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Sample records for models show promise

  1. Bacteriophages show promise as antimicrobial agents.

    Science.gov (United States)

    Alisky, J; Iczkowski, K; Rapoport, A; Troitsky, N

    1998-01-01

    The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed

  2. Prospects of an alternative treatment against Trypanosoma cruzi based on abietic acid derivatives show promising results in Balb/c mouse model.

    Science.gov (United States)

    Olmo, F; Guardia, J J; Marin, C; Messouri, I; Rosales, M J; Urbanová, K; Chayboun, I; Chahboun, R; Alvarez-Manzaneda, E J; Sánchez-Moreno, M

    2015-01-07

    Chagas disease, caused by the protozoa parasite Trypanosoma cruzi, is an example of extended parasitaemia with unmet medical needs. Current treatments based on old-featured benznidazole (Bz) and nifurtimox are expensive and do not fulfil the criteria of effectiveness, and a lack of toxicity devoid to modern drugs. In this work, a group of abietic acid derivatives that are chemically stable and well characterised were introduced as candidates for the treatment of Chagas disease. In vitro and in vivo assays were performed in order to test the effectiveness of these compounds. Finally, those which showed the best activity underwent additional studies in order to elucidate the possible mechanism of action. In vitro results indicated that some compounds have low toxicity (i.e. >150 μM, against Vero cell) combined with high efficacy (i.e. <20 μM) against some forms of T. cruzi. Further in vivo studies on mice models confirmed the expectations of improvements in infected mice. In vivo tests on the acute phase gave parasitaemia inhibition values higher those of Bz, and a remarkable decrease in the reactivation of parasitaemia was found in the chronic phase after immunosuppression of the mice treated with one of the compounds. The morphological alterations found in treated parasites with our derivatives confirmed extensive damage; energetic metabolism disturbances were also registered by (1)H NMR. The demonstrated in vivo activity and low toxicity, together with the use of affordable starting products and the lack of synthetic complexity, put these abietic acid derivatives in a remarkable position toward the development of an anti-Chagasic agent. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Fuel cells show promise as vehicle power source

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    Fuel-cell-powered vehicles appear to offer great promise for energy-saving, high-efficiency transportation. Fuel cells are both highly efficient (50% thermal efficiency has been demonstrated by some) and non-polluting (water being the main by-product). Dramatic improvements in performance have occurred recently due to aerospace and utility RandD efforts. The primary vehicle considered at workshops of laboratory and industrial investigators was a fuel cell/battery hybrid, in which fuel cells are paralleled by batteries. Fuel cells are used for cruising power and battery recharge, while batteries supply transient power for acceleration and starting

  4. Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

    Science.gov (United States)

    A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

  5. Reversible Cysteine Protease Inhibitors Show Promise for a Chagas Disease Cure

    Science.gov (United States)

    Beaulieu, Christian; Black, W. Cameron; Isabel, Elise; Vasquez-Camargo, Fabio; Nath-Chowdhury, Milli; Massé, Frédéric; Mellon, Christophe; Methot, Nathalie

    2014-01-01

    The cysteine protease cruzipain is essential for the viability, infectivity, and virulence of Trypanosoma cruzi, the causative agent of Chagas disease. Thus, inhibitors of cruzipain are considered promising anti-T. cruzi chemotherapeutic agents. Reversible cruzipain inhibitors containing a nitrile “warhead” were prepared and demonstrated 50% inhibitory concentrations (IC50s) as potent as 1 nM in baculovirus-generated cruzipain enzyme assays. In epimastigote and intracellular amastigote in vitro assays, the most potent compounds demonstrated antiparasitic behavior in the 5 to 10 μM IC50 range; however, trypomastigote production from the amastigote form was ∼90 to 95% inhibited at 2 μM. Two key compounds, Cz007 and Cz008, with IC50s of 1.1 and 1.8 nM, respectively, against the recombinant enzyme were tested in a murine model of acute T. cruzi infection, with oral dosing in chow for 28 days at doses from 3 to 50 mg/kg of body weight. At 3 mg/kg of Cz007 and 3 mg/kg of Cz008, the blood parasitemia areas under the concentration-time curves were 16% and 25% of the untreated group, respectively. At sacrifice, 24 days after immunosuppression with cyclophosphamide, parasite presence in blood, heart, and esophagus was evaluated. Based on negative quantitative PCR results in all three tissues, cure rates in surviving animals were 90% for Cz007 at 3 mg/kg, 78% for Cz008 at 3 mg/kg, and 71% for benznidazole, the control compound, at 50 mg/kg. PMID:24323474

  6. Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy.

    Directory of Open Access Journals (Sweden)

    Marion Dalmasso

    Full Text Available With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, ɸAPCEc01, ɸAPCEc02 and ɸAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI between 10-3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections.

  7. Radiance Assimilation Shows Promise for Snowpack Characterization: A 1-D Case Study

    Science.gov (United States)

    Durand, Michael; Kim, Edward; Margulis, Steve

    2008-01-01

    We demonstrate an ensemble-based radiometric data assimilation (DA) methodology for estimating snow depth and snow grain size using ground-based passive microwave (PM) observations at 18.7 and 36.5 GHz collected during the NASA CLPX-1, March 2003, Colorado, USA. A land surface model was used to develop a prior estimate of the snowpack states, and a radiative transfer model was used to relate the modeled states to the observations. Snow depth bias was -53.3 cm prior to the assimilation, and -7.3 cm after the assimilation. Snow depth estimated by a non-DA-based retrieval algorithm using the same PM data had a bias of -18.3 cm. The sensitivity of the assimilation scheme to the grain size uncertainty was evaluated; over the range of grain size uncertainty tested, the posterior snow depth estimate bias ranges from -2.99 cm to -9.85 cm, which is uniformly better than both the prior and retrieval estimates. This study demonstrates the potential applicability of radiometric DA at larger scales.

  8. Duchenne muscular dystrophy models show their age

    OpenAIRE

    Chamberlain, Jeffrey S.

    2010-01-01

    The lack of appropriate animal models has hampered efforts to develop therapies for Duchenne muscular dystrophy (DMD). A new mouse model lacking both dystrophin and telomerase (Sacco et al., 2010) closely mimics the pathological progression of human DMD and shows that muscle stem cell activity is a key determinant of disease severity.

  9. Shared Curriculum Model: A Promising Practice for Education Transformation.

    Science.gov (United States)

    Close, Liz; Gorski, Mary Sue; Sroczynski, Maureen; Farmer, Pat; Wortock, Jean

    2015-12-01

    The shared curriculum model is one of four successful models of academic progression identified through a consensus-building process facilitated by The Future of Nursing: Campaign for Action, with support from the Robert Wood Johnson Foundation, AARP, and the AARP Foundation. Seamless academic progression from the associate degree in nursing (ADN) to the baccalaureate degree in nursing (BSN) is achieved either by simultaneously revising both ADN and BSN curricula or by making targeted adjustments in ADN or BSN curricula to create a unified academic progression. Systematic vetting and definitive agreement on nursing prerequisites and corequisites, general education courses, nursing major content, and general degree requirements are necessary to ensure coordinated degree progression. A standardized set of expectations for beginning professional practice and for unique baccalaureate nursing knowledge ensures vital nursing content across the ADN-to-BSN continuum. Examples of state and regional ADN-to-BSN progression programs using the shared curriculum model are highlighted. The shared curriculum model is a promising practical and sustainable approach to seamless ADN-to-BSN academic progression. Copyright 2015, SLACK Incorporated.

  10. Solutions for Failing High Schools: Converging Visions and Promising Models.

    Science.gov (United States)

    Legters, Nettie; Balfanz, Robert; McPartland, James

    Promising solutions to the failings of traditional comprehensive high schools were reviewed to identify basic principles and strategies for improving high schools nationwide. Selected research studies, policy documents, and promising high school programs were reviewed. The review revealed the following principles for helping high schools better…

  11. Video Self-Modeling: A Promising Strategy for Noncompliant Children.

    Science.gov (United States)

    Axelrod, Michael I; Bellini, Scott; Markoff, Kimberly

    2014-07-01

    The current study investigated the effects of a Video Self-Modeling (VSM) intervention on the compliance and aggressive behavior of three children placed in a psychiatric hospital. Each participant viewed brief video clips of himself following simple adult instructions just prior to the school's morning session and the unit's afternoon free period. A multiple baseline design across settings was used to evaluate the effects of the VSM intervention on compliance with staff instructions and aggressive behavior on the hospital unit and in the hospital-based classroom. All three participants exhibited higher levels of compliance and fewer aggressive episodes during the intervention condition, and the effects were generally maintained when the intervention was withdrawn. Hospital staff reported at the conclusion of the study that the VSM intervention was easy to implement and beneficial for all participants. Taken altogether, the results suggest VSM is a promising, socially acceptable, and proactive intervention approach for improving the behavior of noncompliant children. © The Author(s) 2014.

  12. Silkworm: A Promising Model Organism in Life Science.

    Science.gov (United States)

    Meng, Xu; Zhu, Feifei; Chen, Keping

    2017-09-01

    As an important economic insect, silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae) has numerous advantages in life science, such as low breeding cost, large progeny size, short generation time, and clear genetic background. Additionally, there are rich genetic resources associated with silkworms. The completion of the silkworm genome has further accelerated it to be a modern model organism in life science. Genomic studies showed that some silkworm genes are highly homologous to certain genes related to human hereditary disease and, therefore, are a candidate model for studying human disease. In this article, we provided a review of silkworm as an important model in various research areas, including human disease, screening of antimicrobial agents, environmental safety monitoring, and antitumor studies. In addition, the application potentiality of silkworm model in life sciences was discussed. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  13. Probabilistic language models in cognitive neuroscience: Promises and pitfalls.

    Science.gov (United States)

    Armeni, Kristijan; Willems, Roel M; Frank, Stefan L

    2017-12-01

    Cognitive neuroscientists of language comprehension study how neural computations relate to cognitive computations during comprehension. On the cognitive part of the equation, it is important that the computations and processing complexity are explicitly defined. Probabilistic language models can be used to give a computationally explicit account of language complexity during comprehension. Whereas such models have so far predominantly been evaluated against behavioral data, only recently have the models been used to explain neurobiological signals. Measures obtained from these models emphasize the probabilistic, information-processing view of language understanding and provide a set of tools that can be used for testing neural hypotheses about language comprehension. Here, we provide a cursory review of the theoretical foundations and example neuroimaging studies employing probabilistic language models. We highlight the advantages and potential pitfalls of this approach and indicate avenues for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Time dependent patient no-show predictive modelling development.

    Science.gov (United States)

    Huang, Yu-Li; Hanauer, David A

    2016-05-09

    Purpose - The purpose of this paper is to develop evident-based predictive no-show models considering patients' each past appointment status, a time-dependent component, as an independent predictor to improve predictability. Design/methodology/approach - A ten-year retrospective data set was extracted from a pediatric clinic. It consisted of 7,291 distinct patients who had at least two visits along with their appointment characteristics, patient demographics, and insurance information. Logistic regression was adopted to develop no-show models using two-thirds of the data for training and the remaining data for validation. The no-show threshold was then determined based on minimizing the misclassification of show/no-show assignments. There were a total of 26 predictive model developed based on the number of available past appointments. Simulation was employed to test the effective of each model on costs of patient wait time, physician idle time, and overtime. Findings - The results demonstrated the misclassification rate and the area under the curve of the receiver operating characteristic gradually improved as more appointment history was included until around the 20th predictive model. The overbooking method with no-show predictive models suggested incorporating up to the 16th model and outperformed other overbooking methods by as much as 9.4 per cent in the cost per patient while allowing two additional patients in a clinic day. Research limitations/implications - The challenge now is to actually implement the no-show predictive model systematically to further demonstrate its robustness and simplicity in various scheduling systems. Originality/value - This paper provides examples of how to build the no-show predictive models with time-dependent components to improve the overbooking policy. Accurately identifying scheduled patients' show/no-show status allows clinics to proactively schedule patients to reduce the negative impact of patient no-shows.

  15. Model shows future cut in U.S. ozone levels

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    A joint U.S. auto-oil industry research program says modeling shows that changing gasoline composition can reduce ozone levels for Los Angeles in 2010 and for New York City and Dallas-Fort Worth in 2005. The air quality modeling was based on vehicle emissions research data released late last year (OGJ, Dec. 24, 1990, p. 20). The effort is sponsored by the big three auto manufacturers and 14 oil companies. Sponsors the cars and small trucks account for about one third of ozone generated in the three cities studied but by 2005-10 will account for only 5-9%

  16. Phase Behavior Modeling of Asphaltene Precipitation for Heavy Crudes: A Promising Tool Along with Experimental Data

    Science.gov (United States)

    Tavakkoli, M.; Kharrat, R.; Masihi, M.; Ghazanfari, M. H.; Fadaei, S.

    2012-12-01

    Thermodynamic modeling is known as a promising tool for phase behavior modeling of asphaltene precipitation under different conditions such as pressure depletion and CO2 injection. In this work, a thermodynamic approach is used for modeling the phase behavior of asphaltene precipitation. The precipitated asphaltene phase is represented by an improved solid model, while the oil and gas phases are modeled with an equation of state. The PR-EOS was used to perform flash calculations. Then, the onset point and the amount of precipitated asphaltene were predicted. A computer code based on an improved solid model has been developed and used for predicting asphaltene precipitation data for one of Iranian heavy crudes, under pressure depletion and CO2 injection conditions. A significant improvement has been observed in predicting the asphaltene precipitation data under gas injection conditions. Especially for the maximum value of asphaltene precipitation and for the trend of the curve after the peak point, good agreement was observed. For gas injection conditions, comparison of the thermodynamic micellization model and the improved solid model showed that the thermodynamic micellization model cannot predict the maximum of precipitation as well as the improved solid model. The non-isothermal improved solid model has been used for predicting asphaltene precipitation data under pressure depletion conditions. The pressure depletion tests were done at different levels of temperature and pressure, and the parameters of a non-isothermal model were tuned using three onset pressures at three different temperatures for the considered crude. The results showed that the model is highly sensitive to the amount of solid molar volume along with the interaction coefficient parameter between the asphaltene component and light hydrocarbon components. Using a non-isothermal improved solid model, the asphaltene phase envelope was developed. It has been revealed that at high temperatures, an

  17. Showing that the race model inequality is not violated

    DEFF Research Database (Denmark)

    Gondan, Matthias; Riehl, Verena; Blurton, Steven Paul

    2012-01-01

    important being race models and coactivation models. Redundancy gains consistent with the race model have an upper limit, however, which is given by the well-known race model inequality (Miller, 1982). A number of statistical tests have been proposed for testing the race model inequality in single...... participants and groups of participants. All of these tests use the race model as the null hypothesis, and rejection of the null hypothesis is considered evidence in favor of coactivation. We introduce a statistical test in which the race model prediction is the alternative hypothesis. This test controls...

  18. Cardiac spheroids as promising in vitro models to study the human heart microenvironment

    DEFF Research Database (Denmark)

    Polonchuk, Liudmila; Chabria, Mamta; Badi, Laura

    2017-01-01

    Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart ("cardiac spheroids", CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells an...

  19. The copepod Tigriopus: A promising marine model organism for ecotoxicology and environmental genomics

    Energy Technology Data Exchange (ETDEWEB)

    Raisuddin, Sheikh [Department of Chemistry and the National Research Lab of Marine Molecular and Environmental Bioscience, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Kwok, Kevin W.H. [Swire Institute of Marine Science, Department of Ecology and Biodiversity, University of Hong Kong, Pokfulam, Hong Kong (China); Leung, Kenneth M.Y. [Swire Institute of Marine Science, Department of Ecology and Biodiversity, University of Hong Kong, Pokfulam, Hong Kong (China); Schlenk, Daniel [Department of Environmental Sciences, University of California, Riverside, CA 92521 (United States); Lee, Jae-Seong [Department of Chemistry and the National Research Lab of Marine Molecular and Environmental Bioscience, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)]. E-mail: jslee2@hanyang.ac.kr

    2007-07-20

    There is an increasing body of evidence to support the significant role of invertebrates in assessing impacts of environmental contaminants on marine ecosystems. Therefore, in recent years massive efforts have been directed to identify viable and ecologically relevant invertebrate toxicity testing models. Tigriopus, a harpacticoid copepod has a number of promising characteristics which make it a candidate worth consideration in such efforts. Tigriopus and other copepods are widely distributed and ecologically important organisms. Their position in marine food chains is very prominent, especially with regard to the transfer of energy. Copepods also play an important role in the transportation of aquatic pollutants across the food chains. In recent years there has been a phenomenal increase in the knowledge base of Tigriopus spp., particularly in the areas of their ecology, geophylogeny, genomics and their behavioural, biochemical and molecular responses following exposure to environmental stressors and chemicals. Sequences of a number of important marker genes have been studied in various Tigriopus spp., notably T. californicus and T. japonicus. These genes belong to normal biophysiological functions (e.g. electron transport system enzymes) as well as stress and toxic chemical exposure responses (heat shock protein 20, glutathione reductase, glutathione S-transferase). Recently, 40,740 expressed sequenced tags (ESTs) from T. japonicus, have been sequenced and of them, 5673 ESTs showed significant hits (E-value, >1.0E-05) to the red flour beetle Tribolium genome database. Metals and organic pollutants such as antifouling agents, pesticides, polycyclic aromatic hydrocarbons (PAH) and polychrlorinated biphenyls (PCB) have shown reproducible biological responses when tested in Tigriopus spp. Promising results have been obtained when Tigriopus was used for assessment of risk associated with exposure to endocrine-disrupting chemicals (EDCs). Application of environmental

  20. The copepod Tigriopus: A promising marine model organism for ecotoxicology and environmental genomics

    International Nuclear Information System (INIS)

    Raisuddin, Sheikh; Kwok, Kevin W.H.; Leung, Kenneth M.Y.; Schlenk, Daniel; Lee, Jae-Seong

    2007-01-01

    There is an increasing body of evidence to support the significant role of invertebrates in assessing impacts of environmental contaminants on marine ecosystems. Therefore, in recent years massive efforts have been directed to identify viable and ecologically relevant invertebrate toxicity testing models. Tigriopus, a harpacticoid copepod has a number of promising characteristics which make it a candidate worth consideration in such efforts. Tigriopus and other copepods are widely distributed and ecologically important organisms. Their position in marine food chains is very prominent, especially with regard to the transfer of energy. Copepods also play an important role in the transportation of aquatic pollutants across the food chains. In recent years there has been a phenomenal increase in the knowledge base of Tigriopus spp., particularly in the areas of their ecology, geophylogeny, genomics and their behavioural, biochemical and molecular responses following exposure to environmental stressors and chemicals. Sequences of a number of important marker genes have been studied in various Tigriopus spp., notably T. californicus and T. japonicus. These genes belong to normal biophysiological functions (e.g. electron transport system enzymes) as well as stress and toxic chemical exposure responses (heat shock protein 20, glutathione reductase, glutathione S-transferase). Recently, 40,740 expressed sequenced tags (ESTs) from T. japonicus, have been sequenced and of them, 5673 ESTs showed significant hits (E-value, >1.0E-05) to the red flour beetle Tribolium genome database. Metals and organic pollutants such as antifouling agents, pesticides, polycyclic aromatic hydrocarbons (PAH) and polychrlorinated biphenyls (PCB) have shown reproducible biological responses when tested in Tigriopus spp. Promising results have been obtained when Tigriopus was used for assessment of risk associated with exposure to endocrine-disrupting chemicals (EDCs). Application of environmental

  1. Rapamycin and chloroquine: the in vitro and in vivo effects of autophagy-modifying drugs show promising results in valosin containing protein multisystem proteinopathy.

    Directory of Open Access Journals (Sweden)

    Angèle Nalbandian

    Full Text Available Mutations in the valosin containing protein (VCP gene cause hereditary Inclusion body myopathy (hIBM associated with Paget disease of bone (PDB, frontotemporal dementia (FTD, more recently termed multisystem proteinopathy (MSP. Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem

  2. Complex functionality with minimal computation: Promise and pitfalls of reduced-tracer ocean biogeochemistry models

    Science.gov (United States)

    Galbraith, Eric D.; Dunne, John P.; Gnanadesikan, Anand; Slater, Richard D.; Sarmiento, Jorge L.; Dufour, Carolina O.; de Souza, Gregory F.; Bianchi, Daniele; Claret, Mariona; Rodgers, Keith B.; Marvasti, Seyedehsafoura Sedigh

    2015-12-01

    Earth System Models increasingly include ocean biogeochemistry models in order to predict changes in ocean carbon storage, hypoxia, and biological productivity under climate change. However, state-of-the-art ocean biogeochemical models include many advected tracers, that significantly increase the computational resources required, forcing a trade-off with spatial resolution. Here, we compare a state-of-the art model with 30 prognostic tracers (TOPAZ) with two reduced-tracer models, one with 6 tracers (BLING), and the other with 3 tracers (miniBLING). The reduced-tracer models employ parameterized, implicit biological functions, which nonetheless capture many of the most important processes resolved by TOPAZ. All three are embedded in the same coupled climate model. Despite the large difference in tracer number, the absence of tracers for living organic matter is shown to have a minimal impact on the transport of nutrient elements, and the three models produce similar mean annual preindustrial distributions of macronutrients, oxygen, and carbon. Significant differences do exist among the models, in particular the seasonal cycle of biomass and export production, but it does not appear that these are necessary consequences of the reduced tracer number. With increasing CO2, changes in dissolved oxygen and anthropogenic carbon uptake are very similar across the different models. Thus, while the reduced-tracer models do not explicitly resolve the diversity and internal dynamics of marine ecosystems, we demonstrate that such models are applicable to a broad suite of major biogeochemical concerns, including anthropogenic change. These results are very promising for the further development and application of reduced-tracer biogeochemical models that incorporate "sub-ecosystem-scale" parameterizations.

  3. EXPERT SYSTEMS SHOW PROMISE FOR CUSTOMER INQUIRIES

    Science.gov (United States)

    This article describes results of an agreement between the North Penn Water Authority in Lansdale, Pa., and the US Environmental Protection Agency, Drinking Water Research Division, Cincinnati, Ohio, to study use of expert systems technology in a water utility. The threeyear stud...

  4. From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

    Science.gov (United States)

    Dietz, Volker; Schwab, Martin E

    2017-05-01

    Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

  5. Mathematical modeling based on ordinary differential equations: A promising approach to vaccinology.

    Science.gov (United States)

    Bonin, Carla Rezende Barbosa; Fernandes, Guilherme Cortes; Dos Santos, Rodrigo Weber; Lobosco, Marcelo

    2017-02-01

    New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus.

  6. Fuzzy promises

    DEFF Research Database (Denmark)

    Anker, Thomas Boysen; Kappel, Klemens; Eadie, Douglas

    2012-01-01

    as narrative material to communicate self-identity. Finally, (c) we propose that brands deliver fuzzy experiential promises through effectively motivating consumers to adopt and play a social role implicitly suggested and facilitated by the brand. A promise is an inherently ethical concept and the article...... concludes with an in-depth discussion of fuzzy brand promises as two-way ethical commitments that put requirements on both brands and consumers....

  7. Melanin, a promising radioprotector: Mechanisms of actions in a mice model

    Energy Technology Data Exchange (ETDEWEB)

    Kunwar, A., E-mail: amitbio@rediffmail.com [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Adhikary, B. [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Jayakumar, S. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Barik, A. [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Chattopadhyay, S. [Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Raghukumar, S. [Myko Tech Private Limited, Dona Paula, Goa‐403004 (India); Priyadarsini, K.I., E-mail: kindira@barc.gov.in [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

    2012-10-15

    The radioprotective effect of extracellular melanin, a naturally occurring pigment, isolated from the fungus Gliocephalotrichum simplex was examined in BALB/C mice, and the probable mechanism of action was established. At an effective dose of 50 mg/kg body weight, melanin exhibited both prophylactic and mitigative activities, increasing the 30-day survival of mice by 100% and 60%, respectively, after exposure to radiation (7 Gy, whole body irradiation (WBI)). The protective activity of melanin was primarily due to inhibition of radiation-induced hematopoietic damages as evidenced by improvement in spleen parameters such as index, total cellularity, endogenous colony forming units, and maintenance of circulatory white blood cells and platelet counts. Melanin also reversed the radiation-induced decrease in ERK phosphorylation in splenic tissue, which may be the key feature in its radioprotective action. Additionally, our results indicated that the sustained activation of AKT, JNK and P38 proteins in splenic tissue of melanin pre-treated group may also play a secondary role. This was also supported by the fact that melanin could prevent apoptosis in splenic tissue by decreasing BAX/Bcl-XL ratio, and increasing the expressions of the proliferation markers (PCNA and Cyclin D1), compared to the radiation control group. Melanin also reduced the oxidative stress in hepatic tissue and abrogated immune imbalance by reducing the production of pro-inflammatory cytokines (IL6 and TNFα). In conclusion, our results confirmed that fungal melanin is a very effective radioprotector against WBI and the probable mechanisms of radioprotection are due to modulation in pro-survival (ERK) signaling, prevention of oxidative stress and immunomodulation. -- Highlights: ► Melanin showed promising radioprotection under pre and post irradiation condition. ► Melanin protects the hematopoietic system from radiation induced damage. ► Melanin modulates pro-survival pathways, immune system

  8. In vitro psoriasis models with focus on reconstructed skin models as promising tools in psoriasis research.

    Science.gov (United States)

    Desmet, Eline; Ramadhas, Anesh; Lambert, Jo; Van Gele, Mireille

    2017-06-01

    Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis

  9. META 2f: Probabilistic, Compositional, Multi-dimension Model-Based Verification (PROMISE)

    Science.gov (United States)

    2011-10-01

    TTTech Computertechnik AG, and Vanderbilt University. PROMISE builds on the team’s unique expertise that combines a long history of successful...e.g. 0x800 for IPV4 , 0x806 for ARP, etc.) or as length field (value < 0x600), which indicates the actual length of the Ethernet data payload (46

  10. Acute and chronic sensitivity to copper of a promising ecotoxicological model species, the annual killifish Nothobranchius furzeri.

    Science.gov (United States)

    Philippe, Charlotte; Grégoir, Arnout F; Janssens, Lizanne; Pinceel, Tom; De Boeck, Gudrun; Brendonck, Luc

    2017-10-01

    Nothobranchius furzeri is a promising model for ecotoxicological research due to the species' short life cycle and the production of drought-resistant eggs. Although the species is an emerging vertebrate fish model for several fundamental as well as applied research domains, its potential for ecotoxicological research has not yet been tested. The aim of this study was to characterise the acute and chronic sensitivity of this species to copper as compared to other model organisms. Effects of both acute and chronic copper exposure were tested on survival, life history and physiological traits. We report a 24h-LC 50 of 53.93µg Cu/L, which is situated within the sensitivity range of other model species such as Brook Trout, Fathead Minnow and Rainbow Trout. Moreover, in the full life cycle exposure, we show that an exposure concentration of 10.27µg/L did not cause acute adverse effects (96h), but did cause mortality after prolonged exposure (3-4 weeks). Also chronic, sublethal effects were observed, such as a reduction in growth rate, delayed maturation and postponed reproduction. Based on our results, we define the NOEC at 6.68µg Cu/L, making N. furzeri more sensitive to copper as compared to Brook Trout and Fathead Minnow. We found stimulatory effects on peak fecundity at subinhibitory levels of copper concentrations (hormesis). Finally, we found indications for detoxifying and copper-excreting mechanisms, demonstrating the ability of the fish to cope with this essential metal, even when exposed to stressful amounts. The successful application of current ecotoxicological protocols on N. furzeri and its sensitivity range comparable to that of other model organisms forms the basis to exploit this species in further ecotoxicological practices. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The Integration of Continuous and Discrete Latent Variable Models: Potential Problems and Promising Opportunities

    Science.gov (United States)

    Bauer, Daniel J.; Curran, Patrick J.

    2004-01-01

    Structural equation mixture modeling (SEMM) integrates continuous and discrete latent variable models. Drawing on prior research on the relationships between continuous and discrete latent variable models, the authors identify 3 conditions that may lead to the estimation of spurious latent classes in SEMM: misspecification of the structural model,…

  12. Red blood cells open promising avenues for longitudinal studies of ageing in laboratory, non-model and wild animals.

    Science.gov (United States)

    Stier, Antoine; Reichert, Sophie; Criscuolo, Francois; Bize, Pierre

    2015-11-01

    Ageing is characterized by a progressive deterioration of multiple physiological and molecular pathways, which impair organismal performance and increase risks of death with advancing age. Hence, ageing studies must identify physiological and molecular pathways that show signs of age-related deterioration, and test their association with the risk of death and longevity. This approach necessitates longitudinal sampling of the same individuals, and therefore requires a minimally invasive sampling technique that provides access to the larger spectrum of physiological and molecular pathways that are putatively associated with ageing. The present paper underlines the interest in using red blood cells (RBCs) as a promising target for longitudinal studies of ageing in vertebrates. RBCs provide valuable information on the following six pathways: cell maintenance and turnover (RBC number, size, and heterogeneity), glucose homeostasis (RBC glycated haemoglobin), oxidative stress parameters, membrane composition and integrity, mitochondrial functioning, and telomere dynamics. The last two pathways are specific to RBCs of non-mammalian species, which possess a nucleus and functional mitochondria. We present the current knowledge about RBCs and age-dependent changes in these pathways in non-model and wild species that are especially suitable to address questions related to ageing using longitudinal studies. We discuss how the different pathways relate with survival and lifespan and give information on their genetic and environmental determinants to appraise their evolutionary potential. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Promise(s of mesenchymal stem cells as an in vitro model system to depict pre-diabetic/diabetic milieu in WNIN/GR-Ob mutant rats.

    Directory of Open Access Journals (Sweden)

    Soundarya L Madhira

    Full Text Available BACKGROUND: Development of model systems have helped to a large extent, in bridging gap to understand the mechanism(s of disease including diabetes. Interestingly, WNIN/GR-Ob rats (Mutants, established at National Centre for Laboratory Animals (NCLAS of National Institute of Nutrition (NIN, form a suitable model system to study obesity with Type 2 diabetes (T2D demonstrating several secondary complications (cataract, cardiovascular complications, infertility, nephropathy etc. The present study has been carried out to explore the potent application(s of multipotent stem cells such as bone marrow mesenchymal stem cells (BM-MSCs, to portray features of pre-diabetic/T2D vis-à-vis featuring obesity, with impaired glucose tolerance (IGT, hyperinsulinemia (HI and insulin resistance (IR seen with Mutant rats akin to human situation. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of BM-MSCs (third passage from Mutants, its lean littermate (Lean and parental control (Control were characterized for: proliferation markers, disease memory to mark obesity/T2D/HI/IR which included phased gene expression studies for adipogenic/pancreatic lineages, inflammatory markers and differentiation ability to form mature adipocytes/Insulin-like cellular aggregates (ILCAs. The data showed that BM-MSCs from Mutant demonstrated a state of disease memory, depicted by an upregulated expression of inflammatory markers (IL-6, TNFα; increased stem cell recruitment (Oct-4, Sox-2 and proliferation rates (CD90+/CD29+, PDA, 'S' phase of cell cycle by FACS and BrdU incorporation; accelerated preadipocyte induction (Dact-1, PPARγ2 with a quantitative increase in mature adipocyte formation (Leptin; ILCAs, which were non-responsive to high glucose did confer the Obese/T2D memory in Mutants. Further, these observations were in compliance with the anthropometric data. CONCLUSIONS: Given the ease of accessibility and availability of MSCs, the present study form the basis to report for

  14. Cameroon mid-level providers offer a promising public health dentistry model

    Directory of Open Access Journals (Sweden)

    Achembong Leo

    2012-11-01

    Full Text Available Background Oral health services are inadequate and unevenly distributed in many developing countries, particularly those in sub-Saharan Africa. Rural areas in these countries and poorer sections of the population in urban areas often do not have access to oral health services mainly because of a significant shortage of dentists and the high costs of care. We reviewed Cameroon’s experience with deploying a mid-level cadre of oral health professionals and the feasibility of establishing a more formal and predictable role for these health workers. We anticipate that a task-shifting approach in the provision of dental care will significantly improve the uneven distribution of oral health services particularly in the rural areas of Cameroon, which is currently served by only 3% of the total number of dentists. Methods The setting of this study was the Cameroon Baptist Convention Health Board (BCHB, which has four dentists and 42 mid-level providers. De-identified data were collected manually from the registries of 10 Baptist Convention clinics located in six of Cameroon’s 10 regions and then entered into an Excel format before importing into STATA. A retrospective abstraction of all entries for patient visits starting October 2010, and going back in time until 1500 visits were extracted from each clinic. Results This study showed that mid-level providers in BCHB clinics are offering a full scope of dental work across the 10 clinics, with the exception of treatment for major facial injuries. Mid-level providers alone performed 93.5% of all extractions, 87.5% of all fillings, 96.5% of all root canals, 97.5% of all cleanings, and 98.1% of all dentures. The dentists also typically played a teaching role in training the mid-level providers. Conclusions The Ministry of Health in Cameroon has an opportunity to learn from the BCHB model to expand access to oral health care across the country. This study shows the benefits of using a simple, workable, low

  15. Spatial occupancy models applied to atlas data show Southern Ground Hornbills strongly depend on protected areas.

    Science.gov (United States)

    Broms, Kristin M; Johnson, Devin S; Altwegg, Res; Conquest, Loveday L

    2014-03-01

    Determining the range of a species and exploring species--habitat associations are central questions in ecology and can be answered by analyzing presence--absence data. Often, both the sampling of sites and the desired area of inference involve neighboring sites; thus, positive spatial autocorrelation between these sites is expected. Using survey data for the Southern Ground Hornbill (Bucorvus leadbeateri) from the Southern African Bird Atlas Project, we compared advantages and disadvantages of three increasingly complex models for species occupancy: an occupancy model that accounted for nondetection but assumed all sites were independent, and two spatial occupancy models that accounted for both nondetection and spatial autocorrelation. We modeled the spatial autocorrelation with an intrinsic conditional autoregressive (ICAR) model and with a restricted spatial regression (RSR) model. Both spatial models can readily be applied to any other gridded, presence--absence data set using a newly introduced R package. The RSR model provided the best inference and was able to capture small-scale variation that the other models did not. It showed that ground hornbills are strongly dependent on protected areas in the north of their South African range, but less so further south. The ICAR models did not capture any spatial autocorrelation in the data, and they took an order, of magnitude longer than the RSR models to run. Thus, the RSR occupancy model appears to be an attractive choice for modeling occurrences at large spatial domains, while accounting for imperfect detection and spatial autocorrelation.

  16. Promises from Afar: A Model of International Student Psychological Contract in Business Education

    Science.gov (United States)

    Bordia, Sarbari; Bordia, Prashant; Restubog, Simon Lloyd D.

    2015-01-01

    Despite their significant presence in western business schools, the needs and experiences of international students have not been adequately reflected in the business education literature. We draw upon psychological contract theory--used to understand employer-employee relationships--to develop a novel theoretical model on the international…

  17. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  18. Kind discipline: Developing a conceptual model of a promising school discipline approach.

    Science.gov (United States)

    Winkler, Jennifer L; Walsh, Michele E; de Blois, Madeleine; Maré, Jeannette; Carvajal, Scott C

    2017-06-01

    This formative evaluation develops a novel conceptual model for a discipline approach fostering intrinsic motivation and positive relationships in schools. We used concept mapping to elicit and integrate perspectives on kind discipline from teachers, administrators, and other school staff. Three core themes describing kind discipline emerged from 11 identified clusters: (1) proactively developing a positive school climate, (2) responding to conflict with empathy, accountability, and skill, and (3) supporting staff skills in understanding and sharing expectations. We mapped the identified components of kind discipline onto a social ecological model and found that kind discipline encompasses all levels of that model including the individual, relational, environmental/structural, and even community levels. This contrasts with the dominant individual-behavioral discipline approaches that focus on fewer levels and may not lead to sustained student and staff motivation. The findings illustrate the importance of setting and communicating clear expectations and the need for them to be collaboratively developed. Products of the analysis and synthesis reported here are operationalized materials for teachers grounded in a "be kind" culture code for classrooms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. A critical examination of the youth foyer model for alleviating homelessness: Strengthening a promising evidence base

    Directory of Open Access Journals (Sweden)

    Iris Levin

    2015-12-01

    Full Text Available This article assesses the quality of 15 primary studies that examined the effectiveness of youth foyer or foyer-like programs on the lives of young homeless people. The youth foyer model provides an integrated approach to tackling youth homelessness, connecting affordable accommodation to training and employment. In Australia, there is growing support from government for the development and funding of foyer programs. However to date, there has been very limited development and investment in the evidence base on the effectiveness of this model in Australia or internationally. Following an extensive literature search, we argue that there is a need to lift the standard of the evidence base of youth foyer effectiveness. We discuss two main issues: the difficulty studies had validating claims of foyer effectiveness, and limitations of research design and methodology. The implications of the lack of rigour in the research reviewed are three-fold. Firstly, youth foyer evaluation study quality could be improved by: clearer methodological and model documentation; post intervention follow-up design; comparison of data to non-randomised comparison groups; and a pre-publication peer-review process. This would be supported with clearer expectations from the research community regarding the production and assessment of grey literature. Secondly, while the standard of reporting needs to be raised, the ‘gold standard’ (i.e. randomised controlled trials of research design in the scientific community is not a relevant benchmark in the field of homelessness research. This is due to the complexity of homelessness interventions and the inadequate funding of the homelessness research field. Greater investment in robust research and evaluation should accompany the substantial investment in youth foyer programs in order to accurately appraise the effectiveness of the youth foyer model. Thirdly, the lack of rigour in the studies reviewed suggests gaps in the service

  20. Male Wistar rats show individual differences in an animal model of conformity.

    Science.gov (United States)

    Jolles, Jolle W; de Visser, Leonie; van den Bos, Ruud

    2011-09-01

    Conformity refers to the act of changing one's behaviour to match that of others. Recent studies in humans have shown that individual differences exist in conformity and that these differences are related to differences in neuronal activity. To understand the neuronal mechanisms in more detail, animal tests to assess conformity are needed. Here, we used a test of conformity in rats that has previously been evaluated in female, but not male, rats and assessed the nature of individual differences in conformity. Male Wistar rats were given the opportunity to learn that two diets differed in palatability. They were subsequently exposed to a demonstrator that had consumed the less palatable food. Thereafter, they were exposed to the same diets again. Just like female rats, male rats decreased their preference for the more palatable food after interaction with demonstrator rats that had eaten the less palatable food. Individual differences existed for this shift, which were only weakly related to an interaction between their own initial preference and the amount consumed by the demonstrator rat. The data show that this conformity test in rats is a promising tool to study the neurobiology of conformity.

  1. Promise and problems in using stress triggering models for time-dependent earthquake hazard assessment

    Science.gov (United States)

    Cocco, M.

    2001-12-01

    Earthquake stress changes can promote failures on favorably oriented faults and modify the seismicity pattern over broad regions around the causative faults. Because the induced stress perturbations modify the rate of production of earthquakes, they alter the probability of seismic events in a specified time window. Comparing the Coulomb stress changes with the seismicity rate changes and aftershock patterns can statistically test the role of stress transfer in earthquake occurrence. The interaction probability may represent a further tool to test the stress trigger or shadow model. The probability model, which incorporate stress transfer, has the main advantage to include the contributions of the induced stress perturbation (a static step in its present formulation), the loading rate and the fault constitutive properties. Because the mechanical conditions of the secondary faults at the time of application of the induced load are largely unkown, stress triggering can only be tested on fault populations and not on single earthquake pairs with a specified time delay. The interaction probability can represent the most suitable tool to test the interaction between large magnitude earthquakes. Despite these important implications and the stimulating perspectives, there exist problems in understanding earthquake interaction that should motivate future research but at the same time limit its immediate social applications. One major limitation is that we are unable to predict how and if the induced stress perturbations modify the ratio between small versus large magnitude earthquakes. In other words, we cannot distinguish between a change in this ratio in favor of small events or of large magnitude earthquakes, because the interaction probability is independent of magnitude. Another problem concerns the reconstruction of the stressing history. The interaction probability model is based on the response to a static step; however, we know that other processes contribute to

  2. No more non-model species: the promise of next generation sequencing for comparative immunology.

    Science.gov (United States)

    Dheilly, Nolwenn M; Adema, Coen; Raftos, David A; Gourbal, Benjamin; Grunau, Christoph; Du Pasquier, Louis

    2014-07-01

    Next generation sequencing (NGS) allows for the rapid, comprehensive and cost effective analysis of entire genomes and transcriptomes. NGS provides approaches for immune response gene discovery, profiling gene expression over the course of parasitosis, studying mechanisms of diversification of immune receptors and investigating the role of epigenetic mechanisms in regulating immune gene expression and/or diversification. NGS will allow meaningful comparisons to be made between organisms from different taxa in an effort to understand the selection of diverse strategies for host defence under different environmental pathogen pressures. At the same time, it will reveal the shared and unique components of the immunological toolkit and basic functional aspects that are essential for immune defence throughout the living world. In this review, we argue that NGS will revolutionize our understanding of immune responses throughout the animal kingdom because the depth of information it provides will circumvent the need to concentrate on a few "model" species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Classifying Multi-Model Wheat Yield Impact Response Surfaces Showing Sensitivity to Temperature and Precipitation Change

    Science.gov (United States)

    Fronzek, Stefan; Pirttioja, Nina; Carter, Timothy R.; Bindi, Marco; Hoffmann, Holger; Palosuo, Taru; Ruiz-Ramos, Margarita; Tao, Fulu; Trnka, Miroslav; Acutis, Marco; hide

    2017-01-01

    Crop growth simulation models can differ greatly in their treatment of key processes and hence in their response to environmental conditions. Here, we used an ensemble of 26 process-based wheat models applied at sites across a European transect to compare their sensitivity to changes in temperature (minus 2 to plus 9 degrees Centigrade) and precipitation (minus 50 to plus 50 percent). Model results were analysed by plotting them as impact response surfaces (IRSs), classifying the IRS patterns of individual model simulations, describing these classes and analysing factors that may explain the major differences in model responses. The model ensemble was used to simulate yields of winter and spring wheat at four sites in Finland, Germany and Spain. Results were plotted as IRSs that show changes in yields relative to the baseline with respect to temperature and precipitation. IRSs of 30-year means and selected extreme years were classified using two approaches describing their pattern. The expert diagnostic approach (EDA) combines two aspects of IRS patterns: location of the maximum yield (nine classes) and strength of the yield response with respect to climate (four classes), resulting in a total of 36 combined classes defined using criteria pre-specified by experts. The statistical diagnostic approach (SDA) groups IRSs by comparing their pattern and magnitude, without attempting to interpret these features. It applies a hierarchical clustering method, grouping response patterns using a distance metric that combines the spatial correlation and Euclidian distance between IRS pairs. The two approaches were used to investigate whether different patterns of yield response could be related to different properties of the crop models, specifically their genealogy, calibration and process description. Although no single model property across a large model ensemble was found to explain the integrated yield response to temperature and precipitation perturbations, the

  4. TRE ~ANGUAGE LOTTERY: PROMISES, PROMISES ...

    African Journals Online (AJOL)

    dual children, about which expressions a certain child heard and registered and with what frequency at ... scientific theorizing, suggested the need for another model, allowing d simpler account of the phenotype or .... (1) generate base structures, which are mapped to abstract S-structures including trace by tranSformations,.

  5. Microarray profiling shows distinct differences between primary tumors and commonly used preclinical models in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Weining; Iyer, N. Gopalakrishna; Tay, Hsien Ts’ung; Wu, Yonghui; Lim, Tony K. H.; Zheng, Lin; Song, In Chin; Kwoh, Chee Keong; Huynh, Hung; Tan, Patrick O. B.; Chow, Pierce K. H.

    2015-01-01

    Despite advances in therapeutics, outcomes for hepatocellular carcinoma (HCC) remain poor and there is an urgent need for efficacious systemic therapy. Unfortunately, drugs that are successful in preclinical studies often fail in the clinical setting, and we hypothesize that this is due to functional differences between primary tumors and commonly used preclinical models. In this study, we attempt to answer this question by comparing tumor morphology and gene expression profiles between primary tumors, xenografts and HCC cell lines. Hep G2 cell lines and tumor cells from patient tumor explants were subcutaneously (ectopically) injected into the flank and orthotopically into liver parenchyma of Mus Musculus SCID mice. The mice were euthanized after two weeks. RNA was extracted from the tumors, and gene expression profiling was performed using the Gene Chip Human Genome U133 Plus 2.0. Principal component analyses (PCA) and construction of dendrograms were conducted using Partek genomics suite. PCA showed that the commonly used HepG2 cell line model and its xenograft counterparts were vastly different from all fresh primary tumors. Expression profiles of primary tumors were also significantly divergent from their counterpart patient-derived xenograft (PDX) models, regardless of the site of implantation. Xenografts from the same primary tumors were more likely to cluster together regardless of site of implantation, although heat maps showed distinct differences in gene expression profiles between orthotopic and ectopic models. The data presented here challenges the utility of routinely used preclinical models. Models using HepG2 were vastly different from primary tumors and PDXs, suggesting that this is not clinically representative. Surprisingly, site of implantation (orthotopic versus ectopic) resulted in limited impact on gene expression profiles, and in both scenarios xenografts differed significantly from the original primary tumors, challenging the long

  6. Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy.

    Directory of Open Access Journals (Sweden)

    Estefanía de Munck

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-N-methylamino-L-alanine (L-BMAA, a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.

  7. Model of the synthesis of trisporic acid in Mucorales showing bistability.

    Science.gov (United States)

    Werner, S; Schroeter, A; Schimek, C; Vlaic, S; Wöstemeyer, J; Schuster, S

    2012-12-01

    An important substance in the signalling between individuals of Mucor-like fungi is trisporic acid (TA). This compound, together with some of its precursors, serves as a pheromone in mating between (+)- and (-)-mating types. Moreover, intermediates of the TA pathway are exchanged between the two mating partners. Based on differential equations, mathematical models of the synthesis pathways of TA in the two mating types of an idealised Mucor-fungus are here presented. These models include the positive feedback of TA on its own synthesis. The authors compare three sub-models in view of bistability, robustness and the reversibility of transitions. The proposed modelling study showed that, in a system where intermediates are exchanged, a reversible transition between the two stable steady states occurs, whereas an exchange of the end product leads to an irreversible transition. The reversible transition is physiologically favoured, because the high-production state of TA must come to an end eventually. Moreover, the exchange of intermediates and TA is compared with the 3-way handshake widely used by computers linked in a network.

  8. Human Commercial Models' Eye Colour Shows Negative Frequency-Dependent Selection.

    Directory of Open Access Journals (Sweden)

    Isabela Rodrigues Nogueira Forti

    Full Text Available In this study we investigated the eye colour of human commercial models registered in the UK (400 female and 400 male and Brazil (400 female and 400 male to test the hypothesis that model eye colour frequency was the result of negative frequency-dependent selection. The eye colours of the models were classified as: blue, brown or intermediate. Chi-square analyses of data for countries separated by sex showed that in the United Kingdom brown eyes and intermediate colours were significantly more frequent than expected in comparison to the general United Kingdom population (P<0.001. In Brazil, the most frequent eye colour brown was significantly less frequent than expected in comparison to the general Brazilian population. These results support the hypothesis that model eye colour is the result of negative frequency-dependent selection. This could be the result of people using eye colour as a marker of genetic diversity and finding rarer eye colours more attractive because of the potential advantage more genetically diverse offspring that could result from such a choice. Eye colour may be important because in comparison to many other physical traits (e.g., hair colour it is hard to modify, hide or disguise, and it is highly polymorphic.

