cell disease mice challenged with tumor necrosis factor-α. Co-administration of hydroxyurea and ARQ 092 further reduced the adhesive function of neutrophils in venules and neutrophil transmigration into alveoli, inhibited expression of E-selectin and intercellular adhesion molecule-1 in cremaster vessels, and improved survival in these mice. Ex vivo studies in sickle cell disease mice suggested that co-administration of hydroxyurea and ARQ 092 efficiently blocks neutrophil and platelet activation and that the beneficial effect of hydroxyurea results from nitric oxide production. Our results provide important evidence that ARQ 092 could be a novel drug for the prevention and treatment of acute vaso-occlusive complications in patients with sickle cell disease. PMID:27758820

  15. Development of a method for the direct fermentation of semolina by selected sourdough lactic acid bacteria.

    Science.gov (United States)

    Alfonzo, Antonio; Urso, Valeria; Corona, Onofrio; Francesca, Nicola; Amato, Gaetano; Settanni, Luca; Di Miceli, Giuseppe

    2016-12-19

    Three obligately heterofermentative lactic acid bacteria (LAB) strains (Lactobacillus sanfranciscensis PON100336, Leuconostoc citreum PON10079 and Weissella cibaria PON10030) were used in this study as a multi-species starter culture for sourdough production. The starter inoculum was prepared and propagated in sterile semolina extract (SSE) broth. Acidification kinetics, microbiological counts detected on specific media for sourdough LAB, polymorphic profile comparison and species-specific PCRs evidenced a stability of the liquid inoculum over time determining its suitability for direct addition to semolina. In order to validate this innovative method for the production of durum wheat (Triticum durum Desf) sourdoughs, 15 semolinas (from ten old and five modern genotypes cultivated in Sicily, southern Italy) were used to prepare the SSEs and to produce sourdoughs and finally breads. Chemical and microbiological analyses of the sourdoughs and the evaluation of the quality parameters (weight loss, height, crumb and crust colour, image analysis and volatile organic compound generation) of the resulting breads indicated that the direct addition of the liquid inocula propagated in SSE is a valuable method to stabilise the production of sourdoughs. The differences registered during the technological characterisation of the breads were underlined by the sensory tests and the multivariate analysis and are mainly imputable to the type of semolina.

  16. MiR-206 functions as a tumor suppressor and directly targets K-Ras in human oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lin FO

    2014-09-01

    Full Text Available Feiou Lin,1 Linjie Yao,2 Jin Xiao,3 DengFeng Liu,3 Zhenyu Ni11Department of Orthodontics, 2Department of Pedodontics, 3Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaPurpose: MicroRNA-206 (miR-206 has been proven to be downregulated in many human malignancies and is correlated with tumor progression. However, the roles of miR-206 and its related molecular mechanisms in oral squamous cell carcinoma (OSCC are still unclear. Thus, the aim of this study was to explore the effects of miR-206 in OSCC tumorigenesis and development.Methods: Quantitative real-time polymerase chain reaction was used to detect miR-206 expression in OSCC cell lines and primary tumor tissues. The association of miR-206 expression with clinicopathological factors and prognosis was also analyzed. In addition, the effects of miR-206 on the biological behavior of OSCC cells were investigated. Lastly, the potential regulatory function of miR-206 on K-Ras expression was confirmed.Results: MiR-206 expression was significantly downregulated in OSCC tissue samples and cell lines (both P<0.001. Decreased miR-206 expression was significantly associated with advanced tumor node metastasis (TNM stage, advanced T classifications (ie, size and/or extent of the primary tumor, positive N classification (ie, spread to regional lymph nodes, and shorter overall survival. In addition, upregulation of miR-206 in Tca8113 cells was able to reduce cell proliferation, invasion, and migration and promote cell apoptosis in vitro. Further, K-Ras was confirmed as a direct target of miR-206 by using luciferase reporter assay.Conclusion: These findings indicate that miR-206 may act as a tumor suppressor in OSCC and could serve as a novel therapeutic agent for miR-based therapy.Keywords: miR-206, oral squamous cell carcinoma, prognosis, proliferation, apoptosis, invasion

  17. Influence of the direction of selective laser sintering on machinability of parts from 316L steel

    Science.gov (United States)

    Alexeev, V. P.; Balyakin, A. V.; Khaimovich, A. I.

    2017-02-01

    This work presents the results of research of the impact of layer-by-layer growing of workpieces made of 316L steel on their machinability. The results of determination of residual stresses and measurement of hardness of the workpieces grown have been demonstrated. A series of experimental studies has been performed in order to determine the cutting force which occurs in the process of machining. The microstructure of the workpieces grown has been examined. It has been shown that the workpieces machined using Selective Laser Melting technology have the microstructure which is a totality of ‘microwelded seams’, which have a significant influence on the behavior of deformation processes in case of machining. The studies have shown that in case of lateral milling of the horizontally grown workpiece, the codirectional microwelded borders prevent any significant deformation of the misalignment which increases the cutting force by up to 10% as compared with milling of the vertically grown workpiece.

  18. Dendrite Spacing Selection during Directional Solidification of Pivalic Acid-Ethanol System

    Institute of Scientific and Technical Information of China (English)

    Myung-Jin Suk; Young-Min Park; Youn-Che Kim

    2008-01-01

    Unidirectional solidification of pivalic acid (PVA)-ethanol (Eth) mixture was performed to examine whether an allowable range of primary dendrite spacing definitely exists at a given growth velocity and how the range is history-dependent. PVA-0.59 wt pct Eth was unidirectionally solidified in the range of growth velocity 0.5-64 μm/s at the temperature gradient of 2.3 K/mm. Sequential change in growth velocity was imposed to determine the upper and lower limits for the allowable range of stable spacing. An allowable range of the steady state primary spacing was observed at a given growth velocity, and the extent of the range seems to be dependent on the degree to which step-increase or step-decrease in growth velocity is accomplished. As the degree of sequential change in growth velocity increases, the history-dependence of the selection for the primary dendrite spacing tends to disappear.

  19. Why Is Oral Health Important for Women?

    Science.gov (United States)

    ... About | Contact InfoBites Quick Reference Learn more Children's Oral Health Mouth Breathing Can Cause Major Health Problems Over ... delivered directly to your desktop! more... Why Is Oral Health Important for Women? Article Chapters Why Is Oral ...

  20. Why Is Oral Health Important for Men?

    Science.gov (United States)

    ... About | Contact InfoBites Quick Reference Learn more Children's Oral Health Mouth Breathing Can Cause Major Health Problems Over ... delivered directly to your desktop! more... Why is Oral Health Important for Men? Article Chapters Why is Oral ...

  1. Selective directed self-assembly of coexisting morphologies using block copolymer blends

    Science.gov (United States)

    Stein, A.; Wright, G.; Yager, K. G.; Doerk, G. S.; Black, C. T.

    2016-08-01

    Directed self-assembly (DSA) of block copolymers is an emergent technique for nano-lithography, but is limited in the range of structures possible in a single fabrication step. Here we expand on traditional DSA chemical patterning. A blend of lamellar- and cylinder-forming block copolymers assembles on specially designed surface chemical line gratings, leading to the simultaneous formation of coexisting ordered morphologies in separate areas of the substrate. The competing energetics of polymer chain distortions and chemical mismatch with the substrate grating bias the system towards either line/space or dot array patterns, depending on the pitch and linewidth of the prepattern. This is in contrast to the typical DSA, wherein assembly of a single-component block copolymer on chemical templates generates patterns of either lines/spaces (lamellar) or hexagonal dot arrays (cylinders). In our approach, the chemical template encodes desired local spatial arrangements of coexisting design motifs, self-assembled from a single, sophisticated resist.

  2. Smart Grids – selected objectives and directions of distribution system operator actions

    Directory of Open Access Journals (Sweden)

    Rafał Czyżewski

    2012-03-01

    Full Text Available The paper presents various aspects of the implementation of Smart Grids from the distribution system operator standpoint. It discusses legal conditions of the Smart Grids implementation and their impact on the implementation timing. It describes the current state of the distribution grid and operations management systems infrastructure, indicating the desired direction of their development. It describes the preferred model of interrelations between grid operators and other key stakeholders, especially in the context of the expected establishment of balancing areas. It points out to the relevance of standardization and to the assurance of security of implemented Smart Grid solutions. It also specifies the barriers, which in the authors’ opinion could impede the Smart Grids deployment.

  3. SHAPE SELECTIVE NANO-CATALYSTS: TOWARD DIRECT METHANOL FUEL CELLS APPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Murph, S.

    2010-06-16

    A series of bimetallic core-shell-alloy type Au-Pt nanomaterials with various morphologies, aspect ratios and compositions, were produced in a heterogenous epitaxial fashion. Gold nanoparticles with well-controlled particle size and shape, e.g. spheres, rods and cubes, were used as 'seeds' for platinum growth in the presence of a mild reducing agent, ascorbic acid and a cationic surfactant cethyltrimethyl ammonium bromide (CTAB). The reactions take place in air and water, and are quick, economical and amenable for scaling up. The synthesized nanocatalysts were characterized by electron microscopy techniques and energy dispersive X-ray analysis. Nafion membranes were embedded with the Au-Pt nanomaterials and analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM) for their potential in direct methanol fuel cells applications.

  4. A direct approach to generalised multiple mapping conditioning for selected turbulent diffusion flame cases

    Science.gov (United States)

    Sundaram, Brruntha; Klimenko, Alexander Yuri; Cleary, Matthew John; Ge, Yipeng

    2016-07-01

    This work presents a direct and transparent interpretation of two concepts for modelling turbulent combustion: generalised Multiple Mapping Conditioning (MMC) and sparse-Lagrangian Large Eddy Simulation (LES). The MMC approach is presented as a hybrid between the Probability Density Function (PDF) method and approaches based on conditioning (e.g. Conditional Moment Closure, flamelet, etc.). The sparse-Lagrangian approach, which allows for a dramatic reduction of computational cost, is viewed as an alternative interpretation of the Filtered Density Function (FDF) methods. This work presents simulations of several turbulent diffusion flame cases and discusses the universality of the localness parameter between these cases and the universality of sparse-Lagrangian FDF methods with MMC.

  5. Selective improvement of anosognosia for hemiplegia during transcranial direct current stimulation: a case report.

    Science.gov (United States)

    Gandola, Martina; Sedda, Anna; Manera, Marina; Pingue, Valeria; Salvato, Gerardo; Spitoni, Grazia F; Pistarini, Caterina; Giorgi, Ines; Pizzamiglio, Luigi; Bottini, Gabriella

    2014-12-01

    Right brain damage patients may not complain of a left sided paralysis up to the point of denying it or even claiming of having just moved an otherwise paralyzed limb. This condition is known as anosognosia for hemiplegia (AHP). Recent behavioural experiments suggest that some residual intentionality might be preserved in patients with anosognosia and that the false belief of having moved originates from a failure to notice discrepancies between movement expectancies and the actual state of the motor system. This failure may be caused by a lack of afferent sensory information concerning the movement or alternatively by a direct dysfunction of the brain regions involved in actions' motor monitoring (i.e., the comparator system). Here we examined the effect of anodal transcranial direct current stimulation (tDCS) of the right premotor cortex in a patient with a bilateral lesion, involving predominantly the right hemisphere, and a dense unawareness for his left hemiplegia. During sham or anodal tDCS the patient was requested to judge his ability to perform simple motor actions (i) without actually executing the movement itself ("offline" condition) and after having performed a series of verbally cued finger opposition movements ("online" condition) with (i) eyes-closed or (ii) eyes-open. We found that anodal tDCS induces a significant remission of the false experience of movement only when the patient is requested to actually perform the movement with eyes open. Conversely, the patient's awareness does not improve in both the "offline" condition (in which the patient does not attempt to perform the movement) and in the "online" condition, when vision is precluded ("online" condition, eyes-closed). We conclude that the stimulation of the premotor cortex by tDCS activates brain regions involved in motor monitoring, temporary restoring the ability of the motor comparator system to correctly appreciate afferent information and build up a veridical motor awareness.

  6. Direct ion speciation analysis with ion-selective membranes operated in a sequential potentiometric/time resolved chronopotentiometric sensing mode.

    Science.gov (United States)

    Ghahraman Afshar, Majid; Crespo, Gastón A; Bakker, Eric

    2012-10-16

    Ion-selective membranes based on porous polypropylene membranes doped with an ionophore and a lipophilic cation-exchanger are used here in a new tandem measurement mode that combines dynamic electrochemistry and zero current potentiometry into a single protocol. Open circuit potential measurements yield near-nernstian response slopes in complete analogy to established ion-selective electrode methodology. Such measurements are well established to give direct information on the so-called free ion concentration (strictly, activity) in the sample. The same membrane is here also operated in a constant current mode, in which the localized ion depletion at a transition time is visualized by chronopotentiometry. This dynamic electrochemistry methodology gives information on the labile ion concentration in the sample. The sequential protocol is established on potassium and calcium ion-selective membranes. An increase of the ionophore concentration in the membrane to 180 mM makes it possible to determine calcium concentrations as high as 3 mM by chronopotentiometry, thereby making it possible to directly detect total calcium in undiluted blood samples. Recovery times after current perturbation depend on the current amplitude but can be kept to below 1 min for the polypropylene based ion-selective membranes studied here. Plasticized PVC as membrane material is less suited for this protocol, especially when the measurement at elevated concentrations is desired. An analysis of current amplitudes, transition times, and concentrations shows that the data are described by the Sand equation and that migration effects are insignificant. A numerical model describes the experimental findings with good agreement and gives guidance on the required selectivity in order to observe a well-resolved transition time and on the expected errors due to insufficient selectivity. The simulations suggest that the methodology compares well to that of open circuit potentiometry, despite giving

  7. Direct observation of beauty particles selected by muonic decay in emulsion

    CERN Multimedia

    2002-01-01

    This experiment is a search for beauty particles produced in pairs by $\\pi$ mesons in emulsions. Beauty particles would be identified in emulsion by their characteristic cascade decay through charm particles. This sort of signature would have a completely negligible background. The experiment would have the unique feature of being able to be sensitive to lifetimes as small as those expected for beauty, i.e. $10^{-14}$s < $\\tau$ < $10^{-13}$s. \\\\ Interesting events would be selected by the identification of three muons in the final state, coming from three of the four possible semi-leptonic decays of beauty of charmed particles. Muons would be identified in a hadron absorber equipped with three x-y plane hodoscopes, and 11 x-y-z planes of MWPC. \\\\Although the final sample of events to scan would be the 3 $\\mu$-events resulting from off-line analysis, it is intended to record data for all two-muon events. \\\\ A total of 67 stacks with approximate dimensions 15 x 10 x 5 cm$^{3}$ would be aligned with ...