  9. Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.

    Science.gov (United States)

    Xu, Meiyu; Li, Lina; Ohtsu, Hiroshi; Pittenger, Christopher

    2015-05-19

    Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Complete chloroplast genome sequence of green foxtail (Setaria viridis), a promising model system for C4 photosynthesis.

    Science.gov (United States)

    Wang, Shuo; Gao, Li-Zhi

    2016-09-01

    The complete chloroplast genome of green foxtail (Setaria viridis), a promising model system for C4 photosynthesis, is first reported in this study. The genome harbors a large single copy (LSC) region of 81 016 bp and a small single copy (SSC) region of 12 456  bp separated by a pair of inverted repeat (IRa and IRb) regions of 22 315 bp. GC content is 38.92%. The proportion of coding sequence is 57.97%, comprising of 111 (19 duplicated in IR regions) unique genes, 71 of which are protein-coding genes, four are rRNA genes, and 36 are tRNA genes. Phylogenetic analysis indicated that S. viridis was clustered with its cultivated species S. italica in the tribe Paniceae of the family Poaceae. This newly determined chloroplast genome will provide valuable genetic resources to assist future studies on C4 photosynthesis in grasses.

  11. Visualizing Three-dimensional Slab Geometries with ShowEarthModel

    Science.gov (United States)

    Chang, B.; Jadamec, M. A.; Fischer, K. M.; Kreylos, O.; Yikilmaz, M. B.

    2017-12-01

    Seismic data that characterize the morphology of modern subducted slabs on Earth suggest that a two-dimensional paradigm is no longer adequate to describe the subduction process. Here we demonstrate the effect of data exploration of three-dimensional (3D) global slab geometries with the open source program ShowEarthModel. ShowEarthModel was designed specifically to support data exploration, by focusing on interactivity and real-time response using the Vrui toolkit. Sixteen movies are presented that explore the 3D complexity of modern subduction zones on Earth. The first movie provides a guided tour through the Earth's major subduction zones, comparing the global slab geometry data sets of Gudmundsson and Sambridge (1998), Syracuse and Abers (2006), and Hayes et al. (2012). Fifteen regional movies explore the individual subduction zones and regions intersecting slabs, using the Hayes et al. (2012) slab geometry models where available and the Engdahl and Villasenor (2002) global earthquake data set. Viewing the subduction zones in this way provides an improved conceptualization of the 3D morphology within a given subduction zone as well as the 3D spatial relations between the intersecting slabs. This approach provides a powerful tool for rendering earth properties and broadening capabilities in both Earth Science research and education by allowing for whole earth visualization. The 3D characterization of global slab geometries is placed in the context of 3D slab-driven mantle flow and observations of shear wave splitting in subduction zones. These visualizations contribute to the paradigm shift from a 2D to 3D subduction framework by facilitating the conceptualization of the modern subduction system on Earth in 3D space.

  12. Estimating carbon and showing impacts of drought using satellite data in regression-tree models

    Science.gov (United States)

    Boyte, Stephen; Wylie, Bruce K.; Howard, Danny; Dahal, Devendra; Gilmanov, Tagir G.

    2018-01-01

    Integrating spatially explicit biogeophysical and remotely sensed data into regression-tree models enables the spatial extrapolation of training data over large geographic spaces, allowing a better understanding of broad-scale ecosystem processes. The current study presents annual gross primary production (GPP) and annual ecosystem respiration (RE) for 2000–2013 in several short-statured vegetation types using carbon flux data from towers that are located strategically across the conterminous United States (CONUS). We calculate carbon fluxes (annual net ecosystem production [NEP]) for each year in our study period, which includes 2012 when drought and higher-than-normal temperatures influence vegetation productivity in large parts of the study area. We present and analyse carbon flux dynamics in the CONUS to better understand how drought affects GPP, RE, and NEP. Model accuracy metrics show strong correlation coefficients (r) (r ≥ 94%) between training and estimated data for both GPP and RE. Overall, average annual GPP, RE, and NEP are relatively constant throughout the study period except during 2012 when almost 60% less carbon is sequestered than normal. These results allow us to conclude that this modelling method effectively estimates carbon dynamics through time and allows the exploration of impacts of meteorological anomalies and vegetation types on carbon dynamics.

  13. Lixisenatide, a drug developed to treat type 2 diabetes, shows neuroprotective effects in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    McClean, Paula L; Hölscher, Christian

    2014-11-01

    Type 2 diabetes is a risk factor for developing Alzheimer's disease (AD). In the brains of AD patients, insulin signalling is desensitised. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and analogues such as liraglutide are on the market as treatments for type 2 diabetes. We have previously shown that liraglutide showed neuroprotective effects in the APPswe/PS1ΔE9 mouse model of AD. Here, we test the GLP-1 receptor agonist lixisenatide in the same mouse model and compare the effects to liraglutide. After ten weeks of daily i.p. injections with liraglutide (2.5 or 25 nmol/kg) or lixisenatide (1 or 10 nmol/kg) or saline of APP/PS1 mice at an age when amyloid plaques had already formed, performance in an object recognition task was improved in APP/PS1 mice by both drugs at all doses tested. When analysing synaptic plasticity in the hippocampus, LTP was strongly increased in APP/PS1 mice by either drug. Lixisenatide (1 nmol/kg) was most effective. The reduction of synapse numbers seen in APP/PS1 mice was prevented by the drugs. The amyloid plaque load and dense-core Congo red positive plaque load in the cortex was reduced by both drugs at all doses. The chronic inflammation response (microglial activation) was also reduced by all treatments. The results demonstrate that the GLP-1 receptor agonists liraglutide and lixisenatide which are on the market as treatments for type 2 diabetes show promise as potential drug treatments of AD. Lixisenatide was equally effective at a lower dose compared to liraglutide in some of the parameters measured. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Phenolic Acids from Wheat Show Different Absorption Profiles in Plasma: A Model Experiment with Catheterized Pigs

    DEFF Research Database (Denmark)

    Nørskov, Natalja; Hedemann, Mette Skou; Theil, Peter Kappel

    2013-01-01

    The concentration and absorption of the nine phenolic acids of wheat were measured in a model experiment with catheterized pigs fed whole grain wheat and wheat aleurone diets. Six pigs in a repeated crossover design were fitted with catheters in the portal vein and mesenteric artery to study...... the absorption of phenolic acids. The difference between the artery and the vein for all phenolic acids was small, indicating that the release of phenolic acids in the large intestine was not sufficient to create a porto-arterial concentration difference. Although, the porto-arterial difference was small...... consumed. Benzoic acid derivatives showed low concentration in the plasma (phenolic acids, likely because it is an intermediate in the phenolic acid metabolism...

  15. Etoposide Incorporated into Camel Milk Phospholipids Liposomes Shows Increased Activity against Fibrosarcoma in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Hamzah M. Maswadeh

    2015-01-01

    Full Text Available Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS. Anticancer drug etoposide (ETP was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes. The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

  16. Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes.

    Science.gov (United States)

    Berthelot, Karine; Lecomte, Sophie; Estevez, Yannick; Zhendre, Vanessa; Henry, Sarah; Thévenot, Julie; Dufourc, Erick J; Alves, Isabel D; Peruch, Frédéric

    2014-01-01

    The biomembrane surrounding rubber particles from the hevea latex is well known for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3) are major components, linked on rubber particles, and they have been shown to be involved in rubber synthesis or quality (mass regulation), but their exact function is still to be determined. In this study we highlighted the different modes of interactions of both recombinant proteins with various membrane models (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles) to mimic the latex particle membrane. We combined various biophysical methods (polarization-modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR-FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber particle protein (SRPP) shows less affinity than rubber elongation factor (REF) for the membranes but displays a kind of "covering" effect on the lipid headgroups without disturbing the membrane integrity. Its structure is conserved in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity with changes in its aggregation properties, the amyloid nature of REF, which we previously reported, is not favored in the presence of lipids. REF binds and inserts into membranes. The membrane integrity is highly perturbed, and we suspect that REF is even able to remove lipids from the membrane leading to the formation of mixed micelles. These two homologous proteins show affinity to all membrane models tested but neatly differ in their interacting features. This could imply differential roles on the surface of rubber particles. © 2013.

  17. Ab Initio Modeling Of Friction Reducing Agents Shows Quantum Mechanical Interactions Can Have Macroscopic Manifestation.

    Science.gov (United States)

    Hernández Velázquez, J D; Barroso-Flores, J; Gama Goicochea, A

    2016-11-23

    Two of the most commonly encountered friction-reducing agents used in plastic sheet production are the amides known as erucamide and behenamide, which despite being almost identical chemically, lead to markedly different values of the friction coefficient. To understand the origin of this contrasting behavior, in this work we model brushes made of these two types of linear-chain molecules using quantum mechanical numerical simulations under the density functional theory at the B97D/6-31G(d,p) level of theory. Four chains of erucamide and behenamide were linked to a 2 × 10 zigzag graphene sheet and optimized both in vacuum and in continuous solvent using the SMD implicit solvation model. We find that erucamide chains tend to remain closer together through π-π stacking interactions arising from the double bonds located at C13-C14, a feature behenamide lacks, and thus a more spread configuration is obtained with the latter. It is argued that this arrangement of the erucamide chains is responsible for the lower friction coefficient of erucamide brushes, compared with behenamide brushes, which is a macroscopic consequence of cooperative quantum mechanical interactions. While only quantum level interactions are modeled here, we show that behenamide chains are more spread out in the brush than erucamide chains as a consequence of those interactions. The spread-out configuration allows more solvent particles to penetrate the brush, leading in turn to more friction, in agreement with macroscopic measurements and mesoscale simulations of the friction coefficient reported in the literature.

  18. The perils and promises of microbial abundance: novel natures and model ecosystems, from artisanal cheese to alien seas.

    Science.gov (United States)

    Paxson, Heather; Helmreich, Stefan

    2014-04-01

    Microbial life has been much in the news. From outbreaks of Escherichia coli to discussions of the benefits of raw and fermented foods to recent reports of life forms capable of living in extreme environments, the modest microbe has become a figure for thinking through the presents and possible futures of nature, writ large as well as small. Noting that dominant representations of microbial life have shifted from an idiom of peril to one of promise, we argue that microbes--especially when thriving as microbial communities--are being upheld as model ecosystems in a prescriptive sense, as tokens of how organisms and human ecological relations with them could, should, or might be. We do so in reference to two case studies: the regulatory politics of artisanal cheese and the speculative research of astrobiology. To think of and with microbial communities as model ecosystems offers a corrective to the scientific determinisms we detect in some recent calls to attend to the materiality of scientific objects.

  19. Vortexlet models of flapping flexible wings show tuning for force production and control

    International Nuclear Information System (INIS)

    Mountcastle, A M; Daniel, T L

    2010-01-01

    Insect wings are compliant structures that experience deformations during flight. Such deformations have recently been shown to substantially affect induced flows, with appreciable consequences to flight forces. However, there are open questions related to the aerodynamic mechanisms underlying the performance benefits of wing deformation, as well as the extent to which such deformations are determined by the boundary conditions governing wing actuation together with mechanical properties of the wing itself. Here we explore aerodynamic performance parameters of compliant wings under periodic oscillations, subject to changes in phase between wing elevation and pitch, and magnitude and spatial pattern of wing flexural stiffness. We use a combination of computational structural mechanics models and a 2D computational fluid dynamics approach to ask how aerodynamic force production and control potential are affected by pitch/elevation phase and variations in wing flexural stiffness. Our results show that lift and thrust forces are highly sensitive to flexural stiffness distributions, with performance optima that lie in different phase regions. These results suggest a control strategy for both flying animals and engineering applications of micro-air vehicles.

  20. Showing a model's eye movements in examples does not improve learning of problem-solving tasks

    NARCIS (Netherlands)

    van Marlen, Tim; van Wermeskerken, Margot; Jarodzka, Halszka; van Gog, Tamara

    2016-01-01

    Eye movement modeling examples (EMME) are demonstrations of a computer-based task by a human model (e.g., a teacher), with the model's eye movements superimposed on the task to guide learners' attention. EMME have been shown to enhance learning of perceptual classification tasks; however, it is an

  1. ISO-66, a novel inhibitor of macrophage migration, shows efficacy in melanoma and colon cancer models.

    Science.gov (United States)

    Ioannou, Kyriaki; Cheng, Kai Fan; Crichlow, Gregg V; Birmpilis, Anastasios I; Lolis, Elias J; Tsitsilonis, Ourania E; Al-Abed, Yousef

    2014-10-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, whereas prolonged administration of ISO-66 in mice with established syngeneic melanoma or colon cancer was non-toxic and resulted in a significant decrease in tumor burden. Subsequent ex vivo analysis of mouse splenocytes revealed that the observed decrease in tumor growth rates was likely mediated by the selective in vivo expansion of antitumor-reactive effector cells induced by ISO-66. Compared to other MIF-inactivating strategies employed in vivo, the anticancer activity of ISO-66 is demonstrated to be of equal or better efficacy. Our findings suggest that targeting MIF, via highly specific and stable compounds, such as ISO-66, may be effective for cancer treatment and stimulation of anticancer immune responses.

  2. Classifying multi-model wheat yield impact response surfaces showing sensitivity to temperature and precipitation change

    NARCIS (Netherlands)

    Fronzek, Stefan; Pirttioja, Nina; Carter, Timothy R.; Bindi, Marco; Hoffmann, Holger; Palosuo, Taru; Ruiz-Ramos, Margarita; Tao, Fulu; Trnka, Miroslav; Acutis, Marco; Asseng, Senthold; Baranowski, Piotr; Basso, Bruno; Bodin, Per; Buis, Samuel; Cammarano, Davide; Deligios, Paola; Destain, Marie France; Dumont, Benjamin; Ewert, Frank; Ferrise, Roberto; François, Louis; Gaiser, Thomas; Hlavinka, Petr; Jacquemin, Ingrid; Kersebaum, Kurt Christian; Kollas, Chris; Krzyszczak, Jaromir; Lorite, Ignacio J.; Minet, Julien; Minguez, M.I.; Montesino, Manuel; Moriondo, Marco; Müller, Christoph; Nendel, Claas; Öztürk, Isik; Perego, Alessia; Rodríguez, Alfredo; Ruane, Alex C.; Ruget, Françoise; Sanna, Mattia; Semenov, Mikhail A.; Slawinski, Cezary; Stratonovitch, Pierre; Supit, Iwan; Waha, Katharina; Wang, Enli; Wu, Lianhai; Zhao, Zhigan; Rötter, Reimund P.

    2018-01-01

    Crop growth simulation models can differ greatly in their treatment of key processes and hence in their response to environmental conditions. Here, we used an ensemble of 26 process-based wheat models applied at sites across a European transect to compare their sensitivity to changes in

  3. Classifying multi-model wheat yield impact response surfaces showing sensitivity to temperature and precipitation change

    Czech Academy of Sciences Publication Activity Database

    Fronzek, S.; Pirttioja, N. K.; Carter, T. R.; Bindi, M.; Hoffmann, H.; Palosuo, T.; Ruiz-Ramos, M.; Tao, F.; Trnka, Miroslav; Acutis, M.; Asseng, S.; Baranowski, P.; Basso, B.; Bodin, P.; Buis, S.; Cammarano, D.; Deligios, P.; Destain, M. F.; Dumont, B.; Ewert, F.; Ferrise, R.; Francois, L.; Gaiser, T.; Hlavinka, Petr; Jacquemin, I.; Kersebaum, K. C.; Kollas, C.; Krzyszczak, J.; Lorite, I. J.; Minet, J.; Ines Minguez, M.; Montesino, M.; Moriondo, M.; Mueller, C.; Nendel, C.; Öztürk, I.; Perego, A.; Rodriguez, A.; Ruane, A. C.; Ruget, F.; Sanna, M.; Semenov, M. A.; Slawinski, C.; Stratonovitch, P.; Supit, I.; Waha, K.; Wang, E.; Wu, L.; Zhao, Z.; Rötter, R.

    2018-01-01

    Roč. 159, jan (2018), s. 209-224 ISSN 0308-521X Institutional support: RVO:86652079 Keywords : climate - change * crop models * probabilistic assessment * simulating impacts * british catchments * uncertainty * europe * productivity * calibration * adaptation * Classification * Climate change * Crop model * Ensemble * Sensitivity analysis * Wheat Subject RIV: GC - Agronomy OBOR OECD: Agronomy, plant breeding and plant protection Impact factor: 2.571, year: 2016

  4. The combination of sorafenib and everolimus shows antitumor activity in preclinical models of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Pignochino, Ymera; Dell’Aglio, Carmine; Inghilleri, Simona; Zorzetto, Michele; Basiricò, Marco; Capozzi, Federica; Canta, Marta; Piloni, Davide; Cemmi, Francesca; Sangiolo, Dario; Gammaitoni, Loretta; Soster, Marco; Marchiò, Serena; Pozzi, Ernesto; Morbini, Patrizia; Luisetti, Maurizio; Aglietta, Massimo; Grignani, Giovanni; Stella, Giulia M

    2015-01-01

    Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention. This study aimed to identify ‘druggable’ pathways in MPM and to formulate a targeted approach based on the use of commercially available molecules, such as the multikinase inhibitor sorafenib and the mTOR inhibitor everolimus. We planned a triple approach based on: i) analysis of immunophenotypes and mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No mutations were found in ‘hot spot’ regions of the mTOR upstream genes (e.g. EGFR, KRAS and PIK3CA). Phosphorylated mTOR and ERM were specifically overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination was effective in mTOR and ERM blockade; exerted synergistic effects on the inhibition of MPM cell proliferation; triggered ROS production and consequent AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally administered to MPM-bearing NOD/SCID mice. ERM and mTOR pathways are activated in MPM and ‘druggable’ by a combination of sorafenib and everolimus. Combination therapy is a promising therapeutic strategy against MPM. The online version of this article (doi:10.1186/s12885-015-1363-1) contains supplementary material, which is available to authorized users

  5. Models of alien species richness show moderate predictive accuracy and poor transferability

    Directory of Open Access Journals (Sweden)

    César Capinha

    2018-06-01

    Full Text Available Robust predictions of alien species richness are useful to assess global biodiversity change. Nevertheless, the capacity to predict spatial patterns of alien species richness remains largely unassessed. Using 22 data sets of alien species richness from diverse taxonomic groups and covering various parts of the world, we evaluated whether different statistical models were able to provide useful predictions of absolute and relative alien species richness, as a function of explanatory variables representing geographical, environmental and socio-economic factors. Five state-of-the-art count data modelling techniques were used and compared: Poisson and negative binomial generalised linear models (GLMs, multivariate adaptive regression splines (MARS, random forests (RF and boosted regression trees (BRT. We found that predictions of absolute alien species richness had a low to moderate accuracy in the region where the models were developed and a consistently poor accuracy in new regions. Predictions of relative richness performed in a superior manner in both geographical settings, but still were not good. Flexible tree ensembles-type techniques (RF and BRT were shown to be significantly better in modelling alien species richness than parametric linear models (such as GLM, despite the latter being more commonly applied for this purpose. Importantly, the poor spatial transferability of models also warrants caution in assuming the generality of the relationships they identify, e.g. by applying projections under future scenario conditions. Ultimately, our results strongly suggest that predictability of spatial variation in richness of alien species richness is limited. The somewhat more robust ability to rank regions according to the number of aliens they have (i.e. relative richness, suggests that models of aliens species richness may be useful for prioritising and comparing regions, but not for predicting exact species numbers.

  6. Metabolic modeling of energy balances in Mycoplasma hyopneumoniae shows that pyruvate addition increases growth rate.

    Science.gov (United States)

    Kamminga, Tjerko; Slagman, Simen-Jan; Bijlsma, Jetta J E; Martins Dos Santos, Vitor A P; Suarez-Diez, Maria; Schaap, Peter J

    2017-10-01

    Mycoplasma hyopneumoniae is cultured on large-scale to produce antigen for inactivated whole-cell vaccines against respiratory disease in pigs. However, the fastidious nutrient requirements of this minimal bacterium and the low growth rate make it challenging to reach sufficient biomass yield for antigen production. In this study, we sequenced the genome of M. hyopneumoniae strain 11 and constructed a high quality constraint-based genome-scale metabolic model of 284 chemical reactions and 298 metabolites. We validated the model with time-series data of duplicate fermentation cultures to aim for an integrated model describing the dynamic profiles measured in fermentations. The model predicted that 84% of cellular energy in a standard M. hyopneumoniae cultivation was used for non-growth associated maintenance and only 16% of cellular energy was used for growth and growth associated maintenance. Following a cycle of model-driven experimentation in dedicated fermentation experiments, we were able to increase the fraction of cellular energy used for growth through pyruvate addition to the medium. This increase in turn led to an increase in growth rate and a 2.3 times increase in the total biomass concentration reached after 3-4 days of fermentation, enhancing the productivity of the overall process. The model presented provides a solid basis to understand and further improve M. hyopneumoniae fermentation processes. Biotechnol. Bioeng. 2017;114: 2339-2347. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Simple solvable energy-landscape model that shows a thermodynamic phase transition and a glass transition.

    Science.gov (United States)

    Naumis, Gerardo G

    2012-06-01

    When a liquid melt is cooled, a glass or phase transition can be obtained depending on the cooling rate. Yet, this behavior has not been clearly captured in energy-landscape models. Here, a model is provided in which two key ingredients are considered in the landscape, metastable states and their multiplicity. Metastable states are considered as in two level system models. However, their multiplicity and topology allows a phase transition in the thermodynamic limit for slow cooling, while a transition to the glass is obtained for fast cooling. By solving the corresponding master equation, the minimal speed of cooling required to produce the glass is obtained as a function of the distribution of metastable states.

  8. Modeled hydrologic metrics show links between hydrology and the functional composition of stream assemblages.

    Science.gov (United States)

    Patrick, Christopher J; Yuan, Lester L

    2017-07-01

    Flow alteration is widespread in streams, but current understanding of the effects of differences in flow characteristics on stream biological communities is incomplete. We tested hypotheses about the effect of variation in hydrology on stream communities by using generalized additive models to relate watershed information to the values of different flow metrics at gauged sites. Flow models accounted for 54-80% of the spatial variation in flow metric values among gauged sites. We then used these models to predict flow metrics in 842 ungauged stream sites in the mid-Atlantic United States that were sampled for fish, macroinvertebrates, and environmental covariates. Fish and macroinvertebrate assemblages were characterized in terms of a suite of metrics that quantified aspects of community composition, diversity, and functional traits that were expected to be associated with differences in flow characteristics. We related modeled flow metrics to biological metrics in a series of stressor-response models. Our analyses identified both drying and base flow instability as explaining 30-50% of the observed variability in fish and invertebrate community composition. Variations in community composition were related to variations in the prevalence of dispersal traits in invertebrates and trophic guilds in fish. The results demonstrate that we can use statistical models to predict hydrologic conditions at bioassessment sites, which, in turn, we can use to estimate relationships between flow conditions and biological characteristics. This analysis provides an approach to quantify the effects of spatial variation in flow metrics using readily available biomonitoring data. © 2017 by the Ecological Society of America.

  9. The speed of memory errors shows the influence of misleading information: Testing the diffusion model and discrete-state models.

    Science.gov (United States)

    Starns, Jeffrey J; Dubé, Chad; Frelinger, Matthew E

    2018-05-01

    In this report, we evaluate single-item and forced-choice recognition memory for the same items and use the resulting accuracy and reaction time data to test the predictions of discrete-state and continuous models. For the single-item trials, participants saw a word and indicated whether or not it was studied on a previous list. The forced-choice trials had one studied and one non-studied word that both appeared in the earlier single-item trials and both received the same response. Thus, forced-choice trials always had one word with a previous correct response and one with a previous error. Participants were asked to select the studied word regardless of whether they previously called both words "studied" or "not studied." The diffusion model predicts that forced-choice accuracy should be lower when the word with a previous error had a fast versus a slow single-item RT, because fast errors are associated with more compelling misleading memory retrieval. The two-high-threshold (2HT) model does not share this prediction because all errors are guesses, so error RT is not related to memory strength. A low-threshold version of the discrete state approach predicts an effect similar to the diffusion model, because errors are a mixture of responses based on misleading retrieval and guesses, and the guesses should tend to be slower. Results showed that faster single-trial errors were associated with lower forced-choice accuracy, as predicted by the diffusion and low-threshold models. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Few promising multivariable prognostic models exist for recovery of people with non-specific neck pain in musculoskeletal primary care: a systematic review.

    Science.gov (United States)

    Wingbermühle, Roel W; van Trijffel, Emiel; Nelissen, Paul M; Koes, Bart; Verhagen, Arianne P

    2018-01-01

    Which multivariable prognostic model(s) for recovery in people with neck pain can be used in primary care? Systematic review of studies evaluating multivariable prognostic models. People with non-specific neck pain presenting at primary care. Baseline characteristics of the participants. Recovery measured as pain reduction, reduced disability, or perceived recovery at short-term and long-term follow-up. Fifty-three publications were included, of which 46 were derivation studies, four were validation studies, and three concerned combined studies. The derivation studies presented 99 multivariate models, all of which were at high risk of bias. Three externally validated models generated usable models in low risk of bias studies. One predicted recovery in non-specific neck pain, while two concerned participants with whiplash-associated disorders (WAD). Discriminative ability of the non-specific neck pain model was area under the curve (AUC) 0.65 (95% CI 0.59 to 0.71). For the first WAD model, discriminative ability was AUC 0.85 (95% CI 0.79 to 0.91). For the second WAD model, specificity was 99% (95% CI 93 to 100) and sensitivity was 44% (95% CI 23 to 65) for prediction of non-recovery, and 86% (95% CI 73 to 94) and 55% (95% CI 41 to 69) for prediction of recovery, respectively. Initial Neck Disability Index scores and age were identified as consistent prognostic factors in these three models. Three externally validated models were found to be usable and to have low risk of bias, of which two showed acceptable discriminative properties for predicting recovery in people with neck pain. These three models need further validation and evaluation of their clinical impact before their broad clinical use can be advocated. PROSPERO CRD42016042204. [Wingbermühle RW, van Trijffel E, Nelissen PM, Koes B, Verhagen AP (2018) Few promising multivariable prognostic models exist for recovery of people with non-specific neck pain in musculoskeletal primary care: a systematic review

  11. A Murine Model of Candida glabrata Vaginitis Shows No Evidence of an Inflammatory Immunopathogenic Response.

    Directory of Open Access Journals (Sweden)

    Evelyn E Nash

    Full Text Available Candida glabrata is the second most common organism isolated from women with vulvovaginal candidiasis (VVC, particularly in women with uncontrolled diabetes mellitus. However, mechanisms involved in the pathogenesis of C. glabrata-associated VVC are unknown and have not been studied at any depth in animal models. The objective of this study was to evaluate host responses to infection following efforts to optimize a murine model of C. glabrata VVC. For this, various designs were evaluated for consistent experimental vaginal colonization (i.e., type 1 and type 2 diabetic mice, exogenous estrogen, varying inocula, and co-infection with C. albicans. Upon model optimization, vaginal fungal burden and polymorphonuclear neutrophil (PMN recruitment were assessed longitudinally over 21 days post-inoculation, together with vaginal concentrations of IL-1β, S100A8 alarmin, lactate dehydrogenase (LDH, and in vivo biofilm formation. Consistent and sustained vaginal colonization with C. glabrata was achieved in estrogenized streptozotocin-induced type 1 diabetic mice. Vaginal PMN infiltration was consistently low, with IL-1β, S100A8, and LDH concentrations similar to uninoculated mice. Biofilm formation was not detected in vivo, and co-infection with C. albicans did not induce synergistic immunopathogenic effects. This data suggests that experimental vaginal colonization of C. glabrata is not associated with an inflammatory immunopathogenic response or biofilm formation.

  12. A Murine Model of Candida glabrata Vaginitis Shows No Evidence of an Inflammatory Immunopathogenic Response.

    Science.gov (United States)

    Nash, Evelyn E; Peters, Brian M; Lilly, Elizabeth A; Noverr, Mairi C; Fidel, Paul L

    2016-01-01

    Candida glabrata is the second most common organism isolated from women with vulvovaginal candidiasis (VVC), particularly in women with uncontrolled diabetes mellitus. However, mechanisms involved in the pathogenesis of C. glabrata-associated VVC are unknown and have not been studied at any depth in animal models. The objective of this study was to evaluate host responses to infection following efforts to optimize a murine model of C. glabrata VVC. For this, various designs were evaluated for consistent experimental vaginal colonization (i.e., type 1 and type 2 diabetic mice, exogenous estrogen, varying inocula, and co-infection with C. albicans). Upon model optimization, vaginal fungal burden and polymorphonuclear neutrophil (PMN) recruitment were assessed longitudinally over 21 days post-inoculation, together with vaginal concentrations of IL-1β, S100A8 alarmin, lactate dehydrogenase (LDH), and in vivo biofilm formation. Consistent and sustained vaginal colonization with C. glabrata was achieved in estrogenized streptozotocin-induced type 1 diabetic mice. Vaginal PMN infiltration was consistently low, with IL-1β, S100A8, and LDH concentrations similar to uninoculated mice. Biofilm formation was not detected in vivo, and co-infection with C. albicans did not induce synergistic immunopathogenic effects. This data suggests that experimental vaginal colonization of C. glabrata is not associated with an inflammatory immunopathogenic response or biofilm formation.

  13. Infusing BSCS 5E Instructional Model with Multimedia: A Promising Approach to Develop 21st Century Skills

    Science.gov (United States)

    Senan, Divya C.

    2013-01-01

    The full promise of class room learning is dependent on its ability to incorporate 21st century skills in its instructional design, delivery and implementation. In this increasingly competitive global economy, it is not enough for students to acquire subject-level mastery alone. Skills like creative thinking, problem-solving, communication and…

  14. Global thermal niche models of two European grasses show high invasion risks in Antarctica.

    Science.gov (United States)

    Pertierra, Luis R; Aragón, Pedro; Shaw, Justine D; Bergstrom, Dana M; Terauds, Aleks; Olalla-Tárraga, Miguel Ángel

    2017-07-01

    The two non-native grasses that have established long-term populations in Antarctica (Poa pratensis and Poa annua) were studied from a global multidimensional thermal niche perspective to address the biological invasion risk to Antarctica. These two species exhibit contrasting introduction histories and reproductive strategies and represent two referential case studies of biological invasion processes. We used a multistep process with a range of species distribution modelling techniques (ecological niche factor analysis, multidimensional envelopes, distance/entropy algorithms) together with a suite of thermoclimatic variables, to characterize the potential ranges of these species. Their native bioclimatic thermal envelopes in Eurasia, together with the different naturalized populations across continents, were compared next. The potential niche of P. pratensis was wider at the cold extremes; however, P. annua life history attributes enable it to be a more successful colonizer. We observe that particularly cold summers are a key aspect of the unique Antarctic environment. In consequence, ruderals such as P. annua can quickly expand under such harsh conditions, whereas the more stress-tolerant P. pratensis endures and persist through steady growth. Compiled data on human pressure at the Antarctic Peninsula allowed us to provide site-specific biosecurity risk indicators. We conclude that several areas across the region are vulnerable to invasions from these and other similar species. This can only be visualized in species distribution models (SDMs) when accounting for founder populations that reveal nonanalogous conditions. Results reinforce the need for strict management practices to minimize introductions. Furthermore, our novel set of temperature-based bioclimatic GIS layers for ice-free terrestrial Antarctica provide a mechanism for regional and global species distribution models to be built for other potentially invasive species. © 2017 John Wiley & Sons Ltd.

  15. ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

    Directory of Open Access Journals (Sweden)

    Daniel Komnig

    Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

  16. Progesterone treatment shows benefit in a pediatric model of moderate to severe bilateral brain injury.

    Directory of Open Access Journals (Sweden)

    Rastafa I Geddes

    Full Text Available Controlled cortical impact (CCI models in adult and aged Sprague-Dawley (SD rats have been used extensively to study medial prefrontal cortex (mPFC injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.Twenty-eight-day old (PND 28 male Sprague Dawley rats received sham (n = 24 or CCI (n = 47 injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight or vehicle injections on post-injury days (PID 1-7, subjected to behavioral testing from PID 9-27, and analyzed for lesion size at PID 28.The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.

  17. Enzymatic generation of hydrogen peroxide shows promising antifouling effect

    DEFF Research Database (Denmark)

    Kristensen, J.B.; Olsen, Stefan Møller; Laursen, B.S.

    2010-01-01

    Proteobacteria, tested in microtiter plates. However, enzymatically produced H2O2 released from a coating did not impede biofilm formation by bacteria in natural seawater tested in a biofilm reactor. A field trial revealed a noticeable effect of the enzyme system: after immersion in the North Sea for 97 days...

  18. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    Science.gov (United States)

    ... Ther. 2013 Jul:21(7):135-44. doi:10.1038/mt.2013.87. PMID:23670575. Intravenously Injected Recombinant ... Dermatol. 2013 Jul;133(7):1910-3. doi: 10.1038/jid.2013.10. PMID: 23321924. The mission of ...

  19. New bimetallic EMF cell shows promise in direct energy conversion

    Science.gov (United States)

    Hesson, J. C.; Shimotake, H.

    1968-01-01

    Concentration cell, based upon a thermally regenerative cell principle, produces electrical energy from any large heat source. This experimental bimetallic EMF cell uses a sodium-bismuth alloy cathode and a pure liquid sodium anode. The cell exhibits reliability, corrosion resistance, and high current density performance.

  20. VAN method of short-term earthquake prediction shows promise

    Science.gov (United States)

    Uyeda, Seiya

    Although optimism prevailed in the 1970s, the present consensus on earthquake prediction appears to be quite pessimistic. However, short-term prediction based on geoelectric potential monitoring has stood the test of time in Greece for more than a decade [VarotsosandKulhanek, 1993] Lighthill, 1996]. The method used is called the VAN method.The geoelectric potential changes constantly due to causes such as magnetotelluric effects, lightning, rainfall, leakage from manmade sources, and electrochemical instabilities of electrodes. All of this noise must be eliminated before preseismic signals are identified, if they exist at all. The VAN group apparently accomplished this task for the first time. They installed multiple short (100-200m) dipoles with different lengths in both north-south and east-west directions and long (1-10 km) dipoles in appropriate orientations at their stations (one of their mega-stations, Ioannina, for example, now has 137 dipoles in operation) and found that practically all of the noise could be eliminated by applying a set of criteria to the data.

  1. Stem cells show promising results for lymphoedema treatment

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Quaade, Marlene Louise; Sheikh, Søren Paludan

    2015-01-01

    Abstract Lymphoedema is a debilitating condition, manifesting in excess lymphatic fluid and swelling of subcutaneous tissues. Lymphoedema is as of yet still an incurable condition and current treatment modalities are not satisfactory. The capacity of mesenchymal stem cells to promote angiogenesis......, secrete growth factors, regulate the inflammatory process, and differentiate into multiple cell types make them a potential ideal therapy for lymphoedema. Adipose tissue is the richest and most accessible source of mesenchymal stem cells and they can be harvested, isolated, and used for therapy...... in a single stage procedure as an autologous treatment. The aim of this paper was to review all studies using mesenchymal stem cells for lymphoedema treatment with a special focus on the potential use of adipose-derived stem cells. A systematic search was performed and five preclinical and two clinical...

  2. Experimental Therapy Shows Promise for Type 1 Diabetes

    Science.gov (United States)

    ... triggers cells to take up sugar from the blood. In type 1 diabetes, the immune system The cells and tissues that ... people to eat or drink to raise their blood sugar levels. However, many people with type 1 diabetes can’t tell when their blood sugar is ...

  3. A zebrafish model of glucocorticoid resistance shows serotonergic modulation of the stress response

    Directory of Open Access Journals (Sweden)

    Brian eGriffiths

    2012-10-01

    Full Text Available One function of glucocorticoids is to restore homeostasis after an acute stress response by providing negative feedback to stress circuits in the brain. Loss of this negative feedback leads to elevated physiological stress and may contribute to depression, anxiety and post-traumatic stress disorder. We investigated the early, developmental effects of glucocorticoid signaling deficits on stress physiology and related behaviors using a mutant zebrafish, grs357, with non-functional glucocorticoid receptors. These mutants are morphologically inconspicuous and adult-viable. A previous study of adult grs357 mutants showed loss of glucocorticoid-mediated negative feedback and elevated physiological and behavioral stress markers. Already at five days post-fertilization, mutant larvae had elevated whole body cortisol, increased expression of pro-opiomelanocortin (POMC, the precursor of adrenocorticotropic hormone (ACTH, and failed to show normal suppression of stress markers after dexamethasone treatment. Mutant larvae had larger auditory-evoked startle responses compared to wildtype sibling controls (grwt, despite having lower spontaneous activity levels. Fluoxetine (Prozac treatment in mutants decreased startle responding and increased spontaneous activity, making them behaviorally similar to wildtype. This result mirrors known effects of selective serotonin reuptake inhibitors (SSRIs in modifying glucocorticoid signaling and alleviating stress disorders in human patients. Our results suggest that larval grs357 zebrafish can be used to study behavioral, physiological and molecular aspects of stress disorders. Most importantly, interactions between glucocorticoid and serotonin signaling appear to be highly conserved among vertebrates, suggesting deep homologies at the neural circuit level and opening up new avenues for research into psychiatric conditions.

  4. Evaluating Quantitative and Qualitative Traits of Promising Potato Clones and Commercial Cultivars Using the GGE Bi-plot and AMMI Models

    Directory of Open Access Journals (Sweden)

    D HassanPanah

    2014-07-01

    Full Text Available To evaluate quantitative and qualitative characteristics and stability of marketable tuber yield of 13 promising potato clones, along with three commercial cultivars (Agria, Marfona and Lady Rosetta as checks, an experiment was based on a randomized complete block design with four replications was carried out at the Agricultural and Natural Resources Research Station of Ardabil during 2011 and 2012. During the growing period and after harvest, attributes like number of main stem per plant, plant height, tuber number and weight per plant, total and marketable tuber yield, dry matter percentage, baking type, hollow heart, tuber inner ring and discoloration of raw tuber flesh after 24 hours were measured. Combined ANONA for quantitative traits showed that there were significant differences among promising clones as to total and marketable tuber yield, tuber number and weight per plant, plant height, mean tuber weight, number of main stem per plant and dry matter percentage and their interactions with year in total and marketable tuber yield and tuber number and weight per plant. The clones 396151-7, 397008-5, 397015-8, 397008-2 and 994001-4 were found to have higher total and marketable tuber yield, tuber number and weight per plant and mean tuber weight. These clones produced high and mid-uniform tuber, yellow skin color, yellow and white flesh color, oval round and round tuber shape, mid and shallow eyes, with no hollow heart, tuber inner crack and tuber inner ring, mid-late maturity and mid and high dry matter percentage as compared with control and other clones. In this experiment, GGE Bi-plot and AMMI models were found to be proper methods for selection of 397008-2, 397008-5 and 994001-4 as being high marketable and stable yielding clones.

  5. Metabolic remodeling agents show beneficial effects in the dystrophin-deficient mdx mouse model

    Directory of Open Access Journals (Sweden)

    Jahnke Vanessa E

    2012-08-01

    Full Text Available Abstract Background Duchenne muscular dystrophy is a genetic disease involving a severe muscle wasting that is characterized by cycles of muscle degeneration/regeneration and culminates in early death in affected boys. Mitochondria are presumed to be involved in the regulation of myoblast proliferation/differentiation; enhancing mitochondrial activity with exercise mimetics (AMPK and PPAR-delta agonists increases muscle function and inhibits muscle wasting in healthy mice. We therefore asked whether metabolic remodeling agents that increase mitochondrial activity would improve muscle function in mdx mice. Methods Twelve-week-old mdx mice were treated with two different metabolic remodeling agents (GW501516 and AICAR, separately or in combination, for 4 weeks. Extensive systematic behavioral, functional, histological, biochemical, and molecular tests were conducted to assess the drug(s' effects. Results We found a gain in body and muscle weight in all treated mice. Histologic examination showed a decrease in muscle inflammation and in the number of fibers with central nuclei and an increase in fibers with peripheral nuclei, with significantly fewer activated satellite cells and regenerating fibers. Together with an inhibition of FoXO1 signaling, these results indicated that the treatments reduced ongoing muscle damage. Conclusions The three treatments produced significant improvements in disease phenotype, including an increase in overall behavioral activity and significant gains in forelimb and hind limb strength. Our findings suggest that triggering mitochondrial activity with exercise mimetics improves muscle function in dystrophin-deficient mdx mice.

  6. Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation

    Science.gov (United States)

    Bassingthwaighte, James B.

    2013-01-01

    A four-region (capillary plasma, endothelium, interstitial fluid, cell) multipath model was configured to describe the kinetics of blood-tissue exchange for small solutes in the lung, accounting for regional flow heterogeneity, permeation of cell membranes and through interendothelial clefts, and intracellular reactions. Serotonin uptake data from the Multiple indicator dilution “bolus sweep” experiments of Rickaby and coworkers (Rickaby DA, Linehan JH, Bronikowski TA, Dawson CA. J Appl Physiol 51: 405–414, 1981; Rickaby DA, Dawson CA, and Linehan JH. J Appl Physiol 56: 1170–1177, 1984) and Malcorps et al. (Malcorps CM, Dawson CA, Linehan JH, Bronikowski TA, Rickaby DA, Herman AG, Will JA. J Appl Physiol 57: 720–730, 1984) were analyzed to distinguish facilitated transport into the endothelial cells (EC) and the inhibition of tracer transport by nontracer serotonin in the bolus of injectate from the free uninhibited permeation through the clefts into the interstitial fluid space. The permeability-surface area products (PS) for serotonin via the inter-EC clefts were ∼0.3 ml·g−1·min−1, low compared with the transporter-mediated maximum PS of 13 ml·g−1·min−1 (with Km = ∼0.3 μM and Vmax = ∼4 nmol·g−1·min−1). The estimates of serotonin PS values for EC transporters from their multiple data sets were similar and were influenced only modestly by accounting for the cleft permeability in parallel. The cleft PS estimates in these Ringer-perfused lungs are less than half of those for anesthetized dogs (Yipintsoi T. Circ Res 39: 523–531, 1976) with normal hematocrits, but are compatible with passive noncarrier-mediated transport observed later in the same laboratory (Dawson CA, Linehan JH, Rickaby DA, Bronikowski TA. Ann Biomed Eng 15: 217–227, 1987; Peeters FAM, Bronikowski TA, Dawson CA, Linehan JH, Bult H, Herman AG. J Appl Physiol 66: 2328–2337, 1989) The identification and quantitation of the cleft pathway conductance from these

  7. KEEFEKTIFAN MODEL SHOW NOT TELL DAN MIND MAP PADA PEMBELAJARAN MENULIS TEKS EKSPOSISI BERDASARKAN MINAT PESERTA DIDIK KELAS X SMK

    Directory of Open Access Journals (Sweden)

    Wiwit Lili Sokhipah

    2015-03-01

    Full Text Available Tujuan penelitian ini adalah (1 menentukan keefektifan penggunaan model show not tell pada pembelajaran keterampilan menulis teks eksposisi berdasarkan minat peserta didik SMK Kelas X, (2 menentukan keefektifan penggunaan model mind map pada pembelajaran keterampilan menulis teks eksposisi berdasarkan minat peserta didik SMK kelas X, (3 menentukan keefektifan interaksi show not tell dan mind map pada pembelajaran keterampilan menulis teks eksposisi berdasarkan minat peserta didik SMK kelas X. Penelitian ini adalah quasi experimental design (pretes-postes control group design. Dalam desain ini terdapat dua kelompok eksperimen yakni penerapan model show not tell dalam pembelajaran keterampilan menulis teks eksposisipeserta didik dengan minat tinggi dan penerapan model mind map dalam pembelajaran keterampilan menulis teks eksposisi  peserta didik dengan minat rendah. Hasil penelitian adalah (1 model show not tell efektif digunakan  dalam membelajarkan menulis teks eksposisi bagi peserta didik yang memiliki minat tinggi, (2 model mind map efektif digunakan dalam membelajarkan menulis teks eksposisi bagi peserta didik yang memiliki minat rendah, dan (3 model show not tell lebih efektif digunakan dalam membelajarkan menulis teks eksposisi bagi peserta didik yang memiliki minat tinggi, sedangkan model mind map efektif digunakan dalam membelajarkan teks eksposisi pagi peserta didik yang memiliki minat rendah.

  8. Elicited vs. voluntary promises

    NARCIS (Netherlands)

    Ismayilov, H.; Potters, Jan

    2017-01-01

    We set up an experiment with pre-play communication to study the impact of promise elicitation by trustors from trustees on trust and trustworthiness. When given the opportunity a majority of trustors solicits a promise from the trustee. This drives up the promise making rate by trustees to almost

  9. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Marina Aiello Padilla

    2015-01-01

    Full Text Available Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV. Two bacterial strains were identified as active, with percentages of inhibition (IP equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.

  10. Photons, photosynthesis, and high-performance computing: challenges, progress, and promise of modeling metabolism in green algae

    International Nuclear Information System (INIS)

    Chang, C H; Graf, P; Alber, D M; Kim, K; Murray, G; Posewitz, M; Seibert, M

    2008-01-01

    The complexity associated with biological metabolism considered at a kinetic level presents a challenge to quantitative modeling. In particular, the relatively sparse knowledge of parameters for enzymes with known kinetic responses is problematic. The possible space of these parameters is of high-dimension, and sampling of such a space typifies a combinatorial explosion of possible dynamic states. However, with sufficient quantitative transcriptomics, proteomics, and metabolomics data at hand, these challenges could be met by high-performance software with sampling, fitting, and optimization capabilities. With this in mind, we present the High-Performance Systems Biology Toolkit HiPer SBTK, an evolving software package to simulate, fit, and optimize metabolite concentrations and fluxes within the space of rate and binding parameters associated with detailed enzyme kinetic models. We present our chosen modeling paradigm for the formulation of metabolic pathway models, the means to address the challenge of representing such models in a precise and persistent fashion using the standardized Systems Biology Markup Language, and our second-generation model of H2-associated Chlamydomonas metabolism. Processing of such models for hierarchically parallelized simulation and optimization, job specification by the user through a GUI interface, software capabilities and initial scaling data, and the mapping of the computation to biological questions is also discussed. Moreover, we present near-term future software and model development goals

  11. Plot showing ATLAS limits on Standard Model Higgs production in the mass range 100-600 GeV

    CERN Multimedia

    ATLAS Collaboration

    2011-01-01

    The combined upper limit on the Standard Model Higgs boson production cross section divided by the Standard Model expectation as a function of mH is indicated by the solid line. This is a 95% CL limit using the CLs method in the entire mass range. The dotted line shows the median expected limit in the absence of a signal and the green and yellow bands reflect the corresponding 68% and 95% expected

  12. Plot showing ATLAS limits on Standard Model Higgs production in the mass range 110-150 GeV

    CERN Multimedia

    ATLAS Collaboration

    2011-01-01

    The combined upper limit on the Standard Model Higgs boson production cross section divided by the Standard Model expectation as a function of mH is indicated by the solid line. This is a 95% CL limit using the CLs method in in the low mass range. The dotted line shows the median expected limit in the absence of a signal and the green and yellow bands reflect the corresponding 68% and 95% expected

  13. Political Reputations and Campaign Promises

    OpenAIRE

    Aragones, Enriqueta; Palfrey, Thomas R.; Postlewaite, Andrew

    2006-01-01

    We analyze conditions under which candidates' reputations may affect voters' beliefs over what policy will be implemented by the winning candidate of an election. We develop a model of repeated elections with complete information in which candidates are purely ideological. We analyze an equilibrium in which voters' strategies involve a credible threat to punish candidates who renege on their campaign promises and in which all campaign promises are believed by voters and honored by candidates....

  14. Using euhalophytes to understand salt tolerance and to develop saline agriculture: Suaeda salsa as a promising model.

    Science.gov (United States)

    Song, Jie; Wang, Baoshan

    2015-02-01

    As important components in saline agriculture, halophytes can help to provide food for a growing world population. In addition to being potential crops in their own right, halophytes are also potential sources of salt-resistance genes that might help plant breeders and molecular biologists increase the salt tolerance of conventional crop plants. One especially promising halophyte is Suaeda salsa, a euhalophytic herb that occurs both on inland saline soils and in the intertidal zone. The species produces dimorphic seeds: black seeds are sensitive to salinity and remain dormant in light under high salt concentrations, while brown seeds can germinate under high salinity (e.g. 600 mm NaCl) regardless of light. Consequently, the species is useful for studying the mechanisms by which dimorphic seeds are adapted to saline environments. S. salsa has succulent leaves and is highly salt tolerant (e.g. its optimal NaCl concentration for growth is 200 mm). A series of S. salsa genes related to salt tolerance have been cloned and their functions tested: these include SsNHX1, SsHKT1, SsAPX, SsCAT1, SsP5CS and SsBADH. The species is economically important because its fresh branches have high value as a vegetable, and its seed oil is edible and rich in unsaturated fatty acids. Because it can remove salts and heavy metals from saline soils, S. salsa can also be used in the restoration of salinized or contaminated saline land. Because of its economic and ecological value in saline agriculture, S. salsa is one of the most important halophytes in China. In this review, the value of S. salsa as a source of food, medicine and forage is discussed. Its uses in the restoration of salinized or contaminated land and as a source of salt-resistance genes are also considered. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Modeling Patient No-Show History and Predicting Future Outpatient Appointment Behavior in the Veterans Health Administration.

    Science.gov (United States)

    Goffman, Rachel M; Harris, Shannon L; May, Jerrold H; Milicevic, Aleksandra S; Monte, Robert J; Myaskovsky, Larissa; Rodriguez, Keri L; Tjader, Youxu C; Vargas, Dominic L

    2017-05-01

    Missed appointments reduce the efficiency of the health care system and negatively impact access to care for all patients. Identifying patients at risk for missing an appointment could help health care systems and providers better target interventions to reduce patient no-shows. Our aim was to develop and test a predictive model that identifies patients that have a high probability of missing their outpatient appointments. Demographic information, appointment characteristics, and attendance history were drawn from the existing data sets from four Veterans Affairs health care facilities within six separate service areas. Past attendance behavior was modeled using an empirical Markov model based on up to 10 previous appointments. Using logistic regression, we developed 24 unique predictive models. We implemented the models and tested an intervention strategy using live reminder calls placed 24, 48, and 72 hours ahead of time. The pilot study targeted 1,754 high-risk patients, whose probability of missing an appointment was predicted to be at least 0.2. Our results indicate that three variables were consistently related to a patient's no-show probability in all 24 models: past attendance behavior, the age of the appointment, and having multiple appointments scheduled on that day. After the intervention was implemented, the no-show rate in the pilot group was reduced from the expected value of 35% to 12.16% (p value < 0.0001). The predictive model accurately identified patients who were more likely to miss their appointments. Applying the model in practice enables clinics to apply more intensive intervention measures to high-risk patients. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

  16. A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.

    Science.gov (United States)

    Gharagozloo, P; Gutiérrez-Adán, A; Champroux, A; Noblanc, A; Kocer, A; Calle, A; Pérez-Cerezales, S; Pericuesta, E; Polhemus, A; Moazamian, A; Drevet, J R; Aitken, R J

    2016-02-01

    Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress? Oral administration of a novel antioxidant formulation significantly reduced sperm DNA damage in glutathione peroxidase 5 (GPX5), knockout mice and restored pregnancy rates to near-normal levels in mice subjected to scrotal heat stress. Animal and human studies have documented the adverse effect of sperm DNA damage on fertilization rates, embryo quality, miscarriage rates and the transfer of de novo mutations to offspring. Semen samples of infertile men are known to be deficient in several key antioxidants relative to their fertile counterparts. Antioxidants alone or in combination have demonstrated limited efficacy against sperm oxidative stress and DNA damage in numerous human clinical trials, however these studies have not been definitive and an optimum combination has remained elusive. The efficacy of the antioxidant formulation was evaluated in two well-established mouse models of oxidative stress, scrotal heating and Gpx5 knockout (KO) mice, (n = 12 per experimental group), by two independent laboratories. Mice were provided the antioxidant product in their drinking water for 2-8 weeks and compared with control groups for sperm DNA damage and pregnancy rates. In the Gpx5 KO model, oxidative DNA damage was monitored in spermatozoa by immunocytochemical detection of 8-hydroxy-2'-deoxyguanosine (8OHdG). In the scrotal heat stress model, male fertility was tested by partnering with three females for 5 days. The percentage of pregnant females, number of vaginal plugs, resorptions per litter, and litter size were recorded. Using immunocytochemical detection of 8OHdG as a biomarker of DNA oxidation, analysis of control mice revealed that around 30% of the sperm population was positively stained. This level increased to about 60% in transgenic mice deficient in the

  17. Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management

    Directory of Open Access Journals (Sweden)

    Manuela Gaebler

    2017-09-01

    Full Text Available Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.

  18. Plectasin shows intracellular activity against Staphylococcus aureus in human THP-1 monocytes and in a mouse peritonitis model

    DEFF Research Database (Denmark)

    Brinch, Karoline Sidelmann; Sandberg, Anne; Baudoux, Pierre

    2009-01-01

    was maintained (maximal relative efficacy [E(max)], 1.0- to 1.3-log reduction in CFU) even though efficacy was inferior to that of extracellular killing (E(max), >4.5-log CFU reduction). Animal studies included a novel use of the mouse peritonitis model, exploiting extra- and intracellular differentiation assays...... concentration. These findings stress the importance of performing studies of extra- and intracellular activity since these features cannot be predicted from traditional MIC and killing kinetic studies. Application of both the THP-1 and the mouse peritonitis models showed that the in vitro results were similar...

  19. Experimental results showing the internal three-component velocity field and outlet temperature contours for a model gas turbine combustor

    CSIR Research Space (South Africa)

    Meyers, BC

    2011-09-01

    Full Text Available by the American Institute of Aeronautics and Astronautics Inc. All rights reserved ISABE-2011-1129 EXPERIMENTAL RESULTS SHOWING THE INTERNAL THREE-COMPONENT VELOCITY FIELD AND OUTLET TEMPERATURE CONTOURS FOR A MODEL GAS TURBINE COMBUSTOR BC Meyers*, GC... identifier c Position identifier F Fuel i Index L (Combustor) Liner OP Orifice plate Introduction There are often inconsistencies when comparing experimental and Computational Fluid Dynamics (CFD) simulations for gas turbine combustors [1...

  20. Keeping the Promise

    Science.gov (United States)

    Whissemore, Tabitha

    2016-01-01

    Since its launch in September 2015, Heads Up America has collected information on nearly 125 promise programs across the country, many of which were instituted long before President Barack Obama announced the America's College Promise (ACP) plan in 2015. At least 27 new free community college programs have launched in states, communities, and at…

  1. Methods of modeling TCO residential real estate in the life cycles of buildings as a promising energy efficiency management tool

    Directory of Open Access Journals (Sweden)

    Kulakov Kirill

    2017-01-01

    Full Text Available Building and developing an affordable housing market is a huge challenge for Russia’s national economy. Today, the housing construction industry finds itself in a situation torn by a conflict caused by the simultaneous needs to minimize the housing construction costs in order to make housing more affordable for Russians and to increase the energy efficiency of the housing projects, which is associated with additional costs for developers. To find solutions to this contradictory situation, one needs new theoretical and practical approaches and economic tools. The global economic trend of managing goods and services on the basis of the value of goods and services over the life cycle is also manifested in the construction industry in Russia. The problem of forming a new economic thinking in the housing sector predetermines the perception of the value of housing not only as the price of purchased real estate, but as the equivalent of the total cost of ownership of real estate throughout its life cycle. This approach allows to compensate the initial rise in the cost of construction resulting from the introduction of energy-efficient technologies by savings in the operational phase of the life cycle of the property. In this regard, management of the total cost of real estate ownership based on energy modeling is of high research and practical relevance.

  2. Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study.

    Science.gov (United States)

    Smith, Jennifer A; Anderson, Sarah-Jane; Harris, Kate L; McGillen, Jessica B; Lee, Edward; Garnett, Geoff P; Hallett, Timothy B

    2016-07-01

    Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years. We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up. If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful

  3. Food pattern modeling shows that the 2010 Dietary Guidelines for sodium and potassium cannot be met simultaneously

    Science.gov (United States)

    Maillot, Matthieu; Monsivais, Pablo; Drewnowski, Adam

    2013-01-01

    The 2010 US Dietary Guidelines recommended limiting intake of sodium to 1500 mg/d for people older than 50 years, African Americans, and those suffering from chronic disease. The guidelines recommended that all other people consume less than 2300 mg sodium and 4700 mg of potassium per day. The theoretical feasibility of meeting the sodium and potassium guidelines while simultaneously maintaining nutritional adequacy of the diet was tested using food pattern modeling based on linear programming. Dietary data from the National Health and Nutrition Examination Survey 2001-2002 were used to create optimized food patterns for 6 age-sex groups. Linear programming models determined the boundary conditions for the potassium and sodium content of the modeled food patterns that would also be compatible with other nutrient goals. Linear programming models also sought to determine the amounts of sodium and potassium that both would be consistent with the ratio of Na to K of 0.49 and would cause the least deviation from the existing food habits. The 6 sets of food patterns were created before and after an across-the-board 10% reduction in sodium content of all foods in the Food and Nutrition Database for Dietary Studies. Modeling analyses showed that the 2010 Dietary Guidelines for sodium were incompatible with potassium guidelines and with nutritionally adequate diets, even after reducing the sodium content of all US foods by 10%. Feasibility studies should precede or accompany the issuing of dietary guidelines to the public. PMID:23507224

  4. Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F Saverio; Cossu, Giulio; Elvassore, Nicola

    2016-12-01

    : Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210-240 µm vs. 40-70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from

  5. Climate Modelling Shows Increased Risk to Eucalyptus sideroxylon on the Eastern Coast of Australia Compared to Eucalyptus albens

    Directory of Open Access Journals (Sweden)

    Farzin Shabani

    2017-11-01

    Full Text Available Aim: To identify the extent and direction of range shift of Eucalyptus sideroxylon and E. albens in Australia by 2050 through an ensemble forecast of four species distribution models (SDMs. Each was generated using four global climate models (GCMs, under two representative concentration pathways (RCPs. Location: Australia. Methods: We used four SDMs of (i generalized linear model, (ii MaxEnt, (iii random forest, and (iv boosted regression tree to construct SDMs for species E. sideroxylon and E. albens under four GCMs including (a MRI-CGCM3, (b MIROC5, (c HadGEM2-AO and (d CCSM4, under two RCPs of 4.5 and 6.0. Here, the true skill statistic (TSS index was used to assess the accuracy of each SDM. Results: Results showed that E. albens and E. sideroxylon will lose large areas of their current suitable range by 2050 and E. sideroxylon is projected to gain in eastern and southeastern Australia. Some areas were also projected to remain suitable for each species between now and 2050. Our modelling showed that E. sideroxylon will lose suitable habitat on the western side and will not gain any on the eastern side because this region is one the most heavily populated areas in the country, and the populated areas are moving westward. The predicted decrease in E. sideroxylon’s distribution suggests that land managers should monitor its population closely, and evaluate whether it meets criteria for a protected legal status. Main conclusions: Both Eucalyptus sideroxylon and E. albens will be negatively affected by climate change and it is projected that E. sideroxylon will be at greater risk of losing habitat than E. albens.

  6. Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model

    Directory of Open Access Journals (Sweden)

    Maswadeh HM

    2015-04-01

    Full Text Available Hamzah M Maswadeh,1 Ahmed N Aljarbou,1 Mohammed S Alorainy,2 Arshad H Rahmani,3 Masood A Khan3 1Department of Pharmaceutics, College of Pharmacy, 2Department of Pharmacology and Therapeutics, College of Medicine, 3College of Applied Medical Sciences, Qassim University, Buraydah, Kingdom of Saudi Arabia Abstract: Small unilamellar vesicles from camel milk phospholipids (CML mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC were prepared, and anticancer drugs doxorubicin (Dox or etoposide (ETP were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98% in liposomes (Lip prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP or DPPC-Lip-(Dox + ETP. Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the

  7. Promise Zones for Applicants

    Data.gov (United States)

    Department of Housing and Urban Development — This tool assists applicants to HUD's Promise Zone initiative prepare data to submit with their application by allowing applicants to draw the exact location of the...

  8. 68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

    Science.gov (United States)

    Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

    2017-06-01

    Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

  9. The BACHD Rat Model of Huntington Disease Shows Specific Deficits in a Test Battery of Motor Function.

    Science.gov (United States)

    Manfré, Giuseppe; Clemensson, Erik K H; Kyriakou, Elisavet I; Clemensson, Laura E; van der Harst, Johanneke E; Homberg, Judith R; Nguyen, Huu Phuc

    2017-01-01

    Rationale : Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype. Objective : The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping. Methods : Wild-type (WT) and transgenic animals were tested longitudinally from 2 to 12 months of age. To measure fine motor control, rats were challenged with the pasta handling test and the pellet reaching test. To evaluate gross motor function, animals were assessed by using the holding bar and the grip strength tests. Spontaneous locomotor activity and circadian rhythmicity were assessed in an automated home-cage environment, namely the PhenoTyper. We then integrated existing classical methodologies to test motor function with automated home-cage assessment of motor performance. Results : BACHD rats showed strong impairment in muscle endurance at 2 months of age. Altered circadian rhythmicity and locomotor activity were observed in transgenic animals. On the other hand, reaching behavior, forepaw dexterity and muscle strength were unaffected. Conclusions : The BACHD rat model exhibits certain features of HD patients, like muscle weakness and changes in circadian behavior. We have observed modest but clear-cut deficits in distinct motor phenotypes, thus confirming the validity of this transgenic rat model for treatment and drug discovery purposes.

  10. Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.

    Directory of Open Access Journals (Sweden)

    Patrick Aldrin-Kirk

    Full Text Available Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable

  11. Promising More Information

    Science.gov (United States)

    2003-01-01

    When NASA needed a real-time, online database system capable of tracking documentation changes in its propulsion test facilities, engineers at Stennis Space Center joined with ECT International, of Brookfield, Wisconsin, to create a solution. Through NASA's Dual-Use Program, ECT developed Exdata, a software program that works within the company's existing Promise software. Exdata not only satisfied NASA s requirements, but also expanded ECT s commercial product line. Promise, ECT s primary product, is an intelligent software program with specialized functions for designing and documenting electrical control systems. An addon to AutoCAD software, Promis e generates control system schematics, panel layouts, bills of material, wire lists, and terminal plans. The drawing functions include symbol libraries, macros, and automatic line breaking. Primary Promise customers include manufacturing companies, utilities, and other organizations with complex processes to control.

  12. In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Virginie Desestret

    Full Text Available THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1 and alternatively activated (M2 macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle were intravenously administered during the subacute stage of ischemia (D4 in a model of transient middle cerebral artery occlusion. Functional neuroscores and magnetic resonance imaging endpoints (infarct volumes, blood-brain barrier integrity, phagocytic activity assessed by iron oxide uptake were longitudinally monitored for 2 weeks. This cell-based treatment did not significantly improve any outcome measure compared with vehicle, suggesting that this strategy is not relevant to stroke therapy.

  13. Image-based multiscale mechanical modeling shows the importance of structural heterogeneity in the human lumbar facet capsular ligament.

    Science.gov (United States)

    Zarei, Vahhab; Liu, Chao J; Claeson, Amy A; Akkin, Taner; Barocas, Victor H

    2017-08-01

    The lumbar facet capsular ligament (FCL) primarily consists of aligned type I collagen fibers that are mainly oriented across the joint. The aim of this study was to characterize and incorporate in-plane local fiber structure into a multiscale finite element model to predict the mechanical response of the FCL during in vitro mechanical tests, accounting for the heterogeneity in different scales. Characterization was accomplished by using entire-domain polarization-sensitive optical coherence tomography to measure the fiber structure of cadaveric lumbar FCLs ([Formula: see text]). Our imaging results showed that fibers in the lumbar FCL have a highly heterogeneous distribution and are neither isotropic nor completely aligned. The averaged fiber orientation was [Formula: see text] ([Formula: see text] in the inferior region and [Formula: see text] in the middle and superior regions), with respect to lateral-medial direction (superior-medial to inferior-lateral). These imaging data were used to construct heterogeneous structural models, which were then used to predict experimental gross force-strain behavior and the strain distribution during equibiaxial and strip biaxial tests. For equibiaxial loading, the structural model fit the experimental data well but underestimated the lateral-medial forces by [Formula: see text]16% on average. We also observed pronounced heterogeneity in the strain field, with stretch ratios for different elements along the lateral-medial axis of sample typically ranging from about 0.95 to 1.25 during a 12% strip biaxial stretch in the lateral-medial direction. This work highlights the multiscale structural and mechanical heterogeneity of the lumbar FCL, which is significant both in terms of injury prediction and microstructural constituents' (e.g., neurons) behavior.

  14. Demographical history and palaeodistribution modelling show range shift towards Amazon Basin for a Neotropical tree species in the LGM.

    Science.gov (United States)

    Vitorino, Luciana Cristina; Lima-Ribeiro, Matheus S; Terribile, Levi Carina; Collevatti, Rosane G

    2016-10-13

    We studied the phylogeography and demographical history of Tabebuia serratifolia (Bignoniaceae) to understand the disjunct geographical distribution of South American seasonally dry tropical forests (SDTFs). We specifically tested if the multiple and isolated patches of SDTFs are current climatic relicts of a widespread and continuously distributed dry forest during the last glacial maximum (LGM), the so called South American dry forest refugia hypothesis, using ecological niche modelling (ENM) and statistical phylogeography. We sampled 235 individuals of T. serratifolia in 17 populations in Brazil and analysed the polymorphisms at three intergenic chloroplast regions and ITS nuclear ribosomal DNA. Coalescent analyses showed a demographical expansion at the last c. 130 ka (thousand years before present). Simulations and ENM also showed that the current spatial pattern of genetic diversity is most likely due to a scenario of range expansion and range shift towards the Amazon Basin during the colder and arid climatic conditions associated with the LGM, matching the expected for the South American dry forest refugia hypothesis, although contrasting to the Pleistocene Arc hypothesis. Populations in more stable areas or with higher suitability through time showed higher genetic diversity. Postglacial range shift towards the Southeast and Atlantic coast may have led to spatial genome assortment due to leading edge colonization as the species tracks suitable environments, leading to lower genetic diversity in populations at higher distance from the distribution centroid at 21 ka. Haplotype sharing or common ancestry among populations from Caatinga in Northeast Brazil, Atlantic Forest in Southeast and Cerrado biome and ENM evince the past connection among these biomes.

  15. Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation

    Science.gov (United States)

    2013-01-01

    Background This study investigates the effect of Xiao-Qing-Long-Tang (XQLT) on neurotrophin in an established mouse model of Dermatophagoides pteronyssinus (Der p)-induced acute allergic asthma and in a LA4 cell line model of lung adenoma. The effects of XQLT on the regulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), airway hyper-responsiveness (AHR) and immunoglobulin E were measured. Methods LA4 cells were stimulated with 100 μg/ml Der p 24 h and the supernatant was collected for ELISA analysis. Der p-stimulated LA4 cells with either XQLT pre-treatment or XQLT co-treatment were used to evaluate the XQLT effect on neurotrophin. Balb/c mice were sensitized on days 0 and 7 with a base-tail injection of 50 μg Dermatophagoides pteronyssinus (Der p) that was emulsified in 50 μl incomplete Freund’s adjuvant (IFA). On day 14, mice received an intra-tracheal challenge of 50 μl Der p (2 mg/ml). XQLT (1g/Kg) was administered orally to mice either on days 2, 4, 6, 8, 10 and 12 as a preventive strategy or on day 15 as a therapeutic strategy. Results XQLT inhibited expression of those NGF, BDNF and thymus-and activation-regulated cytokine (TARC) in LA4 cells that were subjected to a Der p allergen. Both preventive and therapeutic treatments with XQLT in mice reduced AHR. Preventive treatment with XQLT markedly decreased NGF in broncho-alveolar lavage fluids (BALF) and BDNF in serum, whereas therapeutic treatment reduced only serum BDNF level. The reduced NGF levels corresponded to a decrease in AHR by XQLT treatment. Reduced BALF NGF and TARC and serum BDNF levels may have been responsible for decreased eosinophil infiltration into lung tissue. Immunohistochemistry showed that p75NTR and TrkA levels were reduced in the lungs of mice under both XQLT treatment protocols, and this reduction may have been correlated with the prevention of the asthmatic reaction by XQLT. Conclusion XQLT alleviated allergic inflammation including AHR, Ig

  16. The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model

    Directory of Open Access Journals (Sweden)

    Fabian Anders

    2017-11-01

    Full Text Available Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP, followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced by episcleral vein cauterization resulted in a considerable impairment of the RGCs and the retinal nerve fiber layer. An intravitreal injection of α-crystallin B at the time of the IOP increase was able to rescue the RGCs, as measured in a functional photopic electroretinogram, retinal nerve fiber layer thickness, and RGC counts. Mass-spectrometry-based proteomics and antibody-microarray measurements indicated that a α-crystallin injection distinctly up-regulated all of the subclasses (α, β, and γ of the crystallin protein family. The creation of an interactive protein network revealed clear correlations between individual proteins, which showed a regulatory shift resulting from the crystallin injection. The neuroprotective properties of α-crystallin B further demonstrate the potential importance of crystallin proteins in developing therapeutic options for glaucoma.

  17. Fourier transform infrared imaging showing reduced unsaturated lipid content in the hippocampus of a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Leskovjan, Andreana C; Kretlow, Ariane; Miller, Lisa M

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic =CH stretching mode at 3012 cm(-1). The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p avoiding progression of the disease.

  18. The Ancient Maya Landscape: Facing the Challenges and Embracing the Promise of Integrating Archaeology, Remote Sensing, Soil Science and Hydrologic Modeling for Coupled Natural and Human Systems.

    Science.gov (United States)

    Murtha, T., Jr.; Duffy, C.; Cook, B. D.; Schroder, W.; Webster, D.; French, K. D.; Alcover, O.; Golden, C.; Balzotti, C.; Shaffer, D.

    2016-12-01

    Relying on a niche inheritance perspective, this paper discusses the long-term spatial and temporal dynamics of land-use management, agricultural decision making and patterns of resource availability in the tropical lowlands of Central America. We introduce and describe ongoing research that addresses a series of long standing questions about coupled natural and human history dynamics in the Central Maya lowlands, emphasizing the role of landscape and region to address these questions. First, we summarize the results of a CNH pilot study focused on the evolution of the regional landscape of Tikal, Guatemala. Particular attention is centered on how we integrated landscape survey, traditional archaeology and soil studies to understand the spatial and temporal dynamics of agricultural land use and intensification over a two thousand period. Additionally, we discuss how these results were integrated into remote sensing, hydrological and erosion models to better understand how past changes in available water and productive land compare to what we know about settlement patterns in the Tikal Region over that same time period. We not only describe how the Maya transformed this landscape, but also how the region influenced changing patterns of settlement and land use. We finish this section with a discussion of some of the unique challenges integrating archaeological information to study CNH dynamics during this pilot study. Second, we introduce a new project designed to `scale up' the pilot study for a macro-regional analysis of the lowland Maya landscape. The new project leverages a uniquely sampled LIDAR data set designed to refine measurements of above ground carbon storage. Our new project quantitatively examines these data for evidence for past human activity. Preliminary results offer a promising path for tightly integrating archaeology, natural science, remote sensing and modeling for studying CNH dynamics in the deep and recent past.

  19. Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer.

    Science.gov (United States)

    Okumura, Masaki; Ichihara, Hideaki; Matsumoto, Yoko

    2018-11-01

    Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

  20. Bioavailability of particulate metal to zebra mussels: Biodynamic modelling shows that assimilation efficiencies are site-specific

    Energy Technology Data Exchange (ETDEWEB)

    Bourgeault, Adeline, E-mail: bourgeault@ensil.unilim.fr [Cemagref, Unite de Recherche Hydrosystemes et Bioprocedes, 1 rue Pierre-Gilles de Gennes, 92761 Antony (France); FIRE, FR-3020, 4 place Jussieu, 75005 Paris (France); Gourlay-France, Catherine, E-mail: catherine.gourlay@cemagref.fr [Cemagref, Unite de Recherche Hydrosystemes et Bioprocedes, 1 rue Pierre-Gilles de Gennes, 92761 Antony (France); FIRE, FR-3020, 4 place Jussieu, 75005 Paris (France); Priadi, Cindy, E-mail: cindy.priadi@eng.ui.ac.id [LSCE/IPSL CEA-CNRS-UVSQ, Avenue de la Terrasse, 91198 Gif-sur-Yvette (France); Ayrault, Sophie, E-mail: Sophie.Ayrault@lsce.ipsl.fr [LSCE/IPSL CEA-CNRS-UVSQ, Avenue de la Terrasse, 91198 Gif-sur-Yvette (France); Tusseau-Vuillemin, Marie-Helene, E-mail: Marie-helene.tusseau@ifremer.fr [IFREMER Technopolis 40, 155 rue Jean-Jacques Rousseau, 92138 Issy-Les-Moulineaux (France)

    2011-12-15

    This study investigates the ability of the biodynamic model to predict the trophic bioaccumulation of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni) and zinc (Zn) in a freshwater bivalve. Zebra mussels were transplanted to three sites along the Seine River (France) and collected monthly for 11 months. Measurements of the metal body burdens in mussels were compared with the predictions from the biodynamic model. The exchangeable fraction of metal particles did not account for the bioavailability of particulate metals, since it did not capture the differences between sites. The assimilation efficiency (AE) parameter is necessary to take into account biotic factors influencing particulate metal bioavailability. The biodynamic model, applied with AEs from the literature, overestimated the measured concentrations in zebra mussels, the extent of overestimation being site-specific. Therefore, an original methodology was proposed for in situ AE measurements for each site and metal. - Highlights: > Exchangeable fraction of metal particles did not account for the bioavailability of particulate metals. > Need for site-specific biodynamic parameters. > Field-determined AE provide a good fit between the biodynamic model predictions and bioaccumulation measurements. - The interpretation of metal bioaccumulation in transplanted zebra mussels with biodynamic modelling highlights the need for site-specific assimilation efficiencies of particulate metals.

  1. Bioavailability of particulate metal to zebra mussels: biodynamic modelling shows that assimilation efficiencies are site-specific.

    Science.gov (United States)

    Bourgeault, Adeline; Gourlay-Francé, Catherine; Priadi, Cindy; Ayrault, Sophie; Tusseau-Vuillemin, Marie-Hélène

    2011-12-01

    This study investigates the ability of the biodynamic model to predict the trophic bioaccumulation of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni) and zinc (Zn) in a freshwater bivalve. Zebra mussels were transplanted to three sites along the Seine River (France) and collected monthly for 11 months. Measurements of the metal body burdens in mussels were compared with the predictions from the biodynamic model. The exchangeable fraction of metal particles did not account for the bioavailability of particulate metals, since it did not capture the differences between sites. The assimilation efficiency (AE) parameter is necessary to take into account biotic factors influencing particulate metal bioavailability. The biodynamic model, applied with AEs from the literature, overestimated the measured concentrations in zebra mussels, the extent of overestimation being site-specific. Therefore, an original methodology was proposed for in situ AE measurements for each site and metal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

    Science.gov (United States)

    Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

    2014-05-01

    The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Promising change, delivering continuity

    DEFF Research Database (Denmark)

    Lund, Jens Friis; Sungusia, Eliezeri; Mabele, Mathew Bukhi

    2017-01-01

    REDD+ is an ambition to reduce carbon emissions from deforestation and forest degradation in the Global South. This ambition has generated unprecedented commitment of political support and financial funds for the forest-development sector. Many academics and people-centered advocacy organizations...... have conceptualized REDD+ as an example of ‘‘green grabbing” and have voiced fears of a potential global rush for land and trees. In this paper we argue that, in practice and up until now, REDD+ resembles longstanding dynamics of the development and conservation industry, where the promise of change...... becomes a discursive commodity that is constantly reproduced and used to generate value and appropriate financial resources. We thus argue for a re-conceptualization of REDD+ as a conservation fad within the broader political economy of development and conservation. We derive this argument from a study...

  4. Advanced imaging techniques show progressive arthropathy following experimentally induced knee bleeding in a factor VIII-/- rat model

    DEFF Research Database (Denmark)

    Sorensen, K. R.; Roepstorff, K.; Petersen, M.

    2015-01-01

    Background: Joint pathology is most commonly assessed by radiogra-phy, but ultrasonography (US) is increasingly recognized for its acces-sibility, safety and ability to show soft tissue changes, the earliestindicators of haemophilic arthropathy (HA). US, however, lacks theability to visualize...

  5. Automated home cage assessment shows behavioral changes in a transgenic mouse model of spinocerebellar ataxia type 17.

    Science.gov (United States)

    Portal, Esteban; Riess, Olaf; Nguyen, Huu Phuc

    2013-08-01

    Spinocerebellar Ataxia type 17 (SCA17) is an autosomal dominantly inherited, neurodegenerative disease characterized by ataxia, involuntary movements, and dementia. A novel SCA17 mouse model having a 71 polyglutamine repeat expansion in the TATA-binding protein (TBP) has shown age related motor deficit using a classic motor test, yet concomitant weight increase might be a confounding factor for this measurement. In this study we used an automated home cage system to test several motor readouts for this same model to confirm pathological behavior results and evaluate benefits of automated home cage in behavior phenotyping. Our results confirm motor deficits in the Tbp/Q71 mice and present previously unrecognized behavioral characteristics obtained from the automated home cage, indicating its use for high-throughput screening and testing, e.g. of therapeutic compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury

    Directory of Open Access Journals (Sweden)

    Samal Zhussupbekova

    2016-07-01

    Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

  7. Betting on change: Tenet deal with Vanguard shows it's primed to try ACO effort, new payment model.

    Science.gov (United States)

    Kutscher, Beth

    2013-07-01

    Tenet Healthcare Corp.'s acquisition of Vanguard Health Systems is a sign the investor-owned chain is willing to take a chance on alternative payment models such as accountable care organizations. There's no certainty that ACOs will deliver the improvements on quality or cost savings, but Vanguard Vice Chairman Keith Pitts, left, says his system's Pioneer ACO in Detroit has already achieved some cost savings.

  8. A network model shows the importance of coupled processes in the microbial N cycle in the Cape Fear River Estuary

    Science.gov (United States)

    Hines, David E.; Lisa, Jessica A.; Song, Bongkeun; Tobias, Craig R.; Borrett, Stuart R.

    2012-06-01

    Estuaries serve important ecological and economic functions including habitat provision and the removal of nutrients. Eutrophication can overwhelm the nutrient removal capacity of estuaries and poses a widely recognized threat to the health and function of these ecosystems. Denitrification and anaerobic ammonium oxidation (anammox) are microbial processes responsible for the removal of fixed nitrogen and diminish the effects of eutrophication. Both of these microbial removal processes can be influenced by direct inputs of dissolved inorganic nitrogen substrates or supported by microbial interactions with other nitrogen transforming pathways such as nitrification and dissimilatory nitrate reduction to ammonium (DNRA). The coupling of nitrogen removal pathways to other transformation pathways facilitates the removal of some forms of inorganic nitrogen; however, differentiating between direct and coupled nitrogen removal is difficult. Network modeling provides a tool to examine interactions among microbial nitrogen cycling processes and to determine the within-system history of nitrogen involved in denitrification and anammox. To examine the coupling of nitrogen cycling processes, we built a nitrogen budget mass balance network model in two adjacent 1 cm3 sections of bottom water and sediment in the oligohaline portion of the Cape Fear River Estuary, NC, USA. Pathway, flow, and environ ecological network analyses were conducted to characterize the organization of nitrogen flow in the estuary and to estimate the coupling of nitrification to denitrification and of nitrification and DNRA to anammox. Centrality analysis indicated NH4+ is the most important form of nitrogen involved in removal processes. The model analysis further suggested that direct denitrification and coupled nitrification-denitrification had similar contributions to nitrogen removal while direct anammox was dominant to coupled forms of anammox. Finally, results also indicated that partial

  9. Earth system model simulations show different feedback strengths of the terrestrial carbon cycle under glacial and interglacial conditions

    Directory of Open Access Journals (Sweden)

    M. Adloff

    2018-04-01

    Full Text Available In simulations with the MPI Earth System Model, we study the feedback between the terrestrial carbon cycle and atmospheric CO2 concentrations under ice age and interglacial conditions. We find different sensitivities of terrestrial carbon storage to rising CO2 concentrations in the two settings. This result is obtained by comparing the transient response of the terrestrial carbon cycle to a fast and strong atmospheric CO2 concentration increase (roughly 900 ppm in Coupled Climate Carbon Cycle Model Intercomparison Project (C4MIP-type simulations starting from climates representing the Last Glacial Maximum (LGM and pre-industrial times (PI. In this set-up we disentangle terrestrial contributions to the feedback from the carbon-concentration effect, acting biogeochemically via enhanced photosynthetic productivity when CO2 concentrations increase, and the carbon–climate effect, which affects the carbon cycle via greenhouse warming. We find that the carbon-concentration effect is larger under LGM than PI conditions because photosynthetic productivity is more sensitive when starting from the lower, glacial CO2 concentration and CO2 fertilization saturates later. This leads to a larger productivity increase in the LGM experiment. Concerning the carbon–climate effect, it is the PI experiment in which land carbon responds more sensitively to the warming under rising CO2 because at the already initially higher temperatures, tropical plant productivity deteriorates more strongly and extratropical carbon is respired more effectively. Consequently, land carbon losses increase faster in the PI than in the LGM case. Separating the carbon–climate and carbon-concentration effects, we find that they are almost additive for our model set-up; i.e. their synergy is small in the global sum of carbon changes. Together, the two effects result in an overall strength of the terrestrial carbon cycle feedback that is almost twice as large in the LGM experiment

  10. Earth system model simulations show different feedback strengths of the terrestrial carbon cycle under glacial and interglacial conditions

    Science.gov (United States)

    Adloff, Markus; Reick, Christian H.; Claussen, Martin

    2018-04-01

    In simulations with the MPI Earth System Model, we study the feedback between the terrestrial carbon cycle and atmospheric CO2 concentrations under ice age and interglacial conditions. We find different sensitivities of terrestrial carbon storage to rising CO2 concentrations in the two settings. This result is obtained by comparing the transient response of the terrestrial carbon cycle to a fast and strong atmospheric CO2 concentration increase (roughly 900 ppm) in Coupled Climate Carbon Cycle Model Intercomparison Project (C4MIP)-type simulations starting from climates representing the Last Glacial Maximum (LGM) and pre-industrial times (PI). In this set-up we disentangle terrestrial contributions to the feedback from the carbon-concentration effect, acting biogeochemically via enhanced photosynthetic productivity when CO2 concentrations increase, and the carbon-climate effect, which affects the carbon cycle via greenhouse warming. We find that the carbon-concentration effect is larger under LGM than PI conditions because photosynthetic productivity is more sensitive when starting from the lower, glacial CO2 concentration and CO2 fertilization saturates later. This leads to a larger productivity increase in the LGM experiment. Concerning the carbon-climate effect, it is the PI experiment in which land carbon responds more sensitively to the warming under rising CO2 because at the already initially higher temperatures, tropical plant productivity deteriorates more strongly and extratropical carbon is respired more effectively. Consequently, land carbon losses increase faster in the PI than in the LGM case. Separating the carbon-climate and carbon-concentration effects, we find that they are almost additive for our model set-up; i.e. their synergy is small in the global sum of carbon changes. Together, the two effects result in an overall strength of the terrestrial carbon cycle feedback that is almost twice as large in the LGM experiment as in the PI experiment

  11. BIM: Promises and reality

    Directory of Open Access Journals (Sweden)

    Svetel Igor

    2014-01-01

    Full Text Available The building information modeling - BIM is a technology developed toward creation of computer based information model that encompasses whole building lifecycle. Toward that goal a number of information technology standards have been developed that enable different professions in AEC to cooperatively develop electronic building model. The paper gives overview of essential technologies, discusses their intended purpose, and gives outline of the currently achieved functionality.

  12. Modelled seasonal influenza mortality shows marked differences in risk by age, sex, ethnicity and socioeconomic position in New Zealand.

    Science.gov (United States)

    Khieu, Trang Q T; Pierse, Nevil; Telfar-Barnard, Lucy Frances; Zhang, Jane; Huang, Q Sue; Baker, Michael G

    2017-09-01

    Influenza is responsible for a large number of deaths which can only be estimated using modelling methods. Such methods have rarely been applied to describe the major socio-demographic characteristics of this disease burden. We used quasi Poisson regression models with weekly counts of deaths and isolates of influenza A, B and respiratory syncytial virus for the period 1994 to 2008. The estimated average mortality rate was 13.5 per 100,000 people which was 1.8% of all deaths in New Zealand. Influenza mortality differed markedly by age, sex, ethnicity and socioeconomic position. Relatively vulnerable groups were males aged 65-79 years (Rate ratio (RR) = 1.9, 95% CI: 1.9, 1.9 compared with females), Māori (RR = 3.6, 95% CI: 3.6, 3.7 compared with European/Others aged 65-79 years), Pacific (RR = 2.4, 95% CI: 2.4, 2.4 compared with European/Others aged 65-79 years) and those living in the most deprived areas (RR = 1.8, 95% CI: 1.3, 2.4) for New Zealand Deprivation (NZDep) 9&10 (the most deprived) compared with NZDep 1&2 (the least deprived). These results support targeting influenza vaccination and other interventions to the most vulnerable groups, in particular Māori and Pacific people and men aged 65-79 years and those living in the most deprived areas. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  13. Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

    Science.gov (United States)

    Greco, Rosaria; Siani, Francesca; Demartini, Chiara; Zanaboni, Annamaria; Nappi, Giuseppe; Davinelli, Sergio; Scapagnini, Giovanni; Tassorelli, Cristina

    2016-01-01

    Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.

  14. Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model.

    Science.gov (United States)

    Sturgeon, Craig; Lan, Jinggang; Fasano, Alessio

    2017-06-01

    Increased small intestinal permeability (IP) has been proposed to be an integral element, along with genetic makeup and environmental triggers, in the pathogenies of chronic inflammatory diseases (CIDs). We identified zonulin as a master regular of intercellular tight junctions linked to the development of several CIDs. We aim to study the role of zonulin-mediated IP in the pathogenesis of CIDs. Zonulin transgenic Hp2 mice (Ztm) were subjected to dextran sodium sulfate (DSS) treatment for 7 days, followed by 4-7 days' recovery and compared to C57Bl/6 (wild-type (WT)) mice. IP was measured in vivo and ex vivo, and weight, histology, and survival were monitored. To mechanistically link zonulin-dependent impairment of small intestinal barrier function with clinical outcome, Ztm were treated with the zonulin inhibitor AT1001 added to drinking water in addition to DSS. We observed increased morbidity (more pronounced weight loss and colitis) and mortality (40-70% compared with 0% in WT) at 11 days post-DSS treatment in Ztm compared with WT mice. Both in vivo and ex vivo measurements showed an increased IP at baseline in Ztm compared to WT mice, which was exacerbated by DSS treatment and was associated with upregulation of zonulin gene expression (fourfold in the duodenum, sixfold in the jejunum). Treatment with AT1001 prevented the DSS-induced increased IP both in vivo and ex vivo without changing zonulin gene expression and completely reverted morbidity and mortality in Ztm. Our data show that zonulin-dependent small intestinal barrier impairment is an early step leading to the break of tolerance with subsequent development of CIDs. © 2017 New York Academy of Sciences.

  15. An inducible transgenic mouse model for immune mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Marcin Cebula

    Full Text Available The liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA_X_CreER(T2 mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b/OVA257-264-specific OT-I T cells to OVA_X_CreER(T2 mice or generated triple transgenic OVA_X CreER(T2_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2 mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA_X_CreER(T2_X_OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA_X_CreER(T2_X_OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.

  16. Individual Diet Modeling Shows How to Balance the Diet of French Adults with or without Excessive Free Sugar Intakes.

    Science.gov (United States)

    Lluch, Anne; Maillot, Matthieu; Gazan, Rozenn; Vieux, Florent; Delaere, Fabien; Vaudaine, Sarah; Darmon, Nicole

    2017-02-20

    Dietary changes needed to achieve nutritional adequacy for 33 nutrients were determined for 1719 adults from a representative French national dietary survey. For each individual, an iso-energy nutritionally adequate diet was generated using diet modeling, staying as close as possible to the observed diet. The French food composition table was completed with free sugar (FS) content. Results were analyzed separately for individuals with FS intakes in their observed diets ≤10% or >10% of their energy intake (named below FS-ACCEPTABLE and FS-EXCESS, respectively). The FS-EXCESS group represented 41% of the total population (average energy intake of 14.2% from FS). Compared with FS-ACCEPTABLE individuals, FS-EXCESS individuals had diets of lower nutritional quality and consumed more energy (2192 vs. 2123 kcal/day), particularly during snacking occasions (258 vs. 131 kcal/day) (all p -values diets were significant increases in fresh fruits, starchy foods, water, hot beverages and plain yogurts; and significant decreases in mixed dishes/sandwiches, meat/eggs/fish and cheese. For FS-EXCESS individuals only, the optimization process significantly increased vegetables and significantly decreased sugar-sweetened beverages, sweet products and fruit juices. The diets of French adults with excessive intakes of FS are of lower nutritional quality, but can be optimized via specific dietary changes.

  17. Landscape evolution models using the stream power incision model show unrealistic behavior when m ∕ n equals 0.5

    Directory of Open Access Journals (Sweden)

    J. S. Kwang

    2017-12-01

    Full Text Available Landscape evolution models often utilize the stream power incision model to simulate river incision: E = KAmSn, where E is the vertical incision rate, K is the erodibility constant, A is the upstream drainage area, S is the channel gradient, and m and n are exponents. This simple but useful law has been employed with an imposed rock uplift rate to gain insight into steady-state landscapes. The most common choice of exponents satisfies m ∕ n = 0.5. Yet all models have limitations. Here, we show that when hillslope diffusion (which operates only on small scales is neglected, the choice m ∕ n = 0.5 yields a curiously unrealistic result: the predicted landscape is invariant to horizontal stretching. That is, the steady-state landscape for a 10 km2 horizontal domain can be stretched so that it is identical to the corresponding landscape for a 1000 km2 domain.

  18. Proteasomes remain intact, but show early focal alteration in their composition in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Agar, Jeffrey N; Hong, Yu; Taylor, David M; Minotti, Sandra; Figlewicz, Denise A; Durham, Heather D

    2008-06-01

    In amyotrophic lateral sclerosis caused by mutations in Cu/Zn-superoxide dismutase (SOD1), altered solubility and aggregation of the mutant protein implicates failure of pathways for detecting and catabolizing misfolded proteins. Our previous studies demonstrated early reduction of proteasome-mediated proteolytic activity in lumbar spinal cord of SOD1(G93A) transgenic mice, tissue particularly vulnerable to disease. The purpose of this study was to identify any underlying abnormalities in proteasomal structure. In lumbar spinal cord of pre-symptomatic mice [postnatal day 45 (P45) and P75], normal levels of structural 20S alpha subunits were incorporated into 20S/26S proteasomes; however, proteasomal complexes separated by native gel electrophoresis showed decreased immunoreactivity with antibodies to beta3, a structural subunit of the 20S proteasome core, and beta5, the subunit with chymotrypsin-like activity. This occurred prior to increase in beta5i immunoproteasomal subunit. mRNA levels were maintained and no association of mutant SOD1 with proteasomes was identified, implicating post-transcriptional mechanisms. mRNAs also were maintained in laser captured motor neurons at a later stage of disease (P100) in which multiple 20S proteins are reduced relative to the surrounding neuropil. Increase in detergent-insoluble, ubiquitinated proteins at P75 provided further evidence of stress on mechanisms of protein quality control in multiple cell types prior to significant motor neuron death.

  19. An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.

    Science.gov (United States)

    Krumm, Stefanie A; Yan, Dan; Hovingh, Elise S; Evers, Taylor J; Enkirch, Theresa; Reddy, G Prabhakar; Sun, Aiming; Saindane, Manohar T; Arrendale, Richard F; Painter, George; Liotta, Dennis C; Natchus, Michael G; von Messling, Veronika; Plemper, Richard K

    2014-04-16

    Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Ferrets infected with the same dose of virus that received post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic, and recovered from infection, whereas control animals succumbed to the disease. Animals that recovered also mounted a robust immune response and were protected against rechallenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found to be attenuated and transmission-impaired compared to the genetic parent virus. These findings may pioneer a path toward an effective morbillivirus therapy that could aid measles eradication by synergizing with vaccination to close gaps in herd immunity due to vaccine refusal.

  20. Amniotic fluid stem cells with low γ-interferon response showed behavioral improvement in Parkinsonism rat model.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chang

    Full Text Available Amniotic fluid stem cells (AFSCs are multipotent stem cells that may be used in transplantation medicine. In this study, AFSCs established from amniocentesis were characterized on the basis of surface marker expression and differentiation potential. To further investigate the properties of AFSCs for translational applications, we examined the cell surface expression of human leukocyte antigens (HLA of these cells and estimated the therapeutic effect of AFSCs in parkinsonian rats. The expression profiles of HLA-II and transcription factors were compared between AFSCs and bone marrow-derived mesenchymal stem cells (BMMSCs following treatment with γ-IFN. We found that stimulation of AFSCs with γ-IFN prompted only a slight increase in the expression of HLA-Ia and HLA-E, and the rare HLA-II expression could also be observed in most AFSCs samples. Consequently, the expression of CIITA and RFX5 was weakly induced by γ-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia nigra were used as a parkinsonian-animal model. Following the negative γ-IFN response AFSCs injection, apomorphine-induced rotation was reduced by 75% in AFSCs engrafted parkinsonian rats but was increased by 53% in the control group after 12-weeks post-transplantation. The implanted AFSCs were viable, and were able to migrate into the brain's circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to γ-IFN implies that AFSCs might have immune-tolerance in γ-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.

  1. Antioxidant and antigenotoxic properties of CeO2 NPs and cerium sulphate: Studies with Drosophila melanogaster as a promising in vivo model.