  8. DNA abasic site-directed formation of fluorescent silver nanoclusters for selective nucleobase recognition

    Science.gov (United States)

    Ma, Kun; Cui, Qinghua; Liu, Guiying; Wu, Fei; Xu, Shujuan; Shao, Yong

    2011-07-01

    DNA single-nucleotide polymorphism (SNP) detection has attracted much attention due to mutation related diseases. Various methods for SNP detection have been proposed and many are already in use. Here, we find that the abasic site (AP site) in the DNA duplex can be developed as a capping scaffold for the generation of fluorescent silver nanoclusters (Ag NCs). As a proof of concept, the DNA sequences from fragments near codon 177 of cancer supression gene p53 were used as a model for SNP detection by in situ formed Ag NCs. The formation of fluorescent Ag NCs in the AP site-containing DNA duplex is highly selective for cytosine facing the AP site and guanines flanking the site and can be employed in situ as readout for SNP detection. The fluorescent signal-on sensing for SNP based on this inorganic fluorophore is substantially advantageous over the previously reported signal-off responses using low-molecular-weight organic ligands. The strong dependence of fluorescent Ag NC formation on the sequences surrounding the AP site was successfully used to identify mutations in codon 177 of cancer supression gene p53. We anticipate that this approach will be employed to develop a practical SNP detection method by locating an AP site toward the midway cytosine in a target strand containing more than three consecutive cytosines.

  9. Direct detection of antiprotons with the Timepix3 in a new electrostatic selection beamline

    Energy Technology Data Exchange (ETDEWEB)

    Pacifico, N., E-mail: nicola.pacifico@cern.ch [Institute of Physics and Technology, University of Bergen, Allgaten 55, 5007 Bergen (Norway); Aghion, S. [Politecnico of Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); INFN Milano, via Celoria 16, 20133 Milano (Italy); Alozy, J. [Physics Department, CERN, 1211 Geneva 23 (Switzerland); Amsler, C.; Ariga, A.; Ariga, T. [Laboratory for High Energy Physics, Albert Einstein Center for Fundamental Physics, University of Bern, 3012 Bern (Switzerland); Bonomi, G. [Department of Mechanical and Industrial Engineering, University of Brescia, via Branze 38, 25123 Brescia (Italy); INFN Pavia, via Bassi 6, 27100 Pavia (Italy); Bräunig, P. [Kirchhoff-Institute for Physics, Heidelberg University, Im Neuenheimer Feld 227, 69120 Heidelberg (Germany); Bremer, J. [Physics Department, CERN, 1211 Geneva 23 (Switzerland); Brusa, R.S. [Department of Physics, University of Trento, via Sommarive 14, 38123 Povo, Trento (Italy); TIFPA/INFN Trento, via Sommarive 14, 38123 Povo, Trento (Italy); Cabaret, L. [Laboratory Aimé Cotton, University of Paris-Sud, ENS Cachan, CNRS, University Paris-Saclay, 91405 Orsay Cedex (France); Caccia, M. [INFN Milano, via Celoria 16, 20133 Milano (Italy); Department of Science, University of Insubria, Via Valleggio 11, 22100 Como (Italy); Campbell, M. [Physics Department, CERN, 1211 Geneva 23 (Switzerland); Caravita, R. [Department of Physics, University of Genova, via Dodecaneso 33, 16146 Genova (Italy); INFN Genova, via Dodecaneso 33, 16146 Genova (Italy); Castelli, F. [INFN Milano, via Celoria 16, 20133 Milano (Italy); Department of Physics, University of Milano, via Celoria 16, 20133 Milano (Italy); Cerchiari, G. [Max Planck Institute for Nuclear Physics, Saupfercheckweg 1, 69117 Heidelberg (Germany); Chlouba, K. [Czech Technical University, Prague, Brehov 7, 11519 Prague 1 (Czech Republic); and others

    2016-09-21

    We present here the first results obtained employing the Timepix3 for the detection and tagging of annihilations of low energy antiprotons. The Timepix3 is a recently developed hybrid pixel detector with advanced Time-of-Arrival and Time-over-Threshold capabilities and has the potential of allowing precise kinetic energy measurements of low energy charged particles from their time of flight. The tagging of the characteristic antiproton annihilation signature, already studied by our group, is enabled by the high spatial and energy resolution of this detector. In this study we have used a new, dedicated, energy selection beamline (GRACE). The line is symbiotic to the AEgIS experiment at the CERN Antiproton Decelerator and is dedicated to detector tests and possibly antiproton physics experiments. We show how the high resolution of the Timepix3 on the Time-of-Arrival and Time-over-Threshold information allows for a precise 3D reconstruction of the annihilation prongs. The presented results point at the potential use of the Timepix3 in antimatter-research experiments where a precise and unambiguous tagging of antiproton annihilations is required.

  10. Direct detection of antiprotons with the Timepix3 in a new electrostatic selection beamline

    Science.gov (United States)

    Pacifico, N.; Aghion, S.; Alozy, J.; Amsler, C.; Ariga, A.; Ariga, T.; Bonomi, G.; Bräunig, P.; Bremer, J.; Brusa, R. S.; Cabaret, L.; Caccia, M.; Campbell, M.; Caravita, R.; Castelli, F.; Cerchiari, G.; Chlouba, K.; Cialdi, S.; Comparat, D.; Consolati, G.; Demetrio, A.; Di Noto, L.; Doser, M.; Dudarev, A.; Ereditato, A.; Evans, C.; Ferragut, R.; Fesel, J.; Fontana, A.; Gerber, S.; Giammarchi, M.; Gligorova, A.; Guatieri, F.; Haider, S.; Holmestad, H.; Huse, T.; Jordan, E.; Kellerbauer, A.; Kimura, M.; Krasnický, D.; Lagomarsino, V.; Lansonneur, P.; Lawler, G.; Lebrun, P.; Llopart, X.; Malbrunot, C.; Mariazzi, S.; Marx, L.; Matveev, V.; Mazzotta, Z.; Nebbia, G.; Nedelec, P.; Oberthaler, M.; Pagano, D.; Penasa, L.; Petracek, V.; Pistillo, C.; Prelz, F.; Prevedelli, M.; Ravelli, L.; Resch, L.; Røhne, O. M.; Rotondi, A.; Sacerdoti, M.; Sandaker, H.; Santoro, R.; Scampoli, P.; Smestad, L.; Sorrentino, F.; Spacek, M.; Storey, J.; Strojek, I. M.; Testera, G.; Tietje, I.; Tlustos, L.; Widmann, E.; Yzombard, P.; Zavatarelli, S.; Zmeskal, J.; Zurlo, N.

    2016-09-01

    We present here the first results obtained employing the Timepix3 for the detection and tagging of annihilations of low energy antiprotons. The Timepix3 is a recently developed hybrid pixel detector with advanced Time-of-Arrival and Time-over-Threshold capabilities and has the potential of allowing precise kinetic energy measurements of low energy charged particles from their time of flight. The tagging of the characteristic antiproton annihilation signature, already studied by our group, is enabled by the high spatial and energy resolution of this detector. In this study we have used a new, dedicated, energy selection beamline (GRACE). The line is symbiotic to the AEgIS experiment at the CERN Antiproton Decelerator and is dedicated to detector tests and possibly antiproton physics experiments. We show how the high resolution of the Timepix3 on the Time-of-Arrival and Time-over-Threshold information allows for a precise 3D reconstruction of the annihilation prongs. The presented results point at the potential use of the Timepix3 in antimatter-research experiments where a precise and unambiguous tagging of antiproton annihilations is required.

  11. DNA abasic site-directed formation of fluorescent silver nanoclusters for selective nucleobase recognition

    Energy Technology Data Exchange (ETDEWEB)

    Ma Kun; Cui Qinghua; Liu Guiying; Wu Fei; Xu Shujuan; Shao Yong, E-mail: yshao@zjnu.cn [Institute of Physical Chemistry, Zhejiang Normal University, Jinhua 321004, Zhejiang (China)

    2011-07-29

    DNA single-nucleotide polymorphism (SNP) detection has attracted much attention due to mutation related diseases. Various methods for SNP detection have been proposed and many are already in use. Here, we find that the abasic site (AP site) in the DNA duplex can be developed as a capping scaffold for the generation of fluorescent silver nanoclusters (Ag NCs). As a proof of concept, the DNA sequences from fragments near codon 177 of cancer supression gene p53 were used as a model for SNP detection by in situ formed Ag NCs. The formation of fluorescent Ag NCs in the AP site-containing DNA duplex is highly selective for cytosine facing the AP site and guanines flanking the site and can be employed in situ as readout for SNP detection. The fluorescent signal-on sensing for SNP based on this inorganic fluorophore is substantially advantageous over the previously reported signal-off responses using low-molecular-weight organic ligands. The strong dependence of fluorescent Ag NC formation on the sequences surrounding the AP site was successfully used to identify mutations in codon 177 of cancer supression gene p53. We anticipate that this approach will be employed to develop a practical SNP detection method by locating an AP site toward the midway cytosine in a target strand containing more than three consecutive cytosines.

  12. Direct UV photolysis of selected pharmaceuticals, personal care products and endocrine disruptors in aqueous solution.

    Science.gov (United States)

    Carlson, Jules C; Stefan, Mihaela I; Parnis, J Mark; Metcalfe, Chris D

    2015-11-01

    Pharmaceuticals and personal care products (PPCPs), and endocrine disrupting compounds (EDCs) are micropollutants of emerging concern that have been detected in the aquatic environment and in some cases, in drinking water at nanogram per liter levels. The goal of this study was to evaluate the removal of 15 model PPCPs and EDCs from water by direct UV photolysis, using either low (LP)-or medium (MP) -pressure mercury vapor arc lamps. Some of the model compounds are either weak bases or weak acids, and therefore, the pKa values were determined or confirmed for those compounds using spectrophotometric titrations. The molar absorption coefficients of ionized and non-ionized forms were also determined. The quantum yields at 253.7 nm in phosphate buffer solutions of pH 7.2 were determined to be 0.033 ± 0.004 for sulfamethoxazole, 0.0035 ± 0.0008 for sulfachloropyridazine, 0.006 ± 0.002 for acetaminophen, 0.34 ± 0.07 for triclosan, 0.35 ± 0.14 for estrone, 0.08 ± 0.05 for 17α-ethinylestradiol, 0.086 ± 0.012 for ibuprofen. The quantum yield for 4-n-nonylphenol photolysis at 253.7 nm varied with the initial concentration from 0.32 ± 0.08 at 23 μg/L to 0.092 ± 0.006 at 230 μg/L. The pseudo-first order rate constants determined for direct photolysis at 253.7 nm of the studied micropollutants followed the order: triclosan ≈ sulfamethoxazole > 4-n-nonylphenol ≈ sulfachloropyridazine ≈ estrone > acetaminophen ≈ 17α-ethinylestradiol ≈ ibuprofen. In contrast to the results observed for the monochromatic radiation (LP lamp), all 15 model compounds photolyzed under exposure to the broadband radiation emitted by the MP lamp. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Predation on rose galls: parasitoids and predators determine gall size through directional selection.

    Directory of Open Access Journals (Sweden)

    Zoltán László

    Full Text Available Both predators and parasitoids can have significant effects on species' life history traits, such as longevity or clutch size. In the case of gall inducers, sporadically there is evidence to suggest that both vertebrate predation and insect parasitoid attack may shape the optimal gall size. While the effects of parasitoids have been studied in detail, the influence of vertebrate predation is less well-investigated. To better understand this aspect of gall size evolution, we studied vertebrate predation on galls of Diplolepis rosae on rose (Rosa canina shrubs. We measured predation frequency, predation incidence, and predation rate in a large-scale observational field study, as well as an experimental field study. Our combined results suggest that, similarly to parasitoids, vertebrate predation makes a considerable contribution to mortality of gall inducer larvae. On the other hand, its influence on gall size is in direct contrast to the effect of parasitoids, as frequency of vertebrate predation increases with gall size. This suggests that the balance between predation and parasitoid attack shapes the optimal size of D. rosae galls.

  14. Direct ELISA kits as a sensitive and selective screening method for abstinence control in urine.

    Science.gov (United States)

    Kirschbaum, Katrin M; Musshoff, Frank; Wilbert, Ansgar; Röhrich, Jörg; Madea, Burkhard

    2011-04-15

    In 2009 cutoff values of assessment criteria to testify abstinence control in order to estimate driving ability were standardized in Germany. The cutoff values are lower than required in existing guidelines like SAMHSA and there is critical discussion about detection of low concentrations by using immunoassay, especially concerning amphetamines in urine (50 ng/ml). In this study Direct ELISA kits were tested for their applicability to identify the absence of amphetamines, cannabinoids, opiates, cocaine, methadone and benzodiazepines in urine. Results were confirmed by LC/MS or GC/MS analyses. Sensitivity, specificity, predictive values (positive as well as negative) and overall misclassification rates were evaluated by contingency tables and were compared to ROC-analyses. Sensitivity results as well as specificity results were satisfying showing sensitivity values higher than 96% for each analyte. The amphetamine test we used showed sensitivity and specificity of 100% and 88%, respectively, even if amphetamine tests usually react with high cross-reactivity. Our study results include high discrimination at required cutoff values between positives and negatives for each drug group and demonstrate that immunological tests complying with requirements of current decreased urine cutoff values for assessment of driving ability do exist.

  15. Direct selective metallization of AlN ceramics induced by laser radiation

    Science.gov (United States)

    Antończak, Arkadiusz J.; Kozioł, Paweł E.; Stepak, Bogusz; Szymczyk, Patrycja; Abramski, Krzysztof M.

    2014-03-01

    Aluminum nitride (AlN) ceramics has a unique characteristic, namely the ability to form conductive structures on its surface directly by laser-induced decomposition of the base material. Various research has been carried out on obtaining low-ohmic structures depending on process parameters such as the laser power, overlap of subsequent pulses and the type of shielding gas (air, nitrogen and argon). This paper focuses on explaining which factors have the greatest impact on the resistance (resistivity) value of obtained structures. In order to explain the effect of the laser fluence (below and above the ablation threshold of aluminum nitride) on the chemical structure of the conductive layers, qualitative EDX analyses were performed. Optimization of the process allowed obtaining a resistivity of the conductive layers at a level of ρ = 0.64·10-6 Ω·m, with a thickness of aluminum up to 10 μm (sheet resistance RS = 10 mΩ/Sr). This technology can be useful in making printed circuit boards (PCB), various types of sensors as well as radio-frequency identification (RFID) and Lab-On-a-Chip (LOC) structures. This technology can also be useful for the production of metamaterials.

  16. Discovery of orally bioavailable cyclohexanol-based NR2B-selective NMDA receptor antagonists with analgesic activity utilizing a scaffold hopping approach.

    Science.gov (United States)

    Anan, Kosuke; Masui, Moriyasu; Hara, Shinichiro; Ohara, Miho; Kume, Masaharu; Yamamoto, Shoichi; Shinohara, Shunji; Tsuji, Hiroki; Shimada, Shinji; Yagi, Shigenori; Hasebe, Nobuyoshi; Kai, Hiroyuki

    2017-09-01

    NR2B subunit containing N-methyl-d-aspartate (NMDA) receptor is an attractive target for chronic pain due to its involvement in disease states and its limited distribution in the central nervous system. Cyclohexanol-based leads 6a and 6c were identified as potent NR2B-selective NMDA antagonists utilizing a scaffold hopping approach. Further optimization of this series through replacement of the amide in the leads with an isoxazole and efforts to optimize the pharmacokinetic profiles led to the discovery of orally available brain penetrants 7k and 7l, which demonstrated analgesic activity in the mouse formalin test at early and late phases. Copyright © 2017. Published by Elsevier Ltd.