    Science.gov (United States)

    Alaraby, Mohamed; Hernández, Alba; Annangi, Balasubramanyam; Demir, Esref; Bach, Jordi; Rubio, Laura; Creus, Amadeu; Marcos, Ricard

    2015-01-01

    Although in vitro approaches are the most used for testing the potential harmful effects of nanomaterials, in vivo studies produce relevant information complementing in vitro data. In this context, we promote the use of Drosophila melanogaster as a suitable in vivo model to characterise the potential risks associated to nanomaterials exposure. The main aim of this study was to evaluate different biological effects associated to cerium oxide nanoparticles (Ce-NPs) and cerium (IV) sulphate exposure. The end-points evaluated were egg-to-adult viability, particles uptake through the intestinal barrier, gene expression and intracellular reactive oxygen species (ROS) production by haemocytes, genotoxicity and antigenotoxicity. Transmission electron microscopy images showed internalisation of Ce-NPs by the intestinal barrier and haemocytes, and significant expression of Hsp genes was detected. In spite of these findings, neither toxicity nor genotoxicity related to both forms of cerium were observed. Interestingly, Ce-NPs significantly reduced the genotoxic effect of potassium dichromate and the intracellular ROS production. No morphological malformations were detected after larvae treatment. This study highlights the importance of D. melanogaster as animal model in the study of the different biological effects caused by nanoparticulated materials, at the time that shows its usefulness to study the role of the intestinal barrier in the transposition of nanomaterials entering via ingestion.

  2. 99mTc-hexoprenaline and 131I-dapoxetine. Preparation, in silico modeling and biological evaluation as promising lung scintigraphy radiopharmaceuticals

    International Nuclear Information System (INIS)

    Rashed, H.M.; Ibrahim, I.T.; Motaleb, M.A.

    2017-01-01

    Hexoprenaline and dapoxetine (two lung selective pharmaceutical compounds) were radiolabeled to produce lung imaging radiopharmaceuticals using 99m Tc and 131 I, respectively. Different factors affecting labeling process were examined and optimum radiochemical purities of 91.3 ± 0.294 and 96.5 ± 0.342% were obtained, respectively. In silico molecular modeling studies for 99m Tc-hexoprenaline and 131 I-dapoxetine were done. Molecular modeling studies of the radiolabeled compounds examined the effect of radiolabeling on structure activity relationship for hexoprenaline and dapoxetine. Biodistribution studies in Swiss albino mice showed poor lung uptake of 99m Tc-hexoprenaline and high uptake for 131 I-dapoxetine (15.26 ± 0.11 and 55.82 ± 0.201%ID/g, respectively) matching the molecular modeling expectations. Consequently, 131 I-dapoxetine could be a hopeful radiopharmaceutical for lung scintigraphic imaging and further studies to radiolabel hexoprenaline with 131 I are recommended. (author)

  3. Vaccines: an ongoing promise?

    Science.gov (United States)

    Alsahli, M; Farrell, R J; Michetti, P

    2001-01-01

    Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

  4. The Promises of Biology and the Biology of Promises

    DEFF Research Database (Denmark)

    Lee, Jieun

    2015-01-01

    commitments with differently imagined futures. I argue that promises are constitutive of the stem cell biology, rather than being derivative of it. Since the biological concept of stem cells is predicated on the future that they promise, the biological life of stem cells is inextricably intertwined...... patients’ bodies in anticipation of materializing the promises of stem cell biology, they are produced as a new form of biovaluable. The promises of biology move beyond the closed circuit of scientific knowledge production, and proliferate in the speculative marketplaces of promises. Part II looks at how...... of technologized biology and biological time can appear promising with the backdrop of the imagined intransigence of social, political, and economic order in the Korean society....

  5. Promising pesticide results

    International Nuclear Information System (INIS)

    Wallace, Paula

    2012-01-01

    Full text: Virotec Global Solutions has announced what it believes is the first successful destruction of intractable organochlorine pesticide contamination in industrial wastewater. Dichlorodiphenyltrichloroethane, otherwise known as DDT, is one of the most intractable and persistent chemical compounds known to man. In February remediation specialist Virotec reported it had been successful in reducing DDT contaminant levels. In addition to destroying DDT in wastewater, Virotec showed its ViroFlow Technology can reduce levels of two DDT metabolites (or breakdown products), DDD and DDE, along with an organo-phosphate insecticide called chlorpyrifos. Virotec was commissioned by a large pesticide and fertiliser company to find a way of using its ViroFlow suite of products to reliably reduce high levels of pesticides and heavy metals from wastewater and stormwater at an industrial site. “Along with our strategic partner Green Shadows Commercial from Tasmania, we were able to successfully reduce DDT from 108 parts per billion to under two parts per billion in industrial wastewater using a combination of ozofractionation and ElectroBind reagent,” said business development manager Gisela Barros. “In addition, we were successful in demonstrating similar reductions in Dichlorodiphenyldichloroethane (DDD) from 15.2 parts per billion to under 0.5 parts per billion, and Dichlorodiphenyldichloroethylene (DDE) from one part per billion to under accurate to around 0.5 parts per billion.” The level of detection for pesticides was 0.5 parts per billion (ppb). In addition, ViroFlow reduced chlorpyrifos from 7,972 ppb to 6.4 ppb, arsenic (a key ingredient in pesticide composition) from 0.13 parts per million (ppm) to 0.002 ppm, and zinc from 0.35 ppm to less than 0.005 ppm. “The significance of these findings cannot be overstated,” Barros said. “DDT and its metabolites are among the most persistent and toxic contaminants to be found in soil and groundwater and

  6. Show and Tell: Video Modeling and Instruction Without Feedback Improves Performance but Is Not Sufficient for Retention of a Complex Voice Motor Skill.

    Science.gov (United States)

    Look, Clarisse; McCabe, Patricia; Heard, Robert; Madill, Catherine J

    2018-02-02

    Modeling and instruction are frequent components of both traditional and technology-assisted voice therapy. This study investigated the value of video modeling and instruction in the early acquisition and short-term retention of a complex voice task without external feedback. Thirty participants were randomized to two conditions and trained to produce a vocal siren over 40 trials. One group received a model and verbal instructions, the other group received a model only. Sirens were analyzed for phonation time, vocal intensity, cepstral peak prominence, peak-to-peak time, and root-mean-square error at five time points. The model and instruction group showed significant improvement on more outcome measures than the model-only group. There was an interaction effect for vocal intensity, which showed that instructions facilitated greater improvement when they were first introduced. However, neither group reproduced the model's siren performance across all parameters or retained the skill 1 day later. Providing verbal instruction with a model appears more beneficial than providing a model only in the prepractice phase of acquiring a complex voice skill. Improved performance was observed; however, the higher level of performance was not retained after 40 trials in both conditions. Other prepractice variables may need to be considered. Findings have implications for traditional and technology-assisted voice therapy. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  7. Few promising multivariable prognostic models exist for recovery of people with non-specific neck pain in musculoskeletal primary care: A systematic review

    NARCIS (Netherlands)

    R.W. Wingbermühle (Roel); E. van Trijffel (Emiel); Nelissen, P.M. (Paul M.); B.W. Koes (Bart); A.P. Verhagen (Arianne)

    2017-01-01

    markdownabstractQuestion: Which multivariable prognostic model(s) for recovery in people with neck pain can be used in primary care? Design: Systematic review of studies evaluating multivariable prognostic models. Participants: People with non-specific neck pain presenting at primary care.

  8. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

    Science.gov (United States)

    Paulsen, Daniela; Urban, Andreas; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Mercer, Andrew A; Limmer, Andreas; Schumak, Beatrix; Knolle, Percy; Ruebsamen-Schaeff, Helga; Weber, Olaf

    2013-01-01

    Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  9. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV and hepatitis C virus (HCV replication in preclinical models.

    Directory of Open Access Journals (Sweden)

    Daniela Paulsen

    Full Text Available Inactivated orf virus (iORFV, strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV and hepatitis B virus (HBV. Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  10. Spatial Heterodyne Observations of Water (SHOW) vapour in the upper troposphere and lower stratosphere from a high altitude aircraft: Modelling and sensitivity analysis

    Science.gov (United States)

    Langille, J. A.; Letros, D.; Zawada, D.; Bourassa, A.; Degenstein, D.; Solheim, B.

    2018-04-01

    A spatial heterodyne spectrometer (SHS) has been developed to measure the vertical distribution of water vapour in the upper troposphere and the lower stratosphere with a high vertical resolution (∼500 m). The Spatial Heterodyne Observations of Water (SHOW) instrument combines an imaging system with a monolithic field-widened SHS to observe limb scattered sunlight in a vibrational band of water (1363 nm-1366 nm). The instrument has been optimized for observations from NASA's ER-2 aircraft as a proof-of-concept for a future low earth orbit satellite deployment. A robust model has been developed to simulate SHOW ER-2 limb measurements and retrievals. This paper presents the simulation of the SHOW ER-2 limb measurements along a hypothetical flight track and examines the sensitivity of the measurement and retrieval approach. Water vapour fields from an Environment and Climate Change Canada forecast model are used to represent realistic spatial variability along the flight path. High spectral resolution limb scattered radiances are simulated using the SASKTRAN radiative transfer model. It is shown that the SHOW instrument onboard the ER-2 is capable of resolving the water vapour variability in the UTLS from approximately 12 km - 18 km with ±1 ppm accuracy. Vertical resolutions between 500 m and 1 km are feasible. The along track sampling capability of the instrument is also discussed.

  11. Boosting ART uptake and retention among HIV-infected pregnant and breastfeeding women and their infants: the promise of innovative service delivery models.

    Science.gov (United States)

    Srivastava, Meena; Sullivan, David; Phelps, B Ryan; Modi, Surbhi; Broyles, Laura N

    2018-01-01

    With the rapid scale-up of antiretroviral treatment (ART) in the "Treat All" era, there has been increasing emphasis on using differentiated models of HIV service delivery. The gaps within the clinical cascade for mothers and their infants suggest that current service delivery models are not meeting families' needs and prompt re-consideration of how services are provided. This article will explore considerations for differentiated care and encourage the ongoing increase of ART coverage through innovative strategies while also addressing the unique needs of mothers and infants. Service delivery models should recognize that the timing of the mother's HIV diagnosis is a critical aspect of determining eligibility. Women newly diagnosed with HIV require a more intensive approach so that adequate counselling and monitoring of ART initiation and response can be provided. Women already on ART with evidence of virologic failure are also at high risk of transmitting HIV to their infants and require close follow-up. However, women stable on ART with a suppressed viral load before conception have a very low likelihood of HIV transmission and thus are strong candidates for multi-month ART dispensing, community-based distribution of ART, adherence clubs, community adherence support groups and longer intervals between clinical visits. A number of other factors should be considered when defining eligibility of mothers and infants for differentiated care, including location of services, viral load monitoring and duration on ART. To provide differentiated care that is client-centred and driven while encompassing a family-based approach, it will be critical to engage mothers, families and communities in models that will optimize client satisfaction, retention in care and quality of services. Differentiated care for mothers and infants represents an opportunity to provide client-centred care that reduces the burden on clients and health systems while improving the quality and uptake

  12. Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

    Science.gov (United States)

    Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

    2015-06-28

    ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

  13. Mastering JavaScript promises

    CERN Document Server

    Hussain, Muzzamil

    2015-01-01

    This book is for all the software and web engineers wanting to apply the promises paradigm to their next project and get the best outcome from it. This book also acts as a reference for the engineers who are already using promises in their projects and want to improve their current knowledge to reach the next level. To get the most benefit from this book, you should know basic programming concepts, have a familiarity with JavaScript, and a good understanding of HTML.

  14. A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity.

    Science.gov (United States)

    Watt, Ari; Moukambi, Felicien; Banadyga, Logan; Groseth, Allison; Callison, Julie; Herwig, Astrid; Ebihara, Hideki; Feldmann, Heinz; Hoenen, Thomas

    2014-09-01

    Work with infectious Ebola viruses is restricted to biosafety level 4 (BSL4) laboratories, presenting a significant barrier for studying these viruses. Life cycle modeling systems, including minigenome systems and transcription- and replication-competent virus-like particle (trVLP) systems, allow modeling of the virus life cycle under BSL2 conditions; however, all current systems model only certain aspects of the virus life cycle, rely on plasmid-based viral protein expression, and have been used to model only single infectious cycles. We have developed a novel life cycle modeling system allowing continuous passaging of infectious trVLPs containing a tetracistronic minigenome that encodes a reporter and the viral proteins VP40, VP24, and GP1,2. This system is ideally suited for studying morphogenesis, budding, and entry, in addition to genome replication and transcription. Importantly, the specific infectivity of trVLPs in this system was ∼ 500-fold higher than that in previous systems. Using this system for functional studies of VP24, we showed that, contrary to previous reports, VP24 only very modestly inhibits genome replication and transcription when expressed in a regulated fashion, which we confirmed using infectious Ebola viruses. Interestingly, we also discovered a genome length-dependent effect of VP24 on particle infectivity, which was previously undetected due to the short length of monocistronic minigenomes and which is due at least partially to a previously unknown function of VP24 in RNA packaging. Based on our findings, we propose a model for the function of VP24 that reconciles all currently available data regarding the role of VP24 in nucleocapsid assembly as well as genome replication and transcription. Ebola viruses cause severe hemorrhagic fevers in humans, with no countermeasures currently being available, and must be studied in maximum-containment laboratories. Only a few of these laboratories exist worldwide, limiting our ability to study

  15. Modeling of isotope fractionation at the catchment scale: How promising is compound specific isotope analysis (CSIA) as a tool for analyzing diffuse pollution by agrochemicals?

    Science.gov (United States)

    Lutz, S. R.; van Meerveld, H. J.; Waterloo, M. J.; Broers, H. P.; van Breukelen, B. M.

    2012-04-01

    Concentration measurements are indispensable for the assessment of subsurface and surface water pollution by agrochemicals such as pesticides. However, monitoring data is often ambiguous and easily misinterpreted as a decrease in concentration could be caused by transformation, dilution or changes in the application of the pesticide. In this context, compound specific isotope analysis (CSIA) has recently emerged as a complementary monitoring technique. It is based on the measurement of the isotopic composition (e.g. δ13C and δ2H) of the contaminant. Since transformation processes are likely accompanied by isotope fractionation, thus a change in this composition, CSIA offers the opportunity to gain additional knowledge about transport and degradation processes as well as to track pollutants back to their sources. Isotopic techniques have not yet been applied in a comprehensive way in the analysis of catchment-wide organic pollution. We therefore incorporated fractionation processes associated with the fate of pesticides into the numerical flow and solute transport model HydroGeoSphere in order to assess the feasibility of CSIA within the context of catchment monitoring. The model was set up for a hypothetical hillslope transect which drains into a river. Reactive solute transport was driven by two pesticides applications within one year and actual data for rainfall and potential evapotranspiration from a meteorological station in the Netherlands. Degradation of the pesticide was assumed to take place at a higher rate under the prevailing oxic conditions in the topsoil than in deeper, anoxic subsurface layers. In terms of CSIA, these two degradation pathways were associated with different strengths of isotope fractionation for both hydrogen and carbon atoms. By simulating changes in δ13C and δ2H, the share of the oxic and the anoxic reaction on the overall degradation could be assessed. Model results suggest that CSIA is suitable for assessing degradation of

  16. Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation.

    Science.gov (United States)

    Cordes, Henrik; Thiel, Christoph; Baier, Vanessa; Blank, Lars M; Kuepfer, Lars

    2018-01-01

    Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism. The applicability of the proposed workflow is illustrated for isoniazid, a first-line antibacterial agent against Mycobacterium tuberculosis , which is known to cause idiosyncratic drug-induced liver injuries (DILI). We combined GSMN models of a human liver with N-acetyl transferase 2 (NAT2)-phenotype-specific PBPK models of isoniazid. The combined PBPK-GSMN models quantitatively describe isoniazid pharmacokinetics, as well as intracellular responses, and changes in the exometabolome in a human liver following isoniazid administration. Notably, intracellular and extracellular responses identified with the PBPK-GSMN models are in line with experimental and clinical findings. Moreover, the drug-induced metabolic perturbations are distributed and attenuated in the metabolic network in a phenotype-dependent manner. Our simulation results show that a simultaneous consideration of both drug pharmacokinetics at the whole-body and metabolism at the cellular level is mandatory to explain drug-induced injuries at the patient level. The proposed workflow extends our mechanistic understanding of the biochemistry underlying adverse events and may be used to prevent drug-induced injuries in the future.

  17. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

    Directory of Open Access Journals (Sweden)

    Sandhya Boyapalle

    Full Text Available Human immunodeficiency virus (HIV types 1 and 2 (HIV-1 and HIV-2 are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162 viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

  18. Climate Envelope Modeling and Dispersal Simulations Show Little Risk of Range Extension of the Shipworm, Teredo navalis (L.), in the Baltic Sea

    Science.gov (United States)

    Appelqvist, Christin; Al-Hamdani, Zyad K.; Jonsson, Per R.; Havenhand, Jon N.

    2015-01-01

    The shipworm, Teredo navalis, is absent from most of the Baltic Sea. In the last 20 years, increased frequency of T. navalis has been reported along the southern Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range-extensions into previously unoccupied areas. We evaluated the effects of historical and projected near-future changes in salinity, temperature, and oxygen on the risk of spread of T. navalis in the Baltic. Specifically, we developed a simple, GIS-based, mechanistic climate envelope model to predict the spatial distribution of favourable conditions for adult reproduction and larval metamorphosis of T. navalis, based on published environmental tolerances to these factors. In addition, we used a high-resolution three-dimensional hydrographic model to simulate the probability of spread of T. navalis larvae within the study area. Climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season and increase the risk of shipworm establishment at the margins of the current range. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread over a wider area typically spread to areas unfavourable for their survival. Overall, therefore, we found no substantive evidence for climate-change related shifts in the distribution of T. navalis in the Baltic Sea, and no evidence for increased risk of spread in the near-future. PMID:25768305

  19. Climate envelope modeling and dispersal simulations show little risk of range extension of the Shipworm, Teredo navalis (L., in the Baltic sea.

    Directory of Open Access Journals (Sweden)

    Christin Appelqvist

    Full Text Available The shipworm, Teredo navalis, is absent from most of the Baltic Sea. In the last 20 years, increased frequency of T. navalis has been reported along the southern Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range-extensions into previously unoccupied areas. We evaluated the effects of historical and projected near-future changes in salinity, temperature, and oxygen on the risk of spread of T. navalis in the Baltic. Specifically, we developed a simple, GIS-based, mechanistic climate envelope model to predict the spatial distribution of favourable conditions for adult reproduction and larval metamorphosis of T. navalis, based on published environmental tolerances to these factors. In addition, we used a high-resolution three-dimensional hydrographic model to simulate the probability of spread of T. navalis larvae within the study area. Climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season and increase the risk of shipworm establishment at the margins of the current range. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread over a wider area typically spread to areas unfavourable for their survival. Overall, therefore, we found no substantive evidence for climate-change related shifts in the distribution of T. navalis in the Baltic Sea, and no evidence for increased risk of spread in the near-future.

  20. Showing Value (Editorial

    Directory of Open Access Journals (Sweden)

    Denise Koufogiannakis

    2009-06-01

    librarians on student achievement. Todd notes, “If we do not show value, we will not have a future. Evidence-based practice is not about the survival of school librarians, it’s about the survival of our students” (40. In this issue we feature school libraries and their connection to evidence based practice. Former Editor-in-Chief, Lindsay Glynn, began putting the wheels in motion for this feature almost a year ago. She invited Carol Gordon and Ross Todd to act as guest editors of the section, drawing upon their contacts and previous work in this field. The result is an issue with five feature articles exploring different aspects of the connection between school libraries and evidence based practice, from the theoretical to the practical. In addition, there is a thought-provoking Commentary by David Loertscher, asking whether we need the evolutionary model of evidence based practice, or something more revolutionary!In addition to the Feature section, we have a well-rounded issue with articles on the topics of library human resources, and the development of a scholars’ portal. As well, there are a record 10 evidence summaries and our educational EBL101 column. I hope there is something for everyone in this issue of EBLIP – enjoy, and see you soon in Stockholm!

  1. Implementing the Kyoto protocol : why JI and CDM show more promise than international emissions trading

    NARCIS (Netherlands)

    Woerdman, E.

    The Kyoto protocol allows developed countries to achieve cost-effective greenhouse gas emission reductions abroad by means of international emissions trading (IET), joint implementation (JI) and the clean development mechanism (CDM). The article argues that JI and CDM projects will be more

  2. Natural Compound Cudraflavone B Shows Promising Anti-inflammatory Properties in Vitro

    Czech Academy of Sciences Publication Activity Database

    Hošek, J.; Bartoš, M.; Chudík, S.; Dall’Acqua, S.; Innocenti, G.; Kartal, M.; Kokoška, L.; Kollár, P.; Kutil, Zsófia; Landa, Přemysl; Marek, R.; Závalová, V.; Žemlička, M.; Šmejkal, K.

    2011-01-01

    Roč. 74, č. 4 (2011), s. 614-619 ISSN 0163-3864 R&D Projects: GA MŠk(CZ) LC06030; GA ČR GP525/09/P528 Institutional research plan: CEZ:AV0Z50380511 Keywords : NF-KAPPA-B * CUDRANIA-TRICUSPIDATA * ROOT BARK Subject RIV: GM - Food Processing Impact factor: 3.128, year: 2011

  3. Nickel-silver composition shows promise as catalyst for hydrogen-oxygen fuel cells

    Science.gov (United States)

    Magerl, J. A.; Murray, J. N.

    1970-01-01

    Carburized 3-1 nickel-silver preparation exhibits considerable catalytic activity, although not as high as platinum black. Cost and availability factors warrant further evaluation of nickel-silver materials.

  4. Comb-push ultrasound shear elastography of breast masses: initial results show promise.

    Science.gov (United States)

    Denis, Max; Mehrmohammadi, Mohammad; Song, Pengfei; Meixner, Duane D; Fazzio, Robert T; Pruthi, Sandhya; Whaley, Dana H; Chen, Shigao; Fatemi, Mostafa; Alizad, Azra

    2015-01-01

    To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE) for classification of breast masses. CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF) beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results. Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s) in comparison to benign masses (3.65 ± 1.36 m/s). Therefore, the stiffness of the mass quantified by the Young's modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC), the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC). CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses.

  5. Comb-push ultrasound shear elastography of breast masses: initial results show promise.

    Directory of Open Access Journals (Sweden)

    Max Denis

    Full Text Available To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE for classification of breast masses.CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results.Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s in comparison to benign masses (3.65 ± 1.36 m/s. Therefore, the stiffness of the mass quantified by the Young's modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC, the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC.CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses.

  6. Show-Bix &

    DEFF Research Database (Denmark)

    2014-01-01

    The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies are...

  7. Nuclear energy: obstacles and promises

    International Nuclear Information System (INIS)

    Bacher, P.

    2003-01-01

    Nuclear energy has distinctive merits (sustainable resources, low costs, no greenhouse gases) but its development must overcome serious hurdles (fear of accidents, radio-phobia, waste management). The large unit size of present-day reactors is compatible only with large electrical grids, and involves a high capital cost. Taking into account these different factors, the paper outlines how nuclear energy may contribute to the reduction of greenhouse gases, and which are the most promising developments. (author)

  8. The promise of cyborg intelligence.

    Science.gov (United States)

    Brown, Michael F; Brown, Alexander A

    2017-03-01

    Yu et al. (2016) demonstrated that algorithms designed to find efficient routes in standard mazes can be integrated with the natural processes controlling rat navigation and spatial choices, and they pointed out the promise of such "cyborg intelligence" for biorobotic applications. Here, we briefly describe Yu et al.'s work, explore its relevance to the study of comparative cognition, and indicate how work involving cyborg intelligence would benefit from interdisciplinary collaboration between behavioral scientists and engineers.

  9. Freedom: A Promise of Possibility.

    Science.gov (United States)

    Bunkers, Sandra Schmidt

    2015-10-01

    The idea of freedom as a promise of possibility is explored in this column. The core concepts from a research study on considering tomorrow (Bunkers, 1998) coupled with humanbecoming community change processes (Parse, 2003) are used to illuminate this notion. The importance of intentionality in human freedom is discussed from both a human science and a natural science perspective. © The Author(s) 2015.

  10. Missing the Promise of Mathematical Modeling

    Science.gov (United States)

    Meyer, Dan

    2015-01-01

    The Common Core State Standards for Mathematics (CCSSM) have exerted enormous pressure on every participant in a child's education. Students are struggling to meet new standards for mathematics learning, and parents are struggling to understand how to help them. Teachers are growing in their capacity to develop new mathematical competencies, and…

  11. Modelling of potentially promising SARS protease inhibitors

    International Nuclear Information System (INIS)

    Plewczynski, Dariusz; Hoffmann, Marcin; Grotthuss, Marcin von; Knizewski, Lukasz; Rychewski, Leszek; Eitner, Krystian; Ginalski, Krzysztof

    2007-01-01

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation

  12. Multimodal Education: A Model with Promise.

    Science.gov (United States)

    Gerler, Edwin R., Jr.; Locke, Don C.

    1980-01-01

    Describes a program that uses Lazarus's factors that contribute to human growth and development as the basis for its program. The modalities covered are given the headings behavior, affect, sensation and imagery, cognition, interpersonal, and diet/physiology. (IRT)

  13. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  14. Corpos sob controle: Um estudo de caso sobre a relação entre corpo e signo no reality show estadunidense America’s Next Top Model

    Directory of Open Access Journals (Sweden)

    Júnior Ratts

    2015-08-01

    Full Text Available Este trabalho tem como objetivo analisar as potencialidades corporais do individuo contemporâneo em sua luta diária pela conquista da individualidade e do reconhecimento coletivo. Para tanto, a pesquisa toma como objeto o reality show estadunidense America’s Next Top Model a fim de tentar compreender melhor, a partir das experiências das candidatas do programa, como se estabelecem as relações táticas e estratégicas entre o sujeito e o mundo e de que forma as expectativas e consequências geradas por esses “embates cotidianos” com a realidade e com o Outro chegam ao corpo, transformando-o numa “arma” e num produto sociocultural

  15. Site-directed mutagenesis and molecular modelling studies show the role of Asp82 and cysteines in rat acylase 1, a member of the M20 family

    International Nuclear Information System (INIS)

    Herga, Sameh; Brutus, Alexandre; Vitale, Rosa Maria; Miche, Helene; Perrier, Josette; Puigserver, Antoine; Scaloni, Andrea; Giardina, Thierry

    2005-01-01

    Acylase 1 from rat kidney catalyzes the hydrolysis of acyl-amino acids. Sequence alignment has shown that this enzyme belongs to the metalloprotein family M20. Site-directed mutagenesis experiments led to the identification of one functionally important amino acid residue located near one of the zinc coordinating residues, which play a critical role in the enzymatic activity. The D82N- and D82E-substituted forms showed no significant activity and very low activity, respectively, along with a loss of zinc coordination. Molecular modelling investigations indicated a putative role of D82 in ensuring a proper protonation of catalytic histidine. In addition, none of the five cysteine residues present in the rat kidney acylase 1 sequence seemed involved in the catalytic process: the loss of activity induced by the C294A substitution was probably due to a conformational change in the 3D structure

  16. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    Directory of Open Access Journals (Sweden)

    Erik Karl Håkan Clemensson

    Full Text Available The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  17. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    Science.gov (United States)

    Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2017-01-01

    The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  18. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma.

    Science.gov (United States)

    Patwardhan, Parag P; Ivy, Kathryn S; Musi, Elgilda; de Stanchina, Elisa; Schwartz, Gary K

    2016-01-26

    Sarcomas are rare but highly aggressive mesenchymal tumors with a median survival of 10-18 months for metastatic disease. Mutation and/or overexpression of many receptor tyrosine kinases (RTKs) including c-Met, PDGFR, c-Kit and IGF1-R drive defective signaling pathways in sarcomas. MGCD516 (Sitravatinib) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. In the present study, we evaluated the efficacy of MGCD516 both in vitro and in mouse xenograft models in vivo. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro. Furthermore, MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth. Efficacy of MGCD516 was superior to imatinib and crizotinib, two other well-studied multi-kinase inhibitors with overlapping target specificities, both in vitro and in vivo. This is the first report describing MGCD516 as a potent multi-kinase inhibitor in different models of sarcoma, superior to imatinib and crizotinib. Results from this study showing blockade of multiple driver signaling pathways provides a rationale for further clinical development of MGCD516 for the treatment of patients with soft-tissue sarcoma.

  19. Show them the money? The role of pay, managerial need support, and justice in a self-determination theory model of intrinsic work motivation.

    Science.gov (United States)

    Olafsen, Anja H; Halvari, Hallgeir; Forest, Jacques; Deci, Edward L

    2015-08-01

    The link between money and motivation has been a debated topic for decades, especially in work organizations. However, field studies investigating the amount of pay in relation to employee motivation is lacking and there have been calls for empirical studies addressing compensation systems and motivation in the work domain. The purpose of this study was to examine outcomes associated with the amount of pay, and perceived distributive and procedural justice regarding pay in relation to those for perceived managerial need support. Participants were 166 bank employees who also reported on their basic psychological need satisfaction and intrinsic work motivation. SEM-analyses tested a self-determination theory (SDT) model, with satisfaction of the competence and autonomy needs as an intervening variable. The primary findings were that amount of pay and employees' perceived distributive justice regarding their pay were unrelated to employees' need satisfaction and intrinsic work motivation, but procedural justice regarding pay did affect these variables. However, managerial need support was the most important factor for promoting need satisfaction and intrinsic work motivation both directly, indirectly, and as a moderator in the model. Hence, the results of the present organizational field study support earlier laboratory experiments within the SDT framework showing that monetary rewards did not enhance intrinsic motivation. This seems to have profound implications for organizations concerned about motivating their employees. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  20. Daily Supplementation of D-ribose Shows No Therapeutic Benefits in the MHC-I Transgenic Mouse Model of Inflammatory Myositis

    Science.gov (United States)

    Coley, William; Rayavarapu, Sree; van der Meulen, Jack H.; Duba, Ayyappa S.; Nagaraju, Kanneboyina

    2013-01-01

    Background Current treatments for idiopathic inflammatory myopathies (collectively called myositis) focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1), leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg) over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures. Results Treatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose. Conclusions Treatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis. PMID:23785461

  1. Daily supplementation of D-ribose shows no therapeutic benefits in the MHC-I transgenic mouse model of inflammatory myositis.

    Directory of Open Access Journals (Sweden)

    William Coley

    Full Text Available BACKGROUND: Current treatments for idiopathic inflammatory myopathies (collectively called myositis focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1, leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures. RESULTS: Treatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose. CONCLUSIONS: Treatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis.

  2. Bifactor Models Show a Superior Model Fit: Examination of the Factorial Validity of Parent-Reported and Self-Reported Symptoms of Attention-Deficit/Hyperactivity Disorders in Children and Adolescents.

    Science.gov (United States)

    Rodenacker, Klaas; Hautmann, Christopher; Görtz-Dorten, Anja; Döpfner, Manfred

    2016-01-01

    Various studies have demonstrated that bifactor models yield better solutions than models with correlated factors. However, the kind of bifactor model that is most appropriate is yet to be examined. The current study is the first to test bifactor models across the full age range (11-18 years) of adolescents using self-reports, and the first to test bifactor models with German subjects and German questionnaires. The study sample included children and adolescents aged between 6 and 18 years recruited from a German clinical sample (n = 1,081) and a German community sample (n = 642). To examine the factorial validity, we compared unidimensional, correlated factors and higher-order and bifactor models and further tested a modified incomplete bifactor model for measurement invariance. Bifactor models displayed superior model fit statistics compared to correlated factor models or second-order models. However, a more parsimonious incomplete bifactor model with only 2 specific factors (inattention and impulsivity) showed a good model fit and a better factor structure than the other bifactor models. Scalar measurement invariance was given in most group comparisons. An incomplete bifactor model would suggest that the specific inattention and impulsivity factors represent entities separable from the general attention-deficit/hyperactivity disorder construct and might, therefore, give way to a new approach to subtyping of children beyond and above attention-deficit/hyperactivity disorder. © 2016 S. Karger AG, Basel.

  3. Chitin fulfilling a biomaterials promise

    CERN Document Server

    Khor, Eugene

    2001-01-01

    The second edition of Chitin underscores the important factors for standardizing chitin processing and characterization. It captures the essential interplay between chitin's assets and limitations as a biomaterial, placing the past promises of chitin in perspective, addressing its present realities and offering insight into what is required to realize chitin's destiny (including its derivative, chitosan) as a biomaterial of the twenty-first century. This book is an ideal guide for both industrialists and researchers with a vested interest in commercializing chitin.An upd

  4. Long-Term Field Data and Climate-Habitat Models Show That Orangutan Persistence Depends on Effective Forest Management and Greenhouse Gas Mitigation

    Science.gov (United States)

    Gregory, Stephen D.; Brook, Barry W.; Goossens, Benoît; Ancrenaz, Marc; Alfred, Raymond; Ambu, Laurentius N.; Fordham, Damien A.

    2012-01-01

    Background Southeast Asian deforestation rates are among the world’s highest and threaten to drive many forest-dependent species to extinction. Climate change is expected to interact with deforestation to amplify this risk. Here we examine whether regional incentives for sustainable forest management will be effective in improving threatened mammal conservation, in isolation and when combined with global climate change mitigation. Methodology/Principal Findings Using a long time-series of orangutan nest counts for Sabah (2000–10), Malaysian Borneo, we evaluated the effect of sustainable forest management and climate change scenarios, and their interaction, on orangutan spatial abundance patterns. By linking dynamic land-cover and downscaled global climate model projections, we determine the relative influence of these factors on orangutan spatial abundance and use the resulting statistical models to identify habitat crucial for their long-term conservation. We show that land-cover change the degradation of primary forest had the greatest influence on orangutan population size. Anticipated climate change was predicted to cause reductions in abundance in currently occupied populations due to decreased habitat suitability, but also to promote population growth in western Sabah by increasing the suitability of presently unoccupied regions. Conclusions/Significance We find strong quantitative support for the Sabah government’s proposal to implement sustainable forest management in all its forest reserves during the current decade; failure to do so could result in a 40 to 80 per cent regional decline in orangutan abundance by 2100. The Sabah orangutan is just one (albeit iconic) example of a forest-dependent species that stands to benefit from sustainable forest management, which promotes conservation of existing forests. PMID:22970145

  5. Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

    Science.gov (United States)

    Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

    2012-01-01

    Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

  6. The deepwater Gulf of Mexico : promises delivered?

    International Nuclear Information System (INIS)

    Pickering, D.R.

    1999-01-01

    A summary review of deepwater Gulf of Mexico (GOM) oil production was presented for the years 1989 to 1998. Trends and prospects in deepwater GOM production and leasing were assessed. Promises and forecasts made in the early 1990s were compared with what actually happened since then. Forecasts in the early 1990s promised deeper, faster and cheaper developments in the deepwater Gulf. Results of the comparison showed that the prognosticators were correct on all three counts. Regarding the future of the Gulf, one can be justified in being optimistic in so far as more experience, robust economics, more and cheaper rigs can be taken as reliable indicators of optimism. In contrast, there are certain negatives to consider, such as low commodity prices, budget constraints, lease expirations, technical challenges and increased competition. . 12 figs

  7. A novel mouse model carrying a human cytoplasmic dynein mutation shows motor behavior deficits consistent with Charcot-Marie-Tooth type 2O disease.

    Science.gov (United States)

    Sabblah, Thywill T; Nandini, Swaran; Ledray, Aaron P; Pasos, Julio; Calderon, Jami L Conley; Love, Rachal; King, Linda E; King, Stephen J

    2018-01-29

    Charcot-Marie-Tooth disease (CMT) is a peripheral neuromuscular disorder in which axonal degeneration causes progressive loss of motor and sensory nerve function. The loss of motor nerve function leads to distal muscle weakness and atrophy, resulting in gait problems and difficulties with walking, running, and balance. A mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2 O disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine into arginine at amino acid 306 (H306R) in DHC. In order to understand the onset and progression of CMT2, we generated a knock-in mouse carrying the corresponding CMT2O mutation (H304R/+). We examined H304R/+ mouse cohorts in a 12-month longitudinal study of grip strength, tail suspension, and rotarod assays. H304R/+ mice displayed distal muscle weakness and loss of motor coordination phenotypes consistent with those of individuals with CMT2. Analysis of the gastrocnemius of H304R/+ male mice showed prominent defects in neuromuscular junction (NMJ) morphology including reduced size, branching, and complexity. Based on these results, the H304R/+ mouse will be an important model for uncovering functions of dynein in complex organisms, especially related to CMT onset and progression.

  8. Exploring the Interactions of the Dietary Plant Flavonoids Fisetin and Naringenin with G-Quadruplex and Duplex DNA, Showing Contrasting Binding Behavior: Spectroscopic and Molecular Modeling Approaches.

    Science.gov (United States)

    Bhattacharjee, Snehasish; Chakraborty, Sandipan; Sengupta, Pradeep K; Bhowmik, Sudipta

    2016-09-01

    Guanine-rich sequences have the propensity to fold into a four-stranded DNA structure known as a G-quadruplex (G4). G4 forming sequences are abundant in the promoter region of several oncogenes and become a key target for anticancer drug binding. Here we have studied the interactions of two structurally similar dietary plant flavonoids fisetin and naringenin with G4 as well as double stranded (duplex) DNA by using different spectroscopic and modeling techniques. Our study demonstrates the differential binding ability of the two flavonoids with G4 and duplex DNA. Fisetin more strongly interacts with parallel G4 structure than duplex DNA, whereas naringenin shows stronger binding affinity to duplex rather than G4 DNA. Molecular docking results also corroborate our spectroscopic results, and it was found that both of the ligands are stacked externally in the G4 DNA structure. C-ring planarity of the flavonoid structure appears to be a crucial factor for preferential G4 DNA recognition of flavonoids. The goal of this study is to explore the critical effects of small differences in the structure of closely similar chemical classes of such small molecules (flavonoids) which lead to the contrasting binding properties with the two different forms of DNA. The resulting insights may be expected to facilitate the designing of the highly selective G4 DNA binders based on flavonoid scaffolds.

  9. Talking with TV shows

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Laursen, Ditte

    2014-01-01

    User interaction with radio and television programmes is not a new thing. However, with new cross-media production concepts such as X Factor and Voice, this is changing dramatically. The second-screen logic of these productions encourages viewers, along with TV’s traditional one-way communication...... mode, to communicate on interactive (dialogue-enabling) devices such as laptops, smartphones and tablets. Using the TV show Voice as our example, this article shows how the technological and situational set-up of the production invites viewers to engage in new ways of interaction and communication...

  10. Talk Show Science.

    Science.gov (United States)

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  11. Obesity in show cats.

    Science.gov (United States)

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  12. Honored Teacher Shows Commitment.

    Science.gov (United States)

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  13. Assessing a five factor model of PTSD: is dysphoric arousal a unique PTSD construct showing differential relationships with anxiety and depression?

    Science.gov (United States)

    Armour, Cherie; Elhai, Jon D; Richardson, Don; Ractliffe, Kendra; Wang, Li; Elklit, Ask

    2012-03-01

    Posttraumatic stress disorder's (PTSD) latent structure has been widely debated. To date, two four-factor models (Numbing and Dysphoria) have received the majority of factor analytic support. Recently, Elhai et al. (2011) proposed and supported a revised (five-factor) Dysphoric Arousal model. Data were gathered from two separate samples; War veterans and Primary Care medical patients. The three models were compared and the resultant factors of the Dysphoric Arousal model were validated against external constructs of depression and anxiety. The Dysphoric Arousal model provided significantly better fit than the Numbing and Dysphoria models across both samples. When differentiating between factors, the current results support the idea that Dysphoric Arousal can be differentiated from Anxious Arousal but not from Emotional Numbing when correlated with depression. In conclusion, the Dysphoria model may be a more parsimonious representation of PTSD's latent structure in these trauma populations despite superior fit of the Dysphoric Arousal model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Service Users perspectives in PROMISE and research.

    Science.gov (United States)

    Rae, Sarah

    2017-09-01

    Since its inception in 2013, PROMISE (PROactive Management of Integrated Services and Environments) has been supporting service users and staff at the Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) on a journey to reduce reliance on force. The author's own personal experiences led to the founding of PROMISE and illustrates how individual experiences can influence a patient to lead change. Coproduction is actively embedded in PROMISE. Patients have been meaningfully involved because they are innovators and problem solvers who bring an alternative viewpoint by the very nature of their condition. A patient is more than just a person who needs to be 'fixed' they are individuals with untapped skills and added insight. There have been 2 separate Patient Advisory Groups (PAGs) since the project was first established. The first Patient Advisory Group was recruited to work with the PROMISE researchers on a study which used a participatory qualitative approach. Drawing on their lived experience and different perspectives the PAG was instrumental in shaping the qualitative study, including the research questions. Their active involvement helped to ensure that that the study was sensitively designed, methodologically robust and ethically sound. The 2 nd PAG was formed in 2016 to give the project an overall steer. Patients in this group contributed to the work on the 'No' Audit and reviewed several CPFT policies such as the Seclusion and Segregation policy which has impacted on frontline practice. They also made a significant contribution to the study design for a funding application that was submitted by the PROMISE team to the National Institute for Health Research (NIHR). Both PAGs were supported by funding from East of England Collaboration for Leadership in Applied Health Research and Care (CLAHRC EoE) and were influential in different ways. An evaluation of the 2 nd PAG which was conducted in June 2017 showed very high satisfaction levels. The free text

  15. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  16. MFTF-progress and promise

    International Nuclear Information System (INIS)

    Thomassen, K.I.

    1980-01-01

    The Mirror Fusion Test Facility (MFTF) has been in construction at Lawrence Livermore National Laboratory (LLNL) for 3 years, and most of the major subsystems are nearing completion. Recently, the scope of this project was expanded to meet new objectives, principally to reach plasma conditions corresponding to energy break-even. To fulfill this promise, the single-cell minimum-B mirror configuration will be replaced with a tandem mirror configuration (MFTF-B). The facility must accordingly be expanded to accomodate the new geometry. This paper briefly discusses the status of the major MFTF subsystems and describes how most of the technological objectives of MFTF will be demonstrated before we install the additional systems necessary to make the tandem. It also summarizes the major features of the expanded facility

  17. The promising opportunity of dismantlement

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    Civil engineering, mechanics and waste conditioning companies are thriving around the market of nuclear facilities dismantlement which is promised to a huge development in the coming decade. This paper presents a map of the opportunities of the dismantlement market throughout Europe (research and power reactors, fuel fabrication plants, spent fuel reprocessing plants) and a cost estimation of a given dismantling work with respect to the different steps of the work. In France a small core of about twenty companies is involved in nuclear dismantlement but the French market is also looking towards foreign specialists of this activity. The British market is also targeted by the French companies but for all the actors the technological or commercial advance gained today will be determining for the future markets. (J.S.)

  18. High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Firdaus S Dhabhar

    Full Text Available In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED, 3 times/week, 10-weeks. The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome, and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th, cytolytic (CTL, and regulatory (Treg T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden, increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression, lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity, and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis. These results suggest that the deleterious effects of high trait anxiety

  19. The energy show

    International Nuclear Information System (INIS)

    1988-01-01

    The Energy Show is a new look at the problems of world energy, where our supplies come from, now and in the future. The programme looks at how we need energy to maintain our standards of living. Energy supply is shown as the complicated set of problems it is - that Fossil Fuels are both raw materials and energy sources, that some 'alternatives' so readily suggested as practical options are in reality a long way from being effective. (author)

  20. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

    Science.gov (United States)

    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  1. Mathematical Profiles and Problem Solving Abilities of Mathematically Promising Students

    Science.gov (United States)

    Budak, Ibrahim

    2012-01-01

    Mathematically promising students are defined as those who have the potential to become the leaders and problem solvers of the future. The purpose of this research is to reveal what problem solving abilities mathematically promising students show in solving non-routine problems and type of profiles they present in the classroom and during problem…

  2. Influence of promised rewards on conflict resolution in healthy participants and patients with Parkinson's disease.

    Science.gov (United States)

    Houvenaghel, Jean-François; Duprez, Joan; Naudet, Florian; Argaud, Soizic; Dondaine, Thibaut; Drapier, Sophie; Robert, Gabriel Hadrien; Drapier, Dominique; Vérin, Marc; Sauleau, Paul

    2016-08-15

    The influence of promised rewards on conflict resolution processes is not clearly defined in the literature, and the underlying mechanisms are poorly understood. Some studies have shown no effect of reward, while others have demonstrated a beneficial influence. In addition, although the basal ganglia are known to play a critical role in the association between motivation and cognition, the influence of promised rewards on conflict resolution processes in Parkinson's disease (PD) has received little attention. In this context, we assessed the influence of promised rewards on both impulse activation and suppression in 36 healthy participants and 36 patients with PD, using a rewarded Simon task. Analysis of performances revealed that promised rewards worsened the overall congruence effect, but only in healthy participants. Although the incentive context did not modulate the congruence effect in patients, by using the activation-suppression model, we were able to show that promised rewards did influence impulse suppression in patients-but not in healthy participants. Suppressing inappropriate response activation in an incentive context appears to be harder in medically treated Parkinson's disease. This indicates that incentive motivation can modulate at least one cognitive process involved in cognitive action control in patients with medically treated PD. The activation-suppression model provides essential additional information concerning the influence of promised rewards on conflict resolution processes in a pathological population. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Directory of Open Access Journals (Sweden)

    Patricia Ferrer

    Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  4. The promise of entrepreneurship education

    DEFF Research Database (Denmark)

    Thrane, Claus; Blenker, Per; Korsgaard, Steffen

    2016-01-01

    into general anomalies; (IV) Constructing innovative solutions; (V) Prototyping; and (VI) Business modelling. Finally, we discuss the implications of the reconceptualized framework in terms of the research questions governing the field of entrepreneurship education, for the practice of entrepreneurship...

  5. Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline.

    Directory of Open Access Journals (Sweden)

    Liliana B Menalled

    2010-03-01

    Full Text Available Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.

  6. Cross-biome transplants of plant litter show decomposition models extend to a broader climatic range but lose predictability at the decadal time scale

    Science.gov (United States)

    William S. Currie; Mark E. Harmon; Ingrid C. Burke; Stephen C. Hart; William J. Parton; Whendee L. Silver

    2009-01-01

    We analyzed results from 10-year long field incubations of foliar and fine root litter from the Long-term lntersite Decomposition Experiment Team (LIDET) study. We tested whether a variety of climate and litter quality variables could be used to develop regression models of decomposition parameters across wide ranges in litter quality and climate and whether these...

  7. Models of Plankton Community Changes during a Warm Water Anomaly in Arctic Waters Show Altered Trophic Pathways with Minimal Changes in Carbon Export

    Directory of Open Access Journals (Sweden)

    Maria Vernet

    2017-05-01

    Full Text Available Carbon flow through pelagic food webs is an expression of the composition, biomass and activity of phytoplankton as primary producers. In the near future, severe environmental changes in the Arctic Ocean are expected to lead to modifications of phytoplankton communities. Here, we used a combination of linear inverse modeling and ecological network analysis to study changes in food webs before, during, and after an anomalous warm water event in the eastern Fram Strait of the West Spitsbergen Current (WSC that resulted in a shift from diatoms to flagellates during the summer (June–July. The model predicts substantial differences in the pathways of carbon flow in diatom- vs. Phaeocystis/nanoflagellate-dominated phytoplankton communities, but relatively small differences in carbon export. The model suggests a change in the zooplankton community and activity through increasing microzooplankton abundance and the switching of meso- and macrozooplankton feeding from strict herbivory to omnivory, detritivory and coprophagy. When small cells and flagellates dominated, the phytoplankton carbon pathway through the food web was longer and the microbial loop more active. Furthermore, one step was added in the flow from phytoplankton to mesozooplankton, and phytoplankton carbon to higher trophic levels is available via detritus or microzooplankton. Model results highlight how specific changes in phytoplankton community composition, as expected in a climate change scenario, do not necessarily lead to a reduction in carbon export.