  17. Oral health and elite sport performance.

    Science.gov (United States)

    Needleman, Ian; Ashley, Paul; Fine, Peter; Haddad, Fares; Loosemore, Mike; de Medici, Akbar; Donos, Nikos; Newton, Tim; van Someren, Ken; Moazzez, Rebecca; Jaques, Rod; Hunter, Glenn; Khan, Karim; Shimmin, Mark; Brewer, John; Meehan, Lyndon; Mills, Steve; Porter, Stephen

    2015-01-01

    While the research base is limited, studies have consistently reported poor oral health in elite athletes since the first report from the 1968 Olympic Games. The finding is consistent both across selected samples attending dental clinics at major competitions and more representative sampling of teams and has led to calls from the International Olympic Committee for more accurate data on oral health. Poor oral health is an important issue directly as it can cause pain, negative effects on appearance and psychosocial effects on confidence and quality of life and may have long-term consequences for treatment burden. Self-reported evidence also suggests an impact on training and performance of athletes. There are many potential challenges to the oral health of athletes including nutritional, oral dehydration, exercise-induced immune suppression, lack of awareness, negative health behaviours and lack of prioritisation. However, in theory, oral diseases are preventable by simple interventions with good evidence of efficacy. The consensus statement aims to raise awareness of the issues of oral health in elite sport and recommends strategies for prevention and health promotion in addition to future research strategies.

  18. Weldon's Search for a Direct Proof of Natural Selection and the Tortuous Path to the Neo-Darwinian Synthesis

    Indian Academy of Sciences (India)

    Amitabh Joshi

    2017-06-01

    W F R Weldon first clearly formulated the principles of naturalselection in terms of what would have to be observed innatural populations in order to conclude that natural selectionwas, indeed, acting in the manner proposed by Darwin.The approach he took was the statistical method developedby Galton, although he was closer to Darwin’s conception ofselection acting on small individual variations than Galtonwas. Weldon, together with Karl Pearson, who supplied thestatistical innovations needed to infer the action of selectionfrom populational data on trait distributions, laid the foundationsof biometry and provided the first clear evidence of bothstabilizing and directional selection in natural populations.

  19. A hierarchical model of goal directed navigation selects trajectories in a visual environment.

    Science.gov (United States)

    Erdem, Uğur M; Milford, Michael J; Hasselmo, Michael E

    2015-01-01

    We have developed a Hierarchical Look-Ahead Trajectory Model (HiLAM) that incorporates the firing pattern of medial entorhinal grid cells in a planning circuit that includes interactions with hippocampus and prefrontal cortex. We show the model's flexibility in representing large real world environments using odometry information obtained from challenging video sequences. We acquire the visual data from a camera mounted on a small tele-operated vehicle. The camera has a panoramic field of view with its focal point approximately 5 cm above the ground level, similar to what would be expected from a rat's point of view. Using established algorithms for calculating perceptual speed from the apparent rate of visual change over time, we generate raw dead reckoning information which loses spatial fidelity over time due to error accumulation. We rectify the loss of fidelity by exploiting the loop-closure detection ability of a biologically inspired, robot navigation model termed RatSLAM. The rectified motion information serves as a velocity input to the HiLAM to encode the environment in the form of grid cell and place cell maps. Finally, we show goal directed path planning results of HiLAM in two different environments, an indoor square maze used in rodent experiments and an outdoor arena more than two orders of magnitude larger than the indoor maze. Together these results bridge for the first time the gap between higher fidelity bio-inspired navigation models (HiLAM) and more abstracted but highly functional bio-inspired robotic mapping systems (RatSLAM), and move from simulated environments into real-world studies in rodent-sized arenas and beyond.

  20. Utilizing ras signaling pathway to direct selective replication of herpes simplex virus-1.

    Directory of Open Access Journals (Sweden)

    Weihong Pan

    Full Text Available Re-engineering the tropism of viruses is an attractive translational strategy for targeting cancer cells. The Ras signal transduction pathway is a central hub for a variety of pro-oncogenic events with a fundamental role in normal and neoplastic physiology. In this work we were interested in linking Ras activation to HSV-1 replication in a direct manner in order to generate a novel oncolytic herpes virus which can target cancer cells. To establish such link, we developed a mutant HSV-1 in which the expression of ICP4 (infected cell protein-4, a viral protein necessary for replication is controlled by activation of ELK, a transcription factor down-stream of the Ras pathway and mainly activated by ERK (extracellular signal-regulated kinase, an important Ras effector pathway. This mutant HSV-1 was named as Signal-Smart 1 (SS1. A series of prostate cells were infected with the SS1 virus. Cells with elevated levels of ELK activation were preferentially infected by the SS1 virus, as demonstrated by increased levels of viral progeny, herpetic glycoprotein C and overall SS1 viral protein production. Upon exposure to SS1, the proliferation, invasiveness and colony formation capabilities of prostate cancer cells with increased ELK activation were significantly decreased (p<0.05, while the rate of apoptosis/necrosis in these cells was increased. Additionally, high Ras signaling cells infected with SS1 showed a prominent arrest in the G1 phase of the cell cycle as compared to cells exposed to parental HSV-1. The results of this study reveal the potential for re-modeling the host-herpes interaction to specifically interfere with the life of cancer cells with increased Ras signaling. SS1 also serves as a "prototype" for development of a family of signal-smart viruses which can target cancer cells on the basis of their signaling portfolio.

  1. Relevance of the selective oestrogen receptor modulators tamoxifen, toremifene and clomiphene in doping field: endogenous steroids urinary profile after multiple oral doses.

    Science.gov (United States)

    Mazzarino, Monica; Braganò, Maria Cristina; de la Torre, Xavier; Molaioni, Francesco; Botrè, Francesco

    2011-11-01

    The present study was performed to investigate the influence of the intake of selective oestrogen receptor modulators on the urinary endogenous steroids profile. For this purpose the circadian variability of luteinizing hormone, follicle-stimulating hormone, testosterone, 5α-androstan-3α,17β-diol, 5β-androstan-3α,17β-diol, epitestosterone, 4-androstenedione, androsterone and etiocholanolone were measured on eight subjects (four males and four females) by gas chromatography-mass spectrometry and chemiluminescent immunometric assay techniques before and after oral administration of multiple doses of either tamoxifen (80 mg for 2 days) or toremifene (120 mg for 2 days) or clomiphene (100 mg for 2 days). The individual baseline variability of the steroids studied was set up by collecting the urine samples every 3 h, for 3 days prior to the treatment; whereas the evaluation of the effects of the oral administration of multiple doses of selective oestrogen receptor modulators on the steroid urinary profile was assessed by collecting urine samples every three hours for at least five days from the first administration. The results of our measurements showed that, only in male subjects, the relative urinary concentrations of testosterone, epitestosterone and 4-androstenedione were significantly altered generally after the second day of drug administration. While no significant effects were recorded in both sexes on the luteinizing hormone, follicle-stimulating hormone, androsterone, etiocholanolone, 5α-androstan-3α,17β-diol and 5β-androstan-3α,17β-diol urinary levels and on testosterone/epitestosterone, 5α-androstan-3α,17β-diol/5β-androstan-3α,17β-diol and androsterone/etiocholanolone ratios. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Rapid Directional Solidification with Ultra-High Temperature Gradient and Cellular Spacing Selection of Cu-Mn Alloy

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The detailed laser surface remelting experiments of Cu-31.4 wt pct Mn and Cu-26.6 wt pct Mn alloys on a 5 kW CO2laser were carried out to study the effects of processing parameters (scanning velocity, output power of laser) on the growthdirection of microstructure in the molten pool and cellular spacing selection under the condition of ultra-high temperaturegradient and rapid directional solidification. The experimental results show that the growth direction of microstructure isstrongly affected by laser processing parameters. The ultra-high temperature gradient directional solidification can be realizedon the surface of samples during laser surface remelting by controlling laser processing parameters, the temperature gradientand growth velocity can reach 106 K/m and 24.1 mm/s, respectively, and the solidification microstructure in the center ofthe molten pool grows along the laser beam scanning direction. There exists a distribution range of cellular spacings underthe laser rapid solidification conditions, and the average spacing decreases with increasing of growth rate. The maximum,λ minimum, λmin, and average primary spacing,λ, as functions of growth rate, Vb, can be given by, λ =12.54V b-0.61,λmin=4.47 Vb-0.52, λ=9.09Vb-0.62, respectively. The experimental results are compared with the current Hunt-Lu model forrapid cellular/dendritic growth, and a good agreement is found.

  3. Oral Cancer Exam

    Medline Plus

    Full Text Available ... Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities Diabetes Heart Disease HIV/AIDS See ... this brochure includes information on symptoms, diagnosis, and treatment of oral cancer, along with definitions of selected medical terms and ...

  4. Oral sex and oral health: An enigma in itself

    Directory of Open Access Journals (Sweden)

    Tarun Kumar

    2015-01-01

    Full Text Available Oral sex is commonly practiced by sexually active couples of various age groups, including male-female and same-gender adolescents. The various type of oral sex practices are fellatio, cunnilingus, and analingus. Oral sex can transmit oral, respiratory, and genital infections from one site in body to the other. Oral health has a direct correlation on the transmission of infection; a cut in the mouth, bleeding gums, lip sores or broken skin increases chances of life-threatening infections. Although oral sex is considered a low risk activity, it is important to use protection such as physical barriers, health and medical issues, ethical issues, and oral hygiene and dental issues. The ulcerations or unhealthy periodontium in mouth accelerates the phenomenon of transmission of infections into the circulation. Thus, consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex.

  5. Discovery of Aryl Aminoquinazoline Pyridones as Potent, Selective, and Orally Efficacious Inhibitors of Receptor Tyrosine Kinase c-Kit

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Essa; Tasker, Andrew; White, Ryan D.; Kunz, Roxanne K.; Human, Jason; Chen, Ning; Bürli, Roland; Hungate, Randall; Novak, Perry; Itano, Andrea; Zhang, Xuxia; Yu, Violeta; Nguyen, Yen; Tudor, Yanyan; Plant, Matthew; Flynn, Shaun; Xu, Yang; Meagher, Kristin L.; Whittington, Douglas A.; Ng, Gordon Y. (Amgen)

    2008-12-09

    Inhibition of c-Kit has the potential to treat mast cell associated fibrotic diseases. We report the discovery of several aminoquinazoline pyridones that are potent inhibitors of c-Kit with greater than 200-fold selectivity against KDR, p38, Lck, and Src. In vivo efficacy of pyridone 16 by dose-dependent inhibition of histamine release was demonstrated in a rodent pharmacodynamic model of mast cell activation.

  6. Direct current stimulation (tDCS) reveals parietal asymmetry in local/global and salience-based selection.

    Science.gov (United States)

    Bardi, Lara; Kanai, Ryota; Mapelli, Daniela; Walsh, Vincent

    2013-03-01

    Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in processing object's global form versus local parts. However the attentional mechanisms subtending visual selection of different levels of information are poorly understood. The classical left hemisphere/local-right hemisphere/global dichotomy has been recently challenged by studies linking the asymmetry of activation in the posterior parietal cortex (PPC) with the relative salience of the stimulus rather than with the local/global level. The present study aimed to assess hemispheric asymmetry in local-global and salience-based selection in hierarchical stimuli by using transcranial direct current stimulation (tDCS). To this end, tDCS has been applied to the PPC of both the hemispheres. Our data revealed that tDCS did affect the selection of the target on the basis of its relative salience in a manner that depended on the tDCS polarity applied to the two hemispheres. This result is in line with previous findings that the left PPC is critically involved in attention for low-salience stimuli in the presence of high-salience distractor information, while right PPC is involved in attending to more salient stimuli. Hemispheric asymmetries were also found in local/global selection. Overall the results suggest that neural activation in the PPC is related to both the salience and the level of stimulus representations mediating responses to hierarchical stimuli. The comparison of the results from Experiments 1 and 2 in local/global-based selection suggests that the effect of stimulation could be completely opposite depending on subtle differences in demands of attentional control (sustained attention vs task switching).

  7. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban – an oral, direct Factor Xa inhibitor

    Directory of Open Access Journals (Sweden)

    Rolf eBurghaus

    2014-11-01

    Full Text Available The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

  8. Selective Insecticide Applications Directed Against Triatoma infestans (Hemiptera: Reduviidae) Affected a Nontarget Secondary Vector of Chagas Disease, Triatoma garciabesi.

    Science.gov (United States)

    Rodríguez-Planes, L I; Vazquez-Prokopec, G M; Cecere, M C; Canale, D M; Gürtler, R E

    2016-01-01

    The control of nondomiciliated triatomine species adapted to peridomestic habitats represents a challenge because they are connected to sylvatic colonies, and pyrethroid insecticides have limited effects outdoors. The effects of residual insecticide spraying have rarely been assessed on secondary triatomines. Triatoma garciabesi (Carcavallo, Martinez, Cichero, Prosen & Ronderos, 1967) is a nontarget vector that inhabits the dry western Chaco region, and a member of the Triatoma sordida Stål 1859 complex. Little is known on the capacity of T. garciabesi to invade and establish viable domestic or peridomestic colonies, and on its response to residual insecticide sprays directed against Triatoma infestans Klug 1834. The presence and abundance of triatomines were assessed by timed manual collections annually or biannually (spring and fall) during 10 yr after a community-wide insecticide spraying campaign and selective insecticide sprays directed against T. infestans in a rural village of northwestern Argentina. T. garciabesi mainly occupied peridomestic habitats associated with chickens, and was unable to colonize human sleeping quarters. Trees with chickens occurred in nearly all houses and were infested in >25% of the occasions. The abundance of bugs at house-compound level was best explained by a generalized estimating equation model that included selective insecticide sprays during the previous semester (negative effects), chicken abundance (positive effects), seasonality, and their interactions. Our results suggest that insecticide applications targeting T. infestans affected the abundance of T. garciabesi, and reduced the likelihood of future infestation.

  9. Directed surfaces structures and interfaces for enhanced electrocatalyst activity, selectivity, and stability for energy conversion reactions

    Energy Technology Data Exchange (ETDEWEB)

    Jaramillo, Thomas F. [Stanford Univ., CA (United States). Dept. of Chemical Engineering. Shriram Center

    2016-04-20

    In this project, we have employed a systematic approach to develop active, selective, and stable catalyst materials for important electrochemical reactions involving energy conversion. In particular, we have focused our attention on developing active catalyst materials for the hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). HER: We have synthesized and investigated several highly active and acid stable non-precious metal HER catalysts, including: [Mo3S13]2- nanoclusters (Nature Chemistry, 2014) and molybdenum phosphosulfide (MoP|S) (Angewandte Chemie, 2014). We have also aimed to engineer these catalyst formulations in a membrane electrode assembly (MEA) for fundamental studies of water electrolysis at high current densities, approximately 1 A/cm2 (ChemSusChem, 2015). We furthermore investigated transition metal phosphide (TMP) catalysts for HER by a combined experimental–theoretical approach (Energy & Environmental Science, 2015). By synthesizing different TMPs and comparing experimentally determined HER activities with the hydrogen adsorption free energies, ΔGH, calculated by density functional theory, we showed that the TMPs follow a volcano relationship for the HER. Using our combined experimental–theoretical model, we predicted that the mixed metal TMP, Fe0.5Co0.5P, should have a near-optimal ΔGH. We synthesized several mixtures of Co and Fe phosphides alloys and confirmed that Fe0.5Co0.5P exhibits the highest HER activity of the investigated TMPs (Energy & Environmental Science, 2015). The understanding gained as to how to improve catalytic activity for the HER, particularly for non-precious metal materials, is important to DOE targets for sustainable H2 production. OER: We have developed a SrIrO3/IrOx catalyst for acidic conditions (submitted, 2016). The Sr

  10. Photocatalytically patterned TiO2 arrays for on-plate selective enrichment of phosphopeptides and direct MALDI MS analysis.