  8. Measuring performance at trade shows

    DEFF Research Database (Denmark)

    Hansen, Kåre

    2004-01-01

    Trade shows is an increasingly important marketing activity to many companies, but current measures of trade show performance do not adequately capture dimensions important to exhibitors. Based on the marketing literature's outcome and behavior-based control system taxonomy, a model is built...... that captures a outcome-based sales dimension and four behavior-based dimensions (i.e. information-gathering, relationship building, image building, and motivation activities). A 16-item instrument is developed for assessing exhibitors perceptions of their trade show performance. The paper presents evidence...

  9. Isogenic Human iPSC Parkinson’s Model Shows Nitrosative Stress-Induced Dysfunction in MEF2-PGC1α Transcription

    OpenAIRE

    Ryan, Scott D.; Dolatabadi, Nima; Chan, Shing Fai; Zhang, Xiaofei; Akhtar, Mohd Waseem; Parker, James; Soldner, Frank; Sunico, Carmen R.; Nagar, Saumya; Talantova, Maria; Lee, Brian; Lopez, Kevin; Nutter, Anthony; Shan, Bing; Molokanova, Elena

    2013-01-01

    Parkinson’s disease (PD) is characterized by loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). An association has been reported between PD and exposure to mitochondrial toxins, including environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived stem cell model of PD allowing comparison of A53T α-synuclein (α-syn) mutant cells and isogenic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations in A...

  10. Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract.

    Science.gov (United States)

    García-Villalba, Rocío; Vissenaekens, Hanne; Pitart, Judit; Romo-Vaquero, María; Espín, Juan C; Grootaert, Charlotte; Selma, María V; Raes, Katleen; Smagghe, Guy; Possemiers, Sam; Van Camp, John; Tomas-Barberan, Francisco A

    2017-07-12

    A TWIN-SHIME system was used to compare the metabolism of pomegranate polyphenols by the gut microbiota from two individuals with different urolithin metabotypes. Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites, and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.

  11. Comparison of G protein sequences of South African street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.

    Science.gov (United States)

    Seo, Wonhyo; Servat, Alexandre; Cliquet, Florence; Akinbowale, Jenkins; Prehaud, Christophe; Lafon, Monique; Sabeta, Claude

    Rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. In South Africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. In this study, pathogenicity differences of South African canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. Comparison of glycoprotein gene sequences revealed amino acid differences that may underpin the observed pathogenicity differences. Cumulatively, our results suggest that the canid rabies virus may be more neurovirulent in mice than the mongoose rabies variant. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  12. Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.

    Science.gov (United States)

    Yun, Jeong H; Morrow, Jarrett; Owen, Caroline A; Qiu, Weiliang; Glass, Kimberly; Lao, Taotao; Jiang, Zhiqiang; Perrella, Mark A; Silverman, Edwin K; Zhou, Xiaobo; Hersh, Craig P

    2017-07-01

    Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip +/- , and Fam13a -/- murine strains exposed chronically to CS. The CS-resistant Fam13a -/- mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a -/- strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.

  13. Novel H7N9 influenza virus shows low infectious dose, high growth rate, and efficient contact transmission in the guinea pig model.

    Science.gov (United States)

    Gabbard, Jon D; Dlugolenski, Daniel; Van Riel, Debby; Marshall, Nicolle; Galloway, Summer E; Howerth, Elizabeth W; Campbell, Patricia J; Jones, Cheryl; Johnson, Scott; Byrd-Leotis, Lauren; Steinhauer, David A; Kuiken, Thijs; Tompkins, S Mark; Tripp, Ralph; Lowen, Anice C; Steel, John

    2014-02-01

    The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation.

  14. Novel H7N9 Influenza Virus Shows Low Infectious Dose, High Growth Rate, and Efficient Contact Transmission in the Guinea Pig Model

    Science.gov (United States)

    Gabbard, Jon D.; Dlugolenski, Daniel; Van Riel, Debby; Marshall, Nicolle; Galloway, Summer E.; Howerth, Elizabeth W.; Campbell, Patricia J.; Jones, Cheryl; Johnson, Scott; Byrd-Leotis, Lauren; Steinhauer, David A.; Kuiken, Thijs; Tompkins, S. Mark; Tripp, Ralph; Lowen, Anice C.

    2014-01-01

    The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation. PMID:24227867

  15. Biomolecular simulations on petascale: promises and challenges

    International Nuclear Information System (INIS)

    Agarwal, Pratul K; Alam, Sadaf R

    2006-01-01

    Proteins work as highly efficient machines at the molecular level and are responsible for a variety of processes in all living cells. There is wide interest in understanding these machines for implications in biochemical/biotechnology industries as well as in health related fields. Over the last century, investigations of proteins based on a variety of experimental techniques have provided a wealth of information. More recently, theoretical and computational modeling using large scale simulations is providing novel insights into the functioning of these machines. The next generation supercomputers with petascale computing power, hold great promises as well as challenges for the biomolecular simulation scientists. We briefly discuss the progress being made in this area

  16. Macrophage inflammatory protein-1α shows predictive value as a risk marker for subjects and sites vulnerable to bone loss in a longitudinal model of aggressive periodontitis.

    Science.gov (United States)

    Fine, Daniel H; Markowitz, Kenneth; Fairlie, Karen; Tischio-Bereski, Debbie; Ferrandiz, Javier; Godboley, Dipti; Furgang, David; Gunsolley, John; Best, Al

    2014-01-01

    Improved diagnostics remains a fundamental goal of biomedical research. This study was designed to assess cytokine biomarkers that could predict bone loss (BL) in localized aggressive periodontitis. 2,058 adolescents were screened. Two groups of 50 periodontally healthy adolescents were enrolled in the longitudinal study. One group had Aggregatibacter actinomycetemcomitans (Aa), the putative pathogen, while the matched cohort did not. Cytokine levels were assessed in saliva and gingival crevicular fluid (GCF). Participants were sampled, examined, and radiographed every 6 months for 2-3 years. Disease was defined as radiographic evidence of BL. Saliva and GCF was collected at each visit, frozen, and then tested retrospectively after detection of BL. Sixteen subjects with Aa developed BL. Saliva from Aa-positive and Aa-negative healthy subjects was compared to subjects who developed BL. GCF was collected from 16 subjects with BL and from another 38 subjects who remained healthy. GCF from BL sites in the 16 subjects was compared to healthy sites in these same subjects and to healthy sites in subjects who remained healthy. Results showed that cytokines in saliva associated with acute inflammation were elevated in subjects who developed BL (i.e., MIP-1α MIP-1β IL-α, IL-1β and IL-8; p<0.01). MIP-1α was elevated 13-fold, 6 months prior to BL. When MIP-1α levels were set at 40 pg/ml, 98% of healthy sites were below that level (Specificity); whereas, 93% of sites with BL were higher (Sensitivity), with comparable Predictive Values of 98%; p<0.0001; 95% C.I. = 42.5-52.7). MIP-1α consistently showed elevated levels as a biomarker for BL in both saliva and GCF, 6 months prior to BL. MIP-1α continues to demonstrate its strong candidacy as a diagnostic biomarker for both subject and site vulnerability to BL.

  17. Macrophage inflammatory protein-1α shows predictive value as a risk marker for subjects and sites vulnerable to bone loss in a longitudinal model of aggressive periodontitis.

    Directory of Open Access Journals (Sweden)

    Daniel H Fine

    Full Text Available Improved diagnostics remains a fundamental goal of biomedical research. This study was designed to assess cytokine biomarkers that could predict bone loss (BL in localized aggressive periodontitis. 2,058 adolescents were screened. Two groups of 50 periodontally healthy adolescents were enrolled in the longitudinal study. One group had Aggregatibacter actinomycetemcomitans (Aa, the putative pathogen, while the matched cohort did not. Cytokine levels were assessed in saliva and gingival crevicular fluid (GCF. Participants were sampled, examined, and radiographed every 6 months for 2-3 years. Disease was defined as radiographic evidence of BL. Saliva and GCF was collected at each visit, frozen, and then tested retrospectively after detection of BL. Sixteen subjects with Aa developed BL. Saliva from Aa-positive and Aa-negative healthy subjects was compared to subjects who developed BL. GCF was collected from 16 subjects with BL and from another 38 subjects who remained healthy. GCF from BL sites in the 16 subjects was compared to healthy sites in these same subjects and to healthy sites in subjects who remained healthy. Results showed that cytokines in saliva associated with acute inflammation were elevated in subjects who developed BL (i.e., MIP-1α MIP-1β IL-α, IL-1β and IL-8; p<0.01. MIP-1α was elevated 13-fold, 6 months prior to BL. When MIP-1α levels were set at 40 pg/ml, 98% of healthy sites were below that level (Specificity; whereas, 93% of sites with BL were higher (Sensitivity, with comparable Predictive Values of 98%; p<0.0001; 95% C.I. = 42.5-52.7. MIP-1α consistently showed elevated levels as a biomarker for BL in both saliva and GCF, 6 months prior to BL. MIP-1α continues to demonstrate its strong candidacy as a diagnostic biomarker for both subject and site vulnerability to BL.

  18. Establishing an ISO 10001-based promise in inpatients care.

    Science.gov (United States)

    Khan, Mohammad Ashiqur Rahman; Karapetrovic, Stanislav

    2015-01-01

    The purpose of this paper is to explore ISO 10001:2007 in planning, designing and developing a customer satisfaction promise (CSP) intended for inpatients care. Through meetings and interviews with research participants, who included a program manager, unit managers and registered nurses, information about potential promises and their implementation was obtained and analyzed. A number of promises were drafted and one was finally selected to be developed as a CSP. Applying the standard required adaptation and novel interpretation. Additionally, ISO 10002:2004 (Clause 7) was used to design the feedback handling activities. A promise initially chosen for development turned out to be difficult to implement, experience that helped in selecting and developing the final promise. Research participants found the ISO 10001-based method useful and comprehensible. This paper presents a specific health care example of how to adapt a standard's guideline in establishing customer promises. The authors show how a promise can be used in alleviating an existing issue (i.e. communication between carers and patients). The learning can be beneficial in various health care settings. To the knowledge, this paper shows the first example of applying ISO 10001:2007 in a health care case. A few activities suggested by the standard are further detailed, and a new activity is introduced. The integrated use of ISO 10001:2007 and 10002:2004 is presented and how one can be "augmented" by the other is demonstrated.

  19. Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

    Science.gov (United States)

    Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

    2017-09-01

    Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

  20. Cyanobacteria: Promising biocatalysts for sustainable chemical production.

    Science.gov (United States)

    Knoot, Cory J; Ungerer, Justin; Wangikar, Pramod P; Pakrasi, Himadri B

    2018-04-06

    Cyanobacteria are photosynthetic prokaryotes showing great promise as biocatalysts for the direct conversion of CO 2 into fuels, chemicals, and other value-added products. Introduction of just a few heterologous genes can endow cyanobacteria with the ability to transform specific central metabolites into many end products. Recent engineering efforts have centered around harnessing the potential of these microbial biofactories for sustainable production of chemicals conventionally produced from fossil fuels. Here, we present an overview of the unique chemistry that cyanobacteria have been co-opted to perform. We highlight key lessons learned from these engineering efforts and discuss advantages and disadvantages of various approaches. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Program impact pathway analysis of a social franchise model shows potential to improve infant and young child feeding practices in Vietnam.

    Science.gov (United States)

    Nguyen, Phuong H; Menon, Purnima; Keithly, Sarah C; Kim, Sunny S; Hajeebhoy, Nemat; Tran, Lan M; Ruel, Marie T; Rawat, Rahul

    2014-10-01

    By mapping the mechanisms through which interventions are expected to achieve impact, program impact pathway (PIP) analysis lays out the theoretical causal links between program activities, outcomes, and impacts. This study examines the pathways through which the Alive & Thrive (A&T) social franchise model is intended to improve infant and young child feeding (IYCF) practices in Vietnam. Mixed methods were used, including qualitative interviews with franchise management board members (n = 12), surveys with health providers (n = 120), counseling observations (n = 160), and household surveys (n = 2045). Six PIP components were assessed: 1) franchise management, 2) training and IYCF knowledge of health providers, 3) service delivery, 4) program exposure and utilization, 5) maternal behavioral determinants (knowledge, beliefs, and intentions) toward optimal IYCF practices, and 6) IYCF practices. Data were collected from A&T-intensive areas (A&T-I; mass media + social franchise) and A&T-nonintensive areas (A&T-NI; mass media only) by using a cluster-randomized controlled trial design. Data from 2013 were compared with baseline where similar measures were available. Results indicate that mechanisms are in place for effective management of the franchise system, despite challenges to routine monitoring. A&T training was associated with increased capacity of providers, resulting in higher-quality IYCF counseling (greater technical knowledge and communication skills during counseling) in A&T-I areas. Franchise utilization increased from 10% in 2012 to 45% in 2013 but fell below the expected frequency of 9-15 contacts per mother-child dyad. Improvements in breastfeeding knowledge, beliefs, intentions, and practices were greater among mothers in A&T-I areas than among those in A&T-NI areas. In conclusion, there are many positive changes along the impact pathway of the franchise services, but challenges in utilization and demand creation should be addressed to achieve the full

  2. Modeling Glaucoma: Retinal Ganglion Cells Generated from Induced Pluripotent Stem Cells of Patients with SIX6 Risk Allele Show Developmental Abnormalities.

    Science.gov (United States)

    Teotia, Pooja; Van Hook, Matthew J; Wichman, Christopher S; Allingham, R Rand; Hauser, Michael A; Ahmad, Iqbal

    2017-11-01

    Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma. Stem Cells 2017;35:2239-2252. © 2017 AlphaMed Press.

  3. Machine-Learning-Based No Show Prediction in Outpatient Visits

    Directory of Open Access Journals (Sweden)

    Carlos Elvira

    2018-03-01

    Full Text Available A recurring problem in healthcare is the high percentage of patients who miss their appointment, be it a consultation or a hospital test. The present study seeks patient’s behavioural patterns that allow predicting the probability of no- shows. We explore the convenience of using Big Data Machine Learning models to accomplish this task. To begin with, a predictive model based only on variables associated with the target appointment is built. Then the model is improved by considering the patient’s history of appointments. In both cases, the Gradient Boosting algorithm was the predictor of choice. Our numerical results are considered promising given the small amount of information available. However, there seems to be plenty of room to improve the model if we manage to collect additional data for both patients and appointments.

  4. A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects.

    Science.gov (United States)

    Suggs, Jennifer A; Melkani, Girish C; Glasheen, Bernadette M; Detor, Mia M; Melkani, Anju; Marsan, Nathan P; Swank, Douglas M; Bernstein, Sanford I

    2017-06-01

    Individuals with inclusion body myopathy type 3 (IBM3) display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K) in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in decreased in vitro

  5. A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects

    Directory of Open Access Journals (Sweden)

    Jennifer A. Suggs

    2017-06-01

    Full Text Available Individuals with inclusion body myopathy type 3 (IBM3 display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in

  6. Unary probabilistic and quantum automata on promise problems

    OpenAIRE

    Gainutdinova, Aida; Yakaryilmaz, Abuzer

    2015-01-01

    We continue the systematic investigation of probabilistic and quantum finite automata (PFAs and QFAs) on promise problems by focusing on unary languages. We show that bounded-error QFAs are more powerful than PFAs. But, in contrary to the binary problems, the computational powers of Las-Vegas QFAs and bounded-error PFAs are equivalent to deterministic finite automata (DFAs). Lastly, we present a new family of unary promise problems with two parameters such that when fixing one parameter QFAs ...

  7. Nuclear energy: Promise and problems

    International Nuclear Information System (INIS)

    Richter, B.

    2005-01-01

    Nuclear energy is having a renaissance driven by both old fashioned supply and demand, and environmental concerns. Oil and gas prices have exploded and show no signs of returning to the levels of only a few years ago. Coal is not in short supply, but the pollution it generates has severe economic and health consequences. Concern about greenhouse gases and global warming has caused the environmental movement to begin a reassessment of the role of nuclear in the world's energy portfolio. The full potential of nuclear energy will be achieved only if governments and the public are satisfied that it is safe, that the radioactive waste can be safely disposed of, and that the risk of the proliferation of nuclear weapons is low. The first criterion has been met with designs that are inherently safer than current LWRs, primarily through design simplification, reducing the number of critical components, and advanced control and monitoring technologies. Operating safety has to be assured through good practices and a rigorous, independent inspection process. The second criterion, waste disposal, is a problem where the science and technology (S and T) communities have the primary role in a solution. Many believe that it is solved in principle, but there has as yet been no solution in practice. I will report on where I think we have gotten and what needs to be done. The third criterion, proliferation resistance, is one that the S and T communities cannot solve on their own. The best that S and T can do is to make proliferation difficult, and to make sure that any attempts are discovered early. The rest can be handled only by enforceable international agreements. Safeguards technology needs more attention. (author)

  8. Tokyo Motor Show 2003; Tokyo Motor Show 2003

    Energy Technology Data Exchange (ETDEWEB)

    Joly, E.

    2004-01-01

    The text which follows present the different techniques exposed during the 37. Tokyo Motor Show. The report points out the great tendencies of developments of the Japanese automobile industry. The hybrid electric-powered vehicles or those equipped with fuel cells have been highlighted by the Japanese manufacturers which allow considerable budgets in the research of less polluting vehicles. The exposed models, although being all different according to the manufacturer, use always a hybrid system: fuel cell/battery. The manufacturers have stressed too on the intelligent systems for navigation and safety as well as on the design and comfort. (O.M.)

  9. Congestion Service Facilities Location Problem with Promise of Response Time

    Directory of Open Access Journals (Sweden)

    Dandan Hu

    2013-01-01

    Full Text Available In many services, promise of specific response time is advertised as a commitment by the service providers for the customer satisfaction. Congestion on service facilities could delay the delivery of the services and hurts the overall satisfaction. In this paper, congestion service facilities location problem with promise of response time is studied, and a mixed integer nonlinear programming model is presented with budget constrained. The facilities are modeled as M/M/c queues. The decision variables of the model are the locations of the service facilities and the number of servers at each facility. The objective function is to maximize the demands served within specific response time promised by the service provider. To solve this problem, we propose an algorithm that combines greedy and genetic algorithms. In order to verify the proposed algorithm, a lot of computational experiments are tested. And the results demonstrate that response time has a significant impact on location decision.

  10. Realizing the promises of marine biotechnology

    NARCIS (Netherlands)

    Luiten, EEM; Akkerman, [No Value; Koulman, A; Kamermans, P; Reith, H; Barbosa, MJ; Sipkema, D; Wijffels, RH

    High-quality research in the field of marine biotechnology is one of the key-factors for successful innovation in exploiting the vast diversity of marine life. However, fascinating scientific research with promising results and claims on promising potential applications (e.g. for pharmaceuticals,

  11. Realizing the promises of marine biotechnology

    NARCIS (Netherlands)

    Luiten, E.E.M.; Akkerman, I.; Koulman, A.; Kamermans, P.; Reith, H.; Barbosa, M.J.; Sipkema, D.; Wijffels, R.H.

    2003-01-01

    High-quality research in the field of marine biotechnology is one of the key-factors for successful innovation in exploiting the vast diversity of marine life. However, fascinating scientific research with promising results and claims on promising potential applications (e.g. for pharmaceuticals,

  12. Tennessee Promise: A Response to Organizational Change

    Science.gov (United States)

    Littlepage, Ben; Clark, Teresa; Wilson, Randal; Stout, Logan

    2018-01-01

    Community colleges in Tennessee, either directly or indirectly, experienced unprecedented change as a result of Tennessee Promise. The present study explored how student support service administrators at three community colleges responded to organizational change as a result of the Tennessee Promise legislation. Investigators selected community…

  13. Medical big data: promise and challenges

    Directory of Open Access Journals (Sweden)

    Choong Ho Lee

    2017-03-01

    Full Text Available The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.

  14. Medical big data: promise and challenges.

    Science.gov (United States)

    Lee, Choong Ho; Yoon, Hyung-Jin

    2017-03-01

    The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.

  15. Financial Technology: The Promise of Blockchain

    OpenAIRE

    Demary, Markus; Demary, Vera

    2017-01-01

    Digitization affects all sectors of the economy. A new and possibly disruptive digital technology is the blockchain, a decentralized ledger, which seems to offer great promise for many financial and business applications.

  16. Stem cell therapy in spinal cord injury: Hollow promise or promising science?

    Directory of Open Access Journals (Sweden)

    Aimee Goel

    2016-01-01

    Full Text Available Spinal cord injury (SCI remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.

  17. Do promises matter? An exploration of the role of promises in psychological contract breach.

    Science.gov (United States)

    Montes, Samantha D; Zweig, David

    2009-09-01

    Promises are positioned centrally in the study of psychological contract breach and are argued to distinguish psychological contracts from related constructs, such as employee expectations. However, because the effects of promises and delivered inducements are confounded in most research, the role of promises in perceptions of, and reactions to, breach remains unclear. If promises are not an important determinant of employee perceptions, emotions, and behavioral intentions, this would suggest that the psychological contract breach construct might lack utility. To assess the unique role of promises, the authors manipulated promises and delivered inducements separately in hypothetical scenarios in Studies 1 (558 undergraduates) and 2 (441 employees), and they measured them separately (longitudinally) in Study 3 (383 employees). The authors' results indicate that breach perceptions do not represent a discrepancy between what employees believe they were promised and were given. In fact, breach perceptions can exist in the absence of promises. Further, promises play a negligible role in predicting feelings of violation and behavioral intentions. Contrary to the extant literature, the authors' findings suggest that promises may matter little; employees are concerned primarily with what the organization delivers.

  18. The path to fulfilling the promise

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, J. [Canadian Nuclear Association, Ottawa, ON (Canada)

    2014-07-01

    'Full text:'Countries work together to develop effective governance and regulation. Canada has made big investments in these areas and it carries a premium for us. The rapid build-out of nuclear technology around the Pacific Rim holds vast promise for our populations in better climate, better air, affordable and reliable electricity, and longer lives. The biggest risk is not another accident: rather, it is the risk of failing to fulfill that promise to our people. Every country that wants the benefits of nuclear must also want to be sure that those benefits are realized and sustained by good governance and regulation. Canada has the people, laws, organizations, public institutions, and relationships that can help our partners fulfill the whole and lasting promise of nuclear technology. (author)

  19. Promising Compilation to ARMv8 POP

    OpenAIRE

    Podkopaev, Anton; Lahav, Ori; Vafeiadis, Viktor

    2017-01-01

    We prove the correctness of compilation of relaxed memory accesses and release-acquire fences from the "promising" semantics of [Kang et al. POPL'17] to the ARMv8 POP machine of [Flur et al. POPL'16]. The proof is highly non-trivial because both the ARMv8 POP and the promising semantics provide some extremely weak consistency guarantees for normal memory accesses; however, they do so in rather different ways. Our proof of compilation correctness to ARMv8 POP strengthens the results of the Kan...

  20. Progress and promise for the MDMA drug development program.

    Science.gov (United States)

    Feduccia, Allison A; Holland, Julie; Mithoefer, Michael C

    2018-02-01

    Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug "Ecstasy." MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.

  1. Prosecuting the Leaders: Promises, Politics and Practicalities

    Directory of Open Access Journals (Sweden)

    Robert Cryer

    2009-02-01

    Full Text Available Given recent developments in relation to the prosecution of international crimes,  it might be thought that one of the last bastions of sovereignty has been breached, and international criminal law has not only entrenched itself in international law. Indeed further to this, it has assumed a supranational position that stands entirely above States, promising justice for all and as a trump card over depredations committed in the name of State sovereignty. After all, Charles Taylor from Liberia is standing trial before the Special Court for Sierra Leone, Slobodan Milošević only escaped judgment by the International Criminal Tribunal for the former

  2. The Promise of Zoomable User Interfaces

    Science.gov (United States)

    Bederson, Benjamin B.

    2011-01-01

    Zoomable user interfaces (ZUIs) have received a significant amount of attention in the 18 years since they were introduced. They have enjoyed some success, and elements of ZUIs are widely used in computers today, although the grand vision of a zoomable desktop has not materialised. This paper describes the premise and promise of ZUIs along with…

  3. Promising carbons for supercapacitors derived from fungi

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hui; Wang, Xiaolei; Yang, Fan; Yang, Xiurong [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 (China)

    2011-06-24

    Activated carbons with promising performance in capacitors are produced from fungi via a hydrothermal assistant pyrolysis approach. This study introduces a facile strategy to discover carbonaceous materials and triggers interest in exploring fungi for material science applications. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. Seaweed: Promising plant of the millennium

    Digital Repository Service at National Institute of Oceanography (India)

    Dhargalkar, V.K.; Pereira, N.

    Seaweeds, one of the important marine living resources could be termed as the futuristically promising plants. These plants have been a source of food, feed and medicine in the orient as well as in the west, since ancient times. Although, seaweeds...

  5. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/ citation .cfm?doid=1740582.1740586

  6. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/citation.cfm?doid=1740582.1740586

  7. 76 FR 13152 - Promise Neighborhoods Program

    Science.gov (United States)

    2011-03-10

    ... comprehensive education reforms that are linked to improved educational outcomes for children and youth in... parents or family members who report talking with their child about the importance of college and career... DEPARTMENT OF EDUCATION RIN 1855-ZA07 Promise Neighborhoods Program Catalog of Federal Domestic...

  8. Green and social bonds - A promising tool

    International Nuclear Information System (INIS)

    Blanc, Dominique; Barochez, Aurelie de; Cozic, Aela

    2013-11-01

    Issues of green bonds, socially responsible bonds and climate bonds are on the rise. Novethic estimates that some Euro 5 billion in such bonds has been issued since the start of 2013 by development banks, the main issuers of this type of debt. The figure is equal to over half of their total issues since 2007. Including local authorities, corporations and banks, a total Euro 8 billion of these bonds has been issued thus far in 2013. Given the size of the bond market, which the OECD estimated at Euro 95,000 billion in 2011, green and social bonds are still something of a niche but have strong growth potential. A number of large issues, from Euro 500 million to Euro 1 billion, were announced at the end of the year. Unlike conventional bonds, green and social bonds are not intended to finance all the activities of the issuer or refinance its debt. They serve instead to finance specific projects, such as producing renewable energy or adapting to climate change, the risk of which is shouldered by the issuer. This makes them an innovative instrument, used to earmark investments in projects with a direct environmental or social benefit rather than simply on the basis of the issuer's sustainable development policy. With financing being sought for the ecological transition, green and social bonds are promising instruments, sketching out at global level the shape of tools adapted to the financing of a green economy. On the strength of these advantages, the interest of responsible investors - the main target of green and social bond issuers - is growing fast. Judging by issuer press releases and the most commonly used currencies, the main subscribers today are US investors, among them CalSTRS and fund managers like Calvert Investment Management and Trillium Asset Management. European asset owners are also starting to focus on green and social bonds. A Novethic survey shows that 13% of them have already subscribed to such an issue or plan to do so. The present study

  9. Short term non-chemical approach to Tuta absoluta and thrips : CATT shows promise against quarantine pests

    NARCIS (Netherlands)

    Arkesteijn, M.; Qiu, Y.

    2015-01-01

    Pests such as insects, mites and nematodes don’t just cause damage, in the case of quarantine pests they can also limit exports. In cooperation with the sector, entomologist Yutong Qiu tested the possibility of using Controlled Atmosphere Temperature Treatment (CATT) in the post harvest phase to

  10. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    Directory of Open Access Journals (Sweden)

    Salvatore Rosanio

    2014-01-01

    Full Text Available This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure.

  11. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons

    OpenAIRE

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any ...

  12. [Absorbable coronary stents. New promising technology].

    Science.gov (United States)

    Erbel, Raimund; Böse, Dirk; Haude, Michael; Kordish, Igor; Churzidze, Sofia; Malyar, Nasser; Konorza, Thomas; Sack, Stefan

    2007-06-01

    Coronary stent implantation started in Germany 20 years ago. In the beginning, the progress was very slow and accelerated 10 years later. Meanwhile, coronary stent implantation is a standard procedure in interventional cardiology. From the beginning of permanent stent implantation, research started to provide temporary stenting of coronary arteries, first with catheter-based systems, later with stent-alone technology. Stents were produced from polymers or metal. The first polymer stent implantation failed except the Igaki-Tamai stent in Japan. Newly developed absorbable polymer stents seem to be very promising, as intravascular ultrasound (IVUS) and optical coherence tomography have demonstrated. Temporary metal stents were developed based on iron and magnesium. Currently, the iron stent is tested in peripheral arteries. The absorbable magnesium stent (Biotronik, Berlin, Germany) was tested in peripheral arteries below the knee and meanwhile in the multicenter international PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting with Absorbable Metal Stents) study. The first magnesium stent implantation was performed on July 30, 2004 after extended experimental testing in Essen. The magnesium stent behaved like a bare-metal stent with low recoil of 5-7%. The stent struts were absorbed when tested with IVUS. Stent struts were not visible by fluoroscopy or computed tomography (CT) as well as magnetic resonance imaging (MRI). That means, that the magnesium stent is invisible and therefore CT and MRI can be used for imaging of interventions. Only using micro-CT the stent struts were visible. The absorption process could be demonstrated in a patient 18 days after implantation due to suspected acute coronary syndrome, which was excluded. IVUS showed a nice open lumen. Stent struts were no longer visible, but replaced by tissue indicating the previous stent location. Coronary angiography after 4 months showed an ischemia-driven target lesion

  13. Risk Aversion in Game Shows

    DEFF Research Database (Denmark)

    Andersen, Steffen; Harrison, Glenn W.; Lau, Morten I.

    2008-01-01

    We review the use of behavior from television game shows to infer risk attitudes. These shows provide evidence when contestants are making decisions over very large stakes, and in a replicated, structured way. Inferences are generally confounded by the subjective assessment of skill in some games......, and the dynamic nature of the task in most games. We consider the game shows Card Sharks, Jeopardy!, Lingo, and finally Deal Or No Deal. We provide a detailed case study of the analyses of Deal Or No Deal, since it is suitable for inference about risk attitudes and has attracted considerable attention....

  14. Perpendicular recording: the promise and the problems

    International Nuclear Information System (INIS)

    Wood, Roger; Sonobe, Yoshiaki; Jin Zhen; Wilson, Bruce

    2001-01-01

    Perpendicular recording has long been advocated as a means of achieving the highest areal densities. In particular, in the context of the 'superparamagnetic limit', perpendicular recording with a soft underlayer promises several key advantages. These advantages include a higher coercivity, thicker media that should permit smaller diameter grains and higher signal-to-noise ratio. Also, the sharper edge-writing will facilitate recording at very high track densities (lower bit aspect ratio). Recent demonstrations of the technology have shown densities comparable with the highest densities reported for longitudinal recording. This paper further examines the promise that perpendicular recording will deliver an increase in areal density two to eight times higher than that achievable with longitudinal recording. There are a number of outstanding issues but the key challenge is to create a low-noise medium with a coercivity that is high and is much larger than the remanent magnetization

  15. Promising Products for Printing and Publishing Market

    Directory of Open Access Journals (Sweden)

    Renata Činčikaitė

    2011-04-01

    Full Text Available The article surveys printing and publishing market and its strong and weak aspects. The concept of a new product is described as well as its lifetime and the necessity of its introduction to the market. The enterprise X operating on the market is analyzed, its strong and weak characteristics are presented. The segmentation of the company consumers is performed. On the basis of the performed analysis the potential promising company products are defined.Article in Lithuanian

  16. Melanoma Vaccines: Mixed Past, Promising Future

    Science.gov (United States)

    Ozao-Choy, Junko; Lee, Delphine J.; Faries, Mark B.

    2014-01-01

    Synopsis Cancer vaccines were one of the earliest forms of immunotherapy to be investigated. Past attempts to vaccinate against cancer, including melanoma, have mixed results, revealing the complexity of what was thought to be a simple concept. However, several recent successes and the combination of improved knowledge of tumor immunology and the advent of new immunomodulators make vaccination a promising strategy for the future. PMID:25245965

  17. The promises and facts of emergent strategy in public management

    DEFF Research Database (Denmark)

    Aagaard, Peter

    Public managers are experiencing a growing demand for innovation. One of the promising approaches to instigating innovation is that of emergent strategic patterns (ESPs). According to the literature, the institutional barriers and drivers of ESPs are shaped by the two dominant public management...... models, NPM (the barriers) and governance (the drivers). However, based on an empirical case study of the institutional barriers and drivers for ESPs in the Danish Crime Prevention Council, this article concludes that ESPs are in fact enabled by a much more mixed management model....

  18. Reality show: um paradoxo nietzschiano

    Directory of Open Access Journals (Sweden)

    Ilana Feldman

    2011-01-01

    Full Text Available

    O fenômeno dos reality shows - e a subseqüente relação entre imagem e verdade - assenta-se sobre uma série de paradoxos. Tais paradoxos podem ser compreendidos à luz do pensamento do filósofo alemão Friedrich Nietzsche, que, através dos usos de formulações paradoxais, concebia a realidade como um mundo de pura aparência e a verdade como um acréscimo ficcional, como um efeito. A ficção é então tomada, na filosofia de Nietzsche, não em seu aspecto falsificante e desrealizador - como sempre pleiteou nossa tradição metafísica -, mas como condição necessária para que certa espécie de invenção possa operar como verdade. Sendo assim, a própria expressão reality show, através de sua formulação paradoxal, engendra explicitamente um mundo de pura aparência, em que a verdade, a parte reality da proposição, é da ordem do suplemento, daquilo que se acrescenta ficcionalmente - como um adjetivo - a show. O ornamento, nesse caso, passa a ocupar o lugar central, apontando para o efeito produzido: o efeito-de-verdade. Seguindo, então, o pensamento nietzschiano e sua atualização na contemporaneidade, investigaremos de que forma os televisivos “shows de realidade” operam paradoxalmente, em consonância com nossas paradoxais práticas culturais.

  19. Does environmental archaeology need an ethical promise?

    DEFF Research Database (Denmark)

    Riede, Felix; Andersen, Per; Price, Neil

    2016-01-01

    formalized ethical codes or promises that not only guide the dissemination of data but oblige scientists to relate to fundamentally political issues. This article couples a survey of the recent environmental ethics literature with two case studies of how past natural hazards have affected vulnerable...... societies in Europe?s prehistory. We ask whether cases of past calamities and their societal effects should play a greater role in public debates and whether archaeologists working with past environmental hazards should be more outspoken in their ethical considerations. We offer no firm answers, but suggest...... that archaeologists engage with debates in human?environment relations at this interface between politics, public affairs and science....

  20. Status and promise of fuel cell technology

    Energy Technology Data Exchange (ETDEWEB)

    Williams, M.C. [National Energy Technology Lab., Pittsburgh, PA (United States). Dept. of Energy

    2001-09-01

    The niche or early entry market penetration by ONSI and its phosphoric acid fuel cell technology has proven that fuel cells are reliable and suitable for premium power and other opportunity fuel niche market applications. Now, new fuel cell technologies - solid oxide fuel cells, molten carbonate fuel cells, and polymer electrolyte fuel cells - are being developed for near-term distributed generation shortly after 2003. Some of the evolving fuel cell systems are incorporating gas turbines in hybrid configurations. The combination of the gas turbine with the fuel cell promises to lower system costs and increase efficiency to enhance market penetration. Market estimates indicate that significant early entry markets exist to sustain the initially high cost of some distributed generation technologies. However, distributed generation technologies must have low introductory first cost, low installation cost, and high system reliability to be viable options in competitive commercial and industrial markets. In the long-term, solid state fuel cell technology with stack costs under $100/kilowatt (kW) promises deeper and wider market penetration in a range of applications including a residential, auxillary power, and the mature distributed generation markets. The solid state energy conversion alliance (SECA) with its vision for fuel cells in 2010 was recently formed to commercialize solid state fuel cells and realize the full potential of the fuel cell technology. Ultimately, the SECA concept could lead to megawatt-size fuel-cell systems for commercial and industrial applications and Vision 21 fuel cell turbine hybrid energy plants in 2015. (orig.)

  1. Promises in intelligent plant control systems

    International Nuclear Information System (INIS)

    Otaduy, P.J.

    1987-01-01

    The control system is the brain of a power plant. The traditional goal of control systems has been productivity. However, in nuclear power plants the potential for disaster requires safety to be the dominant concern, and the worldwide political climate demands trustworthiness for nuclear power plants. To keep nuclear generation as a viable option for power in the future, trust is the essential critical goal which encompasses all others. In most of today's nuclear plants the control system is a hybrid of analog, digital, and human components that focuses on productivity and operates under the protective umbrella of an independent engineered safety system. Operation of the plant is complex, and frequent challenges to the safety system occur which impact on their trustworthiness. Advances in nuclear reactor design, computer sciences, and control theory, and in related technological areas such as electronics and communications as well as in data storage, retrieval, display, and analysis have opened a promise for control systems with more acceptable human brain-like capabilities to pursue the required goals. This paper elaborates on the promise of futuristic nuclear power plants with intelligent control systems and addresses design requirements and implementation approaches

  2. PROMISING FINANCING SCHEME OF HEALTH INSURANCE IN UKRAINE

    Directory of Open Access Journals (Sweden)

    Martha Slavitych

    2016-11-01

    Full Text Available The promising financing scheme of health insurance in Ukraine should be found at the present stage of its development. The health care system in Ukraine is cumbersome and outdated. It is based on the Semashko model with rigid management and financing procedures. The disadvantages accumulated in the national health care system due to lack of modernization, disregard of the population needs, non-use of modern global trends, the inefficient operation of the system and the high level of corruption cause the underlying situation. The decision of new government policy in the sector is introduction of new financial mechanisms, in order to ensure human rights in the health sector. Methodology. The study is based on a comparison of systems of financing of medicine in Ukraine and in other countries, provided advantages and disadvantages of each model. Results showed that the availability of medical services is the key problem in any society. The availability of health care services is primarily determined by the proportion of services guaranteed by the government (government guarantees. In some countries such as the United States, practically the whole medicine is funded by voluntary health insurance (VHI. In Europe the mandatory health insurance (MHI and government funding are the most significant source of funds. Practical importance. The improvement of the demographic situation, the preservation and improvement of public health, improvement of social equity and citizens' rights in respect of medical insurance. Value/originality. Premiums for health insurance are the source of funding. Based on the new model requirements it is necessary to create an appropriate regulation, which would determine its organizational and regulatory framework. This process is primarily determined by identification and setting rules governing the relationship between patients, health care providers and insurers, creation of the conditions and the implementation of quality

  3. Analysis of promising sustainable renovation concepts

    DEFF Research Database (Denmark)

    Vanhoutteghem, Lies; Tommerup, Henrik M.; Svendsen, Svend

    This report focuses on analyses of the most promising existing sustainable renovation concepts, i.e. full-service concepts and technical concepts, for single-family houses. As a basis for the analyses a detailed building stock analysis was carried out. Furthermore, as a basis a general working...... method for proposals on package solutions for sustainable renovation was described. The method consists of four steps, going from investigation of the house to proposal for sustainable renovation, detailed planning and commissioning after renovation. It could be used by teams of consultants...... of the building envelope and the electricity required to run the system. Positive impact on the indoor environment can be expected. Thermal comfort will be improved by insulation and air-tightness measures that will increase surface temperatures and reduce draught from e.g. badly insulated windows. A ventilation...

  4. Halopentacenes: Promising Candidates for Organic Semiconductors

    International Nuclear Information System (INIS)

    Gong-He, Du; Zhao-Yu, Ren; Ji-Ming, Zheng; Ping, Guo

    2009-01-01

    We introduce polar substituents such as F, Cl, Br into pentacene to enhance the dissolubility in common organic solvents while retaining the high charge-carrier mobilities of pentacene. Geometric structures, dipole moments, frontier molecule orbits, ionization potentials and electron affinities, as well as reorganization energies of those molecules, and of pentacene for comparison, are successively calculated by density functional theory. The results indicate that halopentacenes have rather small reorganization energies (< 0.2 eV), and when the substituents are in position 2 or positions 2 and 9, they are polarity molecules. Thus we conjecture that they can easily be dissolved in common organic solvents, and are promising candidates for organic semiconductors. (condensed matter: electronicstructure, electrical, magnetic, and opticalproperties)

  5. Underexploited tropical plants with promising economic value

    Energy Technology Data Exchange (ETDEWEB)

    1975-01-01

    The apparent advantages of staple plants over the minor tropical plants often result only from the disproportionate research attention they have been given. A world-wide inquiry resulted in a list of 400 promising but neglected species. The 36 most important species are described in compact monographs and concern cereals (Echinochloa turnerana, grain amaranths, quinua and Zosterea mazina), roots and tubers (Arrachacha, cocoyams and taro), vegetables (chaya, hearts of palms, wax gourd, winged bean), fruits (durian, mangosteen, naranjilla, pejibaye, pummelo, soursop, uvilla), oilseeds (babassu palm, buffalo gourd, Caryocar species, Hessenia polycarpa and jojoba), forage (Acacia albida, Brosimum alicastrum Cassia sturtii, saltbushes and tamarugo) and other crops (buriti palm, Calathea lutea, candelilla, guar, guayule, Paspalum vaginatum, ramie and Spirulina).

  6. Nanomedicine delivers promising treatments for rheumatoid arthritis.

    Science.gov (United States)

    Prasad, Leena Kumari; O'Mary, Hannah; Cui, Zhengrong

    2015-01-01

    An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease.

  7. Symptom profiles of subsyndromal depression in disease clusters of diabetes, excess weight, and progressive cerebrovascular conditions: a promising new type of finding from a reliable innovation to estimate exhaustively specified multiple indicators–multiple causes (MIMIC models

    Directory of Open Access Journals (Sweden)

    Francoeur RB

    2016-12-01

    Full Text Available Richard B Francoeur School of Social Work, Adelphi University, Garden City, NY, USA Abstract: Addressing subsyndromal depression in cerebrovascular conditions, diabetes, and obesity reduces morbidity and risk of major depression. However, depression may be masked because self-reported symptoms may not reveal dysphoric (sad mood. In this study, the first wave (2,812 elders from the New Haven Epidemiological Study of the Elderly (EPESE was used. These population-weighted data combined a stratified, systematic, clustered random sample from independent residences and a census of senior housing. Physical conditions included progressive cerebrovascular disease (CVD; hypertension, silent CVD, stroke, and vascular cognitive impairment [VCI] and co-occurring excess weight and/or diabetes. These conditions and interactions (clusters simultaneously predicted 20 depression items and a latent trait of depression in participants with subsyndromal (including subthreshold depression (11≤ Center for Epidemiologic Studies Depression Scale [CES-D] score ≤27. The option for maximum likelihood estimation with standard errors that are robust to non-normality and non-independence in complex random samples (MLR in Mplus and an innovation created by the author were used for estimating unbiased effects from latent trait models with exhaustive specification. Symptom profiles reveal masked depression in 1 older males, related to the metabolic syndrome (hypertension–overweight–diabetes; silent CVD–overweight; and silent CVD–diabetes and 2 older females or the full sample, related to several diabetes and/or overweight clusters that involve stroke or VCI. Several other disease clusters are equivocal regarding masked depression; a couple do emphasize dysphoric mood. Replicating findings could identify subgroups for cost-effective screening of subsyndromal depression. Keywords: depression, diabetes, overweight, cerebrovascular disease, hypertension, metabolic

  8. Combined MRI and ³¹P-MRS investigations of the ACTA1(H40Y mouse model of nemaline myopathy show impaired muscle function and altered energy metabolism.

    Directory of Open Access Journals (Sweden)

    Charlotte Gineste

    Full Text Available Nemaline myopathy (NM is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1 account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y. Skeletal muscle anatomy (hindlimb muscles and fat volumes and energy metabolism were studied using MRI and (31Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1-150 Hz and a fatigue protocol (80 stimuli at 40 Hz. H40Y mice showed a reduction of both absolute (-40% and specific (-25% maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40% and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.

  9. Predictive Validity of an Empirical Approach for Selecting Promising Message Topics: A Randomized-Controlled Study

    Science.gov (United States)

    Lee, Stella Juhyun; Brennan, Emily; Gibson, Laura Anne; Tan, Andy S. L.; Kybert-Momjian, Ani; Liu, Jiaying; Hornik, Robert

    2016-01-01

    Several message topic selection approaches propose that messages based on beliefs pretested and found to be more strongly associated with intentions will be more effective in changing population intentions and behaviors when used in a campaign. This study aimed to validate the underlying causal assumption of these approaches which rely on cross-sectional belief–intention associations. We experimentally tested whether messages addressing promising themes as identified by the above criterion were more persuasive than messages addressing less promising themes. Contrary to expectations, all messages increased intentions. Interestingly, mediation analyses showed that while messages deemed promising affected intentions through changes in targeted promising beliefs, messages deemed less promising also achieved persuasion by influencing nontargeted promising beliefs. Implications for message topic selection are discussed. PMID:27867218

  10. Antarctic Lithosphere Studies: Progress, Problems and Promise

    Science.gov (United States)

    Dalziel, I. W. D.; Wilson, T. J.

    2017-12-01

    In the sixty years since the International Geophysical Year, studies of the Antarctic lithosphere have progressed from basic geological observations and sparse geophysical measurements to continental-scale datasets of radiometric dates, ice thickness, bedrock topography and characteristics, seismic imaging and potential fields. These have been augmented by data from increasingly dense broadband seismic and geodetic networks. The Antarctic lithosphere is known to have been an integral part, indeed a "keystone" of the Pangea ( 250-185Ma) and Gondwanaland ( 540-180 Ma) supercontinents. It is widely believed to have been part of hypothetical earlier supercontinents Rodinia ( 1.0-0.75 Ga) and Columbia (Nuna) ( 2.0-1.5 Ga). Despite the paucity of exposure in East Antarctica, the new potential field datasets have emboldened workers to extrapolate Precambrian geological provinces and structures from neighboring continents into Antarctica. Hence models of the configuration of Columbia and its evolution into Rodinia and Gondwana have been proposed, and rift-flank uplift superimposed on a Proterozoic orogenic root has been hypothesized to explain the Gamburtsev Subglacial Mountains. Mesozoic-Cenozoic rifting has imparted a strong imprint on the West Antarctic lithosphere. Seismic tomographic evidence reveals lateral variation in lithospheric thickness, with the thinnest zones within the West Antarctic rift system and underlying the Amundsen Sea Embayment. Upper mantle low velocity zones are extensive, with a deeper mantle velocity anomaly underlying Marie Byrd Land marking a possible mantle plume. Misfits between crustal motions measured by GPS and GIA model predictions can, in part, be linked with the changes in lithosphere thickness and mantle rheology. Unusually high uplift rates measured by GPS in the Amundsen region can be interpreted as the response of regions with thin lithosphere and weak mantle to late Holocene ice mass loss. Horizontal displacements across the TAM

  11. Investigation of new superhard carbon allotropes with promising electronic properties

    Energy Technology Data Exchange (ETDEWEB)

    Kvashnina, Yulia A.; Kvashnin, Alexander G. [Technological Institute for Superhard and Novel Carbon Materials, 7a Centralnaya Street, Troitsk, Moscow 142190 (Russian Federation); Moscow Institute of Physics and Technology, 9 Institutsky Lane, 141700 Dolgoprudny (Russian Federation); Sorokin, Pavel B., E-mail: psorokin@iph.krasn.ru [Technological Institute for Superhard and Novel Carbon Materials, 7a Centralnaya Street, Troitsk, Moscow 142190 (Russian Federation); Moscow Institute of Physics and Technology, 9 Institutsky Lane, 141700 Dolgoprudny (Russian Federation); Emanuel Institute of Biochemical Physics of RAS, 4 Kosigina St., Moscow 119334 (Russian Federation)

    2013-11-14

    During the systematic search for a new superhard carbon allotrope, we predicted three structures with promising physical properties. Our electronic structure calculations show that these materials have a semiconducting band gap and a high carrier mobility comparable with diamond. The simulated x-ray diffraction patterns of the proposed materials are in a good agreement with the experimental X-ray spectra. Evaluated phase transition pressures from graphite to the new proposed carbon phases are smaller than 25 GPa and close to the experimental values.