    Science.gov (United States)

    Wang, Hui; Duan, Jicheng; Cheng, Quan

    2011-03-01

    We report the development of photocatalytically patterned TiO(2) arrays for selective on-plate enrichment and direct matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis of phosphopeptides. A thin TiO(2) nanofilm with controlled porosity is prepared on gold-covered glass slides by a layer-by-layer (LbL) deposition/calcination process. The highly porous and rough nanostructure offers high surface area for selective binding of phosphorylated species. The patterned arrays are generated using an octadecyltrichlorosilane (OTS) coating in combination of UV irradiation with a photomask, followed by NaOH etching. The resulting hydrophilic TiO(2) spots are thus surrounded by a hydrophobic OTS layer, which can facilitate the enrichment of low-abundance components by confining a large volume sample into a small area. The TiO(2) arrays exhibit high specificity toward phosphopeptides in complex samples including phosphoprotein digests and human serum, and the detection can be made in the fmole range. Additional advantages of the arrays include excellent stability, reusability/reproducibility, and low cost. This method has been successfully applied to the analysis of phosphopeptides in nonfat milk. The patterned TiO(2) arrays provide an attractive interface for performing on-plate reactions, including selective capture of target species for MALDI-MS analysis, and can serve as a versatile lab-on-a-chip platform for high throughput analysis in phosphoproteome research.

  11. Oral Medication

    Science.gov (United States)

    ... Size: A A A Listen En Español Oral Medication The first treatment for type 2 diabetes blood ... new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money ...

  12. GABA(A receptors containing the α2 subunit are critical for direction-selective inhibition in the retina.

    Directory of Open Access Journals (Sweden)

    Olivia Nicola Auferkorte

    Full Text Available Far from being a simple sensor, the retina actively participates in processing visual signals. One of the best understood aspects of this processing is the detection of motion direction. Direction-selective (DS retinal circuits include several subtypes of ganglion cells (GCs and inhibitory interneurons, such as starburst amacrine cells (SACs. Recent studies demonstrated a surprising complexity in the arrangement of synapses in the DS circuit, i.e. between SACs and DS ganglion cells. Thus, to fully understand retinal DS mechanisms, detailed knowledge of all synaptic elements involved, particularly the nature and localization of neurotransmitter receptors, is needed. Since inhibition from SACs onto DSGCs is crucial for generating retinal direction selectivity, we investigate here the nature of the GABA receptors mediating this interaction. We found that in the inner plexiform layer (IPL of mouse and rabbit retina, GABA(A receptor subunit α2 (GABA(AR α2 aggregated in synaptic clusters along two bands overlapping the dendritic plexuses of both ON and OFF SACs. On distal dendrites of individually labeled SACs in rabbit, GABA(AR α2 was aligned with the majority of varicosities, the cell's output structures, and found postsynaptically on DSGC dendrites, both in the ON and OFF portion of the IPL. In GABA(AR α2 knock-out (KO mice, light responses of retinal GCs recorded with two-photon calcium imaging revealed a significant impairment of DS responses compared to their wild-type littermates. We observed a dramatic drop in the proportion of cells exhibiting DS phenotype in both the ON and ON-OFF populations, which strongly supports our anatomical findings that α2-containing GABA(ARs are critical for mediating retinal DS inhibition. Our study reveals for the first time, to the best of our knowledge, the precise functional localization of a specific receptor subunit in the retinal DS circuit.

  13. Oral myiasis

    OpenAIRE

    Thalaimalai Saravanan; Mathan A Mohan; Meera Thinakaran; Saneem Ahammed

    2015-01-01

    Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability ...

  14. Selective versus comprehensive neck dissection in the treatment of patients with a pathologically node-positive neck with or without microscopic extracapsular spread in oral squamous cell carcinoma.

    Science.gov (United States)

    Feng, Z; Gao, Y; Niu, L X; Peng, X; Guo, C B

    2014-10-01

    The objective of this study was to compare the prognosis and complications between selective neck dissection (SND) and comprehensive neck dissection (CND) for patients with a pathologically node-positive neck in squamous cell carcinoma of the tongue and the floor of the mouth. This was a retrospective cohort study. There was no significant difference between the SND group and the CND group in 3-year neck control rate (86.2% vs. 85.9%, P=0.797) or disease-specific survival (DSS) rate (64.6% vs. 61.9%, P=0.646). Further analyses of the respective 3-year DSS rates in the SND and CND subgroups were as follows: pN1 without extracapsular spread (ECS), 67.7% vs. 72.2%, P=0.851; pN2b without ECS, 64.7% vs. 68.8%, P=0.797; and pN+ with ECS, 57.1% vs. 60.0%, P=0.939. Of note, there were significantly fewer complications in the SND group compared with the CND group (7.3% vs. 20.0%, P=0.032). Multivariate analysis showed that the modality of neck treatment, pN+ status, and microscopic ECS did not serve as independent prognostic factors. SND plus adjuvant radiotherapy is a management strategy of high efficiency and minor morbidity for selected oral cancer patients with a pN+ neck with or without microscopic ECS.

  15. Patient acceptability, safety and access: A balancing act for selecting age-appropriate oral dosage forms for paediatric and geriatric populations.

    Science.gov (United States)

    Walsh, Jennifer; Ranmal, Sejal R; Ernest, Terry B; Liu, Fang

    2017-07-11

    The selection and design of age-appropriate formulations intended for use in paediatric and geriatric patients are dependent on multiple factors affecting patient acceptability, safety and access. The development of an economic and effective product relies on a balanced consideration of the risks and benefits of these factors. This review provides a comprehensive and up-to-date analysis of oral dosage forms considering key aspects of formulation design including dosage considerations, ease of use, tolerability and safety, manufacturing complexity, stability, supply and cost. Patient acceptability has been examined utilising an evidence-based approach to evaluate regulatory guidance and literature. Safety considerations including excipients and potential risk of administration errors of the different dosage forms are also discussed, together with possible manufacturing and supply challenges. Age appropriate drug product design should consider and compare i) acceptability ii) safety and iii) access, although it is important to recognise that these factors must be balanced against each other, and in some situations a compromise may need to be reached when selecting an age-appropriate formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Genomic signatures of local directional selection in a high gene flow marine organism; the Atlantic cod (Gadus morhua

    Directory of Open Access Journals (Sweden)

    Mittelholzer Christian

    2009-12-01

    Full Text Available Abstract Background Marine fishes have been shown to display low levels of genetic structuring and associated high levels of gene flow, suggesting shallow evolutionary trajectories and, possibly, limited or lacking adaptive divergence among local populations. We investigated variation in 98 gene-associated single nucleotide polymorphisms (SNPs for evidence of selection in local populations of Atlantic cod (Gadus morhua L. across the species distribution. Results Our global genome scan analysis identified eight outlier gene loci with very high statistical support, likely to be subject to directional selection in local demes, or closely linked to loci under selection. Likewise, on a regional south/north transect of central and eastern Atlantic populations, seven loci displayed strongly elevated levels of genetic differentiation. Selection patterns among populations appeared to be relatively widespread and complex, i.e. outlier loci were generally not only associated with one of a few divergent local populations. Even on a limited geographical scale between the proximate North Sea and Baltic Sea populations four loci displayed evidence of adaptive evolution. Temporal genome scan analysis applied to DNA from archived otoliths from a Faeroese population demonstrated stability of the intra-population variation over 24 years. An exploratory landscape genetic analysis was used to elucidate potential effects of the most likely environmental factors responsible for the signatures of local adaptation. We found that genetic variation at several of the outlier loci was better correlated with temperature and/or salinity conditions at spawning grounds at spawning time than with geographic distance per se. Conclusion These findings illustrate that adaptive population divergence may indeed be prevalent despite seemingly high levels of gene flow, as found in most marine fishes. Thus, results have important implications for our understanding of the interplay of

  17. Effective immunity to dental caries: selective induction of secretory immunity by oral administration of Streptococcus mutans in rodents.

    Science.gov (United States)

    Michalek, S M; McGhee, J R; Arnold, R R; Mestecky, J

    1978-01-01

    1) The selective induction of secretory antibody is antigen dose dependent. A dose of 10(7) or 10(8) S. mutans CFU (per gram of diet) elicited a significant response, while a higher dose (10(9) CFU/gram) resulted in an apparent state of unresponsiveness. 2) A lowly virulent mutant of S. mutans 6715 (C4) induced protective s-IgA antibodies against challenge with a highly virulent species (C211). Cross protection among serotypes of S. mutans has been achieved. 3) Bovine milk with antibodies to S. mutans significantly reduced the level of caries lesions in rats fed this lyophilized milk and challenged with the homologous, virulent S. mutans strains.

  18. AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - Results of two parallel first-in-human phase I studies

    NARCIS (Netherlands)

    Omlin, A.; Jones, R. J.; Van Der Noll, R.; Satoh, T.; Niwakawa, M.; Smith, S. A.; Graham, J.; Ong, M.; Finkelman, R. D.; Schellens, J. H M; Zivi, A.; Crespo, M.; Riisnaes, R.; Nava-Rodrigues, D.; Malone, M. D.; Dive, C.; Sloane, R.; Moore, D.; Alumkal, J. J.; Dymond, A.; Dickinson, P. A.; Ranson, M.; Clack, G.; De Bono, J.; Elliott, T.

    2015-01-01

    Background: AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). Methods: In study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a

  19. Direct and selective production of propene from bio-ethanol on Sc-loaded IN2O3 catalysts.

    Science.gov (United States)

    Iwamoto, Masakazu; Mizuno, Shouta; Tanaka, Masashi

    2013-05-27

    Propene, one of key building blocks for manufacturing plastics and chemicals, could be directly and stably produced from ethanol in good yields. The conversion degree of ethanol to propene reached approximately 60 mol% by using a 3 atom% scandium-loaded indium oxide catalyst at 823 K in the presence of water and hydrogen. The introduction of Sc prevented the reduction of In2O3 to In metal during the reaction, and that of water decreased the coke formation. Both additions resulted in longer lifetimes of the catalysts. The hydrogen addition increased the conversion of acetone to propene. The reaction pathways are also suggested on the basis of the product distributions and the pulse experiments, ethanol→acetaldehyde→acetone→propene, which is quite different from the shape-selective catalysis on zeolites and the dimerization-metathesis of ethene on nickel ion-loaded silica catalysts.

  20. Effect of selective elimination of the oral flora on mucositis in irradiated head and neck cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Spijkervet, F.K.; Van Saene, H.K.; Van Saene, J.J.; Panders, A.K.; Vermey, A.; Mehta, D.M.; Fidler, V. (Univ. of Groningen (Netherlands))

    1991-03-01

    Recently it has been reported that chlorhexidine 0.1% rinsing was not successful in eradication of gram-negative bacilli in patients who have head and neck cancer. These bacilli could play a role in irradiation mucositis. This study reports the effect of lozenges containing 2 mg polymyxin E, 1.8 mg tobramycin, and 10 mg amphotericin B qid on the oropharyngeal flora in 15 irradiated head and neck cancer patients. The results were compared with those of a previous study in two groups of 15 patients comparing chlorhexidine rinsing with placebo. In all patients using lozenges, eradication of gram-negative bacilli and yeasts was achieved within 3 weeks. A significant increase of enterococci was found. Mucositis was significantly reduced compared with the previous two groups. All patients showed erythema only, whereas 80% of both the placebo and chlorhexidine rinsing patients suffered from severe mucositis, with signs of pseudomembranes developing from the third week of conventional irradiation protocol. The effect of selective elimination of gram-negative bacilli from the oropharynx and the prevention of severe mucositis may be explained by the eradication of these bacteria and/or neutralization of salivary endotoxin, released by gram-negative bacilli, mediating the inflammatory processes.

  1. Lack of experimental evidence to support mcr-1-positive escherichia coli strain selection during oral administration of colistin at recommended and higher dose given by gavage in weaned piglets.

    Science.gov (United States)

    Viel, Alexis; Henri, Jérôme; Perrin-Guyomard, Agnès; Laroche, Julian; Couet, William; Grégoire, Nicolas; Laurentie, Michel

    2017-06-28

    In this study, we assessed the selective effect of colistin orally administered to healthy weaned piglets harbouring an intestinal mcr-1-positive Escherichia coli strain. Maximum recommended dose and a higher dose often used in European pig farms were given by gavage. No selection of the mcr-1-positive strain was observed in our controlled conditions whatever the dose. Further investigations in real farming conditions seem necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  2. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines

    Science.gov (United States)

    Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

    2016-01-01

    The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation). For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin The advice for warfarin is fundamentally unchanged from British Society of Gastroenterology (BSG) 2008 guidance. Direct Oral Anticoagulants (DOAC) For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation); For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥48 h before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30–50 mL/min we recommend that the last dose of DOAC be taken 72 h before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID:26873868

  3. Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis.

    Science.gov (United States)

    Nagata, Naoyoshi; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Watanabe, Kazuhiro; Akiyama, Junichi; Uemura, Naomi; Niikura, Ryota

    2017-09-05

    To compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures. Using the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups. In the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk. The risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. [Clinical characteristics of patients with atrial fibrillation treated with direct oral anticoagulants attended in primary care setting. The SILVER-AP study].

    Science.gov (United States)

    de la Figuera, Mariano; Cinza, Sergio; Marín, Nuria; Egocheaga, Isabel; Prieto, Miguel Angel

    2017-07-29

    To analyse the clinical characteristics and management of patients with non-valvular atrial fibrillation (NVAF) treated with direct oral anticoagulants (DOAC). Observational, cross-sectional and multicentre study. Autonomous Communities in which the general practitioner can prescribe DOAC (n=9). The study included a total of 790 patients on chronic treatment with anticoagulants, and on whom therapy was changed, as well as being currently on treatment with DOAC for at least for 3 months. A record was made of the sociodemographic and clinical management date. Mean age was 78.6±8.4 years, and 50.5% of patients were men. Mean CHADS2 score was 2.6±1.2, mean CHA2DS2-VASc score was 4.3±1.6, and the mean HAS-BLED score was 2.3±1.0. Mean duration of treatment with DOAC was 15.8±12.5 months. Rivaroxaban was the DOAC most frequently prescribed (57.8%), followed by dabigatran (23.7%), and apixaban (18.5%). Of the patients receiving rivaroxaban, 70.2% were taking the dose of 20mg/daily. Of the patients receiving dabigatran, 41.7% were taking the dose of 150mg twice daily, and in the case of apixaban, 56.2% were taking the dose of 5mg twice daily. Satisfaction (ACTS Burdens scale 52.0±7.2 and ACTS Benefits scale 12.1±2.2), and therapeutic adherence (97.8% of patients took their medication regularly) with DOAC were high. Patients treated with DOAC in Spain have a high thromboembolic risk. A significant proportion of patients receive a lower dose of DOAC than that recommended according to their clinical profile. Satisfaction and medication adherence are high. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  5. Direct Observation of Charge Separation on Anatase TiO2 Crystals with Selectively Etched {001} Facets.