  12. [Rapid prototyping: a very promising method].

    Science.gov (United States)

    Haverman, T M; Karagozoglu, K H; Prins, H-J; Schulten, E A J M; Forouzanfar, T

    2013-03-01

    Rapid prototyping is a method which makes it possible to produce a three-dimensional model based on two-dimensional imaging. Various rapid prototyping methods are available for modelling, such as stereolithography, selective laser sintering, direct laser metal sintering, two-photon polymerization, laminated object manufacturing, three-dimensional printing, three-dimensional plotting, polyjet inkjet technology,fused deposition modelling, vacuum casting and milling. The various methods currently being used in the biomedical sector differ in production, materials and properties of the three-dimensional model which is produced. Rapid prototyping is mainly usedforpreoperative planning, simulation, education, and research into and development of bioengineering possibilities.

  13. The promise of Lean in health care.

    Science.gov (United States)

    Toussaint, John S; Berry, Leonard L

    2013-01-01

    An urgent need in American health care is improving quality and efficiency while controlling costs. One promising management approach implemented by some leading health care institutions is Lean, a quality improvement philosophy and set of principles originated by the Toyota Motor Company. Health care cases reveal that Lean is as applicable in complex knowledge work as it is in assembly-line manufacturing. When well executed, Lean transforms how an organization works and creates an insatiable quest for improvement. In this article, we define Lean and present 6 principles that constitute the essential dynamic of Lean management: attitude of continuous improvement, value creation, unity of purpose, respect for front-line workers, visual tracking, and flexible regimentation. Health care case studies illustrate each principle. The goal of this article is to provide a template for health care leaders to use in considering the implementation of the Lean management system or in assessing the current state of implementation in their organizations. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  14. Hyperthermia: Clinical promise and current challenges

    International Nuclear Information System (INIS)

    Kapp, D.S.

    1987-01-01

    Local-regional hyperthermia (HT) when used in conjunction with radiation therapy (XRT), has been shown in numerous clinical trials to result in considerable improvement in response rates and local tumor control rates when compared with treatment by XRT alone. Although considerable progress has been made in understanding the biological basis for hyperthermia induced cytotoxicity and radiosensitization, additional research remains in establishing the optimal treatment schedules for the clinical utilization of HT-XRT. The number of HT treatments; the sequencing of HT and XRT; the frequency of administration of HT; and the ideal temperature-time parameters all remain to be better defined for the clinical setting. The role of tumor blood flow on the thermal distributions also warrants further investigation. In addition, considerable effort is needed to improve hyperthermia equipment in order to provide more uniform therapeutic temperature distributions (temperatures ≥42.5%C). Better heating equipment is particularly needed for the treatment of deep seeted tumors. Pertinent clinical literature will be presented summarizing the clinical promise of hyperthermia and the above mentioned clinical challenges

  15. Uterine transplantation: a promising surrogate to surrogacy?

    Science.gov (United States)

    Grynberg, Michael; Ayoubi, Jean-Marc; Bulletti, Carlo; Frydman, Rene; Fanchin, Renato

    2011-03-01

    Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. © 2011 New York Academy of Sciences.

  16. Candida Biofilms: Threats, Challenges, and Promising Strategies

    Science.gov (United States)

    Cavalheiro, Mafalda; Teixeira, Miguel Cacho

    2018-01-01

    Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed. PMID:29487851

  17. Artificial Intelligence in Surgery: Promises and Perils.

    Science.gov (United States)

    Hashimoto, Daniel A; Rosman, Guy; Rus, Daniela; Meireles, Ozanan R

    2018-07-01

    The aim of this review was to summarize major topics in artificial intelligence (AI), including their applications and limitations in surgery. This paper reviews the key capabilities of AI to help surgeons understand and critically evaluate new AI applications and to contribute to new developments. AI is composed of various subfields that each provide potential solutions to clinical problems. Each of the core subfields of AI reviewed in this piece has also been used in other industries such as the autonomous car, social networks, and deep learning computers. A review of AI papers across computer science, statistics, and medical sources was conducted to identify key concepts and techniques within AI that are driving innovation across industries, including surgery. Limitations and challenges of working with AI were also reviewed. Four main subfields of AI were defined: (1) machine learning, (2) artificial neural networks, (3) natural language processing, and (4) computer vision. Their current and future applications to surgical practice were introduced, including big data analytics and clinical decision support systems. The implications of AI for surgeons and the role of surgeons in advancing the technology to optimize clinical effectiveness were discussed. Surgeons are well positioned to help integrate AI into modern practice. Surgeons should partner with data scientists to capture data across phases of care and to provide clinical context, for AI has the potential to revolutionize the way surgery is taught and practiced with the promise of a future optimized for the highest quality patient care.

  18. Candida Biofilms: Threats, Challenges, and Promising Strategies.

    Science.gov (United States)

    Cavalheiro, Mafalda; Teixeira, Miguel Cacho

    2018-01-01

    Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis , and Candida parapsilosis , highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

  19. Bioavailability of curcumin: problems and promises.

    Science.gov (United States)

    Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B

    2007-01-01

    Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

  20. A promising poison information centre model for Africa

    Directory of Open Access Journals (Sweden)

    Carine Marks

    2016-06-01

    Conclusion: A number of benefits might result from such a poisons centre network hub, including: (1 Improved cooperation between countries on poisoning problems; (2 Harmonisation and strengthening of research and surveillance; (3 Common standards and best practices e.g. regulating chemicals, data management, and staff training; and (4 Greater bargaining power to secure resources. Further investigation is needed to identify the most suitable location for the network hub, the activities it should fulfil, and the availability of specialists in poisons information who could become members of the hub.

  1. The promise of innovation: Nuclear energy horizons

    International Nuclear Information System (INIS)

    Mourogov, V.

    2003-01-01

    The 21st century promises the most open, competitive, and globalized markets in human history, as well as the most rapid pace of technological change ever. For nuclear energy, as any other, that presents challenges. Though the atom now supplies a good share of world electricity, its share of total energy is relatively small, anywhere from four to six per cent depending on how it is calculated. And, while energy is most needed in the developing world, four of every five nuclear plants are in industrialized countries. Critical problems that need to be overcome are well known - high capital costs for new plants, and concerns over proliferation risks and safety, (including safety of waste disposal) stand high among them. The IAEA and other programmes are confronting these problems through ambitious initiatives involving both industrialized and developing countries. They include the collaborative efforts known as the Generation-IV International Forum (GIF) and the IAEA International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). They use ideas, results and the best experiences from today's research and development tools and advanced types of nuclear energy systems to meet tomorrow's challenges. Though the market often decides the fate of new initiatives, the market is not always right for the common good. Governments, and the people that influence them, play an indispensable role in shaping progress in energy fields for rich and poor countries alike. They shoulder the main responsibilities for fundamental science, basic research, and long-term investments. For energy in particular, government investment and support will prove instrumental in the pace of innovation toward long-term options that are ready to replace limited fossil fuel supplies, and respond to the growing premium put on clean energy alternatives. Yet governments cannot go it alone. The challenges are too diverse and complex, and public concerns - about proliferation or safety - go beyond

  2. The epigenetic promise for prostate cancer diagnosis.

    Science.gov (United States)

    Van Neste, Leander; Herman, James G; Otto, Gaëtan; Bigley, Joseph W; Epstein, Jonathan I; Van Criekinge, Wim

    2012-08-01

    Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology. One gene in particular, GSTP1, has been widely studied in prostate cancer. Therefore a meta-analysis has been conducted to examine the role of this and other genes and the potential contribution to prostate cancer management and screening refinement. More than 30 independent, peer reviewed studies have reported a consistently high sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy tissue. The meta-analysis combined and compared these results. GSTP1 methylation detection can serve an important role in prostate cancer managment. The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of this and other genes and prostate cancer. Detection of DNA methylation in genes, including GSTP1, could serve an important role in clinical practice. Copyright © 2011 Wiley Periodicals, Inc.

  3. Candida Biofilms: Threats, Challenges, and Promising Strategies

    Directory of Open Access Journals (Sweden)

    Mafalda Cavalheiro

    2018-02-01

    Full Text Available Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

  4. Enantioselectivity of mass spectrometry: challenges and promises.

    Science.gov (United States)

    Awad, Hanan; El-Aneed, Anas

    2013-01-01

    With the fast growing market of pure enantiomer drugs and bioactive molecules, new chiral-selective analytical tools have been instigated including the use of mass spectrometry (MS). Even though MS is one of the best analytical tools that has efficiently been used in several pharmaceutical and biological applications, traditionally MS is considered as a "chiral-blind" technique. This limitation is due to the MS inability to differentiate between two enantiomers of a chiral molecule based merely on their masses. Several approaches have been explored to assess the potential role of MS in chiral analysis. The first approach depends on the use of MS-hyphenated techniques utilizing fast and sensitive chiral separation tools such as liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled to MS detector. More recently, several alternative separation techniques have been evaluated such as supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC); the latter being a hybrid technique that combines the efficiency of CE with the selectivity of LC. The second approach is based on using the MS instrument solely for the chiral recognition. This method depends on the behavioral differences between enantiomers towards a foreign molecule and the ability of MS to monitor such differences. These behavioral differences can be divided into three types: (i) differences in the enantiomeric affinity for association with the chiral selector, (ii) differences of the enantiomeric exchange rate with a foreign reagent, and (iii) differences in the complex MS dissociation behaviors of the enantiomers. Most recently, ion mobility spectrometry was introduced to qualitatively and quantitatively evaluate chiral compounds. This article provides an overview of MS role in chiral analysis by discussing MS based methodologies and presenting the challenges and promises associated with each approach. © 2013 Wiley Periodicals, Inc.

  5. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    International Nuclear Information System (INIS)

    Aurisicchio, Luigi; Ciliberto, Gennaro

    2011-01-01

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost

  6. Understanding retirement: the promise of life-span developmental frameworks.

    Science.gov (United States)

    Löckenhoff, Corinna E

    2012-09-01

    The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

  7. Agent-Based Computing: Promise and Perils

    OpenAIRE

    Jennings, N. R.

    1999-01-01

    Agent-based computing represents an exciting new synthesis both for Artificial Intelligence (AI) and, more genrally, Computer Science. It has the potential to significantly improve the theory and practice of modelling, designing and implementing complex systems. Yet, to date, there has been little systematic analysis of what makes an agent such an appealing and powerful conceptual model. Moreover, even less effort has been devoted to exploring the inherent disadvantages that stem from adoptin...

  8. The flinders sensitive line rats, a genetic model of depression, show abnormal serotonin receptor mRNA expression in the brain that is reversed by 17beta-estradiol.

    Science.gov (United States)

    Osterlund, M K; Overstreet, D H; Hurd, Y L

    1999-12-10

    The possible link between estrogen and serotonin (5-HT) in depression was investigated using a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats, in comparison to control Flinders Resistant Line rats. The mRNA levels of the estrogen receptor (ER) alpha and beta subtypes and the 5-HT(1A) and 5-HT(2A) receptors were analyzed in several limbic-related areas of ovariectomized FSL and FRL rats treated with 17beta-estradiol (0.15 microg/g) or vehicle. The FSL animals were shown to express significantly lower levels of the 5-HT(2A) receptor transcripts in the perirhinal cortex, piriform cortex, and medial anterodorsal amygdala and higher levels in the CA 2-3 region of the hippocampus. The only significant difference between the rat lines in ER mRNA expression was found in the medial posterodorsal amygdala, where the FSL rats showed lower ERalpha expression levels. Overall, estradiol treatment increased 5-HT(2A) and decreased 5-HT(1A) receptor mRNA levels in several of the examined regions of both lines. Thus, in many areas, estradiol was found to regulate the 5-HT receptor mRNA expression in the opposite direction to the alterations found in the FSL rats. These findings further support the implication of 5-HT receptors, in particular the 5-HT(2A) subtype, in the etiology of affective disorders. Moreover, the ability of estradiol to regulate the expression of the 5-HT(1A) and 5-HT(2A) receptor genes might account for the reported influence of gonadal hormones in mood and depression.

  9. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    Science.gov (United States)

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Pre-Assessment: Promises and Cautions

    Science.gov (United States)

    Guskey, Thomas R.; McTighe, Jay

    2016-01-01

    Nearly every modern instructional planning model, differentiation approach, and personalized learning system incorporates some form of re-assessment. Yet there's scant research evidence that teachers use pre-assessment in ways that improve learning, according to Guskey and McTighe. To increase the likelihood that pre-assessment will be worth the…

  11. Client/Server Architecture Promises Radical Changes.

    Science.gov (United States)

    Freeman, Grey; York, Jerry

    1991-01-01

    This article discusses the emergence of the client/server paradigm for the delivery of computer applications, its emergence in response to the proliferation of microcomputers and local area networks, the applicability of the model in academic institutions, and its implications for college campus information technology organizations. (Author/DB)

  12. Restructuring Schools: Promising Practices and Policies.

    Science.gov (United States)

    Hallinan, Maureen T., Ed.

    Chapters in this book focus on a wide array of educational issues that command attention at the end of the 20th century. Various aspects of contemporary schooling are explored, and models of school organization and functioning are proposed in the following chapters: (1) "Achievement-Oriented School Design" (James S. Coleman); (2)…

  13. Stem cell therapy: the great promise in lung disease.

    Science.gov (United States)

    Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno

    2008-06-01

    Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.

  14. Problems, challenges and promises: perspectives on precision medicine.

    Science.gov (United States)

    Duffy, David J

    2016-05-01

    The 'precision medicine (systems medicine)' concept promises to achieve a shift to future healthcare systems with a more proactive and predictive approach to medicine, where the emphasis is on disease prevention rather than the treatment of symptoms. The individualization of treatment for each patient will be at the centre of this approach, with all of a patient's medical data being computationally integrated and accessible. Precision medicine is being rapidly embraced by biomedical researchers, pioneering clinicians and scientific funding programmes in both the European Union (EU) and USA. Precision medicine is a key component of both Horizon 2020 (the EU Framework Programme for Research and Innovation) and the White House's Precision Medicine Initiative. Precision medicine promises to revolutionize patient care and treatment decisions. However, the participants in precision medicine are faced with a considerable central challenge. Greater volumes of data from a wider variety of sources are being generated and analysed than ever before; yet, this heterogeneous information must be integrated and incorporated into personalized predictive models, the output of which must be intelligible to non-computationally trained clinicians. Drawing primarily from the field of 'oncology', this article will introduce key concepts and challenges of precision medicine and some of the approaches currently being implemented to overcome these challenges. Finally, this article also covers the criticisms of precision medicine overpromising on its potential to transform patient care. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. The NPT regime: Progress and promises

    International Nuclear Information System (INIS)

    Dhanapala, Jayantha

    2001-01-01

    Full text: Thesis. The 'NPT regime' has arrived at a fateful crossroads. Though extended indefinitely in 1995, its future is my no means secure. The future 'progress' of this treaty will depend upon whether the 'promises' of its States parties are fully implemented and, eventually, upon the treaty's success in achieving fully universal membership. Challenges The treaty faces many short-term and longer-term challenges: Short term - The first Preparatory Committee meeting for the 2005 Review Conference will meet next year. NNWS will want to see some evidence of progress on nuclear disarmament (Art. VI), along the lines prescribed in the 13 'practical steps' agreed at the last Review Conference. Yet progress has been set back by: uncertainties over the future of the ABM Treaty; the failure of START II and the CTBT to enter into force; the lack of a FISMAT treaty and a treaty establishing a NWFZ in Central Asia; continued qualitative improvements in nuclear weapons; hints that nuclear testing may one day resume; the persistence of doctrines of first-use, pre-emptive use, and use against states that use CBW. Other compliance-related questions will arise over safeguards (e.g. the inability of the IAEA to conduct inspections in the DPRK; signs of a breakdown of the norm of full-scope IAEA safeguards, e.g. in South Asia). There are also concerns over the implementation of non-proliferation commitments (e.g. persisting allegations about nuclear weapon programmes in existing NNWS). The terrorist attacks in New York and Washington, D.C. on 11 September should also serve as a reminder of the new terrorist dangers relating to the possible use of weapons of mass destruction and unorthodox delivery systems. Longer term - Selectivity in the enforcement of NPT norms; unilateralism; IAEA funding uncertainties and shortfalls; difficulties in reaching universal membership (India, Pakistan, and Israel); continuing compliance problems with respect to both non-proliferation and

  16. The Promise of a College Scholarship Transforms a District

    Science.gov (United States)

    Ritter, Gary W.; Ash, Jennifer

    2016-01-01

    Promise programs are place-based scholarships, generally tied to a city or school district, offering near-universal access to all living in the "place." While Promise programs share some characteristics with other scholarship programs, they're unique because they seek to change communities and schools. Underlying such promise programs is…

  17. Rose garden promises of intelligent tutoring systems: Blossom or thorn

    Science.gov (United States)

    Shute, Valerie J.

    1991-01-01

    Intelligent tutoring systems (ITS) have been in existence for over a decade. However, few controlled evaluation studies have been conducted comparing the effectiveness of these systems to more traditional instruction methods. Two main promises of ITSs are examined: (1) Engender more effective and efficient learning in relation to traditional formats; and (2) Reduce the range of learning outcome measures where a majority of individuals are elevated to high performance levels. Bloom (1984) has referred to these as the two sigma problem; to achieve two standard deviation improvements with tutoring over traditional instruction methods. Four ITSs are discussed in relation to the two promises. These tutors have undergone systematic, controlled evaluations: (1) The LISP tutor (Anderson Farrell and Sauers, 1984); (2) Smithtown (Shute and Glaser, in press); (3) Sherlock (Lesgold, Lajoie, Bunzo and Eggan, 1990); and (4) The Pascal ITS (Bonar, Cunningham, Beatty and Well, 1988). Results show that these four tutors do accelerate learning with no degradation in final outcome. Suggestions for improvements to the design and evaluation of ITSs are discussed.

  18. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

    Science.gov (United States)

    Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

    2018-01-01

    Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

  19. Duplex-imprinted nano well arrays for promising nanoparticle assembly

    Science.gov (United States)

    Li, Xiangping; Manz, Andreas

    2018-02-01

    A large area nano-duplex-imprint technique is presented in this contribution using natural cicada wings as stamps. The glassy wings of the cicada, which are abundant in nature, exhibit strikingly interesting nanopillar structures over their membrane. This technique, with excellent performance despite the nonplanar surface of the wings, combines both top-down and bottom-up nanofabrication techniques. It transitions micro-nanofabrication from a cleanroom environment to the bench. Two different materials, dicing tape with an acrylic layer and a UV optical adhesive, are used to make replications at the same time, thus achieving duplex imprinting. The promise of a large volume of commercial manufacturing of these nanostructure elements can be envisaged through this contribution to speeding up the fabrication process and achieving a higher throughput. The contact angle of the replicated nanowell arrays before and after oxygen plasma was measured. Gold nanoparticles (50 nm) were used to test how the nanoparticles behaved on the untreated and plasma-treated replica surface. The experiments show that promising nanoparticle self-assembly can be obtained.

  20. Lactoferrin and prematurity: a promising milk protein?

    Science.gov (United States)

    Ochoa, Theresa J; Sizonenko, Stéphane V

    2017-02-01

    Lactoferrin (Lf) is the major whey protein in milk, with multiple beneficial health effects including direct antimicrobial activities, anti-inflammatory effects, and iron homeostasis. Oral Lf supplementation in human preterm infants has been shown to reduce the incidence of sepsis and necrotizing enterocolitis. In preclinical models of antenatal stress and perinatal brain injury, bovine Lf protected the developing brain from neuronal loss, improved connectivity, increased neurotrophic factors, and decreased inflammation. It also supported brain development and cognition. Further, Lf can prevent preterm delivery by reducing proinflammatory factors and inhibiting premature cervix maturation. We review here the latest research on Lf in the field of neonatology.

  1. The role of entry into regional markets in fulfilling brand promise

    Directory of Open Access Journals (Sweden)

    Ali Ghasemi

    2014-12-01

    Full Text Available This paper presents an empirical investigation to study the role of entry into regional markets in fulfilling brand promise. The study designs two questionnaires, one for measuring brand promise and the other for measuring export capabilities, in Likert scale and distributes it among 250 randomly selected producers who were involved in production and development of various products in city of Esfahan, Iran. Cronbach alphas were calculated for brand promise and export capabilities as 0.856 and 0.812, respectively. Using structural equation modeling, the study has detected seven factors including product development, public advocacy, strategic orientation, customer satisfaction, competitive pressures, organizational capabilities and distribution strategies.

  2. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    Science.gov (United States)

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings.

  3. Expedited remedial action -- A promising opportunity at your doorstep

    Energy Technology Data Exchange (ETDEWEB)

    Newman, E.R.

    1996-12-31

    The Expedited Remedial Action Program or ERAP carries great promise and is limited to no more than 30 sites, there are a number of slots now available, and the legislature will soon be considering a reauthorization of the full state Superfund program, which expires in June 1998, to reportedly be based to a great extent on the ERAP model. The ERAP provides for: (1) The early identification of fair and equitable shares of liability, including an orphan share, where appropriate, to be paid by the state; (2) The elimination of all joint and several liability; (3) Cleanup levels and remedies based on the foreseeable planned use of the site; (4) Site specific risk assessments based on the latest risk assessment protocols; (5) Use of an arbitrator to quickly resolve all significant liability and technical disputes; and (6) Broad and timely releases from future liability upon completion of cleanup.

  4. Multivariate meta-analysis: Potential and promise

    Science.gov (United States)

    Jackson, Dan; Riley, Richard; White, Ian R

    2011-01-01

    The multivariate random effects model is a generalization of the standard univariate model. Multivariate meta-analysis is becoming more commonly used and the techniques and related computer software, although continually under development, are now in place. In order to raise awareness of the multivariate methods, and discuss their advantages and disadvantages, we organized a one day ‘Multivariate meta-analysis’ event at the Royal Statistical Society. In addition to disseminating the most recent developments, we also received an abundance of comments, concerns, insights, critiques and encouragement. This article provides a balanced account of the day's discourse. By giving others the opportunity to respond to our assessment, we hope to ensure that the various view points and opinions are aired before multivariate meta-analysis simply becomes another widely used de facto method without any proper consideration of it by the medical statistics community. We describe the areas of application that multivariate meta-analysis has found, the methods available, the difficulties typically encountered and the arguments for and against the multivariate methods, using four representative but contrasting examples. We conclude that the multivariate methods can be useful, and in particular can provide estimates with better statistical properties, but also that these benefits come at the price of making more assumptions which do not result in better inference in every case. Although there is evidence that multivariate meta-analysis has considerable potential, it must be even more carefully applied than its univariate counterpart in practice. Copyright © 2011 John Wiley & Sons, Ltd. PMID:21268052

  5. Vote Buying or Campaign Promises? Electoral Strategies When Party Credibility is Limited

    OpenAIRE

    Hanusch, Marek; Keefer, Philip; Vlaicu, Razvan

    2016-01-01

    What explains significant variation across countries in the use of vote buying instead of campaign promises to secure voter support? This paper explicitly models the tradeoff parties face between engaging in vote buying and making campaign promises, and explores the distributional consequences of this decision, in a setting where party credibility can vary. When parties are less credible they spend more on vote buying and target vote buying more heavily toward groups that do not believe campa...

  6. Nanomedicine: Perspective and promises with ligand-directed molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pan Dipanjan [Department of Medicine, Washington University Medical School, St. Louis, MO (United States)], E-mail: dipanjan@wustl.edu; Lanza, Gregory M.; Wickline, Samuel A. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Caruthers, Shelton D. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Philips Healthcare, Andover, MA (United States)], E-mail: scaruthers@cmrl.wustl.edu

    2009-05-15

    Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

  7. The Promise of Neuroprotective Agents in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Judith ePotashkin

    2011-11-01

    Full Text Available Parkinson’s Disease is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.

  8. The Sociological Imagination and Its Promise Fifty Years Later

    Directory of Open Access Journals (Sweden)

    Carlos Frade

    2009-11-01

    Full Text Available This paper offers a restatement of Wright Mills’ The Sociological Imagination and tries to judge whether its promise can be credibly renewed today by addressing the question about the present and future possibilities of the social sciences as free forms of enquiry. Relying on Weber, Mills and other thinkers, the paper sustains that the possibilities for a truly free social science essentially depend on three major ‘conditions’: the subjective stance or vocation, the sociological imagination proper, and an independent social science politics, conditions whose apt names can also be ‘love’, ‘insight’ and ‘courage’. An analysis of the presence and strength of each of these conditions in contemporary social science and in academia shows the magnitude of the task faced for the existence of a free social science.

  9. Nanomedicine: Perspective and promises with ligand-directed molecular imaging

    International Nuclear Information System (INIS)

    Pan Dipanjan; Lanza, Gregory M.; Wickline, Samuel A.; Caruthers, Shelton D.

    2009-01-01

    Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

  10. Metformin: A Hopeful Promise in Aging Research

    Science.gov (United States)

    Novelle, Marta G.; Ali, Ahmed; Diéguez, Carlos; Bernier, Michel; de Cabo, Rafael

    2016-01-01

    Even though the inevitable process of aging by itself cannot be considered a disease, it is directly linked to life span and is the driving force behind all age-related diseases. It is an undisputable fact that age-associated diseases are among the leading causes of death in the world, primarily in industrialized countries. During the last several years, an intensive search of antiaging treatments has led to the discovery of a variety of drugs that promote health span and/or life extension. The biguanide compound metformin is widely used for treating people with type 2 diabetes and appears to show protection against cancer, inflammation, and age-related pathologies. Here, we summarize the recent developments about metformin use in translational aging research and discuss its role as a potential geroprotector. PMID:26931809

  11. Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity.

    Directory of Open Access Journals (Sweden)

    Vijee Mohan

    Full Text Available Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS, carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1 involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima'D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future.

  12. Nursing Education Transformation: Promising Practices in Academic Progression.

    Science.gov (United States)

    Gorski, Mary Sue; Farmer, Patricia D; Sroczynski, Maureen; Close, Liz; Wortock, Jean M

    2015-09-01

    Health care has changed over the past decade; yet, nursing education has not kept pace with social and scientific advances. The Institute of Medicine report, The Future of Nursing: Leading Change, Advancing Health, called for a more highly educated nursing work-force and an improved nursing education system. Since the release of that report, the Future of Nursing: Campaign for Action, supported by the Robert Wood Johnson Foundation, AARP, and the AARP Foundation, has worked with nursing education leaders to better understand existing and evolving nursing education structures. Through a consensus-building process, four overarching promising practice models, with an emphasis on seamless academic progression, emerged to advance the goals of education transformation. Key nurse educators and other stakeholders refined those models through a series of meetings, collaborative partnerships, and focused projects that were held across the United States. This article summarizes that process and provides a description of the models, challenges, common themes, recommendations, and progress to date. Copyright 2015, SLACK Incorporated.

  13. Lean in healthcare: the unfilled promise?

    Science.gov (United States)

    Radnor, Zoe J; Holweg, Matthias; Waring, Justin

    2012-02-01

    In an effort to improve operational efficiency, healthcare services around the world have adopted process improvement methodologies from the manufacturing sector, such as Lean Production. In this paper we report on four multi-level case studies of the implementation of Lean in the English NHS. Our results show that this generally involves the application of specific Lean 'tools', such as 'kaizen blitz' and 'rapid improvement events', which tend to produce small-scale and localised productivity gains. Although this suggests that Lean might not currently deliver the efficiency improvements desired in policy, the evolution of Lean in the manufacturing sector also reveals this initial focus on the 'tool level'. In moving to a more system-wide approach, however, we identify significant contextual differences between healthcare and manufacturing that result in two critical breaches of the assumptions behind Lean. First, the customer and commissioner in the private sector are the one and the same, which is essential in determining 'customer value' that drives process improvement activities. Second, healthcare is predominantly designed to be capacity-led, and hence there is limited ability to influence demand or make full use of freed-up resources. What is different about this research is that these breaches can be regarded as not being primarily 'professional' in origin but actually more 'organisational' and 'managerial' and, if not addressed could severely constrain Lean's impact on healthcare productivity at the systems level. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Geoffroea decorticans for Biofuels: A Promising Feedstock

    Directory of Open Access Journals (Sweden)

    Claudia Santibáñez

    2017-01-01

    Full Text Available In this work, chañar (Geoffroea decorticans fruit is evaluated as a potential feedstock for biodiesel and biomass pellets production with reference to some relevant properties. The fatty acid profile of this oil (83% unsaturated acids is found to be comparable to similar seed oils which have been attempted for biodiesel production. As a result, the methyl esters (biodiesel obtained from this oil exhibits high quality properties. Chañar biodiesel quality meets all other biodiesel international standards (ASTM D6751 and EN 14214. Moreover, the husk that surrounds the kernel showed a high potential for usage as densified solid fuels. The results demonstrate that chañar husks pellets have a higher calorific value when compared with other biomass pellets, typically, approximately 21 MJ kg−1 with 1.8% of ashes (which is equivalent to that obtained from the combustion of pellets produced from forest wastes. This study indicates that chañar can be used as a multipurpose energy crop in semiarid regions for biodiesel and densified solid fuels (pellets production.

  15. Commercialization of IGCC technology looks promising

    International Nuclear Information System (INIS)

    Smith, D.J.

    1992-01-01

    This paper reports that a major focus of the latest round of the U.S. Department of Energy's Clean Coal Technology Program was three large-scale, high-efficiency electricity generating projects which will rely on coal gasification rather than burning the coal directly. The three projects are: Toms Creek integrated gasification combined-cycle (IGCC) demonstration project. The aim of the project is to demonstrate improved coal-to-power efficiencies in an integrated gasification combined-cycle process. According to the DOE, the Toms Creek project will show that significant reductions in SO 2 and NO x emissions can be accomplished through the use of IGCC technology. On completion of the project, 107 MW of electric capacity will be added to the grid. Pinon Pine IGCC power project. The project's aim is to demonstrate that IGCC plants can be constructed at significantly lower capital costs, and with higher thermal efficiencies, than conventional power generation technologies. It will also demonstrate the effectiveness of hot gas cleanup for low-sulfur western coals. Wasbash River coal gasification repowering project

  16. Cinnamon, a promising prospect towards Alzheimer's disease.

    Science.gov (United States)

    Momtaz, Saeideh; Hassani, Shokoufeh; Khan, Fazlullah; Ziaee, Mojtaba; Abdollahi, Mohammad

    2018-04-01

    Over the last decades, an exponential increase of efforts concerning the treatment of Alzheimer's disease (AD) has been practiced. Phytochemicals preparations have a millenary background to combat various pathological conditions. Various cinnamon species and their biologically active ingredients have renewed the interest towards the treatment of patients with mild-to-moderate AD through the inhibition of tau protein aggregation and prevention of the formation and accumulation of amyloid-β peptides into the neurotoxic oligomeric inclusions, both of which are considered to be the AD trademarks. In this review, we presented comprehensive data on the interactions of a number of cinnamon polyphenols (PPs) with oxidative stress and pro-inflammatory signaling pathways in the brain. In addition, we discussed the potential association between AD and diabetes mellitus (DM), vis-à-vis the effluence of cinnamon PPs. Further, an upcoming prospect of AD epigenetic pathophysiological conditions and cinnamon has been sighted. Data was retrieved from the scientific databases such as PubMed database of the National Library of Medicine, Scopus and Google Scholar without any time limitation. The extract of cinnamon efficiently inhibits tau accumulations, Aβ aggregation and toxicity in vivo and in vitro models. Indeed, cinnamon possesses neuroprotective effects interfering multiple oxidative stress and pro-inflammatory pathways. Besides, cinnamon modulates endothelial functions and attenuates the vascular cell adhesion molecules. Cinnamon PPs may induce AD epigenetic modifications. Cinnamon and in particular, cinnamaldehyde seem to be effective and safe approaches for treatment and prevention of AD onset and/or progression. However, further molecular and translational research studies as well as prolonged clinical trials are required to establish the therapeutic safety and efficacy in different cinnamon spp. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Promising new developments in cancer chemotherapy.

    Science.gov (United States)

    Ferrante, K; Winograd, B; Canetta, R

    1999-01-01

    attractive target for intervention in several aspects of tumor progression. Local production of MMPs with subsequent degradation of the extracellular matrix is implicated in supporting tumor growth, invasion, and angiogenesis. The development of orally active, nontoxic MMP inhibitors is critical since these compounds will likely require chronic administration in conjunction with other therapies. Oncogenes and tumor suppressor genes are appealing targets for therapy since they are thought to be responsible for a significant number of cancers. Mutations in the Ras oncogene occur with great frequency in a number of human cancers including lung, pancreas, and colon cancer. Clinical development of potent and selective inhibitors of farnesyltransferase, the Ras-processing enzyme, is ongoing. These compounds uncouple Ras activity, affect tumor growth, and have demonstrated significant antitumor activity against experimental models of human cancer. The exciting compounds and novel therapeutic approaches currently under investigation by Bristol-Myers Squibb Pharmaceutical Research Institute offer great potential as effective cancer chemotherapy agents for the near future.

  18. A promising hybrid approach to SPECT attenuation correction

    International Nuclear Information System (INIS)

    Lewis, N.H.; Faber, T.L.; Corbett, J.R.; Stokely, E.M.

    1984-01-01

    Most methods for attenuation compensation in SPECT either rely on the assumption of uniform attenuation, or use slow iteration to achieve accuracy. However, hybrid methods that combine iteration with simple multiplicative correction can accommodate nonuniform attenuation, and such methods converge faster than other iterative techniques. The authors evaluated two such methods, which differ in use of a damping factor to control convergence. Both uniform and nonuniform attenuation were modeled, using simulated and phantom data for a rotating gamma camera. For simulations done with 360 0 data and the correct attenuation map, activity levels were reconstructed to within 5% of the correct values after one iteration. Using 180 0 data, reconstructed levels in regions representing lesion and background were within 5% of the correct values in three iterations; however, further iterations were needed to eliminate the characteristic streak artifacts. The damping factor had little effect on 360 0 reconstruction, but was needed for convergence with 180 0 data. For both cold- and hot-lesion models, image contrast was better from the hybrid methods than from the simpler geometric-mean corrector. Results from the hybrid methods were comparable to those obtained using the conjugate-gradient iterative method, but required 50-100% less reconstruction time. The relative speed of the hybrid methods, and their accuracy in reconstructing photon activity in the presence of nonuniform attenuation, make them promising tools for quantitative SPECT reconstruction

  19. Local and global trust based on the concept of promises

    NARCIS (Netherlands)

    Bergstra, J.; Burgess, M.

    2009-01-01

    We use the notion of a promise to define local trust between agents possessing autonomous decision-making. An agent is trustworthy if it is expected that it will keep a promise. This definition satisfies most commonplace meanings of trust. Reputation is then an estimation of this expectation value

  20. The pragmatics of NPP presidential campaign promises in Ghana's ...

    African Journals Online (AJOL)

    The paper discusses election campaign promises under Commissives, an aspect of Speech Act Theory, and Political Discourse Analysis (PDA). It considers the importance of context and looks at the social settings that are connected with promises. It examines the semantics, pragmatics and the structure of campaign ...

  1. Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy.

    Science.gov (United States)

    Redler, Gage; Jones, Kevin C; Templeton, Alistair; Bernard, Damian; Turian, Julius; Chu, James C H

    2018-03-01

    Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance. © 2018 American Association of Physicists in Medicine.

  2. Can metabotyping help deliver the promise of personalised nutrition?

    Science.gov (United States)

    O'Donovan, Clare B; Walsh, Marianne C; Gibney, Michael J; Gibney, Eileen R; Brennan, Lorraine

    2016-02-01

    Over a decade since the completion of the human genome sequence, the promise of personalised nutrition available to all has yet to become a reality. While the definition was originally very gene-focused, in recent years, a model of personalised nutrition has emerged with the incorporation of dietary, phenotypic and genotypic information at various levels. Developing on from the idea of personalised nutrition, the concept of targeted nutrition has evolved which refers to the delivery of tailored dietary advice at a group level rather than at an individual level. Central to this concept is metabotyping or metabolic phenotyping, which is the ability to group similar individuals together based on their metabolic or phenotypic profiles. Applications of the metabotyping concept extend from the nutrition to the medical literature. While there are many examples of the metabotype approach, there is a dearth in the literature with regard to the development of tailored interventions for groups of individuals. This review will first explore the effectiveness of personalised nutrition in motivating behaviour change and secondly, examine potential novel ways for the delivery of personalised advice at a population level through a metabotyping approach. Based on recent findings from our work, we will demonstrate a novel strategy for the delivery of tailored dietary advice at a group level using this concept. In general, there is a strong emerging evidence to support the effectiveness of personalised nutrition; future work should ascertain if targeted nutrition can motivate behaviour change in a similar manner.

  3. Prediction-Oriented Marker Selection (PROMISE): With Application to High-Dimensional Regression.

    Science.gov (United States)

    Kim, Soyeon; Baladandayuthapani, Veerabhadran; Lee, J Jack

    2017-06-01

    In personalized medicine, biomarkers are used to select therapies with the highest likelihood of success based on an individual patient's biomarker/genomic profile. Two goals are to choose important biomarkers that accurately predict treatment outcomes and to cull unimportant biomarkers to reduce the cost of biological and clinical verifications. These goals are challenging due to the high dimensionality of genomic data. Variable selection methods based on penalized regression (e.g., the lasso and elastic net) have yielded promising results. However, selecting the right amount of penalization is critical to simultaneously achieving these two goals. Standard approaches based on cross-validation (CV) typically provide high prediction accuracy with high true positive rates but at the cost of too many false positives. Alternatively, stability selection (SS) controls the number of false positives, but at the cost of yielding too few true positives. To circumvent these issues, we propose prediction-oriented marker selection (PROMISE), which combines SS with CV to conflate the advantages of both methods. Our application of PROMISE with the lasso and elastic net in data analysis shows that, compared to CV, PROMISE produces sparse solutions, few false positives, and small type I + type II error, and maintains good prediction accuracy, with a marginal decrease in the true positive rates. Compared to SS, PROMISE offers better prediction accuracy and true positive rates. In summary, PROMISE can be applied in many fields to select regularization parameters when the goals are to minimize false positives and maximize prediction accuracy.

  4. Quantifying Neonatal Sucking Performance: Promise of New Methods.

    Science.gov (United States)

    Capilouto, Gilson J; Cunningham, Tommy J; Mullineaux, David R; Tamilia, Eleonora; Papadelis, Christos; Giannone, Peter J

    2017-04-01

    Neonatal feeding has been traditionally understudied so guidelines and evidence-based support for common feeding practices are limited. A major contributing factor to the paucity of evidence-based practice in this area has been the lack of simple-to-use, low-cost tools for monitoring sucking performance. We describe new methods for quantifying neonatal sucking performance that hold significant clinical and research promise. We present early results from an ongoing study investigating neonatal sucking as a marker of risk for adverse neurodevelopmental outcomes. We include quantitative measures of sucking performance to better understand how movement variability evolves during skill acquisition. Results showed the coefficient of variation of suck duration was significantly different between preterm neonates at high risk for developmental concerns (HRPT) and preterm neonates at low risk for developmental concerns (LRPT). For HRPT, results indicated the coefficient of variation of suck smoothness increased from initial feeding to discharge and remained significantly greater than healthy full-term newborns (FT) at discharge. There was no significant difference in our measures between FT and LRPT at discharge. Our findings highlight the need to include neonatal sucking assessment as part of routine clinical care in order to capture the relative risk of adverse neurodevelopmental outcomes at discharge. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. The promise of N-acetylcysteine in neuropsychiatry.

    Science.gov (United States)

    Berk, Michael; Malhi, Gin S; Gray, Laura J; Dean, Olivia M

    2013-03-01

    N-Acetylcysteine (NAC) targets a diverse array of factors germane to the pathophysiology of multiple neuropsychiatric disorders including glutamatergic transmission, the antioxidant glutathione, neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways. This review summarises the areas where the mechanisms of action of NAC overlap with known pathophysiological elements, and offers a précis of current literature regarding the use of NAC in disorders including cocaine, cannabis, and smoking addictions, Alzheimer's and Parkinson's diseases, autism, compulsive and grooming disorders, schizophrenia, depression, and bipolar disorder. There are positive trials of NAC in all these disorders, and although many of these require replication and are methodologically preliminary, this makes it one of the most promising drug candidates in neuropsychiatric disorders. The efficacy pattern of NAC interestingly shows little respect for the current diagnostic systems. Its benign tolerability profile, its action on multiple operative pathways, and the emergence of positive trial data make it an important target to investigate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Polyphenols as Promising Drugs against Main Breast Cancer Signatures

    Directory of Open Access Journals (Sweden)

    María Losada-Echeberría

    2017-11-01

    Full Text Available Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs and epidermal growth factor receptor 2 (HER2. Tumors with none of these receptors are classified as triple negative breast cancer (TNBC and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation.

  7. Plants’ Natural Products as Alternative Promising Anti-Candida Drugs

    Science.gov (United States)

    Soliman, Sameh; Alnajdy, Dina; El-Keblawy, Ali A.; Mosa, Kareem A.; Khoder, Ghalia; Noreddin, Ayman M.

    2017-01-01

    Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID:28989245

  8. Polyphenols as Promising Drugs against Main Breast Cancer Signatures

    Science.gov (United States)

    Herranz-López, María; Micol, Vicente

    2017-01-01

    Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs) and epidermal growth factor receptor 2 (HER2). Tumors with none of these receptors are classified as triple negative breast cancer (TNBC) and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation. PMID:29112149

  9. Albendazole as a promising molecule for tumor control.

    Science.gov (United States)

    Castro, L S E P W; Kviecinski, M R; Ourique, F; Parisotto, E B; Grinevicius, V M A S; Correia, J F G; Wilhelm Filho, D; Pedrosa, R C

    2016-12-01

    This work evaluated the antitumor effects of albendazole (ABZ) and its relationship with modulation of oxidative stress and induction of DNA damage. The present results showed that ABZ causes oxidative cleavage on calf-thymus DNA suggesting that this compound can break DNA. ABZ treatment decreased MCF-7 cell viability (EC 50 =44.9 for 24h) and inhibited MCF-7 colony formation (~67.5% at 5μM). Intracellular ROS levels increased with ABZ treatment (~123%). The antioxidant NAC is able to revert the cytotoxic effects, ROS generation and loss of mitochondrial membrane potential of MCF-7 cells treated with ABZ. Ehrlich carcinoma growth was inhibited (~32%) and survival time was elongated (~50%) in animals treated with ABZ. Oxidative biomarkers (TBARS and protein carbonyl levels) and activity of antioxidant enzymes (CAT, SOD and GR) increased, and reduced glutathione (GSH) was depleted in animals treated with ABZ, indicating an oxidative stress condition, leading to a DNA damage causing phosphorylation of histone H2A variant, H2AX, and triggering apoptosis signaling, which was confirmed by increasing Bax/Bcl-xL rate, p53 and Bax expression. We propose that ABZ induces oxidative stress promoting DNA fragmentation and triggering apoptosis and inducing cell death, making this drug a promising leader molecule for development of new antitumor drugs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Gravitational-wave astronomy: delivering on the promises

    Science.gov (United States)

    Schutz, B. F.

    2018-05-01

    Now that LIGO and Virgo have begun to detect gravitational-wave events with regularity, the field of gravitational-wave astronomy is beginning to realize its promise. Binary black holes and, very recently, binary neutron stars have been observed, and we are already learning much from them. The future, with improved sensitivity, more detectors and detectors like LISA in different frequency bands, has even more promise to open a completely hidden side of the Universe to our exploration. This article is part of a discussion meeting issue `The promises of gravitational-wave astronomy'.

  11. Gravitational-wave astronomy: delivering on the promises.

    Science.gov (United States)

    Schutz, B F

    2018-05-28

    Now that LIGO and Virgo have begun to detect gravitational-wave events with regularity, the field of gravitational-wave astronomy is beginning to realize its promise. Binary black holes and, very recently, binary neutron stars have been observed, and we are already learning much from them. The future, with improved sensitivity, more detectors and detectors like LISA in different frequency bands, has even more promise to open a completely hidden side of the Universe to our exploration.This article is part of a discussion meeting issue 'The promises of gravitational-wave astronomy'. © 2018 The Author(s).

  12. Understanding the promises and premises of online health platforms

    Directory of Open Access Journals (Sweden)

    José Van Dijck

    2016-06-01

    Full Text Available This article investigates the claims and complexities involved in the platform-based economics of health and fitness apps. We examine a double-edged logic inscribed in these platforms, promising to offer personal solutions to medical problems while also contributing to the public good. On the one hand, online platforms serve as personalized data-driven services to their customers. On the other hand, they allegedly serve public interests, such as medical research or health education. In doing so, many apps employ a diffuse discourse, hinging on terms like “sharing,” “open,” and “reuse” when they talk about data extraction and distribution. The analytical approach we adopt in this article is situated at the nexus of science and technology studies, political economy, and the sociology of health and illness. The analysis concentrates on two aspects: datafication (the use and reuse of data and commodification (a platform’s deployment of governance and business models. We apply these analytical categories to three specific platforms: 23andMe, PatientsLikeMe, and Parkinson mPower. The last section will connect these individual examples to the wider implications of health apps’ data flows, governance policies, and business models. Regulatory bodies commonly focus on the (medical safety and security of apps, but pay scarce attention to health apps’ techno-economic governance. Who owns user-generated health data and who gets to benefit? We argue that it is important to reflect on the societal implications of health data markets. Governments have the duty to provide conceptual clarity in the grand narrative of transforming health care and health research.

  13. Hydrogen storage in Mg: a most promising material

    International Nuclear Information System (INIS)

    Jain, I.P.; Jain, A.; Lal, C.

    2009-01-01

    In the last one decade hydrogen has attracted worldwide interest as an energy carrier. This has generated comprehensive investigations on the technology involved and how to solve the problems of production, storage and applications of hydrogen. The interest in hydrogen as energy of the future is due to it being a clean energy, most abundant element in the universe, the lightest fuel and richest in energy per unit mass. Hydrogen as a fuel can be used to cook food, drive cars, jet planes, run factories and for all our domestic energy requirements. It can provide cheap electricity. In short, hydrogen shows the solution and also allows the progressive and non-traumatic transition of today's energy sources, towards feasible safe reliable and complete sustainable energy chains. The present article deals with the hydrogen storage in metal hydrides with particular interest in Mg as it has potential to become one of the most promising storage materials. Many metals combine chemically with Hydrogen to form a class of compounds known as Hydrides. These hydrides can discharge hydrogen as and when needed by raising their temperature or pressure. An optimum hydrogen-storage material is required to have various properties viz. high hydrogen capacity per unit mass and unit volume which determines the amount of available energy, low dissociation temperature, moderate dissociation pressure, low heat of formation in order to minimize the energy necessary for hydrogen release, low heat dissipation during the exothermic hydride formation, reversibility, limited energy loss during charge and discharge of hydrogen, fast kinetics, high stability against O 2 and moisture for long cycle life, cyclibility, low cost of recycling and charging infrastructures and high safety. So far most of the hydrogen storage alloys such as LaNi 5 , TiFe, TiMn 2 , have hydrogen storage capacities, not more than 2 wt% which is not satisfactory for practical application as per DOE Goal. A group of Mg based

  14. Self-Synchronization: Splendid Promise or Dangerous Delusion

    National Research Council Canada - National Science Library

    Hatter, Steven

    2000-01-01

    ... with extraordinary efficiency and precision. Proponents of Network-Centric Warfare build upon the optimism in JV 2010 by offering a war-fighting paradigm that promises "an information superiority enabled concept of operations that generates...

  15. Promise Zone Round 2 Applicant Geography and Goal Data

    Data.gov (United States)

    Department of Housing and Urban Development — This dataset includes Promise Zone initiative round II applicant project data from 111 urban, rural, and tribal communities who consented to share their application...

  16. Children's rights, international human rights and the promise of ...

    African Journals Online (AJOL)

    Children's rights, international human rights and the promise of Islamic legal theory. ... Law, Democracy & Development ... law but also religion and ethics, thus offering a multidimensional approach covering the total personality of the child.

  17. Why do people keep their promises? An overview of strategic commitment

    Directory of Open Access Journals (Sweden)

    Miranda del Corral

    2015-07-01

    Full Text Available Strategic commitments, such as promises and threats, pose several problems to the standard model of economic rationality: first, they can only arise when there is an incentive to free ride; second, they need to be credible in order to manipulate the others' behaviour; third, once the commitment has succeeded, it is no longer in the agent's self interest to fulfil her commitment. Why, then, do people keep their promises (and threats? This paper reviews the literature concerning the problem of commitment within the scope of pro-sociality and cooperation, and examines two mechanisms that enable credibility and trust: reputation and social emotions

  18. Forecast of promising areas for uranium prospection at the metamorphic Massif of Isla de la Juventud

    International Nuclear Information System (INIS)

    Gongora, L.E.; Macola, E.; Sanchez, J.; Torres, J.C.; Alaminos, C.; LLanes, A.; Morales, M.

    1995-01-01

    A mineralization conceptual model for uranium of the metamorphic Massif of Isla de la Juventud was established taking into account the study of the geological and metallogenic characteristic of the territory. The determined indications of mineralization were plotted on the geological map in order to conform a forecasting map and the selection of 22 hypothetical promising areas was carried out. As result of the field words three really promising areas were selected. A group of exploration techniques needed to evaluate the targets areas is presented

  19. Telepsychiatry in the developing world: Whither promised joy?

    Directory of Open Access Journals (Sweden)

    Subho Chakrabarti

    2016-01-01

    Full Text Available Telepsychiatry, the use of information and communication technologies to provide psychiatric services from a distance, has matured as a mode of service delivery and has expanded its reach since its inception. Telepsychiatry promotes equality of access to high-quality specialized care for underserved users. It enables, empowers and brings about high levels of satisfaction among users. Telepsychiatry can deliver a broad array of clinical services and support several other nonclinical activities. Accumulated evidence demonstrates that clinical outcomes of telepsychiatric interventions are comparable to conventional treatment among patients of all ages, ethnicities, cultures, and diagnostic groups across diverse clinical settings. However, negative attitudes, concerns about the quality of the evidence, doubts about cost-effectiveness, technological vagaries, uncertainty regarding the doctor–patient alliance, and a number of legal, ethical and regulatory hurdles continue to hinder the widespread implementation of telepsychiatric services. A particularly disappointing aspect has been the lack of development of telepsychiatric services in developing countries, where they are required the most because of the large mental-health gap in care with the more traditional forms of services. Problems of costs, lack of infrastructure and connectivity, shortage of trained personnel, sociocultural differences, limited data on effectiveness, and lack of institutional support are the principal challenges to the wider adoption of telepsychiatry in these resource-constrained countries. It is evident that much more effort by all stakeholders, innovative solutions, and hybrid models of care are required before telepsychiatry is able to fulfil its true potential and bring about the promised change in mental health outcomes in the developing world.

  20. Posttransplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: A promising clinical alternative to the conventional intrahepatic site.

    Science.gov (United States)

    Komatsu, H; Rawson, J; Barriga, A; Gonzalez, N; Mendez, D; Li, J; Omori, K; Kandeel, F; Mullen, Y

    2018-04-01

    Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-basic fibroblast growth factor. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mm Hg, compared to 45 mm Hg under ambient air. In vitro, islets cultured under 140 mm Hg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mm Hg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with postoperative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Copenhagen's climate finance promise: six key questions

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, J. Timmons [Brown University (United States); Stadelmann, Martin [University of Zurich (Switzerland); Huq, Saleemul

    2010-02-15

    One clear promise emerged from the confusion of the 2009 climate talks in Copenhagen. This was to provide short- and long-term 'climate finance' to help developing countries – especially the most vulnerable – adapt to climate impacts. The promise seemed simple enough: wealthier nations would pledge US$10 billion a year from 2010-2012, ramping up to US$100 billion a year starting in 2020. This was also touted as a way to help developing countries avoid high-carbon pathways of development by adopting lower-emitting power sources such as solar or natural gas. But a closer look at the Copenhagen promise unearths at least six big questions – any one of which could seriously challenge the trust these funds were designed to build.

  2. Promise-based management: the essence of execution.

    Science.gov (United States)

    Sull, Donald N; Spinosa, Charles

    2007-04-01

    Critical initiatives stall for a variety of reasons--employee disengagement, a lack of coordination between functions, complex organizational structures that obscure accountability, and so on. To overcome such obstacles, managers must fundamentally rethink how work gets done. Most of the challenges stem from broken or poorly crafted commitments. That's because every company is, at its heart, a dynamic network of promises made between employees and colleagues, customers, outsourcing partners, or other stakeholders. Executives can overcome many problems in the short-term and foster productive, reliable workforces for the long-term by practicing what the authors call "promise-based management," which involves cultivating and coordinating commitments in a systematic way. Good promises share five qualities: They are public, active, voluntary, explicit, and mission based. To develop and execute an effective promise, the "provider" and the "customer" in the deal should go through three phases of conversation. The first, achieving a meeting of minds, entails exploring the fundamental questions of coordinated effort: What do you mean? Do you understand what I mean? What should I do? What will you do? Who else should we talk to? In the next phase, making it happen, the provider executes on the promise. In the final phase, closing the loop, the customer publicly declares that the provider has either delivered the goods or failed to do so. Leaders must weave and manage their webs of promises with great care-encouraging iterative conversation and making sure commitments are fulfilled reliably. If they do, they can enhance coordination and cooperation among colleagues, build the organizational agility required to seize new business opportunities, and tap employees' entrepreneurial energies.

  3. Big data analytics in healthcare: promise and potential.

    Science.gov (United States)

    Raghupathi, Wullianallur; Raghupathi, Viju

    2014-01-01

    To describe the promise and potential of big data analytics in healthcare. The paper describes the nascent field of big data analytics in healthcare, discusses the benefits, outlines an architectural framework and methodology, describes examples reported in the literature, briefly discusses the challenges, and offers conclusions. The paper provides a broad overview of big data analytics for healthcare researchers and practitioners. Big data analytics in healthcare is evolving into a promising field for providing insight from very large data sets and improving outcomes while reducing costs. Its potential is great; however there remain challenges to overcome.

  4. Promising design options for the encapsulated nuclear heat source reactor

    Energy Technology Data Exchange (ETDEWEB)

    Conway, L.; Carelli, M.D.; Dzodzo, M. [Westinghouse Science and Technology, Pittsburgh, PA (United States); Hossain, Q.; Brown, N.W. [Lawrence Livermore National Lab., CA (United States); Wade, D.C.; Sienick, J.J. [Argonne National Lab., IL (United States); Greenspan, E.; Kastenberg, W.E.; Saphier, D. [University of California Dept of Nuclear Engineering, Berkeley, CA (United States)

    2001-07-01

    Promising design options for the Encapsulated Nuclear Heat Source (ENHS) liquid-metal cooled fast reactor were identified during the first year of the DOE NERI program sponsored feasibility study. Many opportunities for incorporation of innovations in design and fabrication were identified. Three of the innovations are hereby described: a novel IHX (intermediate heat exchanger) made of a relatively small number of rectangular channels, an ENHS module design featuring 100% natural circulation, and a novel conceptual design of core support and fuelling. As a result of the first year study the ENHS concept appears more practical and more promising than perceived at the outset of this study. (authors)

  5. Promising design options for the encapsulated nuclear heat source reactor

    International Nuclear Information System (INIS)

    Conway, L.; Carelli, M.D.; Dzodzo, M.; Hossain, Q.; Brown, N.W.; Wade, D.C.; Sienick, J.J.; Greenspan, E.; Kastenberg, W.E.; Saphier, D.

    2001-01-01

    Promising design options for the Encapsulated Nuclear Heat Source (ENHS) liquid-metal cooled fast reactor were identified during the first year of the DOE NERI program sponsored feasibility study. Many opportunities for incorporation of innovations in design and fabrication were identified. Three of the innovations are hereby described: a novel IHX (intermediate heat exchanger) made of a relatively small number of rectangular channels, an ENHS module design featuring 100% natural circulation, and a novel conceptual design of core support and fuelling. As a result of the first year study the ENHS concept appears more practical and more promising than perceived at the outset of this study. (authors)

  6. Improving low-performing high schools: searching for evidence of promise.

    Science.gov (United States)

    Fleischman, Steve; Heppen, Jessica

    2009-01-01

    Noting that many of the nation's high schools are beset with major problems, such as low student reading and math achievement, high dropout rates, and an inadequate supply of effective teachers, Steve Fleischman and Jessica Heppen survey a range of strategies that educators have used to improve low-performing high schools. The authors begin by showing how the standards-based school reform movement, together with the No Child Left Behind Act requirement that underperforming schools adopt reforms supported by scientifically based research, spurred policy makers, educators, and researchers to create and implement a variety of approaches to attain improvement. Fleischman and Heppen then review a number of widely adopted reform models that aim to change "business as usual" in low-performing high schools. The models include comprehensive school reform programs, dual enrollment and early college high schools, smaller learning communities, specialty (for example, career) academies, charter high schools, and education management organizations. In practice, say the authors, many of these improvement efforts overlap, defying neat distinctions. Often, reforms are combined to reinforce one another. The authors explain the theories that drive the reforms, review evidence of their reforms' effectiveness to date, and suggest what it will take to make them work well. Although the reforms are promising, the authors say, few as yet have solid evidence of systematic or sustained success. In concluding, Fleischman and Heppen emphasize that the reasons for a high school's poor performance are so complex that no one reform model or approach, no matter how powerful, can turn around low-performing schools. They also stress the need for educators to implement each reform program with fidelity to its requirements and to support it for the time required for success. Looking to the future, the authors suggest steps that decision makers, researchers, and sponsors of research can take to promote

  7. Dual Component Removable Partial Denture shows improved ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-02-18

    Feb 18, 2009 ... 2Faculty of Dentistry, the University of Hong Kong, Hong Kong. 3Department of ... an example of poor oral condition caused mainly by periodontitis, and ... working model of the Dual Component Removable Partial Denture.

  8. CRISPR-Cas9: a promising genetic engineering approach in cancer research

    Science.gov (United States)

    Ratan, Zubair Ahmed; Son, Young-Jin; Uddin, Bhuiyan Mohammad Mahtab; Yusuf, Md. Abdullah; Zaman, Sojib Bin; Kim, Jong-Hoon; Banu, Laila Anjuman

    2018-01-01

    Bacteria and archaea possess adaptive immunity against foreign genetic materials through clustered regularly interspaced short palindromic repeat (CRISPR) systems. The discovery of this intriguing bacterial system heralded a revolutionary change in the field of medical science. The CRISPR and CRISPR-associated protein 9 (Cas9) based molecular mechanism has been applied to genome editing. This CRISPR-Cas9 technique is now able to mediate precise genetic corrections or disruptions in in vitro and in vivo environments. The accuracy and versatility of CRISPR-Cas have been capitalized upon in biological and medical research and bring new hope to cancer research. Cancer involves complex alterations and multiple mutations, translocations and chromosomal losses and gains. The ability to identify and correct such mutations is an important goal in cancer treatment. In the context of this complex cancer genomic landscape, there is a need for a simple and flexible genetic tool that can easily identify functional cancer driver genes within a comparatively short time. The CRISPR-Cas system shows promising potential for modeling, repairing and correcting genetic events in different types of cancer. This article reviews the concept of CRISPR-Cas, its application and related advantages in oncology. PMID:29434679

  9. Biomedical and Clinical Promises of Human Pluripotent Stem Cells for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Nopporn Jongkamonwiwat

    2013-01-01

    Full Text Available Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and induced pluripotent stem cells (iPSCs provide genetically matched neurons for treating patients. These hPSC-derived neurons can also be used for disease modeling and drug screening. Since the most urgent problem today in transplantation is the lack of suitable donor organs and tissues, the derivation of neural progenitor cells from hPSCs has opened a new avenue for regenerative medicine. In this review, we summarize the recent reports that show how to generate neural derivatives from hPSCs, and discuss the current evidence of using these cells in animal studies. We also highlight the possibilities and concerns of translating these hPSC-derived neurons for biomedical and clinical uses in order to fight against neurological disorders.

  10. A zinc, copper and citric acid biocomplex shows promise for control of Xylella fastidiosa subsp. pauca in olive trees in Apulia region (southern Italy)

    Science.gov (United States)

    The bacterium Xylella fastidiosa subsp. pauca is associated with the “olive quick decline syndrome” in the Apulia region of southern Italy. To investigate control of this phytopathogen, a compound containing zinc and copper complexed with citric-acid hydracids (Dentamet®) was evaluated for in vitro ...

  11. PERFORMANCE OF UPLAND RICE PROMISING LINES AND VARIETIES AS INTERCROPPING OF PLANTATION

    Directory of Open Access Journals (Sweden)

    Amrizal Yusuf

    2013-01-01

    Full Text Available In 2008, introduction of upland rice promising lines and varieties as intercropping rubber plant had been done at Sibunga-Bunga Hilir village STM Hulu Sub District, Deli Serdang District, North Sumatra Province, there are two promise line and two pre-eminent upland rice varieties were planted among six until 18 mounths old rubber plants. Aim of this assessment was to improving productivity and farmers income through the utilization of land available under rubber plants by upland rice. The assessment was conducted using 2.0 ha upland done by three cooperator farmers and 1, 5 ha done by non-cooperator farmers. The activity was started in September 2008 and was completed January 2009. A field day was done on 13 January 2009. The result of the assessment showed that TB409-B-TB-14-3 promise lines gave the highest yield (4.32 t per ha, followed by TB490C-TB-1-2-1 (4, 28 t per ha, Situ Patenggang variety (3.66 t per ha and Limboto variety (3.17 t per ha. The financial analysis for TB409-B-TB-14-3 promise line showed that net profit of IDR 5.42 m per ha, with a B/C ratio of 0.63. Break event point was reached at IDR 1.989 per kg giving positive margin of IDR 1.211 per kg.

  12. UV Photography Shows Hidden Sun Damage

    Science.gov (United States)

    ... mcat1=de12", ]; for (var c = 0; c UV photography shows hidden sun damage A UV photograph gives ... developing skin cancer and prematurely aged skin. Normal photography UV photography 18 months of age: This boy's ...

  13. Penguin Promises: Encouraging Aquarium Visitors to Take Conservation Action

    Science.gov (United States)

    Mann, Judy Brenda; Ballantyne, Roy; Packer, Jan

    2018-01-01

    This study investigates the impact of an innovative conservation action campaign called "Penguin Promises" implemented at uShaka Sea World in Durban, South Africa. Communication tools included interpretive signage, exhibits with and without animals, presentations, and personal interactions, along with a specially designed postcard, on…

  14. 7 T renal MRI : challenges and promises

    NARCIS (Netherlands)

    de Boer, A.; Hoogduin, J.M.; Blankestijn, P.J.; Li, X.; Luijten, P.R.; Metzger, G.J.; Raaijmakers, A.J.E.; Umutlu, L.; Visser, F.; Leiner, T.

    The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to

  15. Vascular regenerative surgery : promised land for tissue engineers?

    NARCIS (Netherlands)

    Fortunato, T.M.; De Bank, P.A.; Pula, G.

    2017-01-01

    Cardiovascular cell therapy is a promising new eld for the development of treatments for cardiovascular diseases, which remain a major cause of mortality around the world. In this review, we highlight the options currently available for the development of speci c cell therapy approaches applied to

  16. Promising Practices in Drug Treatment: Findings from Southeast Asia

    Science.gov (United States)

    Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…

  17. Augmented Reality Based Doppler Lidar Data Visualization: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    Cherukuru N. W.

    2016-01-01

    As a proof of concept, we used the lidar data from a recent field campaign and developed a smartphone application to view the lidar scan in augmented reality. In this paper, we give a brief methodology of this feasibility study, present the challenges and promises of using AR technology in conjunction with Doppler wind lidars.

  18. The Math Promise: Celebrating at Home and School

    Science.gov (United States)

    Legnard, Danielle; Austin, Susan

    2014-01-01

    The Math Promise is a contract that family members make with one another. They commit to spending mathematical time together; getting to know each other's mathematical thinking and understanding; and finding time to play math games, solve problems, and notice mathematics in their daily lives. Whether parents and children are cooking in the…

  19. Vachellia karroo leaf meal: a promising non-conventional feed ...

    African Journals Online (AJOL)

    Vachellia karroo leaf meal: a promising non-conventional feed resource for improving goat production in low-input farming systems of Southern Africa. ... Vachellia karroo possesses desirable fatty acid profiles, and high protein and mineral contents that can improve animal performance. Presently, the use of V. karroo for ...

  20. Alq3 nanorods: promising building blocks for optical devices.

    Science.gov (United States)

    Chen, Wei; Peng, Qing; Li, Yadong

    2008-07-17

    Monodisperse Alq3 nanorods with hexagonal-prism-like morphology are produced via a facile, emulsion based synthesis route. The photoluminescence of individual nanorods differs from the bulk material. These nanorods are promising building blocks for novel optical devices. Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Understanding the promises and premises of online health platforms

    NARCIS (Netherlands)

    van Dijck, J.; Poell, T.

    2016-01-01

    This article investigates the claims and complexities involved in the platform-based economics of health and fitness apps. We examine a double-edged logic inscribed in these platforms, promising to offer personal solutions to medical problems while also contributing to the public good. On the one

  2. Toward a transnational history of technology : meanings, promises, pitfalls

    NARCIS (Netherlands)

    Vleuten, van der E.B.A.

    2008-01-01

    This essay investigates the possibility of a transnational history of technology. It takes the current, large scale research program Tensions of Europe: Technology and the Making of Europe, 1950–2000 as its point of departure. The grand promises of the recent transnational turn in historiography,

  3. Why do promises affect trustworthiness, or do they?

    NARCIS (Netherlands)

    Ismayilov, Huseyn; Potters, Jan

    2016-01-01

    We set out to test whether the effect of promises on trustworthiness derives from the fact that they are made (internal consistency) or that they are received (social obligation). The results of an experimental trust game appeared at first to support the former mechanism. Even when trustee messages

  4. Promising Teacher Practices: Students' Views about Their Science Learning

    Science.gov (United States)

    Moeed, Azra; Easterbrook, Matthew

    2016-01-01

    Internationally, conceptual and procedural understanding, understanding the Nature of Science, and scientific literacy are considered worthy goals of school science education in modern times. The empirical study presented here reports on promising teacher practices that in the students' views afford learning opportunities and support their science…

  5. EVALUATION OF SOME BASIC TRAITS OF A PROMISING ...

    African Journals Online (AJOL)

    User

    Green Dwarf crossed Vanuatu Tall (SGD x VTT) coconut hybrid as the most promising planting material in the context of ... The study indicated that the yield performance of the SGD x ... important crop in the economies of the coastal areas of ... In the Western Region, it is esti- ... Tall (WAT) which have varying levels of resis-.

  6. The Promise of Motivational Interviewing in School Mental Health

    Science.gov (United States)

    Frey, Andy J.; Cloud, Richard N.; Lee, Jon; Small, Jason W.; Seeley, John R.; Feil, Edward G.; Walker, Hill M.; Golly, Annemieke

    2011-01-01

    In recent years, the science of developing and implementing interventions addressing school-related risk factors has produced many advances. This article addresses the promise of a cross-disciplinary practice approach known as motivational interviewing in school settings. Specifically, the supporting evidence as well as the process and principles…

  7. Infliximab (Revellex(R)): a promise fulfilled?: medicine in practice ...

    African Journals Online (AJOL)

    Infliximab (Revellex(R)): a promise fulfilled?: medicine in practice. JP Wright. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners ...

  8. Postmodernism and the need for story and promise: How Robert ...

    African Journals Online (AJOL)

    If this is true, it poses great challenges for the Christian faith to be communicated and accepted within this context. This article assesses how Jenson's theology attempts to address postmodernism's need for a new story and promise. It concludes that Jenson's theology, as a Trinitarian theology, forms a coherent answer to ...

  9. The Promised Savior in Pre-Islamic Great Religions

    Directory of Open Access Journals (Sweden)

    Mahin Arab

    2014-08-01

    Full Text Available Since the ancient times the belief in the rise of the Reformer has been a fundamental principle. Many of the holy prophets have announced the advent of new prophet. Moreover in the announcements and indications of predecessors there are always allusions to "the Last Promised" and "the Savior of Last Days" under such titles as "Kalki", "Fifth Buddha", "Soshyans", "Messiah", "The Son of Man" and so on and so forth. Of course there are different types of belief in the last reformer in religions. In one place the Savior is merely a social reformer while in another place he is only after the spiritual salvation of people and even sometimes he undertakes both tasks. On the other hand, the Last Promised is once nationalist and once seeks to save the whole world.    This essay seeks to assay the views of pre-Islamic great religions including Zoroastrianism, Judaism, Christianity, Hinduism and Buddhism as to the Promised Savior. This essay is an analytico-descriptive research which has based itself on the first hand works comprising the sacred scriptures of religions and proceeds through the typological analyses of idea of the Promised in religions.    Zoroastrianism: the idea of the Promised has been tied to the notion of Soshyant. Generally speaking, this notion alludes to a group of people who periodically emerge at the end of every millennium of the last three millennia of world's age so as to uproot evil and renew the world, the last one of these reformers is Soshyans. According to the aforementioned typology, Zoroastrian idea of Last Savior is among the Promised who saves the whole world. Moreover Zoroastrian Promised cannot be declared only a social savior as he is not wholly detached from people's spirituality too. From another point of view, Zoroastrian idea of the Promised represents a universal and not nationalist savior who is relatively a human and not divine entity who emerges in the last millennium of world's age.    Judaism: in the

  10. The Promised Savior in Pre-Islamic Great Religions

    Directory of Open Access Journals (Sweden)

    Mahin Arab

    2014-09-01

    Full Text Available Since the ancient times the belief in the rise of the Reformer has been a fundamental principle. Many of the holy prophets have announced the advent of new prophet. Moreover in the announcements and indications of predecessors there are always allusions to "the Last Promised" and "the Savior of Last Days" under such titles as "Kalki", "Fifth Buddha", "Soshyans", "Messiah", "The Son of Man" and so on and so forth. Of course there are different types of belief in the last reformer in religions. In one place the Savior is merely a social reformer while in another place he is only after the spiritual salvation of people and even sometimes he undertakes both tasks. On the other hand, the Last Promised is once nationalist and once seeks to save the whole world.    This essay seeks to assay the views of pre-Islamic great religions including Zoroastrianism, Judaism, Christianity, Hinduism and Buddhism as to the Promised Savior. This essay is an analytico-descriptive research which has based itself on the first hand works comprising the sacred scriptures of religions and proceeds through the typological analyses of idea of the Promised in religions.    Zoroastrianism: the idea of the Promised has been tied to the notion of Soshyant. Generally speaking, this notion alludes to a group of people who periodically emerge at the end of every millennium of the last three millennia of world's age so as to uproot evil and renew the world, the last one of these reformers is Soshyans. According to the aforementioned typology, Zoroastrian idea of Last Savior is among the Promised who saves the whole world. Moreover Zoroastrian Promised cannot be declared only a social savior as he is not wholly detached from people's spirituality too. From another point of view, Zoroastrian idea of the Promised represents a universal and not nationalist savior who is relatively a human and not divine entity who emerges in the last millennium of world's age.    Judaism: in the

  11. Educational Outreach: The Space Science Road Show

    Science.gov (United States)

    Cox, N. L. J.

    2002-01-01

    The poster presented will give an overview of a study towards a "Space Road Show". The topic of this show is space science. The target group is adolescents, aged 12 to 15, at Dutch high schools. The show and its accompanying experiments would be supported with suitable educational material. Science teachers at schools can decide for themselves if they want to use this material in advance, afterwards or not at all. The aims of this outreach effort are: to motivate students for space science and engineering, to help them understand the importance of (space) research, to give them a positive feeling about the possibilities offered by space and in the process give them useful knowledge on space basics. The show revolves around three main themes: applications, science and society. First the students will get some historical background on the importance of space/astronomy to civilization. Secondly they will learn more about novel uses of space. On the one hand they will learn of "Views on Earth" involving technologies like Remote Sensing (or Spying), Communication, Broadcasting, GPS and Telemedicine. On the other hand they will experience "Views on Space" illustrated by past, present and future space research missions, like the space exploration missions (Cassini/Huygens, Mars Express and Rosetta) and the astronomy missions (Soho and XMM). Meanwhile, the students will learn more about the technology of launchers and satellites needed to accomplish these space missions. Throughout the show and especially towards the end attention will be paid to the third theme "Why go to space"? Other reasons for people to get into space will be explored. An important question in this is the commercial (manned) exploration of space. Thus, the questions of benefit of space to society are integrated in the entire show. It raises some fundamental questions about the effects of space travel on our environment, poverty and other moral issues. The show attempts to connect scientific with

  12. Artificial Intelligence and the Future of Education: Big Promises-Bigger Challenges%Artificial Intelligence and the Future of Education:Big Promises-Bigger Challenges

    Institute of Scientific and Technical Information of China (English)

    Jonathan Michael Spector; Du Jing

    2017-01-01

    The history of educational technology in the last 50 years contains few instances of dramatic improvements in learning based on the adoption of a particular technology.An example involving artificial intelligence occurred in the 1990s with the development of intelligent tutoring systems (ITSs).What happened with ITSs was that their success was limited to well-defined and relatively simple declarative and procedural leaming tasks (e.g.,learning how to write a recursive function in LISP;doing multi-column addition),and improvements that were observed tended to be more limited than promised (e.g.,one standard deviation improvement at best rather than the promised standard deviation improvement).Still,there was some progress in terms of how to conceptualize learning.A seldom documented limitation was the notion of only viewing learning from only content and cognitive perspectives (i.e.,in terms of memory limitations,prior knowledge,bug libraries,learning hierarchies and sequences etc.).Little attention was paid to education conceived more broadly than developing specific cognitive skills with highly constrained problems.New technologies offer the potential to create dynamic and multi-dimensional models of a particular leamer,and to track large data sets of learning activities,resources,interventions,and outcomes over a great many leamers.Using those data to personalize learning for a particular leamer developing knowledge,competence and understanding in a specific domain of inquiry is finally a real possibility.While the potential to make significant progress is clearly possible,the reality is less not so promising.There are many as yet unmet challenging some of which will be mentioned in this paper.A persistent worry is that educational technologists and computer scientists will again promise too much,too soon at too little cost and with too little effort and attention to the realities in schools and universities.

  13. 2008 LHC Open Days Physics: the show

    CERN Multimedia

    2008-01-01

    A host of events and activities await visitors to the LHC Open Days on 5 and 6 April. A highlight will be the physics shows funded by the European Physical Society (EPS), which are set to surprise and challenge children and adults alike! School children use their experience of riding a bicycle to understand how planets move around the sun (Copyright : Circus Naturally) Participating in the Circus Naturally show could leave a strange taste in your mouth! (Copyright : Circus Naturally) The Rino Foundation’s experiments with liquid nitrogen can be pretty exciting! (Copyright: The Rino Foundation)What does a bicycle have in common with the solar system? Have you ever tried to weigh air or visualise sound? Ever heard of a vacuum bazooka? If you want to discover the answers to these questions and more then come to the Physics Shows taking place at the CERN O...

  14. Online Italian fandoms of American TV shows

    Directory of Open Access Journals (Sweden)

    Eleonora Benecchi

    2015-06-01

    Full Text Available The Internet has changed media fandom in two main ways: it helps fans connect with each other despite physical distance, leading to the formation of international fan communities; and it helps fans connect with the creators of the TV show, deepening the relationship between TV producers and international fandoms. To assess whether Italian fan communities active online are indeed part of transnational online communities and whether the Internet has actually altered their relationship with the creators of the original text they are devoted to, qualitative analysis and narrative interviews of 26 Italian fans of American TV shows were conducted to explore the fan-producer relationship. Results indicated that the online Italian fans surveyed preferred to stay local, rather than using geography-leveling online tools. Further, the sampled Italian fans' relationships with the show runners were mediated or even absent.

  15. Show Them You Really Want the Job

    Science.gov (United States)

    Perlmutter, David D.

    2012-01-01

    Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

  16. A Talk Show from the Past.

    Science.gov (United States)

    Gallagher, Arlene F.

    1991-01-01

    Describes a two-day activity in which elementary students examine voting rights, the right to assemble, and women's suffrage. Explains the game, "Assemble, Reassemble," and a student-produced talk show with five students playing the roles of leaders of the women's suffrage movement. Profiles Elizabeth Cady Stanton, Lucretia Mott, Susan…

  17. Laser entertainment and light shows in education

    Science.gov (United States)

    Sabaratnam, Andrew T.; Symons, Charles

    2002-05-01

    Laser shows and beam effects have been a source of entertainment since its first public performance May 9, 1969, at Mills College in Oakland, California. Since 1997, the Photonics Center, NgeeAnn Polytechnic, Singapore, has been using laser shows as a teaching tool. Students are able to exhibit their creative skills and learn at the same time how lasers are used in the entertainment industry. Students will acquire a number of skills including handling three- phase power supply, operation of cooling system, and laser alignment. Students also acquire an appreciation of the arts, learning about shapes and contours as they develop graphics for the shows. After holography, laser show animation provides a combination of the arts and technology. This paper aims to briefly describe how a krypton-argon laser, galvanometer scanners, a polychromatic acousto-optic modulator and related electronics are put together to develop a laser projector. The paper also describes how students are trained to make their own laser animation and beam effects with music, and at the same time have an appreciation of the operation of a Class IV laser and the handling of optical components.

  18. The Last Great American Picture Show

    NARCIS (Netherlands)

    Elsaesser, Thomas; King, Noel; Horwath, Alexander

    2004-01-01

    The Last Great American Picture Show brings together essays by scholars and writers who chart the changing evaluations of the American cinema of the 1970s, sometimes referred to as the decade of the lost generation, but now more and more recognized as the first New Hollywood, without which the

  19. 'Show me the money': energy projects financing

    International Nuclear Information System (INIS)

    Ball, C.

    2006-01-01

    This paper describes the business and business model of Corpfinance International (CFI). CFI consists of three businesses: structured financing, private equity/corporate finance advisory and securitization. Furthermore, CFI is the lender of record acting on behalf of and based on strong relationship with various Life Insurance Companies, Pension Funds and International Banks. CFI has in-house expertise in support of its lending advisory and investing activities

  20. Reality, ficción o show

    Directory of Open Access Journals (Sweden)

    Sandra Ruíz Moreno

    2002-01-01

    Full Text Available Para tener un punto de vista claro y objetivo frente a la polémica establecida en torno al programa “Protagonistas de novela” y la tendiente proliferación de los reality show en las parrillas de programación de la televisión colombiana, se realizó un análisis de texto y contenido de dicho programa, intentando definirlo desde sus posibilidades de realidad, ficción y show. Las unidades de análisis y el estudio de su tratamiento arrojaron un alto contenido que gira en torno a las emociones del ser humano relacionadas con la convivencia, tratadas a manera de show y con algunos aportes textuales de ficción, pero sin su elemento mediador básico, el actor, quitándole toda la posibilidad de tener un tratamiento con la profundidad, distancia y ética que requieren los temas de esta índole. El resultado es un formato que sólo busca altos índices de sintonía y que pertenece más a la denominada televisión “trash”, que a una búsqueda de realidad del hombre y mucho menos de sociedad.

  1. Image is more than a uniform: the promise of assurance.

    Science.gov (United States)

    Wocial, Lucia D; Sego, Kelly; Rager, Carrie; Laubersheimer, Shellee; Everett, Linda Q

    2014-05-01

    The purpose of this qualitative study was to explore the meaning of the phrase "image of the nurse" in the context of the desired brand experience of assurance. A brand is a promise that lives in the minds of consumers. Nurses play a key role in delivering on the brand promise of a hospital. Using focus groups, the authors applied a deductive approach to generate data. Discussion transcripts were analyzed by establishing codes and identifying themes. The most frequent comment from participants was that for nurses to communicate assurance, they must 1st be clean, well groomed, and understated in overall appearance. Nurse behaviors that reassure patients include being present with patients, helping patients know what to expect, and demonstrating a consistent team approach. Overall appearance and behaviors define the image of nurses and contribute significantly to the brand of assurance.

  2. Natural Flavonoids as Promising Analgesic Candidates: A Systematic Review.

    Science.gov (United States)

    Xiao, Xiao; Wang, Xiaoyu; Gui, Xuan; Chen, Lu; Huang, Baokang

    2016-11-01

    Due to the chemical structural diversity and various analgesic mechanisms, an increasing number of studies indicated that some flavonoids from medicinal plants could be promising candidates for new natural analgesic drugs, which attract high interests of advanced users and academic researchers. The aim of this systematic review is to report flavonoids and its derivatives as new analgesic candidates based on the pharmacological evidences. Sixty-four papers were found concerning the potential analgesic activity of 46 flavonoids. In this case, the evidence for analgesic activity of flavonoids and total flavonoids was investigated. Meanwhile, the corresponding analgesic mechanism of flavonoids was discussed by generalizing and analyzing the current publications. Based on this review, the conclusion can be drawn that some flavonoids are promising candidates for painful conditions and deserve particular attention in further research and development. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

  3. Promise assessment: A corollary to risk assessment for characterizing benefits

    International Nuclear Information System (INIS)

    Sholtis, J.A. Jr.

    1993-01-01

    Decisions involving the use of hazardous technologies are often made based on risk-benefit considerations. This is the case for U.S. space mission use of nuclear power and propulsion systems, where launch decisions are made within the office of the President. A great deal of time and effort is spent characterizing the risk for each nuclear-powered space mission. However, this is not so for benefits, even though they are no less important. To correct this situation, a new technical term--promise--is defined, and a new methodology--promise assessment--is proposed. This paper introduces and advances this concept, addresses its future application, as a tool, can be developed sufficiently and applied to methodically identify and characterized benefits. Further, it can introduce a degree of balance when judgments concerning the use of hazardous technologies are involved

  4. When a desired home death does not occur: the consequences of broken promises.

    Science.gov (United States)

    Topf, Lorrianne; Robinson, Carole A; Bottorff, Joan L

    2013-08-01

    Evidence shows that most people prefer to die at home; however, the majority of expected deaths occur away from home. Although home deaths require family caregiver (FCG) commitment and care, we understand very little about their experiences in this context. The study's aim was to gain a better understanding of the experiences of FCGs when circumstances prevented a desired home death for a family member with advanced cancer. An interpretive description approach was used. Data collection involved semistructured interviews. Field notes and reflective journaling aided interpretive and analytical processes. The study was conducted in western Canada and included 18 bereaved FCGs. FCGs were committed to the promises made to care for their family member at home until death. These promises were challenged by a lack of preparedness for caregiving, difficulty accessing professional support and information, and frustration with the inadequate help they received. The events that precipitated dying family members leaving their home for hospital or hospice were unexpected and often influenced by FCGs' lack of situation-specific knowledge and ability to cope with complex caregiving responsibilities. FCGs found it extremely challenging to reconcile with breaking their promise to care at home until death and many were unable to do so. FCGs' despair about not being able to keep their promise for a home death was related to complicated bereavement. Prospective studies of the experiences of FCGs who are aiming for home deaths are needed to identify both short- and long-term interventions to effectively support death at home.

  5. Realising the promise of Tanzania’s wildlife management areas

    DEFF Research Database (Denmark)

    Homewood, Katherine; Lund, Jens Friis; Keane, Aidan

    2017-01-01

    Tanzania’s Community Wildlife Management Areas (CWMAs) – originally called Wildlife Management Areas (WMAs) – were intended to benefit both people and wildlife. However, for their first two decades, CWMAs have been characterised by land conflict, wildlife damage to people and crops, lack of tourism...... potential and high administration costs among other negative impacts. Can rethinking how CWMAs are run bring about the benefits once promised?...

  6. The Promise and Perils of Stem Cell Therapeutics

    OpenAIRE

    Daley, George Q.

    2012-01-01

    Stem cells are the seeds of tissue repair and regeneration and a promising source for novel therapies. However, apart from hematopoietic stem cell (HSC) transplantation for hematologic disease, essentially all other stem cell treatments remain experimental. High hopes have inspired numerous clinical trials, but it has been difficult to obtain unequivocal evidence for robust clinical benefit, likely owing to our primitive state of knowledge about therapeutic mechanisms. Outside the standard cl...

  7. KirCII- promising tool for polyketide diversification

    DEFF Research Database (Denmark)

    Musiol-Kroll, Ewa Maria; Härtner, Thomas; Kulik, Andreas

    2014-01-01

    Kirromycin is produced by Streptomyces collinus Tü 365. This compound is synthesized by a large assembly line of type I polyketide synthases and non-ribosomal peptide synthetases (PKS I/NRPS), encoded by the genes kirAI-kirAVI and kirB. The PKSs KirAI-KirAV have no acyltransferase domains integra...... introducing the non-native substrates in an in vivo context. Thus, KirCII represents a promising tool for polyketide diversification....

  8. Discovery and therapeutic promise of selective androgen receptor modulators.

    Science.gov (United States)

    Chen, Jiyun; Kim, Juhyun; Dalton, James T

    2005-06-01

    Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects.

  9. The Presentation of Science in Everyday Life: The Science Show

    Science.gov (United States)

    Watermeyer, Richard

    2013-01-01

    This paper constitutes a case-study of the "science show" model of public engagement employed by a company of science communicators focused on the popularization of science, technology, engineering and mathematics (STEM) subject disciplines with learner constituencies. It examines the potential of the science show to foster the interest…

  10. Promising Themes for Antismoking Campaigns Targeting Youth and Young Adults.

    Science.gov (United States)

    Brennan, Emily; Gibson, Laura A; Kybert-Momjian, Ani; Liu, Jiaying; Hornik, Robert C

    2017-01-01

    Behavior change campaigns typically try to change beliefs that influence behaviors, with targeted beliefs comprising the campaign theme. We present an empirical approach for choosing among a large number of potential themes, and results from the implementation of this approach for campaigns aimed at 4 behavioral targets: (1) preventing smoking initiation among youth, and (2) preventing initiation, (3) stopping progression to daily smoking and (4) encouraging cessation among young adults. An online survey of 13- to 17-year-olds and 18- to 25-year-olds in the United States (US), in which 20 potential campaign themes were represented by 154 beliefs. For each behavioral target, themes were ranked based on the strength of belief-intention and belief-behavior associations and size of the population not already endorsing the beliefs. The most promising themes varied across behavioral targets but 3 were consistently promising: consequences of smoking for mood, social acceptance and social popularity. Using a robust and systematic approach, this study provides campaign developers with empirical data to inform their selection of promising themes. Findings related to the campaign to prevent initiation among youth informed the development of the US Food and Drug Administration's "The Real Cost" campaign.

  11. Myopes show increased susceptibility to nearwork aftereffects.

    Science.gov (United States)

    Ciuffreda, K J; Wallis, D M

    1998-09-01

    Some aspects of accommodation may be slightly abnormal (or different) in myopes, compared with accommodation in emmetropes and hyperopes. For example, the initial magnitude of accommodative adaptation in the dark after nearwork is greatest in myopes. However, the critical test is to assess this initial accommodative aftereffect and its subsequent decay in the light under more natural viewing conditions with blur-related visual feedback present, if a possible link between this phenomenon and clinical myopia is to be considered. Subjects consisted of adult late- (n = 11) and early-onset (n = 13) myopes, emmetropes (n = 11), and hyperopes (n = 9). The distance-refractive state was assessed objectively using an autorefractor immediately before and after a 10-minute binocular near task at 20 cm (5 diopters [D]). Group results showed that myopes were most susceptible to the nearwork aftereffect. It averaged 0.35 D in initial magnitude, with considerably faster posttask decay to baseline in the early-onset (35 seconds) versus late-onset (63 seconds) myopes. There was no myopic aftereffect in the remaining two refractive groups. The myopes showed particularly striking accommodatively related nearwork aftereffect susceptibility. As has been speculated and found by many others, transient pseudomyopia may cause or be a precursor to permanent myopia or myopic progression. Time-integrated increased retinal defocus causing axial elongation is proposed as a possible mechanism.

  12. Ancient bacteria show evidence of DNA repair

    DEFF Research Database (Denmark)

    Johnson, Sarah Stewart; Hebsgaard, Martin B; Christensen, Torben R

    2007-01-01

    -term survival of bacteria sealed in frozen conditions for up to one million years. Our results show evidence of bacterial survival in samples up to half a million years in age, making this the oldest independently authenticated DNA to date obtained from viable cells. Additionally, we find strong evidence...... geological timescales. There has been no direct evidence in ancient microbes for the most likely mechanism, active DNA repair, or for the metabolic activity necessary to sustain it. In this paper, we couple PCR and enzymatic treatment of DNA with direct respiration measurements to investigate long...... that this long-term survival is closely tied to cellular metabolic activity and DNA repair that over time proves to be superior to dormancy as a mechanism in sustaining bacteria viability....

  13. Microbiological and environmental issues in show caves.

    Science.gov (United States)

    Saiz-Jimenez, Cesareo

    2012-07-01

    Cultural tourism expanded in the last half of the twentieth century, and the interest of visitors has come to include caves containing archaeological remains. Some show caves attracted mass tourism, and economical interests prevailed over conservation, which led to a deterioration of the subterranean environment and the rock art. The presence and the role of microorganisms in caves is a topic that is often ignored in cave management. Knowledge of the colonisation patterns, the dispersion mechanisms, and the effect on human health and, when present, over rock art paintings of these microorganisms is of the utmost importance. In this review the most recent advances in the study of microorganisms in caves are presented, together with the environmental implications of the findings.

  14. Prudent management of utility assets -- Problem or promise?

    International Nuclear Information System (INIS)

    Hatch, D.; Serwinowski, M.

    1998-01-01

    As utilities move into a deregulated market, the extent and nature of their asset base, as well as, the manner in which they have managed it, may play a key factor in the form of regulatory recovery. Utilities must face the issue of stranded assets. One form of addressing this issue is using ''EVA'', Economic Value Added as a mechanism to form financial models for prudent asset management. The authors present an approach to this challenging aspect of deregulation. They focus on the following utility assets: buildings/facilities, and excess real physical assets. Primarily focusing on Niagara Mohawk, two or three case studies are used to demonstrate how proactive management and EVA analysis transforms underperforming utility assets. These will be presented in a way that can show benefits for all utility stakeholders such as cost avoidance, load growth, real estate tax savings, stranded asset reductions, environmental gains, corporate image enhancement, and regulatory/governmental gains; over and above possible economic gains. Examples will be given that include the transformation of utility assets into award winning commercial, residential, and industrial developments as well as recreational/park lands and greenways. Similarly, other examples will show the many tangible and intangible benefits of an effective investment recovery and waste stream management program. Various strategies will also be presented that detail how utilities can begin to develop a total comprehensive plan for their asset portfolio. The first step in realizing and maximizing EVA towards a portfolio of assets is a change in corporate policy--one from passive ownership to active prudent management. Service and cost will drive competition resulting from full deregulation. To drive down costs, utilities will need to become more efficient in dealing with their asset base. By embracing an EVA model on an entire asset portfolio, utilities can prepare and excel in the newly shaped marketplace

  15. NASA GIBS Use in Live Planetarium Shows

    Science.gov (United States)

    Emmart, C. B.

    2015-12-01

    The American Museum of Natural History's Hayden Planetarium was rebuilt in year 2000 as an immersive theater for scientific data visualization to show the universe in context to our planet. Specific astrophysical movie productions provide the main daily programming, but interactive control software, developed at AMNH allows immersive presentation within a data aggregation of astronomical catalogs called the Digital Universe 3D Atlas. Since 2006, WMS globe browsing capabilities have been built into a software development collaboration with Sweden's Linkoping University (LiU). The resulting Uniview software, now a product of the company SCISS, is operated by about fifty planetariums around that world with ability to network amongst the sites for global presentations. Public presentation of NASA GIBS has allowed authoritative narratives to be presented within the range of data available in context to other sources such as Science on a Sphere, NASA Earth Observatory and Google Earth KML resources. Specifically, the NOAA supported World Views Network conducted a series of presentations across the US that focused on local ecological issues that could then be expanded in the course of presentation to national and global scales of examination. NASA support of for GIBS resources in an easy access multi scale streaming format like WMS has tremendously enabled particularly facile presentations of global monitoring like never before. Global networking of theaters for distributed presentations broadens out the potential for impact of this medium. Archiving and refinement of these presentations has already begun to inform new types of documentary productions that examine pertinent, global interdependency topics.

  16. Design, challenge, and promise of stimuli-responsive nanoantibiotics

    Science.gov (United States)

    Edson, Julius A.; Kwon, Young Jik

    2016-10-01

    Over the past few years, there have been calls for novel antimicrobials to combat the rise of drug-resistant bacteria. While some promising new discoveries have met this call, it is not nearly enough. The major problem is that although these new promising antimicrobials serve as a short-term solution, they lack the potential to provide a long-term solution. The conventional method of creating new antibiotics relies heavily on the discovery of an antimicrobial compound from another microbe. This paradigm of development is flawed due to the fact that microbes can easily transfer a resistant mechanism if faced with an environmental pressure. Furthermore, there has been some evidence to indicate that the environment of the microbe can provide a hint as to their virulence. Because of this, the use of materials with antimicrobial properties has been garnering interest. Nanoantibiotics, (nAbts), provide a new way to circumvent the current paradigm of antimicrobial discovery and presents a novel mechanism of attack not found in microbes yet; which may lead to a longer-term solution against drug-resistance formation. This allows for environment-specific activation and efficacy of the nAbts but may also open up and create new design methods for various applications. These nAbts provide promise, but there is still ample work to be done in their development. This review looks at possible ways of improving and optimizing nAbts by making them stimuli-responsive, then consider the challenges ahead, and industrial applications.[Figure not available: see fulltext.