    Science.gov (United States)

    Liu, Xiaogang; Dong, Guojun; Li, Shaopeng; Lu, Gongxuan; Bi, Yingpu

    2016-03-09

    Synchronous illumination X-ray photoelectron spectroscopy (SIXPS) was employed for the first time to directly identify the photogenerated charge separation and transfer on anatase TiO2 single-crystals with selectively etched {001} facets. More specifically, for the TiO2 crystals with intact {001} and {101} facets, most of photogenerated charge carriers rapidly recombined, and no evident electron-hole separation was detected. With selectively etching on {001} facets, high efficient charge separation via hole transfer to titanium and electron to oxygen was clearly observed. However, when the {001} facets were completely etched into a hollow structure, the recombination for photogenerated electron-hole pairs would dominate again. These demonstrations clearly reveal that the appropriate corrosion on {001} facets could facilitate more efficient electron-hole separation and transfer. As expected, the optimized TiO2 microcrystals with etched {001} facets could achieve a hydrogen generation rate of 74.3 μmol/h/g, which is nearly 7 times higher than the intact-TiO2 crystals.

  6. Template-Free Electroless Plating of Gold Nanowires: Direct Surface Functionalization with Shape-Selective Nanostructures for Electrochemical Applications.

    Science.gov (United States)

    Muench, Falk; Schaefer, Sandra; Hagelüken, Lorenz; Molina-Luna, Leopoldo; Duerrschnabel, Michael; Kleebe, Hans-Joachim; Brötz, Joachim; Vaskevich, Alexander; Rubinstein, Israel; Ensinger, Wolfgang

    2017-09-13

    Metal nanowires (NWs) represent a prominent nanomaterial class, the interest in which is fueled by their tunable properties as well as their excellent performance in, for example, sensing, catalysis, and plasmonics. Synthetic approaches to obtain metal NWs mostly produce colloids or rely on templates. Integrating such nanowires into devices necessitates additional fabrication steps, such as template removal, nanostructure purification, or attachment. Here, we describe the development of a facile electroless plating protocol for the direct deposition of gold nanowire films, requiring neither templates nor complex instrumentation. The method is general, producing three-dimensional nanowire structures on substrates of varying shape and composition, with different seed types. The aqueous plating bath is prepared by ligand exchange and partial reduction of tetrachloroauric acid in the presence of 4-dimethylaminopyridine and formaldehyde. Gold deposition proceeds by nucleation of new grains on existing nanostructure tips and thus selectively produces curvy, polycrystalline nanowires of high aspect ratio. The nanofabrication potential of this method is demonstrated by producing a sensor electrode, whose performance is comparable to that of known nanostructures and discussed in terms of the catalyst architecture. Due to its flexibility and simplicity, shape-selective electroless plating is a promising new tool for functionalizing surfaces with anisotropic metal nanostructures.

  7. Direct Determination of Potassium—Sodium Activity Ratio in Soil Suspension with Two Ion—Selective Electrodes

    Institute of Scientific and Technical Information of China (English)

    LIHONG-YAN; JIGUO-LIANG

    1991-01-01

    A K+-selective electrode and a Na+-selective electrode were used to construct a measuring cell without liquid-junction for the determination of the ion activity ratio of K+ to Na+ in soil suspensions.The measured cell potential was not affected by the total electrolyte concentration when the total cation concentration was 10-1-10-3 mol L-1 and the concentration ratio Ck+/CNa+ was 10:1 to 1:50.When the concentration ratios were equal to 1 and the total electrolyte concentrations were 10-2 and 10-3 mol L-1,the ion activity ratio measurenent would not be affected by pH in the pH range of 3.5 to 11.5 and 4.4 to 11 respectively.Ions other than H+ have no remarkable influence on the measurement.The ion activity ratio of K+ to Na+ measured directly in soil suspension agree well with those in centrifuged supernant solution.The relative deviation was within 4%.From the measured ion activity ratio,the difference of the bonding energies of K+ and Na+ ions was calculated.

  8. Rapidly Evolving Mitochondrial Genome and Directional Selection in Mitochondrial Genes in the Parasitic Wasp Nasonia (Hymenoptera: Pteromalidae)

    Science.gov (United States)

    Raychoudhury, Rhitoban; Lavrov, Dennis V.; Werren, John H.

    2008-01-01

    We sequenced the nearly complete mtDNA of 3 species of parasitic wasps, Nasonia vitripennis (2 strains), Nasonia giraulti, and Nasonia longicornis, including all 13 protein-coding genes and the 2 rRNAs, and found unusual patterns of mitochondrial evolution. The Nasonia mtDNA has a unique gene order compared with other insect mtDNAs due to multiple rearrangements. The mtDNAs of these wasps also show nucleotide substitution rates over 30 times faster than nuclear protein-coding genes, indicating among the highest substitution rates found in animal mitochondria (normally <10 times faster). A McDonald and Kreitman test shows that the between-species frequency of fixed replacement sites relative to silent sites is significantly higher compared with within-species polymorphisms in 2 mitochondrial genes of Nasonia, atp6 and atp8, indicating directional selection. Consistent with this interpretation, the Ka/Ks (nonsynonymous/synonymous substitution rates) ratios are higher between species than within species. In contrast, cox1 shows a signature of purifying selection for amino acid sequence conservation, although rates of amino acid substitutions are still higher than for comparable insects. The mitochondrial-encoded polypeptides atp6 and atp8 both occur in F0F1ATP synthase of the electron transport chain. Because malfunction in this fundamental protein severely affects fitness, we suggest that the accelerated accumulation of replacements is due to beneficial mutations necessary to compensate mild-deleterious mutations fixed by random genetic drift or Wolbachia sweeps in the fast evolving mitochondria of Nasonia. We further propose that relatively high rates of amino acid substitution in some mitochondrial genes can be driven by a “Compensation-Draft Feedback”; increased fixation of mildly deleterious mutations results in selection for compensatory mutations, which lead to fixation of additional deleterious mutations in nonrecombining mitochondrial genomes, thus

  9. Rapidly evolving mitochondrial genome and directional selection in mitochondrial genes in the parasitic wasp nasonia (hymenoptera: pteromalidae).

    Science.gov (United States)

    Oliveira, Deodoro C S G; Raychoudhury, Rhitoban; Lavrov, Dennis V; Werren, John H

    2008-10-01

    We sequenced the nearly complete mtDNA of 3 species of parasitic wasps, Nasonia vitripennis (2 strains), Nasonia giraulti, and Nasonia longicornis, including all 13 protein-coding genes and the 2 rRNAs, and found unusual patterns of mitochondrial evolution. The Nasonia mtDNA has a unique gene order compared with other insect mtDNAs due to multiple rearrangements. The mtDNAs of these wasps also show nucleotide substitution rates over 30 times faster than nuclear protein-coding genes, indicating among the highest substitution rates found in animal mitochondria (normally mitochondrial genes of Nasonia, atp6 and atp8, indicating directional selection. Consistent with this interpretation, the Ka/Ks (nonsynonymous/synonymous substitution rates) ratios are higher between species than within species. In contrast, cox1 shows a signature of purifying selection for amino acid sequence conservation, although rates of amino acid substitutions are still higher than for comparable insects. The mitochondrial-encoded polypeptides atp6 and atp8 both occur in F0F1ATP synthase of the electron transport chain. Because malfunction in this fundamental protein severely affects fitness, we suggest that the accelerated accumulation of replacements is due to beneficial mutations necessary to compensate mild-deleterious mutations fixed by random genetic drift or Wolbachia sweeps in the fast evolving mitochondria of Nasonia. We further propose that relatively high rates of amino acid substitution in some mitochondrial genes can be driven by a "Compensation-Draft Feedback"; increased fixation of mildly deleterious mutations results in selection for compensatory mutations, which lead to fixation of additional deleterious mutations in nonrecombining mitochondrial genomes, thus accelerating the process of amino acid substitutions.

  10. The effects of nifekalant hydrochloride on the spatial dispersion of repolarization after direct current defibrillation in patients with oral amiodarone and β-blocker therapy

    Directory of Open Access Journals (Sweden)

    Keiko Maeda

    2014-06-01

    Conclusions: NIF suppressed the deterioration of the SDR after ICD shock. This might be one of the mechanisms by which NIF suppresses recurrence of ventricular tachyarrhythmia just after ICD shock in patients with oral amiodarone and β-blocker therapy.

  11. A comparison of a modified sequential oral sensory approach to an applied behavior-analytic approach in the treatment of food selectivity in children with autism spectrum disorder.

    Science.gov (United States)

    Peterson, Kathryn M; Piazza, Cathleen C; Volkert, Valerie M

    2016-09-01

    Treatments of pediatric feeding disorders based on applied behavior analysis (ABA) have the most empirical support in the research literature (Volkert & Piazza, 2012); however, professionals often recommend, and caregivers often use, treatments that have limited empirical support. In the current investigation, we compared a modified sequential oral sensory approach (M-SOS; Benson, Parke, Gannon, & Muñoz, 2013) to an ABA approach for the treatment of the food selectivity of 6 children with autism. We randomly assigned 3 children to ABA and 3 children to M-SOS and compared the effects of treatment in a multiple baseline design across novel, healthy target foods. We used a multielement design to assess treatment generalization. Consumption of target foods increased for children who received ABA, but not for children who received M-SOS. We subsequently implemented ABA with the children for whom M-SOS was not effective and observed a potential treatment generalization effect during ABA when M-SOS preceded ABA.

  12. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.

    Science.gov (United States)

    Zanin-Zhorov, Alexandra; Weiss, Jonathan M; Nyuydzefe, Melanie S; Chen, Wei; Scher, Jose U; Mo, Rigen; Depoil, David; Rao, Nishta; Liu, Ben; Wei, Jianlu; Lucas, Sarah; Koslow, Matthew; Roche, Maria; Schueller, Olivier; Weiss, Sara; Poyurovsky, Masha V; Tonra, James; Hippen, Keli L; Dustin, Michael L; Blazar, Bruce R; Liu, Chuan-ju; Waksal, Samuel D

    2014-11-25

    Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor γt protein levels in T cells derived from healthy subjects or rheumatoid arthritis patients. Simultaneously, treatment with KD025 also promotes the suppressive function of regulatory T cells through up-regulation of STAT5 phosphorylation and positive regulation of forkhead box p3 expression. The administration of KD025 in vivo down-regulates the progression of collagen-induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2 signaling appears to be instrumental in regulating the balance between proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may therefore restore disrupted immune homeostasis and have a role in the treatment of autoimmunity.

  13. Effects of oral contraceptives on selected parameters of the homeostatic control system in young women having a sudden disorder of the auditory and/or balance system.

    Science.gov (United States)

    Urbaniak, Joanna; Zielińska-Bliźniewska, Hanna; Miłoński, Jarosław; Pietkiewicz, Piotr; Kuśmierczyk, Krzysztof; Olszewski, Jurek

    2015-02-01

    The purpose of the paper was to assess the effects of oral contraceptives on selected parameters of the homeostatic control system in women having a sudden disorder of the auditory and/or balance system. The study included 105 young women divided into two groups: Group I--52 women with the disorder of the auditory and/or balance system using hormonal contraceptives for at least 2 months, aged 20-49; and Group II--53 women without any disorder of the auditory and/or balance system using hormonal contraceptives for at least 2 months, aged 18-40. The patients included in the study underwent a full otoneurological evaluation, detailed laryngological diagnostics and an evaluation of selected parameters of the homeostatic control system--fibrinogen level, D-dimer level, evaluation of APTT and PT indicator, plasma estradiol and progesterone with the Roche Cobas analyser by means of chemiluminescence. The vertigo occurring in the study group was most often central (59.6% of cases), mixed with compensation in 36.6% of cases, and peripheral only in 3.8% of cases, indicating labyrinth damage in 40.4% of cases. An analysis of the progesterone level, considering the menstrual cycle phase in the group, showed that its value was abnormal in 51.0% of women in the study group and 47.1% in the control group. In their own studies, the authors observed that the estradiol level in the plasma, considering the menstrual cycle phase in the study group, was abnormal in 41.2% of women and that the differences in its concentration were statistically significant in the study and control groups (p = 0.005), which may have a negative impact on the possibility of a thromboembolic episode.

  14. The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.

    Science.gov (United States)

    Avnit-Sagi, Tali; Kantorovich, Lia; Kredo-Russo, Sharon; Hornstein, Eran; Walker, Michael D

    2009-01-01

    microRNAs (miRNAs) are known to play an essential role in controlling a broad range of biological processes including animal development. Accordingly, many miRNAs are expressed preferentially in one or a small number of cell types. Yet the mechanisms responsible for this selectivity are not well understood. The aim of this study was to elucidate the molecular basis of cell-specific expression of the pri-miR-375 gene, which is selectively expressed in pancreatic islets, and has been implicated both in the development of islets, and the function of mature pancreatic beta cells. An evolutionarily conserved 768 bp region of DNA upstream of the pri-miR-375 gene was linked to GFP and luciferase reporter genes, and expression monitored in transgenic mice and transfected cultured cells. Deletion and targeted mutagenesis analysis was used to evaluate the functional significance of sequence blocks within the upstream fragment. 5'-RACE analysis was used for mapping the pri-miR-375 gene transcription start site. The conserved 768 bp region was able to direct preferential expression of a GFP reporter gene to pancreatic islets in transgenic mice. Deletion analysis using a luciferase reporter gene in transfected cultured cell lines confirmed the cell specificity of the putative promoter region, and identified several key cis-elements essential for optimal activity, including E-boxes and a TATA sequence. Consistent with this, 5'-RACE analysis identified a transcription start site within this DNA region, 24 bp downstream of the TATA sequence. These studies define the promoter of the pri-miR-375 gene, and show that islet-specific expression of the pri-miR-375 gene is controlled at the transcriptional level. Detailed analysis of the transcriptional mechanisms controlling expression of miRNA genes will be essential to permit a comprehensive understanding of the complex role of miRNAs such as miR-375 in developmental processes.

  15. Validation of a Minor Modification to the Soleris® Direct Yeast and Mold Vial and Selective Supplement.

    Science.gov (United States)

    Alles, Susan; McDougal, Susan; Caballero, Oscar; Mozola, Mark; Rice, Jennifer

    2015-01-01

    Here we describe results of a study to validate minor reagent formulation changes to the Soleris Direct Yeast and Mold (DYM) automated growth-based method for semi-quantitative detection of yeast and mold in food products. In order to reduce the maximum concentration of the selective agent chloramphenicol in the Soleris reagents, chloramphenicol was removed from the selective supplement and added to the vial growth medium itself. Therefore, both the vial medium and supplement have been reformulated in an alternative version of the method. A probability of detection (POD) statistical model was used to compare Soleris results at multiple test thresholds (dilutions) with plate counts determined using the U.S. Food and Drug Administration Bacteriological Analytical Manual dilution plating procedure. Three matrixes were tested; yogurt, tomato juice, and cocoa powder. POD analysis showed that the percentage of positive Soleris tests at various test thresholds were within the limits predicted by the reference method plate counts for all matrixes evaluated. Real-time stability data on three manufactured lots showed that the modified Soleris vial and supplement are stable for at a minimum of 10 months when stored at 2-8°C. In sum, results presented here demonstrate that the modifications to the Soleris DYM vial and supplement do not impact method performance. The modified Soleris DYM method can be used as an accurate alternative to conventional dilution plating procedures for semi-quantitative determination of yeast and mold at threshold levels, while saving as much as 3 days in analysis time.

  16. Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE KPT-335 in spontaneous canine cancer: results of a phase I study.

    Directory of Open Access Journals (Sweden)

    Cheryl A London

    Full Text Available BACKGROUND: The purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1 against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability. METHODS AND FINDINGS: Canine tumor cell lines derived from non-Hodgkin lymphoma (NHL, mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations of SINE compounds; NHL cells were particularly sensitive with IC50 concentrations ranging from 2-42 nM. A Phase I clinical trial of KPT-335 was performed in 17 dogs with NHL (naive or relapsed, mast cell tumor or osteosarcoma. The maximum tolerated dose was 1.75 mg/kg given orally twice/week (Monday/Thursday although biologic activity was observed at 1 mg/kg. Clinical benefit (CB including partial response to therapy (PR, n = 2 and stable disease (SD, n = 7 was observed in 9/14 dogs with NHL with a median time to progression (TTP for responders of 66 days (range 35-256 days. A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days. Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities. CONCLUSIONS: This study provides evidence that the novel orally bioavailable XPO1 inhibitor KPT-335 is safe and exhibits activity in a relevant, spontaneous large animal model of cancer. Data from this study provides critical new information that lays the groundwork for evaluation of SINE compounds in human cancer.

  17. The Combination of Direct and Confined Laser Ablation Mechanisms for the Selective Structuring of Thin Silicon Nitride Layers

    Science.gov (United States)

    Rapp, Stephan; Heinrich, Gerrit; Domke, Matthias; Huber, Heinz P.

    In the production process of microelectronic devices and high efficiency solar cells, local openings in thin dielectric layers are required. Instead of photolithographic, laser based processing enables to open these dielectric layers locally in a low-cost mass production step. In this work, thin silicon nitride layers deposited on planar silicon wafers are processed by single infrared Gaussian shaped 660 fs laser pulses. The transparent silicon nitride layer, becoming absorptive at fluences higher than 0.3 J/cm2, is selectively removed by confined ablation at fluences below that value. At pulse peak fluences exceeding 1.0 J/cm2 a "SiNx island"is created by direct ablation in the spot center. In this article, theselective SiNx ablation by a combination of confined and direct laser ablation at the medium pulse peak fluence of 0.5 J/cm2 is investigated. To clarify the influence of the nonlinear absorption in the pulse center, the ablation behavior is investigated by time- and space-resolved pump-probe microscopy experiments. The results showphase changes in the silicon and in the silicon nitride in the first picoseconds after excitation, the ablation onset at around 10 ps and the subsequent mechanical materialmotion after a few nanoseconds. The actual silicon nitride layer removal starts after around 10 ns, whereas confined ablation processes are the driving mechanisms even in the nonlinearly absorbing spot center. A comparison of the energetic ablation efficiency of the SiNx layer system to further dielectric thin films shows no detrimental influence of the nonlinear absorbance.

  18. Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review.

    Science.gov (United States)

    Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio

    2014-01-01

    Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70-1.11) and index DVT (RR: 0.93; 95% CI: 0.75-1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83-5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49-2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01-1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10-0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than, standard

  19. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  20. An Experiment to Observe Directly Beauty Particles Selected by Muonic Decay in Emulsion & to Estimate their Lifetimes

    CERN Multimedia

    2002-01-01

    A hybrid experiment to observe directly particles with open beauty and estimate their lifetimes is proposed. The experiment will take place in a @p|- beam at 360 GeV/c. Events of the type @p|-N @A B$\\bar{B}$X will be produced in a thick emulsion, allowing for a lifetime range of 10|-|1|5~-~10|-|1|2~s. The decay vertices of B and $\\bar{B}$ and of the subsequent charm decays will be identified in emulsion. \\\\ \\\\ The precise location of the production vertex will be measured by high precision (50@mm~pitch) silicon microstrip detectors. A set of planes of such detectors will be placed in front of the target to measure the incoming beam particle, and another set of planes, together with 16~planes of MWPC's will be plac target to measure the secondaries. \\\\ \\\\ The semi-leptonic decays of B's and C's are used to create a selective trigger. The data taking will be triggered by l@m with an angle to the beam @a~$>$~30~mrad, or by~@$>$~2@m. Transverse momentum cuts will be applied off-line.\\\\ \\\\ The muons are identified...

  1. Oral Thrush

    Science.gov (United States)

    ... feeding mothers In addition to the distinctive white mouth lesions, infants may have trouble feeding or be fussy ... candidiasis (yeast infection) patient information. American Academy of Oral & Maxillofacial Pathology. http://www.aaomp.org/public/oral-candidiasis.php. ...

  2. Prevention of oral diseases and oral health promotion.

    Science.gov (United States)

    Gift, H C

    1991-06-01

    Research and activities, as promoted in 1989 and 1990, in oral disease prevention and health promotion are summarized. Significant syntheses of research findings have occurred, as a result of planning and workship activities, which will direct oral health promotion in the 1990s. Original research on established and new preventive therapies for dental caries, periodontal diseases, oral mucosal alterations, soft-tissue lesions, precancers and cancers, and trauma are reported, opportunities to prevent oral diseases or maintain oral health through changes in individual behaviors, professional orientation, and social and environmental changes are addressed.

  3. Oral Dysfunction

    OpenAIRE

    鈴木, 規子; スズキ, ノリコ; Noriko, SUZUKI

    2004-01-01

    The major oral functions can be categorized as mastication, swallowing, speech and respiratory functions. Dysfunction of these results in dysphagia, speech disorders and abnormal respiration (such as Sleep Apnea). These functions relate to dentistry in the occurrence of : (1) oral preparatory and oral phases, (2) articulation disorders and velopharyngeal incompetence (VPI), and (3) mouth breathing, respiratory and blowing disorders. These disorders are related to oral and maxillofacial diseas...

  4. Combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin improves fulminant pseudomembranous colitis by reducing the elevated endogenous cannabinoids and inflammatory cytokines: report of a case.

    Science.gov (United States)

    Kimura, Yoshihide; Sato, Koichi; Tokuda, Hiroshi; Hashiguchi, Teruto; Maruyama, Ikuro; Orito, Etsuro; Dohi, Yasuaki; Joh, Takashi

    2008-01-01

    This paper reports a case of fulminant pseudo-membranous colitis which did not lead to septic shock. The case was improved by combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin. Direct hemoperfusion using polymyxin B-immobilized fiber has been demonstrated to have excellent therapeutic effects for the treatment of septic shock by removing circulating lipopolysaccharide. In the present case, the combination therapy dramatically improved clinical status of the patient. The clinical improvement occurred in parallel with a decrease in APACHE II score (from 20 to 14 points), serum levels of endogenous cannabinoids (anandamide and 2-arachidonylglycerol), and inflammatory cytokine (interleukin-6). Thus, direct hemoperfusion is strongly recommended in cases of fulminant pseudomembranous colitis, because direct hemoperfusion using polymyxin B-immobilized fiber reduces inflammatory cytokines by absorbing endogenous cannabinoids and, thereby, improves the patient's condition.

  5. Integrated modelling of the clinical pharmacokinetics of SDZ HTF 919, a novel selective 5-HT4 receptor agonist, following oral and intravenous administration.

    Science.gov (United States)

    Appel-Dingemanse, S; Lemarechal, M O; Kumle, A; Hubert, M; Legangneux, E

    1999-05-01

    The purpose of the present study was to assess the pharmacokinetics of the novel selective 5-HT4 receptor agonist SDZ HTF 919 (HTF) including food effect, absolute bioavailability, interoccasion and intersubject variabilities. In the randomized, open-label, three treatment, four period crossover study, HTF was administered to 12 young healthy male subjects as a 12 mg tablet (twice under fasted and once under fed conditions) and a 3 mg intravenous (i.v.) infusion over 40 min (fasted). Pharmacokinetic parameters were obtained by noncompartmental methods. A more comprehensive pharmacokinetic characterization was achieved by integrated modelling of oral (p.o.) and i.v. data. To describe the absorption phase a Weibull function and a classical first order input function were compared. Noncompartmental pharmacokinetic analysis revealed a rapid absorption (tmax 1.3 h, fasted), an absolute bioavailability of 11+/-3%, a biphasic disposition phase with a terminal half-life of 11+/-5 h, a clearance of 77+/-15 l h-1, and a volume of distribution at steady state of 368+/-223 l. The coefficients of interoccasion and interindividual variability in Cmax and AUC ranged between 17 and 28%. Food intake caused a delay (tmax 2.0 h) and decrease in absorption with consequently lower systemic exposure ( approximately 5% absolute bioavailability). Integrated p.o./i.v. pharmacokinetic modelling with a Weibull input function allowed accurate description of individual profiles. Modelling of the data from the p.o. dosing improved the description of the terminal phase by inclusion of the i. v. data and additionally provided quantitative characterization of the absorption phase. The pharmacokinetics of HTF could be well described by an integrated modelling approach for both p.o. and i.v. data. The derived model will provide guidance in the design of future studies.

  6. The influence of the body mass index (BMI) on selected parameters of the coagulation system in patients with disorders of the balance system taking oral contraceptives.

    Science.gov (United States)

    Bielińska, Marzena; Urbaniak, Joanna; Kuśmierczyk, Krzysztof; Olszewski, Jurek; Pietkiewicz, Piotr

    2016-07-10

    The objective of the paper is to evaluate the influence of the body mass index (BMI) on selected parameters of the coagulation system in patients with disorders of the balance system taking oral contraceptives. 105 young women participated in the study who were divided into 2 groups. Group I: 52 women disorders of the balance system taking hormonal contraceptives for at least 2 months, between the age of 20-49; Group II: 53 women with no disorders of the balance system taking hormonal contraceptives for at least 2 months, between the age of 18-40. Patients entering the study underwent full otoneurological examination, detailed laryngological assessment and the examination of selected parameters of the hemostasis system, including the evaluation of fibrinogen and D-dimer levels, APTT and PT, estradiol and progesterone concentrations in the blood serum and evaluation of the body mass index (BMI). Central vertigo was the most common type of vertigo in the study group (59,6% of cases). Other vertigo types in this group included compensated vertigo of mixed origin (36,6% of cases) and peripheral vertigo (only 3,8% of cases), which indicates that 40.4% of the cases suffer from damage to the labyrinth. The analysis of the concentration of estradiol in the blood serum revealed, after consideration of a menstrual cycle phase, that estradiol concentration exceeded normative values significantly more often in the study group than in the control group and that estradiol concentration was significantly less frequently below the norm in the study group; the difference was statistically significant (p=0,048). The body mass index (BMI) of women participating in the study significantly correlated with the concentration of D-dimers only in the study group (p=0,35 vs p=0,012). Evaluating the body mass index before administering hormonal contraception can be useful to eliminate other risk factors for thromboembolism. In order to prevent potential thromboembolism episodes

  7. Dissecting direct and indirect readout of cAMP receptor protein DNA binding using an inosine and 2,6-diaminopurine in vitro selection system

    DEFF Research Database (Denmark)

    Lindemose, Søren; Nielsen, Peter E.; Møllegaard, Niels Erik

    2008-01-01

    is functionally intact. The majority of the selected sites contain the natural consensus sequence TGTGAN(6)TCACA (i.e. TITIDN(6)TCDCD). Thus, direct readout of the consensus sequence is independent of minor groove conformation. Consequently, the indirect readout known to occur in the TG/CA base pair step (primary......The DNA interaction of the Escherichia coli cyclic AMP receptor protein (CRP) represents a typical example of a dual recognition mechanism exhibiting both direct and indirect readout. We have dissected the direct and indirect components of DNA recognition by CRP employing in vitro selection...... kink site) in the consensus sequence is not affected by I-D substitutions. In contrast, the flanking regions are selected as I/C rich sequences (mostly I-tracts) instead of A/T rich sequences which are known to strongly increase CRP binding, thereby demonstrating almost exclusive indirect readout...

  8. Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review

    Directory of Open Access Journals (Sweden)

    Gómez-Outes A

    2014-11-01

    Full Text Available Antonio Gómez-Outes,1 Mª Luisa Suárez-Gea,1 Ramón Lecumberri,2 Ana Isabel Terleira-Fernández,3,4 Emilio Vargas-Castrillón3,41Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS, Madrid, Spain; 2Department of Hematology, University Clinic of Navarra, Pamplona, Spain; 3Department of Clinical Pharmacology, Hospital Clínico, Madrid, Spain; 4Department of Pharmacology, Universidad Complutense, Madrid, SpainAbstract: Pulmonary embolism (PE is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT are considered expressions of the same disease, termed as venous thromboembolism (VTE. In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41% had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70–1.11 and index DVT (RR: 0.93; 95% CI: 0.75–1.16 (P for subgroup differences =0.76. VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83–5.03 and in patients with index DVT (RR: 1.11; 95% CI: 0.49–2.50 (P for subgroup differences =0.32. In trials that compared DOAC

  9. The effect of selective photosuppression of sensitized pathogenic microflora: Part I. Influence on pathogenic organisms causing pyoinflammatory processes in oral cavity

    Science.gov (United States)

    Masychev, Viktor I.; Risovannaya, Olga N.

    2005-03-01

    The effectiveness of Bacteriotoxic light therapy (BTL) in many respects depends on the right choice of the photo sensitizer and used parameters of laser radiation. Experimental studies in vitro have revealed the presence of correlation dependence between the photo sensitizer Radachlorine, energy density, irradiation duration executed with low energy diode laser and the number of viable bacterial cells causing the development of inflammatory affection of oral cavity. BTL in parameters defined in the experiments develops bactericidal action on pathogenic microflora of oral cavity.

  10. Directing Group in Decarboxylative Cross-Coupling: Copper-Catalyzed Site-Selective C-N Bond Formation from Nonactivated Aliphatic Carboxylic Acids.

    Science.gov (United States)

    Liu, Zhao-Jing; Lu, Xi; Wang, Guan; Li, Lei; Jiang, Wei-Tao; Wang, Yu-Dong; Xiao, Bin; Fu, Yao

    2016-08-03

    Copper-catalyzed directed decarboxylative amination of nonactivated aliphatic carboxylic acids is described. This intramolecular C-N bond formation reaction provides efficient access to the synthesis of pyrrolidine and piperidine derivatives as well as the modification of complex natural products. Moreover, this reaction presents excellent site-selectivity in the C-N bond formation step through the use of directing group. Our work can be considered as a big step toward controllable radical decarboxylative carbon-heteroatom cross-coupling.

  11. Assortative mating and directional or stabilizing selection for a non-linear function of traits in Tribolium.

    Science.gov (United States)

    Campo, J L; Gil, M G

    1993-01-12

    Assortative or random mating following selection in either direction on a non-linear index (experiment 1) or stabilizing selection for pupal length (experiment 2) were carried out for five generations in two lines of Tribolium castaneum (A and R, respectively), with three replicates each. The selected proportion was 25% in all lines. In experiment 1, the selection criterion was designed to increase the aggregate value of adult weight and the first- and second-order powers of pupal length. The A and R lines gave significant responses for the aggregate value (184 ± 6 and 161 ± 14, respectively), pupal length (0.74 ± 0.02 and 0.64 ± 0.05, respectively), and adult weight (0.79 ± 0.03 and 0.78 ± 0.12, respectively). Although the A line was not significantly better than the R line, there was a consistent advantage for assortative mating over random mating, the mean response for aggregate value and pupal length being approximately 1.15 times greater for the A line. In experiment 2 the selection criterion was the square of the deviation from the mean pupal length (stabilizing selection); both lines did not show any change for pupal length. The phenotypic variance showed a significant decrease in the A and R lines, due to a decrease in between-family variance. The assortatively and randomly mated lines were similar for these changes in phenotypic variation. RESUMEN: Aparemiento clasificado y selección direccional o estabilizante para una función no lineal en Tribolium. Dos líneas de Tribolium castaneum fueron seleccionadas direccionalmente para un índice no lineal (experimento 1) o estabilizantemente para longitud de pupa (experimento 2), apareando los animales seleccionados clasificadamente (A) o aleatoriamente (R). Había tres repeticiones por experimento y línea, siendo la proporción de selección el 25%. En el experimento 1, el objetivo de selección incluía el peso adulto así como la longitud de pupa y su cuadrado. Ambas líneas dieron respuesta

  12. [Treatment with inhibitors of new oral direct anticoagulants in patients with severe bleedings or urgent surgical procedures. The new dabigatran antidote: the place of idarucizumab in clinical practice].

    Science.gov (United States)

    Boda, Zoltán

    2016-03-20

    Only vitamin K antagonists could be applied as oral anticoagulants over the past six decades. Coumarols have narrow therapeutic range, and unpredictable anticoagulant effects are resulted by multiple drug interactions. Therefore, regular routine monitoring of the international normalized ratio is necessary. There are two groups of factor-specific anticoagulants: molecules with anti-FIIa (dabigatran) and anti-FXa (rivaroxaban, apixaban and edoxaban) effect. Author summarizes the most important clinical features of the new oral anticoagulants, their indications and the possibilities of laboratory controls. Bleedings are the most important side effects of anticoagulants. This review summarizes the current published evidences for new oral anticoagulants reversal (non-specific and specific) agents, especially in cases with severe acute bleedings or urgent surgery procedures. It reports on how to use inhibitors, the recommended doses and the most important clinical results. The review focuses on idarucizumab - already approved by the U.S. Food and Drug Administration and the European Medicines Agency - which has a key role as the first specific inhibitor of dabigatran.

  13. Direct and correlated responses to selection in two lines of rabbits selected for feed efficiency under ad libitum and restricted feeding: II. Carcass and meat quality.

    Science.gov (United States)

    Molette, C; Gilbert, H; Larzul, C; Balmisse, E; Ruesche, J; Manse, H; Tircazes, A; Theau-Clément, M; Joly, T; Gidenne, T; Garreau, H; Drouilhet, L

    2016-01-01

    To get insights into selection criteria for feed efficiency, 2 rabbit lines have been created: the ConsoResidual line was selected for residual feed intake (RFI) with ad libitum feeding and the ADGrestrict line was selected for ADG under restricted feeding. The aim of the present study was to evaluate the impact on carcass and meat quality of the genetic selections. This comparison was performed using 2 different feeding strategies corresponding to the selection design. Carcass and meat quality traits were recorded for the 3 lines (ConsoResidual, ADGrestrict, and an unselected control [generation 0 {G0}]) in the 2 feeding systems (ad libitum and restricted) for 163 animals. Concerning the line effect, the BW at 63 d old was higher for the ADGrestrict line compared with the G0 and ConsoResidual lines ( rabbits did not exhibit a different carcass yield but showed different carcass traits. Indeed, the ConsoResidual rabbits had a higher hind leg yield ( rabbits. The ADGrestrict line had an intermediate perirenal fat yield compared with the other 2 lines. The G0 line always exhibited higher fat yields. Concerning meat quality, the ConsoResidual rabbits showed a lower ultimate pH ( rabbits. The feeding level had a strong effect on the gastrointestinal tract ( = 0.0004) and the carcass yield ( = 0.001). The latter was decreased in restricted rabbits. The effects of feeding strategy on meat quality were detrimental in the case of restricted feeding. Even if the ultimate pH was slightly higher in restricted rabbits ( = 0.0002), the carcass chilling loss ( = 0.0005) and the drip loss during 6 d ( feed seems to be less adversely correlated with carcass traits and meat quality traits but it leads to an increase in the live weight of the rabbits. Adversely, the selection on RFI, without affecting growth rate, would not modify age at slaughter because growth rate is not affected, but it might induce detrimental effects on meat quality.

  14. Discovery of N-(4-(2-Amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a Selective and Orally Efficacious Inhibitor of the Met Kinase Superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Gretchen M.; An, Yongmi; Cai, Zhen-Wei; Chen, Xiao-Tao; Clark, Cheryl; Cornelius, Lyndon A.M.; Dai, Jun; Gullo-Brown, Johnni; Gupta, Ashok; Henley, Benjamin; Hunt, John T.; Jeyaseelan, Robert; Kamath, Amrita; Kim, Kyoung; Lippy, Jonathan; Lombardo, Louis J.; Manne, Veeraswamy; Oppenheimer, Simone; Sack, John S.; Schmidt, Robert J.; Shen, Guoxiang; Stefanski, Kevin; Tokarski, John S.; Trainor, George L.; Wautlet, Barri S.; Wei, Donna; Williams, David K.; Zhang, Yingru; Zhang, Yueping; Fargnoli, Joseph; Borzilleri, Robert M.; (BMS)

    2009-12-01

    Substituted N-(4-(2-aminopyridin-4-yloxy)-3-fluoro-phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamides were identified as potent and selective Met kinase inhibitors. Substitution of the pyridine 3-position gave improved enzyme potency, while substitution of the pyridone 4-position led to improved aqueous solubility and kinase selectivity. Analogue 10 demonstrated complete tumor stasis in a Met-dependent GTL-16 human gastric carcinoma xenograft model following oral administration. Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclinical safety profiles, 10 has been advanced into phase I clinical trials.

  15. Early processing variations in selective attention to the color and direction of moving stimuli during 30 days head-down bed rest

    Science.gov (United States)

    Wang, Lin-Jie; He, Si-Yang; Niu, Dong-Bin; Guo, Jian-Ping; Xu, Yun-Long; Wang, De-Sheng; Cao, Yi; Zhao, Qi; Tan, Cheng; Li, Zhi-Li; Tang, Guo-Hua; Li, Yin-Hui; Bai, Yan-Qiang

    2013-11-01

    Dynamic variations in early selective attention to the color and direction of moving stimuli were explored during a 30 days period of head-down bed rest. Event-related potentials (ERPs) were recorded at F5, F6, P5, P6 scalp locations in seven male subjects who attended to pairs of bicolored light emitting diodes that flashed sequentially to produce a perception of movement. Subjects were required to attend selectively to a critical feature of the moving target, e.g., color or direction. The tasks included: a no response task, a color selective response task, a moving direction selective response task, and a combined color-direction selective response task. Subjects were asked to perform these four tasks on: the 3rd day before bed rest; the 3rd, 15th and 30th day during the bed rest; and the 5th day after bed rest. Subjects responded quickly to the color than moving direction and combined color-direction response. And they had a longer reaction time during bed rest on the 15th and 30th day during bed rest after a relatively quicker response on the 3rd day. Using brain event-related potentials technique, we found that in the color selective response task, the mean amplitudes of P1 and N1 for target ERPs decreased in the 3rd day during bed rest and 5th day after bed rest in comparison with pre-bed rest, 15th day and 30th day during bed rest. In the combined color-direction selective response task, the P1 latencies for target ERPs on the 3rd and 30th day during bed rest were longer than on the 15th day during bed rest. As 3rd day during bed rest was in the acute adaptation period and 30th day during bed rest was in the relatively adaptation stage of head-down bed rest, the results help to clarify the effects of bed rest on different task loads and patterns of attention. It was suggested that subjects expended more time to give correct decision in the head-down tilt bed rest state. A difficulty in the recruitment of brain resources was found in feature selection task

  16. Direct phase selection of initial phases from single-wavelength anomalous dispersion (SAD) for the improvement of electron density and ab initio structure determination

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chung-De [National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu 30076, Taiwan (China); National Tsing Hua University, Hsinchu, Taiwan (China); Huang, Yen-Chieh [National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu 30076, Taiwan (China); Chiang, Hsin-Lin [National Tsing Hua University, Hsinchu, Taiwan (China); Hsieh, Yin-Cheng; Guan, Hong-Hsiang; Chuankhayan, Phimonphan [National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu 30076, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@nsrrc.org.tw [National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu 30076, Taiwan (China); National Tsing Hua University, Hsinchu, Taiwan (China); National Cheng Kung University, Tainan City 701, Taiwan (China); National Cheng Kung University, Tainan City 701, Taiwan (China)

    2014-09-01

    A novel direct phase-selection method to select optimized phases from the ambiguous phases of a subset of reflections to replace the corresponding initial SAD phases has been developed. With the improved phases, the completeness of built residues of protein molecules is enhanced for efficient structure determination. Optimization of the initial phasing has been a decisive factor in the success of the subsequent electron-density modification, model building and structure determination of biological macromolecules using the single-wavelength anomalous dispersion (SAD) method. Two possible phase solutions (ϕ{sub 1} and ϕ{sub 2}) generated from two symmetric phase triangles in the Harker construction for the SAD method cause the well known phase ambiguity. A novel direct phase-selection method utilizing the θ{sub DS} list as a criterion to select optimized phases ϕ{sub am} from ϕ{sub 1} or ϕ{sub 2} of a subset of reflections with a high percentage of correct phases to replace the corresponding initial SAD phases ϕ{sub SAD} has been developed. Based on this work, reflections with an angle θ{sub DS} in the range 35–145° are selected for an optimized improvement, where θ{sub DS} is the angle between the initial phase ϕ{sub SAD} and a preliminary density-modification (DM) phase ϕ{sub DM}{sup NHL}. The results show that utilizing the additional direct phase-selection step prior to simple solvent flattening without phase combination using existing DM programs, such as RESOLVE or DM from CCP4, significantly improves the final phases in terms of increased correlation coefficients of electron-density maps and diminished mean phase errors. With the improved phases and density maps from the direct phase-selection method, the completeness of residues of protein molecules built with main chains and side chains is enhanced for efficient structure determination.

  17. ARTIFICIAL SELECTION FOR DEVELOPMENTAL TIME IN DROSOPHILA-MELANOGASTER IN RELATION TO THE EVOLUTION OF AGING - DIRECT AND CORRELATED RESPONSES

    NARCIS (Netherlands)

    ZWAAN, B; BIJLSMA, R; HOEKSTRA, RF

    1995-01-01

    A wild-type strain of Drosophila melanogaster was successfully selected for both fast and slow larval development. The realized heritabilities (h(2)) ranged from 0.20 to 0.30 for the fast lines and 0.35 to 0.60 for the slow lines. The selection applied is relevant in relation to the evolution of agi

  18. Dual-tree cosine-modulated filter bank with linear-phase individual filters: an alternative shift-invariant and directional-selective transform.

    Science.gov (United States)

    Liang, Lili; Liu, Han

    2013-12-01

    Dual-tree transforms have recently received much attention for the properties of shift-invariance and directional-selectivity. However, their designs generally encounter fractional-delay constraints, and become more complicated for providing linear-phase (LP) individual filters and flexible directional-selectivity, two important properties in image processing. In this paper, we propose an alternative shift-invariant and directional-selective transform-the dual-tree cosine-modulated filter bank (DTCMFB). In the proposed DTCMFB, its primal and dual filter banks are derived by cosine-modulating one LP prototype filter, and thus its design involves no fractional-delay constraints. Meanwhile, the derived modulation technique guarantees each individual filter to be LP and the LP condition is satisfied without any constraint on the prototype filter. By separable operations, the DTCMFB is extended to two-dimensions. The resulting 2D DTCMFB can provide much more flexible directional-selectivity. Finally, several simulations are given to verify the proposed DTCMFB, and the experiments on nonlinear approximation and image denoising are presented to demonstrate its potential in image processing.

  19. Oral histoplasmosis

    Directory of Open Access Journals (Sweden)

    Patil Karthikeya

    2009-01-01

    Full Text Available Histoplasmosis is a systemic fungal disease that takes various clinical forms, among which oral lesions are rare. The disseminated form of the disease that usually occurs in association with Human Immunodeficiency Virus (HIV is one of the AIDS-defining diseases. Isolated oral histoplasmosis, without systemic involvement, with underlying immunosuppression due to AIDS is very rare. We report one such case of isolated oral histoplasmosis in a HIV-infected patient.

  20. Genome-wide Scan of 29,141 African Americans Finds No Evidence of Directional Selection since Admixture

    Science.gov (United States)

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Caporaso, Neil; Casey, Graham; Deming, Sandra L.; Diver, W. Ryan; Gapstur, Susan M.; Gillanders, Elizabeth M.; Harris, Curtis C.; Henderson, Brian E.; Ingles, Sue A.; Isaacs, William; De Jager, Phillip L.; John, Esther M.; Kittles, Rick A.; Larkin, Emma; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Tucker, Margaret A.; Wiencke, John K.; Witte, John S.; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Chanock, Stephen J.; Haiman, Christopher A.; Reich, David; Price, Alkes L.

    2014-01-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study’s conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas. PMID:25242497

  1. Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture.

    Science.gov (United States)

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C; Ambrosone, Christine B; Amos, Christopher; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bock, Cathryn H; Caporaso, Neil; Casey, Graham; Deming, Sandra L; Diver, W Ryan; Gapstur, Susan M; Gillanders, Elizabeth M; Harris, Curtis C; Henderson, Brian E; Ingles, Sue A; Isaacs, William; De Jager, Phillip L; John, Esther M; Kittles, Rick A; Larkin, Emma; McNeill, Lorna H; Millikan, Robert C; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret; Strom, Sara S; Tucker, Margaret A; Wiencke, John K; Witte, John S; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A; Zheng, Wei; Ziegler, Regina G; Chanock, Stephen J; Haiman, Christopher A; Reich, David; Price, Alkes L

    2014-10-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.

  2. Direct and Highly Selective Conversion of Synthesis Gas into Lower Olefins: Design of a Bifunctional Catalyst Combining Methanol Synthesis and Carbon-Carbon Coupling.

    Science.gov (United States)

    Cheng, Kang; Gu, Bang; Liu, Xiaoliang; Kang, Jincan; Zhang, Qinghong; Wang, Ye

    2016-04-01

    The direct synthesis of lower (C2 to C4) olefins, key building-block chemicals, from syngas (H2/CO), which can be derived from various nonpetroleum carbon resources, is highly attractive, but the selectivity for lower olefins is low because of the limitation of the Anderson-Schulz-Flory distribution. We report that the coupling of methanol-synthesis and methanol-to-olefins reactions with a bifunctional catalyst can realize the direct conversion of syngas to lower olefins with exceptionally high selectivity. We demonstrate that the choice of two active components and the integration manner of the components are crucial to lower olefin selectivity. The combination of a Zr-Zn binary oxide, which alone shows higher selectivity for methanol and dimethyl ether even at 673 K, and SAPO-34 with decreased acidity offers around 70% selectivity for C2-C4 olefins at about 10% CO conversion. The micro- to nanoscale proximity of the components favors the lower olefin selectivity.

  3. Efficient attentional selection predicts distractor devaluation: event-related potential evidence for a direct link between attention and emotion.

    Science.gov (United States)

    Kiss, Monika; Goolsby, Brian A; Raymond, Jane E; Shapiro, Kimron L; Silvert, Laetitia; Nobre, Anna C; Fragopanagos, Nickolaos; Taylor, John G; Eimer, Martin

    2007-08-01

    Links between attention and emotion were investigated by obtaining electrophysiological measures of attentional selectivity together with behavioral measures of affective evaluation. Participants were asked to rate faces that had just been presented as targets or distractors in a visual search task. Distractors were rated as less trustworthy than targets. To study the association between the efficiency of selective attention during visual search and subsequent emotional responses, the N2pc component was quantified as a function of evaluative judgments. Evaluation of distractor faces (but not target faces) covaried with selective attention. On trials where distractors were later judged negatively, the N2pc emerged earlier, demonstrating that attention was strongly biased toward target events, and distractors were effectively inhibited. When previous distractors were judged positively, the N2pc was delayed, indicating unfocused attention to the target and less distractor suppression. Variations in attentional selectivity across trials can predict subsequent emotional responses, strongly suggesting that attention is closely associated with subsequent affective evaluation.

  4. Gamma-aminobutyric acid and GABA_A receptors are involved in directional selectivity of pretectal neurons in pigeons

    Institute of Scientific and Technical Information of China (English)

    肖泉; 付煜西; 胡婧; 高洪峰; 王书荣

    2000-01-01

    The present study describes the effects of gamma-aminobutyric acid (GABA) and its antagonists, bicuculline and 2-hydroxysaclofen, on visual responses of neurons in the pigeon nucleus lentiformis mesencephali (nLM). The results indicate that GABA significantly reduces both spontaneous activity and visual responsiveness, and GABAA antagonist bicuculline but not GABAB antagonist 2-hydroxysaclofen enhances visual responses of nLM cells examined. Furthermore, inhibition produced by motion in the null-direction of pretectal neurons is diminished by bicuculline but not by 2-hydroxysaclofen. It is therefore concluded that the null-direction inhibition of directional cells in the pigeon nLM is predominantly mediated by GABA and GABAA receptors. This inhibition may at least in part underlie directional asymmetry of optokinetic responses.

  5. ORALLY ACTIVE CARBAMATE PRODRUGS OF THE SELECTIVE DOPAMINE AGONIST N-0437 - INVIVO ACTIVITIES IN THE 6-OHDA TURNING MODEL AND INVITRO ACTIVITIES

    NARCIS (Netherlands)

    DENDAAS, [No Value; DEBOER, P; TEPPER, PG; ROLLEMA, H; HORN, AS

    The in-vivo activities of eight carbamate prodrugs of the D2-agonist N-0437 were determined by examining the effects of the prodrugs, after their oral administration in rats with unilateral 6-OHDA lesions of the striatum. The resulting contralateral turning was used as an index of the activity of

  6. Genomic signatures of local directional selection in a high gene flow marine organism, the Atlantic cod (Gadus morhua)

    DEFF Research Database (Denmark)

    Eg Nielsen, Einar; Hansen, Jakob Hemmer; Poulsen, Nina Aagaard;

    2009-01-01

    Background: Marine fishes have been shown to display low levels of genetic structuring and associated high levels of gene flow, suggesting shallow evolutionary trajectories and, possibly, limited or lacking adaptive divergence among local populations. We investigated variation in 98 gene...... selection in local demes, or closely linked to loci under selection. Likewise, on a regional south/north transect of central and eastern Atlantic populations, seven loci displayed strongly elevated levels of genetic differentiation. Selection patterns among populations appeared to be relatively widespread...... archived otoliths from a Faeroese population demonstrated stability of the intra-population variation over 24 years. An exploratory landscape genetic analysis was used to elucidate potential effects of the most likely environmental factors responsible for the signatures of local adaptation. We found...

  7. Direct estimates of natural selection in Iberia indicate calcium absorption was not the only driver of lactase persistence in Europe.

    Science.gov (United States)

    Sverrisdóttir, Oddny Ósk; Timpson, Adrian; Toombs, Jamie; Lecoeur, Cecile; Froguel, Philippe; Carretero, Jose Miguel; Arsuaga Ferreras, Juan Luis; Götherström, Anders; Thomas, Mark G

    2014-04-01

    Lactase persistence (LP) is a genetically determined trait whereby the enzyme lactase is expressed throughout adult life. Lactase is necessary for the digestion of lactose--the main carbohydrate in milk--and its production is downregulated after the weaning period in most humans and all other mammals studied. Several sources of evidence indicate that LP has evolved independently, in different parts of the world over the last 10,000 years, and has been subject to strong natural selection in dairying populations. In Europeans, LP is strongly associated with, and probably caused by, a single C to T mutation 13,910 bp upstream of the lactase (LCT) gene (-13,910*T). Despite a considerable body of research, the reasons why LP should provide such a strong selective advantage remain poorly understood. In this study, we examine one of the most widely cited hypotheses for selection on LP--that fresh milk consumption supplemented the poor vitamin D and calcium status of northern Europe's early farmers (the calcium assimilation hypothesis). We do this by testing for natural selection on -13,910*T using ancient DNA data from the skeletal remains of eight late Neolithic Iberian individuals, whom we would not expect to have poor vitamin D and calcium status because of relatively high incident UVB light levels. None of the eight samples successfully typed in the study had the derived T-allele. In addition, we reanalyze published data from French Neolithic remains to both test for population continuity and further examine the evolution of LP in the region. Using simulations that accommodate genetic drift, natural selection, uncertainty in calibrated radiocarbon dates, and sampling error, we find that natural selection is still required to explain the observed increase in allele frequency. We conclude that the calcium assimilation hypothesis is insufficient to explain the spread of LP in Europe.

  8. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI).

    Science.gov (United States)

    Leonardi, Sergio; Rao, Sunil V; Harrington, Robert A; Bhatt, Deepak L; Gibson, C Michael; Roe, Matthew T; Kochman, Janusz; Huber, Kurt; Zeymer, Uwe; Madan, Mina; Gretler, Daniel D; McClure, Matthew W; Paynter, Gayle E; Thompson, Vivian; Welsh, Robert C

    2010-07-01

    Despite current dual-antiplatelet therapy with aspirin and clopidogrel, adverse clinical events continue to occur during and after percutaneous coronary intervention (PCI). The failure of clopidogrel to provide optimal protection may be related to delayed onset of action, interpatient variability in its effect, and an insufficient level of platelet inhibition. Furthermore, the irreversible binding of clopidogrel to the P2Y(12) receptor for the life span of the platelet is associated with increased bleeding risk especially during urgent or emergency surgery. Novel antiplatelet agents are required to improve management of patients undergoing PCI. Elinogrel is a potent, direct-acting (ie, non-prodrug), selective, competitive, and reversible P2Y(12) inhibitor available in both intravenous and oral formulations. The INNOVATE-PCI study is a phase 2 randomized, double-blind, clopidogrel-controlled trial to evaluate the safety, tolerability, and preliminary efficacy of this novel antiplatelet agent in patients undergoing nonurgent PCI.

  9. Direct Utilization of Liquid Fuels in SOFC for Portable Applications: Challenges for the Selection of Alternative Anodes

    Directory of Open Access Journals (Sweden)

    Massimiliano Cimenti

    2009-06-01

    Full Text Available Solid oxide fuel cells (SOFC have the advantage of being able to operate with fuels other than hydrogen. In particular, liquid fuels are especially attractive for powering portable applications such as small power generators or auxiliary power units, in which case the direct utilization of the fuel would be convenient. Although liquid fuels are easier to handle and transport than hydrogen, their direct use in SOFC can lead to anode deactivation due to carbon formation, especially on traditional nickel/yttria stabilized zirconia (Ni/YSZ anodes. Significant advances have been made in anodic materials that are resistant to carbon formation but often these materials are less electrochemically active than Ni/YSZ. In this review the challenges of using liquid fuels directly in SOFC, in terms of gas-phase and catalytic reactions within the anode chamber, will be discussed and the alternative anode materials so far investigated will be compared.

  10. Magnetoelastoelectric coupling in core-shell nanoparticles enabling directional and mode-selective magnetic control of THz beam propagation.

    Science.gov (United States)

    Dutta, Moumita; Natarajan, Kamaraju; Betal, Soutik; Prasankumar, Rohit P; Bhalla, Amar S; Guo, Ruyan

    2017-09-14

    Magnetoelastoelectric coupling in an engineered biphasic multiferroic nanocomposite enables a novel magnetic field direction-defined propagation control of terahertz (THz) waves. These core-shell nanoparticles are comprised of a ferromagnetic cobalt ferrite core and a ferroelectric barium titanate shell. An assembly of these nanoparticles, when operated in external magnetic fields, exhibits a controllable amplitude modulation when the magnetic field is applied antiparallel to the THz wave propagation direction; yet the same assembly displays an additional phase modulation when the magnetic field is applied along the propagation direction. While field-induced magnetostriction of the core leads to amplitude modulation, phase modulation is a result of stress-mediated piezoelectricity of the outer ferroelectric shell.

  11. Gamma-aminobutyric acid and GABAA receptors are involved in directional selectivity of pretectal neurons in pigeons

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The present study describes the effects of gamma-aminobutyric acid (GABA) and itsantagonists, bicuculline and 2-hydroxysaclofen, on visual responses of neurons in the pigeon nucleuslentiformis mesencephali (nLM). The results indicate that GABA significantly reduces bothspontaneous activity and visual responsiveness, and GABAA antagonist bicuculline but not GABABantagonist 2-hydroxysaclofen enhances visual responses of nLM cells examined. Furthermore,inhibition produced by motion in the null-direction of pretectal neurons is diminished by bicucullinebut not by 2-hydroxysaclofen. It is therefore concluded that the null-direction inhibition of directionalcells in the pigeon nLM is predominantly mediated by GABA and GABAA receptors. This inhibitionmay at least in part underlie directional asymmetry of optokinetic responses.

  12. Direct Observation of Xe and Kr Adsorption in a Xe-Selective Microporous Metal-Organic Framework.

    Science.gov (United States)

    Chen, Xianyin; Plonka, Anna M; Banerjee, Debasis; Krishna, Rajamani; Schaef, Herbert T; Ghose, Sanjit; Thallapally, Praveen K; Parise, John B

    2015-06-10

    The cryogenic separation of noble gases is energy-intensive and expensive, especially when low concentrations are involved. Metal-organic frameworks (MOFs) containing polarizing groups within their pore spaces are predicted to be efficient Xe/Kr solid-state adsorbents, but no experimental insights into the nature of the Xe-network interaction are available to date. Here we report a new microporous MOF (designated SBMOF-2) that is selective toward Xe over Kr under ambient conditions, with a Xe/Kr selectivity of about 10 and a Xe capacity of 27.07 wt % at 298 K. Single-crystal diffraction results show that the Xe selectivity may be attributed to the specific geometry of the pores, forming cages built with phenyl rings and enriched with polar -OH groups, both of which serve as strong adsorption sites for polarizable Xe gas. The Xe/Kr separation in SBMOF-2 was investigated with experimental and computational breakthrough methods. These experiments showed that Kr broke through the column first, followed by Xe, which confirmed that SBMOF-2 has a real practical potential for separating Xe from Kr. Calculations showed that the capacity and adsorption selectivity of SBMOF-2 are comparable to those of the best-performing unmodified MOFs such as NiMOF-74 or Co formate.

  13. Pharmacokinetics and estimated bioavailability of grapiprant, a novel selective prostaglandin E2 receptor antagonist, after oral administration in fasted and fed dogs.

    Science.gov (United States)

    Łebkowska-Wieruszewska, B; Barsotti, G; Lisowski, A; Gazzano, A; Owen, H; Giorgi, M

    2017-01-01

    To assess the effect of food intake on the pharmacokinetics of grapiprant administered orally at 2 mg/kg, and to estimate its oral bioavailability in dogs. Eight healthy female Labrador Retriever dogs, aged 4-10 years were used. In the initial trial two dogs were administered a 0.5 mg/kg I/V bolus of grapiprant dissolved in ethanol. In the second trial, six dogs were assigned to two treatment groups, using a randomised cross-over design, and received 2 mg/kg of grapiprant orally, as pure powder, after fasting for 12 hours or after being fed. Blood samples were collected at preassigned times up to 36 hours after administration, and concentrations of grapiprant in plasma determined using validated high performance liquid chromatography. After I/V administration in the two dogs the terminal half life was 5.30 and 6.06 hours, clearance was 444 and 476 mL/hours/kg, and volume of distribution was 3,642 and 3,883 mL/kg. Compared with fasted dogs, oral administration in fed dogs resulted in reduced median peak concentrations in plasma (1,598 vs. 614 ng/mL) and delayed median time of peak concentration (1.0 vs. 3.0 hours). The estimated bioavailability in fasted and fed dogs was 111.9 and 59.1%, respectively. Concentrations of grapiprant in plasma following oral administration, in either fed or fasted dogs, remained higher than 164 ng/mL for up to 6 hours. This concentration has been estimated to be the minimal effective concentration required to control pain in dogs. Oral administration of 2 mg/kg grapiprant in fed and fasted dogs resulted in different pharmacokinetics of the drug, but did not influence the length of time when concentrations in plasma exceeded theoretical effective concentrations. Further studies are necessary to verify these findings using pharmacokinetic-pharmacodynamic studies and in clinical subjects.

  14. Clock gene variation is associated with breeding phenology and maybe under directional selection in the migratory barn swallow.

    Directory of Open Access Journals (Sweden)

    Manuela Caprioli

    Full Text Available BACKGROUND: In diverse taxa, photoperiodic responses that cause seasonal physiological and behavioural shifts are controlled by genes, including the vertebrate Clock orthologues, that encode for circadian oscillator mechanisms. While the genetic network behind circadian rhythms is well described, relatively few reports e