  17. Geoscience is Important? Show Me Why

    Science.gov (United States)

    Boland, M. A.

    2017-12-01

    "The public" is not homogenous and no single message or form of messaging will connect the entire public with the geosciences. One approach to promoting trust in, and engagement with, the geosciences is to identify specific sectors of the public and then develop interactions and communication products that are immediately relevant to that sector's interests. If the content and delivery are appropriate, this approach empowers people to connect with the geosciences on their own terms and to understand the relevance of the geosciences to their own situation. Federal policy makers are a distinct and influential subgroup of the general public. In preparation for the 2016 presidential election, the American Geosciences Institute (AGI) in collaboration with its 51 member societies prepared Geoscience for America's Critical Needs: Invitation to a National Dialogue, a document that identified major geoscience policy issues that should be addressed in a national policy platform. Following the election, AGI worked with eight other geoscience societies to develop Geoscience Policy Recommendations for the New Administration and the 115th Congress, which outlines specific policy actions to address national issues. State and local decision makers are another important subgroup of the public. AGI has developed online content, factsheets, and case studies with different levels of technical complexity so people can explore societally-relevant geoscience topics at their level of technical proficiency. A related webinar series is attracting a growing worldwide audience from many employment sectors. Partnering with government agencies and other scientific and professional societies has increased the visibility and credibility of these information products with our target audience. Surveys and other feedback show that these products are raising awareness of the geosciences and helping to build reciprocal relationships between geoscientists and decision makers. The core message of all

  18. eHealth Applications Promising Strategies for Behavior Change

    CERN Document Server

    Noar, Seth M

    2012-01-01

    eHealth Applications: Promising Strategies for Behavior Change provides an overview of technological applications in contemporary health communication research, exploring the history and current uses of eHealth applications in disease prevention and management. This volume focuses on the use of these technology-based interventions for public health promotion and explores the rapid growth of an innovative interdisciplinary field. The chapters in this work discuss key eHealth applications by presenting research examining a variety of technology-based applications. Authors Seth M. Noar and Nancy

  19. New NOx cleaning technology helps the government fulfil promise

    International Nuclear Information System (INIS)

    2006-01-01

    The Norwegian, Bergen-based company ECO Energy has recently launched a new cleaning technology halving NO x emissions from industry plants without requiring large investments. Thus, governmental promises to finance NO x cleaning equipment for Norwegian industry have become a less expensive to reach. ECO Energy has ensured world patent on the 'stopNOx' technology. Its method consists of adding water and urea to oil before the combustion process. The technology has been applied in Italy, reducing NO x emissions from industry in average with above 50 percent (ml)

  20. The microeconomics of personalized medicine: today's challenge and tomorrow's promise.

    Science.gov (United States)

    Davis, Jerel C; Furstenthal, Laura; Desai, Amar A; Norris, Troy; Sutaria, Saumya; Fleming, Edd; Ma, Philip

    2009-04-01

    'Personalized medicine' promises to increase the quality of clinical care and, in some cases, decrease health-care costs. Despite this, only a handful of diagnostic tests have made it to market, with mixed success. Historically, the challenges in this field were scientific. However, as discussed in this article, with the maturation of the '-omics' sciences, it now seems that the major barriers are increasingly related to economics. Overcoming the poor microeconomic alignment of incentives among key stakeholders is therefore crucial to catalysing the further development and adoption of personalized medicine, and we propose several actions that could help achieve this goal.

  1. Tradeoffs in fuel cycle performance for most promising options - 15346

    International Nuclear Information System (INIS)

    Taiwo, T.; Kim, T.K.; Feng, B.; Stauff, N.; Hoffman, E.; Ganda, F.; Todosow, M.; Brown, N.; Raitses, G.; Gehin, J.; Powers, J.; Youinou, G.; Hiruta, H.; Wigeland, R.

    2015-01-01

    A recent Evaluation and Screening (E/S) study of nuclear fuel cycle options was conducted by grouping all potential options into 40 Evaluation Groups (EGs) based on similarities in fundamental physics characteristics and fuel cycle performance. Through a rigorous evaluation process considering benefit and challenge metrics, 4 of these EGs were identified by the E/S study as 'most promising'. All 4 involve continuous recycle of U/Pu or U/TRU with natural uranium feed in fast critical reactors. However, these most promising EGs also include fuel cycle groups with variations on feed materials, neutron spectra, and reactor criticality. Therefore, the impacts of the addition of natural thorium fuel feed to a system that originally only used natural uranium fuel feed, using an intermediate spectrum instead of a fast spectrum, and using externally-driven systems versus critical reactors were evaluated. It was found that adding thorium to the natural uranium feed mixture leads to lower burnup, higher mass flows, and degrades fuel cycle benefit metrics (waste management, resource utilization, etc.) for fuel cycles that continuously recycle U/Pu or U/TRU. Adding thorium results in fissions of 233 U instead of just 239 Pu and in turn results in a lower average number of neutrons produced per absorption (η) for the fast reactor system. For continuous recycling systems, the lower η results in lower excess reactivity and subsequently lower achievable fuel burnup. This in turn leads to higher mass flows (fabrication, reprocessing, disposal, etc.) to produce a given amount of energy and subsequent lower metrics performance. The investigated fuel cycle options with intermediate spectrum reactors also exhibited degraded performance in the benefit metrics compared to fast spectrum reactors. Similarly, this is due to lower η values as the spectrum softens. The best externally-driven systems exhibited similar performance as fast critical reactors in terms of mass flows

  2. Dimeric Surfactants: Promising Ingredients of Cosmetics and Toiletries

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    2013-11-01

    Full Text Available Surfactants are an essential ingredient for cosmetic, toiletries and personal care products for enhancing their performance. Dimeric surfactants demonstrate superiority compared to conventional surfactants in all areas of application. Dimeric surfactants are extremely promising for utilization in various cosmetic formulations viz. shampoo, lotions, creams, conditioners etc. These surfactants possess extremely unique surface properties viz. lower surface tension, unique micellization, low critical micelle concentration (CMC and antimicrobial activity, higher solubilization etc. Dimerics enhance the performances of cosmetics in an extraordinary manner and provide eco-friendly preparations for human epidermis.

  3. N-cinnamoylated aminoquinolines as promising antileishmanial agents.

    Science.gov (United States)

    Vale-Costa, S; Costa-Gouveia, J; Pérez, B; Silva, T; Teixeira, C; Gomes, P; Gomes, M S

    2013-10-01

    A series of cinnamic acid conjugates of primaquine and chloroquine were evaluated for their in vitro antileishmanial activities. Although primaquine derivatives had modest activity, chloroquine conjugates exhibited potent activity against both promastigotes (50% inhibitory concentration [IC50] = 2.6 to 21.8 μM) and intramacrophagic amastigotes (IC50 = 1.2 to 9.3 μM) of Leishmania infantum. Both the high activity of these chloroquine analogues and their mild-to-low toxicity toward host cells make them promising leads for the discovery of new antileishmanial agents.

  4. Autoignition of straight-run naphtha: A promising fuel for advanced compression ignition engines

    KAUST Repository

    Alabbad, Mohammed

    2017-11-24

    Naphtha, a low-octane distillate fuel, has been proposed as a promising low-cost fuel for advanced compression ignition engine technologies. Experimental and modelling studies have been conducted in this work to assess autoignition characteristics of naphtha for use in advanced engines. Ignition delay times of a certified straight-run naphtha fuel, supplied by Haltermann Solutions, were measured in a shock tube and a rapid comparison machine over wide ranges of experimental conditions (20 and 60 bar, 620–1223 K, ϕ = 0.5, 1 and 2). The Haltermann straight-run naphtha (HSRN) has research octane number (RON) of 60 and motor octane number (MON) of 58.3, with carbon range spanning C3–C9. Reactivity of HSRN was compared, via experiments and simulations, with three suitably formulated surrogates: a two-component PRF (n-heptane/iso-octane) surrogate, a three-component TPRF (toluene/n-heptane/iso-octane) surrogate, and a six-component surrogate. All surrogates reasonably captured the ignition delays of HSRN at high and intermediate temperatures. However, at low temperatures (T < 750 K), the six-component surrogate performed the best in emulating the reactivity of naphtha fuel. Temperature sensitivity and rate of production analyses revealed that the presence of cyclo-alkanes in naphtha inhibits the overall fuel reactivity. Zero-dimensional engine simulations showed that PRF is a good autoignition surrogate for naphtha at high engine loads, however, the six-component surrogate is needed to match the combustion phasing of naphtha at low engine loads.

  5. Autoignition of straight-run naphtha: A promising fuel for advanced compression ignition engines

    KAUST Repository

    Alabbad, Mohammed; Issayev, Gani; Badra, Jihad; Voice, Alexander K.; Giri, Binod; Djebbi, Khalil; Ahmed, Ahfaz; Sarathy, Mani; Farooq, Aamir

    2017-01-01

    Naphtha, a low-octane distillate fuel, has been proposed as a promising low-cost fuel for advanced compression ignition engine technologies. Experimental and modelling studies have been conducted in this work to assess autoignition characteristics of naphtha for use in advanced engines. Ignition delay times of a certified straight-run naphtha fuel, supplied by Haltermann Solutions, were measured in a shock tube and a rapid comparison machine over wide ranges of experimental conditions (20 and 60 bar, 620–1223 K, ϕ = 0.5, 1 and 2). The Haltermann straight-run naphtha (HSRN) has research octane number (RON) of 60 and motor octane number (MON) of 58.3, with carbon range spanning C3–C9. Reactivity of HSRN was compared, via experiments and simulations, with three suitably formulated surrogates: a two-component PRF (n-heptane/iso-octane) surrogate, a three-component TPRF (toluene/n-heptane/iso-octane) surrogate, and a six-component surrogate. All surrogates reasonably captured the ignition delays of HSRN at high and intermediate temperatures. However, at low temperatures (T < 750 K), the six-component surrogate performed the best in emulating the reactivity of naphtha fuel. Temperature sensitivity and rate of production analyses revealed that the presence of cyclo-alkanes in naphtha inhibits the overall fuel reactivity. Zero-dimensional engine simulations showed that PRF is a good autoignition surrogate for naphtha at high engine loads, however, the six-component surrogate is needed to match the combustion phasing of naphtha at low engine loads.

  6. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Directory of Open Access Journals (Sweden)

    Stéphanie Pérot

    Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

  7. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Science.gov (United States)

    Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

  8. Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.

    Science.gov (United States)

    Zhao, Jiacheng; Lai, Haiwang; Lu, Hongxu; Barner-Kowollik, Christopher; Stenzel, Martina H; Xiao, Pu

    2016-09-12

    Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 μg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.

  9. Quantum probability and cognitive modeling: some cautions and a promising direction in modeling physics learning.

    Science.gov (United States)

    Franceschetti, Donald R; Gire, Elizabeth

    2013-06-01

    Quantum probability theory offers a viable alternative to classical probability, although there are some ambiguities inherent in transferring the quantum formalism to a less determined realm. A number of physicists are now looking at the applicability of quantum ideas to the assessment of physics learning, an area particularly suited to quantum probability ideas.

  10. 7 T renal MRI: challenges and promises.

    Science.gov (United States)

    de Boer, Anneloes; Hoogduin, Johannes M; Blankestijn, Peter J; Li, Xiufeng; Luijten, Peter R; Metzger, Gregory J; Raaijmakers, Alexander J E; Umutlu, Lale; Visser, Fredy; Leiner, Tim

    2016-06-01

    The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to inhomogeneity of the radiofrequency field and due to specific absorption rate (SAR) constraints. A number of studies has been published in the field of renal 7 T imaging. While the focus initially was on anatomic imaging and renal MR angiography, later studies have explored renal functional imaging. Although anatomic imaging remains somewhat limited by inhomogeneous excitation and SAR constraints, functional imaging results are promising. The increased SNR at 7 T has been particularly advantageous for blood oxygen level-dependent and arterial spin labelling MRI, as well as sodium MR imaging, thanks to changes in field-strength-dependent magnetic properties. Here, we provide an overview of the currently available literature on renal 7 T MRI. In addition, we provide a brief overview of challenges and opportunities in renal 7 T MR imaging.

  11. Surface modification of promising cerium oxide nanoparticles for nanomedicine applications

    KAUST Repository

    Nanda, Himansu Sekhar

    2016-11-14

    Cerium oxide nanoparticles (CNPs) or nanoceria have emerged as a potential nanomedicine for the treatment of several diseases such as cancer. CNPs have a natural tendency to aggregate or agglomerate in their bare state, which leads to sedimentation in a biological environment. Since the natural biological environment is essentially aqueous, nanoparticle surface modification using suitable biocompatible hydrophilic chemical moieties is highly desirable to create effective aqueous dispersions. In this report, (6-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-hexyl)triethoxysilane was used as a functional, biocompatible organosilane to modify the surface of CNPs to produce promising nanoparticles which open substantial therapeutic avenues. The surface modified nanoparticles were produced in situ via an ammonia-induced ethylene glycol-assisted precipitation method and were characterized using complimentary characterization techniques. The interaction between the functional moiety and the nanoparticle was studied using powerful cross polarization/magic angle sample spinning solid state nuclear magnetic resonance spectroscopy. The surface-modified nanoparticles were extremely small and demonstrated a significant improvement in aqueous dispersibility. Moreover, the existence of a strong ionic coordination between the functional moiety and the surface of the nanoparticle was realised, indicating that the surface modified nanoceria are stable and that the nanoparticles should demonstrate an enhanced circulation time in a biological environment. The surface modification approach should be promising for the production of CNPs for nanomedicine applications. © The Royal Society of Chemistry.

  12. Young children mostly keep, and expect others to keep, their promises.

    Science.gov (United States)

    Kanngiesser, Patricia; Köymen, Bahar; Tomasello, Michael

    2017-07-01

    Promises are speech acts that create an obligation to do the promised action. In three studies, we investigated whether 3- and 5-year-olds (N=278) understand the normative implications of promising in prosocial interactions. In Study 1, children helped a partner who promised to share stickers. When the partner failed to uphold the promise, 3- and 5-year-olds protested and referred to promise norms. In Study 2, when children in this same age range were asked to promise to continue a cleaning task-and they agreed-they persisted longer on the task and mentioned their obligation more frequently than without such a promise. They also persisted longer after a promise than after a cleaning reminder (Study 3). In prosocial interactions, thus, young children feel a normative obligation to keep their promises and expect others to keep their promises as well. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. A new biocompatible nanocomposite as a promising constituent of sunscreens.

    Science.gov (United States)

    Amin, Rehab M; Elfeky, Souad A; Verwanger, Thomas; Krammer, Barbara

    2016-06-01

    Skin naturally uses antioxidants to protect itself from the damaging effects of sunlight. If this is not sufficient, other measures have to be taken. Like this, hydroxyapatite has the potential to be applied as an active constituent of sunscreens since calcium phosphate absorbs in the ultraviolet region (UV). The objective of the present work was to synthesize a hydroxyapatite-ascorbic acid nanocomposite (HAp/AA-NC) as a new biocompatible constituent of sunscreens and to test its efficiency with skin cell models. The synthesized HAp/AA-NC was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, absorption spectrophotometry and X-ray diffraction analysis. The protective effect of the construct was tested with respect to viability and intracellular reactive oxygen species (ROS) generation of primary human dermal fibroblasts (SKIN) and human epidermal keratinocytes (HaCaT). Both cell lines were irradiated with UV light, λmax=254 nm with a fluence of 25 mJ cm(-2) to mimic the effect of UV radiation of sunlight on the skin. Results showed that HAp/AA-NC had a stimulating effect on the cell viability of both, HaCaT and SKIN cells, relative to the irradiated control. Intracellular ROS significantly decreased in UV irradiated cells when treated with HAp/AA-NC. We conclude that the synthesized HAp/AA-NC have been validated in vitro as a skin protector against the harmful effect of UV-induced ROS. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents

    Directory of Open Access Journals (Sweden)

    Jean J. Vanden Eynde

    2016-04-01

    Full Text Available A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b. subspecies: T.b. brucei and T.b. rhodesiense, Trypanosoma cruzi, Leishmania donovani and two Plasmodium falciparum subspecies: a chloroquine-sensitive strain (NF54 and a chloroquine-resistant strain (K1. The in vitro cytotoxicity was determined against rat myoblast cells (L6. Seven compounds (5, 6, 10, 11, 12, 14, 15 showed high potency against both strains of T. brucei and P. falciparum with the inhibitory concentrations for 50% (IC50 in the nanomolar range (IC50 = 1–96 nM. None of the tested derivatives was significantly active against T. cruzi or L. donovani. Three of the more potent compounds (5, 6, 11 were evaluated in vivo in mice infected with the drug-sensitive (Lab 110 EATRO and KETRI 2002 or drug-resistant (KETRI 2538 and KETRI 1992 clinical isolates of T. brucei. Compounds 5 and 6 were highly effective in curing mice infected with the drug-sensitive strains, including a drug-resistant strain KETRI 2538, but were ineffective against KETRI 1992. Thermal melting of DNA and molecular modeling studies indicate AT-rich DNA sequences as possible binding sites for these compounds. Several of the tested compounds are suitable leads for the development of improved antiparasitic agents.

  15. Ganoderma spp.: A Promising Adjuvant Treatment for Breast Cancer

    Science.gov (United States)

    Suárez-Arroyo, Ivette J.; Loperena-Alvarez, Yaliz; Rosario-Acevedo, Raysa; Martínez-Montemayor, Michelle M.

    2017-01-01

    For the past several decades, cancer patients in the U.S. have chosen the use of natural products as an alternative or complimentary medicine approach to treat or improve their quality of life via reduction or prevention of the side effects during or after cancer treatment. The genus Ganoderma includes about 80 species of mushrooms, of which several have been used for centuries in traditional Asian medicine for their medicinal properties, including anticancer and immunoregulatory effects. Numerous bioactive compounds seem to be responsible for their healing effects. Among the approximately 400 compounds produced by Ganoderma spp., triterpenes, peptidoglycans and polysaccharides are the major physiologically-active constituents. Ganoderma anticancer effects are attributed to its efficacy in reducing cancer cell survival and growth, as well as by its chemosensitizing role. In vitro and in vivo studies have been conducted in various cancer cells and animal models; however, in this review, we focus on Ganoderma’s efficacy on breast cancers. Evidence shows that some species of Ganoderma have great potential as a natural therapeutic for breast cancer. Nevertheless, further studies are needed to investigate their potential in the clinical setting and to translate our basic scientific findings into therapeutic interventions for cancer patients. PMID:28758107

  16. Sarcoma Spheroids and Organoids—Promising Tools in the Era of Personalized Medicine

    Directory of Open Access Journals (Sweden)

    Gianluca Colella

    2018-02-01

    Full Text Available Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes. Their low incidence and high level of histopathological heterogeneity have greatly limited progress in their treatment, and trials of clinical sarcoma are less frequent than trials of other carcinomas. The main advantage of 3D cultures from tumor cells or biopsy is that they provide patient-specific models of solid tumors, and they overcome some limitations of traditional 2D monolayer cultures by reflecting cell heterogeneity, native histologic architectures, and cell–extracellular matrix interactions. Recent advances promise that these models can help bridge the gap between preclinical and clinical research by providing a relevant in vitro model of human cancer useful for drug testing and studying metastatic and dormancy mechanisms. However, additional improvements of 3D models are expected in the future, specifically the inclusion of tumor vasculature and the immune system, to enhance their full ability to capture the biological features of native tumors in high-throughput screening. Here, we summarize recent advances and future perspectives of spheroid and organoid in vitro models of rare sarcomas that can be used to investigate individual molecular biology and predict clinical responses. We also highlight how spheroid and organoid culture models could facilitate the personalization of sarcoma treatment, provide specific clinical scenarios, and discuss the relative strengths and limitations

  17. Gene therapy for the inner ear: challenges and promises.

    Science.gov (United States)

    Ryan, Allen F; Dazert, Stefan

    2009-01-01

    Since the recognition of genes as the discrete units of heritability, and of DNA as their molecular substrate, the utilization of genes for therapeutic purposes has been recognized as a potential means of correcting genetic disorders. The tools of molecular biology, which allow the manipulation of DNA sequence, provided the means to put this concept into practice. However, progress in the implementation of these ideas has been slow. Here we review the history of the idea of gene therapy and the complexity of genetic disorders. We also discuss the requirements for sequence-based therapy to be accomplished for different types of inherited diseases, as well as the methods available for gene manipulation. The challenges that have limited the applications of gene therapy are reviewed, as are ethical concerns. Finally, we discuss the promise of gene therapy to address inherited and acquired disorders of the inner ear. Copyright (c) 2009 S. Karger AG, Basel.

  18. Augmented Reality Based Doppler Lidar Data Visualization: Promises and Challenges

    Science.gov (United States)

    Cherukuru, N. W.; Calhoun, R.

    2016-06-01

    Augmented reality (AR) is a technology in which the enables the user to view virtual content as if it existed in real world. We are exploring the possibility of using this technology to view radial velocities or processed wind vectors from a Doppler wind lidar, thus giving the user an ability to see the wind in a literal sense. This approach could find possible applications in aviation safety, atmospheric data visualization as well as in weather education and public outreach. As a proof of concept, we used the lidar data from a recent field campaign and developed a smartphone application to view the lidar scan in augmented reality. In this paper, we give a brief methodology of this feasibility study, present the challenges and promises of using AR technology in conjunction with Doppler wind lidars.

  19. BMI-1, a promising therapeutic target for human cancer

    Science.gov (United States)

    WANG, MIN-CONG; LI, CHUN-LI; CUI, JIE; JIAO, MIN; WU, TAO; JING, LI; NAN, KE-JUN

    2015-01-01

    BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types. PMID:26622537

  20. Adaptation finance: How can Durban deliver on past promises?

    Energy Technology Data Exchange (ETDEWEB)

    Ciplet, David; Roperts, J. Timmons; He, Linlang; Fields, Spencer [Brown University (United States); Khan, Mizan [North South University (Bangladesh)

    2011-11-15

    There is an ever-widening chasm between the support developing countries need to adapt to climate change, and the funding promised and delivered by wealthy nations. While UN climate meetings endlessly debate terms such as 'new and additional' or 'balanced allocation', even some basic commitments to adaptation funding are going unfulfilled. And as we approach the final year of the 'fast-start' phase for climate finance, there is no plan for the crucial 'scale-up' period of 2013–2019, when contributions must swell tenfold. At the Durban negotiations, countries should take three steps to ensure the developed world can meet its agreed responsibilities: establish funding sources based on international trade; define annual targets for the scale-up; and adopt a transparent, centralised accounting system.

  1. The promises and prospects of worldwide wireless power transfer

    International Nuclear Information System (INIS)

    Van Voorhies, K.L.; Smith, J.E.

    1991-01-01

    The promise of worldwide wireless power transfer began with the pioneering work of Nikola Tesla about 100 years ago. His principal approach is summarized. The viability of such a system must still be demonstrated and many questions remain. Potentially, a wireless system can transfer power more efficiently and flexibly, especially to and from remote regions. This paper includes principle elements of worldwide wireless power transfer: the source: an oscillator/transmitter, the path: the cavity bounded by the earth and the ionosphere, and the receiver: a means of extracting power from the path. The system transfers and stores energy via the resonance modes of the cavity. The key challenges facing demonstration of technical feasibility are in finding an efficient means of coupling power into and out of the earth-ionosphere cavity, and in devising a feasible receiver that is both small and efficient. Along with demonstrating technical feasibility, new research must consider safety, environmental impact, susceptibility to weather, and effects on weather

  2. The promise of 'sporting bodies' in phenomenological thinking

    DEFF Research Database (Denmark)

    Ravn, Susanne; Høffding, Simon

    2017-01-01

    phenomenology to empirically investigate the domain of sport and exercise, phenomenologists employ empirical data to substantiate their claims concerning foundational conditions of our being-in-the-world. In this article, we suggest a way to enhance the collaboration between the two fields by pointing out......For decades, qualitative researchers have used phenomenological thinking to advance reflections on particular kinds of lifeworlds. As emphasised by Allen-Collinson phenomenology offers a continuing promise of ‘bringing the body back in’ to theories on sport and physical activity. Turning...... and giving examples of the resource of ‘the factual variation.’ Coined by Shaun Gallagher and developed from the Husserlian eidetic variation, the factual variation uses exceptional cases, normally from pathology, to shed new light on foundational phenomenological concepts. Drawing on our research of sports...

  3. Ecoinformatics (Big Data) for Agricultural Entomology: Pitfalls, Progress, and Promise.

    Science.gov (United States)

    Rosenheim, Jay A; Gratton, Claudio

    2017-01-31

    Ecoinformatics, as defined in this review, is the use of preexisting data sets to address questions in ecology. We provide the first review of ecoinformatics methods in agricultural entomology. Ecoinformatics methods have been used to address the full range of questions studied by agricultural entomologists, enabled by the special opportunities associated with data sets, nearly all of which have been observational, that are larger and more diverse and that embrace larger spatial and temporal scales than most experimental studies do. We argue that ecoinformatics research methods and traditional, experimental research methods have strengths and weaknesses that are largely complementary. We address the important interpretational challenges associated with observational data sets, highlight common pitfalls, and propose some best practices for researchers using these methods. Ecoinformatics methods hold great promise as a vehicle for capitalizing on the explosion of data emanating from farmers, researchers, and the public, as novel sampling and sensing techniques are developed and digital data sharing becomes more widespread.

  4. Advertising and drugs: a world of images and promises

    Directory of Open Access Journals (Sweden)

    Jurema Barros Dantas

    2010-11-01

    Full Text Available The aim of this article is to discuss the relation between the contemporary use and advertising of pharmaceutical drugs based on the so-called culture of consumption. We discuss advertising as a means of strengthening the belief in the power of these drugs, presenting them as a synthesis of science and technology to promote health and well being and, particularly, as a quick solution for typical problems of the contemporary world. The obligation to buy the latest medicines is becoming a symbol of social affirmation as well as the only way to weaken our daily problems. Using a logic of consumption as ownership, we create, with the help of advertising, a world of promises concerning immediate solutions, easily sold through on line shopping, supermarkets, department stores and shopping centers. We discuss this set of contemporary practices and values which are turning our way of life into a disposable product.   Keywords: advertising; consumption; pharmaceutical drugs.

  5. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

  6. High-entropy bulk metallic glasses as promising magnetic refrigerants

    International Nuclear Information System (INIS)

    Huo, Juntao; Huo, Lishan; Li, Jiawei; Men, He; Wang, Xinmin; Chang, Chuntao; Wang, Jun-Qiang; Li, Run-Wei; Inoue, Akihisa

    2015-01-01

    In this paper, the Ho 20 Er 20 Co 20 Al 20 RE 20 (RE = Gd, Dy, and Tm) high-entropy bulk metallic glasses (HE-BMGs) with good magnetocaloric properties are fabricated successfully. The HE-BMGs exhibit a second-order magnetic phase transition. The peak of magnetic entropy change (ΔS M pk ) and refrigerant capacity (RC) reaches 15.0 J kg −1 K −1 and 627 J kg −1 at 5 T, respectively, which is larger than most rare earth based BMGs. The heterogeneous nature of glasses also contributes to the large ΔS M pk and RC. In addition, the magnetic ordering temperature, ΔS M pk and RC can be widely tuned by alloying different rare earth elements. These results suggest that the HE-BMGs are promising magnetic refrigerant at low temperatures

  7. The Colombian Left: A Paradoxical Past; A Promising Future?

    Directory of Open Access Journals (Sweden)

    Charles Bergquist

    2017-07-01

    Full Text Available The essay explores the paradoxical history of the left in Colombia: how and why one of the weakest lefts in Latin America brought about the strongest and most lasting Marxist insurrection in the hemisphere in the decades following the Cuban Revolution. The article argues that the terms of this paradox are related, that the historic weakness of the left partly explains the force and longevity of revolutionary guerrillas, and that said paradox helps clarify not only the failure of several attempts to achieve a negotiated settlement of the armed conflict, but also the negative vote in the October 2016 plebiscite. Finally, it envisions a more promising future for the country’s left, provided that a lasting peace is consolidated.

  8. Views on Turkey's impending ESCO market: Is it promising?

    International Nuclear Information System (INIS)

    Okay, Esin; Okay, Nesrin; Konukman, Alp Er S.; Akman, Ugur

    2008-01-01

    Turkey's Energy Efficiency Law (EEL) came into force in May 2007. The EEL will transform energy policies implemented in the government and private sectors. The law and upcoming regulations will offer opportunities for the impending Energy Service Company (ESCO) market in Turkey. In this work, we briefly review the ESCO literature and its financing mechanisms in the world, and present our views with regard to the funding and related risks that are likely to be associated with the forthcoming Turkish ESCO market. These views are backed up with Turkish credit and banking market performance and the lessons learned from implementation of some EU-related projects involving the banking sector and small-and-medium-sized firms. We conclude that in order to create a promising competitive ESCO market, Turkey's policy must be to sustain its average 5% growth rate achieved lately for the coming decade, finish the structural reforms which will invite necessary capital inflows to ensure an economic stability and financing

  9. Realizing the promise of social psychology in improving public health.

    Science.gov (United States)

    Klein, William M P; Shepperd, James A; Suls, Jerry; Rothman, Alexander J; Croyle, Robert T

    2015-02-01

    The theories, phenomena, empirical findings, and methodological approaches that characterize contemporary social psychology hold much promise for addressing enduring problems in public health. Indeed, social psychologists played a major role in the development of the discipline of health psychology during the 1970s and 1980s. The health domain allows for the testing, refinement, and application of many interesting and important research questions in social psychology, and offers the discipline a chance to enhance its reach and visibility. Nevertheless, in a review of recent articles in two major social-psychological journals (Personality and Social Psychology Bulletin and Journal of Personality and Social Psychology), we found that only 3.2% of 467 studies explored health-related topics. In this article, we identify opportunities for research at the interface of social psychology and health, delineate barriers, and offer strategies that can address these barriers as the discipline continues to evolve. © 2014 by the Society for Personality and Social Psychology, Inc.

  10. Latin America’s information technologies: promises and realities

    Directory of Open Access Journals (Sweden)

    Estela Mastromatteo

    2009-11-01

    Full Text Available This contribution emphasizes that in order to achieve a real and sustainable human development in Latin America, and for this region to be part of the information society is extremely important to create conditions for a free access to information, education for everyone and  permanently, and a development in science and technology destined to serve society. Access to information and information technology are major promises in this era, but at the same time, become new forms of exclusion. In Latin America the two realities coexist. Is crucial in the solution, to rethink the ethics of information and values that underlie it, respect for human rights, the commitment of societies and our leaders. Highlights the role of libraries as mediators in the production process, organization and retrieval of information access, in safeguarding the freedom of information and the right to free expression through technology, with ethics and values into a real development in Latin America.

  11. Personalised Medicine and the Economy of Biotechnological Promise.

    Science.gov (United States)

    Sturdy, Steve

    2017-04-01

    Rather than seek to distinguish hype from legitimate promise, it may be more helpful to think about personalised medicine as embodying a promissory economy which serves both to mobilize resources for research and - partly at least - to determine the ends to which that research is directed. Personalised medicine is a development of the larger promissory economy of medical biotechnology. As such, it systematically conflates public benefit with the pursuit of commercial and especially pharmaceutical interests. Consequently, research and development in personalised medicine tends to favour the production of expensive new treatments over unprofitable forms of prevention or more effective use of older therapies. A rebalancing of research priorities is needed to favour the pursuit of public benefit, even when it does not deliver private profits. This will in turn require sustained reflection, self-criticism and often self-denial on the part of public research funders and the scientists they support.

  12. Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Robert J. Torphy

    2017-12-01

    Full Text Available Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3, B and T lymphocyte attenuator (BTLA, programmed death-1 homolog (PD-1H, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1, and the poliovirus receptor (PVR-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy.

  13. Mice lacking neuropeptide Y show increased sensitivity to cocaine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Woldbye, David Paul Drucker

    2012-01-01

    There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction...

  14. Targets and results of the Brazilian Biodiesel Incentive Program – Has it reached the Promised Land?

    International Nuclear Information System (INIS)

    Rathmann, Régis; Szklo, Alexandre; Schaeffer, Roberto

    2012-01-01

    Highlights: ► We test the assumptions that justified the Brazilian Biodiesel Production Program. ► The “Promised Land” has not been reached, particularly from a socioeconomic standpoint. ► The generation of jobs in the agricultural sector has been much lower than expected. -- Abstract: This study tests the assumptions that justified the establishment of the Brazilian Biodiesel Production Program (PNPB), to see whether this program has achieved its promised results. Given the connection between socioeconomic, political, technological and environmental issues, the study performs an analysis covering these different dimensions. From the socioeconomic standpoint, findings of the study show that the generation of jobs in the agricultural sector has been much lower than the expected 1.3-million-job creation figure. From the standpoint of reducing the outflow of foreign exchange because of potentially lower demand for imported diesel, the option for the methanol instead of ethanol production route has led to an increased net outflow, as the greater need to import methanol to produce biodiesel more than offsets the lesser need to import mineral diesel. Nevertheless, even though the “Promised Land” has not been reached, particularly from a socioeconomic standpoint, the premises of energy efficiency and the potential to mitigate GHG emissions appear to be on solid ground. In this respect, the input/output energy ratio of producing soy-based biodiesel and the GHG mitigation potential of pure biodiesel justify the continuing effort to improve the PNPB to achieve more promising results in relation to the other indicators.

  15. Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

    Science.gov (United States)

    Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

    2018-06-01

    Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy

  16. A new biocompatible nanocomposite as a promising constituent of sunscreens

    Energy Technology Data Exchange (ETDEWEB)

    Amin, Rehab M., E-mail: rehabamin@niles.edu.eg [Department of Laser Applications in Photochemistry, National Institute of Laser Enhanced Sciences, Cairo University (Egypt); Elfeky, Souad A. [Department of Laser Applications in Photochemistry, National Institute of Laser Enhanced Sciences, Cairo University (Egypt); University of Bath, Department of Chemistry, Bath BA2 7AY (United Kingdom); Verwanger, Thomas; Krammer, Barbara [Department of Molecular Biology, University of Salzburg, Hellbrunnerstr. 34, 5020 Salzburg (Austria)

    2016-06-01

    Skin naturally uses antioxidants to protect itself from the damaging effects of sunlight. If this is not sufficient, other measures have to be taken. Like this, hydroxyapatite has the potential to be applied as an active constituent of sunscreens since calcium phosphate absorbs in the ultraviolet region (UV). The objective of the present work was to synthesize a hydroxyapatite–ascorbic acid nanocomposite (HAp/AA-NC) as a new biocompatible constituent of sunscreens and to test its efficiency with skin cell models. The synthesized HAp/AA-NC was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, absorption spectrophotometry and X-ray diffraction analysis. The protective effect of the construct was tested with respect to viability and intracellular reactive oxygen species (ROS) generation of primary human dermal fibroblasts (SKIN) and human epidermal keratinocytes (HaCaT). Both cell lines were irradiated with UV light, λ{sub max} = 254 nm with a fluence of 25 mJ cm{sup −2} to mimic the effect of UV radiation of sunlight on the skin. Results showed that HAp/AA-NC had a stimulating effect on the cell viability of both, HaCaT and SKIN cells, relative to the irradiated control. Intracellular ROS significantly decreased in UV irradiated cells when treated with HAp/AA-NC. We conclude that the synthesized HAp/AA-NC have been validated in vitro as a skin protector against the harmful effect of UV-induced ROS. - Highlights: • Hydroxyapatite–ascorbic acid nanocomposites were synthesized and characterized. • The prepared composites had a stimulating effect on the skin cell viability. • Reactive oxygen species decreased in UV-irradiated nanocomposite treated cells. • Hydroxyapatite–ascorbic acid nanocomposites could be used in sunscreens.

  17. A new biocompatible nanocomposite as a promising constituent of sunscreens

    International Nuclear Information System (INIS)

    Amin, Rehab M.; Elfeky, Souad A.; Verwanger, Thomas; Krammer, Barbara

    2016-01-01

    Skin naturally uses antioxidants to protect itself from the damaging effects of sunlight. If this is not sufficient, other measures have to be taken. Like this, hydroxyapatite has the potential to be applied as an active constituent of sunscreens since calcium phosphate absorbs in the ultraviolet region (UV). The objective of the present work was to synthesize a hydroxyapatite–ascorbic acid nanocomposite (HAp/AA-NC) as a new biocompatible constituent of sunscreens and to test its efficiency with skin cell models. The synthesized HAp/AA-NC was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, absorption spectrophotometry and X-ray diffraction analysis. The protective effect of the construct was tested with respect to viability and intracellular reactive oxygen species (ROS) generation of primary human dermal fibroblasts (SKIN) and human epidermal keratinocytes (HaCaT). Both cell lines were irradiated with UV light, λ_m_a_x = 254 nm with a fluence of 25 mJ cm"−"2 to mimic the effect of UV radiation of sunlight on the skin. Results showed that HAp/AA-NC had a stimulating effect on the cell viability of both, HaCaT and SKIN cells, relative to the irradiated control. Intracellular ROS significantly decreased in UV irradiated cells when treated with HAp/AA-NC. We conclude that the synthesized HAp/AA-NC have been validated in vitro as a skin protector against the harmful effect of UV-induced ROS. - Highlights: • Hydroxyapatite–ascorbic acid nanocomposites were synthesized and characterized. • The prepared composites had a stimulating effect on the skin cell viability. • Reactive oxygen species decreased in UV-irradiated nanocomposite treated cells. • Hydroxyapatite–ascorbic acid nanocomposites could be used in sunscreens.

  18. A Systematic Review of Promising Strategies of Faith-Based Cancer Education and Lifestyle Interventions Among Racial/Ethnic Minority Groups.

    Science.gov (United States)

    Hou, Su-I; Cao, Xian

    2017-09-13

    Church-based interventions have been used to reach racial/ethnic minorities. In order to develop effective programs, we conducted a comprehensive systematic review of faith-based cancer prevention studies (2005~2016) to examine characteristics and promising strategies. Combination terms "church or faith-based or religion," "intervention or program," and "cancer education or lifestyle" were used in searching the five major databases: CINAHL; ERIC; Health Technology Assessments; MEDLINE; and PsycInfo. A total of 20 studies met study criteria. CDC's Community Guide was used to analyze and review group interventions. Analyses were organized by two racial groups: African American (AA) and Latino/Hispanic American groups. Results showed most studies reviewed focused on breast cancer alone or in combination with other cancers. Studies of Latino/Hispanic groups targeted more on uninsured, Medicare, or Medicaid individuals, whereas AA studies generally did not include specific insurance criteria. The sample sizes of the AA studies were generally larger. The majority of these studies reviewed used pre-post, posttest only with control group, or quasi-experience designs. The Health Belief Model was the most commonly used theory in both groups. Community-based participatory research and empowerment/ecological frameworks were also used frequently in the Latino/Hispanic studies. Small media and group education were the top two most popular intervention strategies in both groups. Although one-on-one strategy was used in some Latino studies, neither group used reducing client out-of-pocket costs strategy. Client reminders could also be used more in both groups as well. Current review showed church-based cancer education programs were effective in changing knowledge, but not always screening utilization. Results show faith-based cancer educational interventions are promising. To maximize intervention impact, future studies might consider using stronger study designs, incorporating a

  19. The effect of priming with a love concept on blood donation promise.

    Science.gov (United States)

    Charles-Sire, Virginie; Guéguen, Nicolas; Meineri, Sébastien; Martin, Angélique; Bullock, Andrea

    2014-02-01

    This field study on blood donor behavior tests the effectiveness of semantic priming on donor intention and commitment. Using face-to-face interactions, participants were primed with the concept of love and solicited to promise blood to the French National Blood Bank. Results showed a significant effect on willingness to donate blood and on donor commitment. The relatively simple and easily implemented technique used in this study could be of interest in improving performance of recruitment and retention campaigns. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Evaluation of N,N-dialkylamides as promising process extractants

    International Nuclear Information System (INIS)

    Pathak, P N; Prabhu, D R; Kanekar, A S; Manchanda, V K

    2010-01-01

    Studies carried out at BARC, India on the development of new extractants for reprocessing of spent fuel suggested that while straight chain N,N-dihexyloctanamide (DHOA) is promising alternative to TBP for the reprocessing of irradiated uranium based fuels, branched chain N,N-di(2-ethylhexyl)isobutyramide (D2EHIBA) is suitable for the selective recovery of 233 U from irradiated Th. In advanced fuel cycle scenarios, the coprocessing of U/Pu stream appears attractive particularly with respect to development of proliferation resistant technologies. DHOA extracted Pu(IV) more efficiently than TBP, both at trace-level concentration as well as under uranium/plutonium loading conditions. Uranium extraction behavior of DHOA was however, similar to that of TBP during the extraction cycle. Stripping behavior of U and Pu (without any reductant) was better for DHOA than that of TBP. It was observed during batch studies that whereas 99% Pu is stripped in four stages in case of DHOA, only 89% Pu is stripped in case of TBP under identical experimental conditions. DHOA offered better fission product decontamination than that of TBP. GANEX (Group ActiNide EXtraction) and ARTIST (Amide-based Radio-resources Treatment with Interim Storage of Transuranics) processes proposed for actinide partitioning use branched chain amides for the selective extraction of uranium from spent fuel feed solutions. The branched-alkyl monoamide (BAMA) proposed to be used in ARTIST process is N,N-di-(2-ethylhexyl)butyramide (D2EHBA). In this context, the extraction behavior of U(VI) and Pu(IV) were compared using D2EHIBA, TBP, and D2EHBA under similar concentration of nitric acid (0.5 - 6M) and of uranium (0-50g/L). These studies suggested that D2EHIBA is a promising extractant for selective extraction of uranium over plutonium in process streams. Similarly, D2EHIBA offered distinctly better decontamination of 233 U over Th and fission products under THOREX feed conditions. The possibility of simultaneous

  1. Evaluation of N,N-dialkylamides as promising process extractants

    Science.gov (United States)

    Pathak, P. N.; Prabhu, D. R.; Kanekar, A. S.; Manchanda, V. K.

    2010-03-01

    Studies carried out at BARC, India on the development of new extractants for reprocessing of spent fuel suggested that while straight chain N,N-dihexyloctanamide (DHOA) is promising alternative to TBP for the reprocessing of irradiated uranium based fuels, branched chain N,N-di(2-ethylhexyl)isobutyramide (D2EHIBA) is suitable for the selective recovery of 233U from irradiated Th. In advanced fuel cycle scenarios, the coprocessing of U/Pu stream appears attractive particularly with respect to development of proliferation resistant technologies. DHOA extracted Pu(IV) more efficiently than TBP, both at trace-level concentration as well as under uranium/plutonium loading conditions. Uranium extraction behavior of DHOA was however, similar to that of TBP during the extraction cycle. Stripping behavior of U and Pu (without any reductant) was better for DHOA than that of TBP. It was observed during batch studies that whereas 99% Pu is stripped in four stages in case of DHOA, only 89% Pu is stripped in case of TBP under identical experimental conditions. DHOA offered better fission product decontamination than that of TBP. GANEX (Group ActiNide EXtraction) and ARTIST (Amide-based Radio-resources Treatment with Interim Storage of Transuranics) processes proposed for actinide partitioning use branched chain amides for the selective extraction of uranium from spent fuel feed solutions. The branched-alkyl monoamide (BAMA) proposed to be used in ARTIST process is N,N-di-(2-ethylhexyl)butyramide (D2EHBA). In this context, the extraction behavior of U(VI) and Pu(IV) were compared using D2EHIBA, TBP, and D2EHBA under similar concentration of nitric acid (0.5 — 6M) and of uranium (0-50g/L). These studies suggested that D2EHIBA is a promising extractant for selective extraction of uranium over plutonium in process streams. Similarly, D2EHIBA offered distinctly better decontamination of 233U over Th and fission products under THOREX feed conditions. The possibility of simultaneous

  2. The promise of e-health--a Canadian perspective.

    Science.gov (United States)

    Alvarez, Richard C

    2004-01-01

    Canadians value their health care system above any other social programme. Canada's system of health care faces significant financial and population pressures, relating to cost, access, quality, accountability, and the intergration of information and communication technologies (ICTs). The health-system also faces certain unique challenges that include care delivery within a highly decentralised system of financing and accountability, and care delivery to a significant portion of the population sparsely distributed across a land mass of 10 million square kilometres, in areas of extreme climatic conditions. All of these challenges are significant catalysts in the development of technologies that aim to significantly mitigate or eliminate these selfsame challenges. The system is undergoing widespread review, nationally and within each province and territory, where the bulk of care provision is financed and managed. The challenges are being addressed by national, regional and provincial initiatives in the public, private and not-for-profit sectors. The promise of e-health lies in the manner and degree to which it can mitigate or resolve these challenges to the health system and build on advancements in ICTs supporting the development of a health infostructure. Canada is actively developing and implementing technological solutions to deliver health information and health care services across the country. These solutions, while exciting and promising, also present new challenges, particularly in regard to acceptable standards, choice of technologies, overcoming traditional jurisdictional boundaries, up-front investment, and privacy and confidentiality. Many organizations and governments are working to address these challenges. Canada Health Infoway, a not-for-profit corporation, was founded by the first ministers in 2001 to accelerate the establishment of an interoperable, pan-Canadian electronic health record. It works with partners in the federal, provincial and

  3. Show Horse Welfare: Horse Show Competitors' Understanding, Awareness, and Perceptions of Equine Welfare.

    Science.gov (United States)

    Voigt, Melissa A; Hiney, Kristina; Richardson, Jennifer C; Waite, Karen; Borron, Abigail; Brady, Colleen M

    2016-01-01

    The purpose of this study was to gain a better understanding of stock-type horse show competitors' understanding of welfare and level of concern for stock-type show horses' welfare. Data were collected through an online questionnaire that included questions relating to (a) interest and general understanding of horse welfare, (b) welfare concerns of the horse show industry and specifically the stock-type horse show industry, (c) decision-making influences, and (d) level of empathic characteristics. The majority of respondents indicated they agree or strongly agree that physical metrics should be a factor when assessing horse welfare, while fewer agreed that behavioral and mental metrics should be a factor. Respondent empathy levels were moderate to high and were positively correlated with the belief that mental and behavioral metrics should be a factor in assessing horse welfare. Respondents indicated the inhumane practices that most often occur at stock-type shows include excessive jerking on reins, excessive spurring, and induced excessive unnatural movement. Additionally, respondents indicated association rules, hired trainers, and hired riding instructors are the most influential regarding the decisions they make related to their horses' care and treatment.

  4. The Emerging Promise of Business EcoSystems

    Directory of Open Access Journals (Sweden)

    Peter Carbone

    2009-01-01

    Full Text Available This article highlights the relevance of new business models and ecosystems in the knowledge-era economy. We begin with an introduction then argue that the shift in what is valued drives the need for new business models. The third section provides examples of innovative business models. The fourth section describes two key roles in an ecosystem: keystone and niche player. Finally, the last section provides the conclusions of this article.

  5. Gene editing as a promising approach for respiratory diseases.

    Science.gov (United States)

    Bai, Yichun; Liu, Yang; Su, Zhenlei; Ma, Yana; Ren, Chonghua; Zhao, Runzhen; Ji, Hong-Long

    2018-03-01

    Respiratory diseases, which are leading causes of mortality and morbidity in the world, are dysfunctions of the nasopharynx, the trachea, the bronchus, the lung and the pleural cavity. Symptoms of chronic respiratory diseases, such as cough, sneezing and difficulty breathing, may seriously affect the productivity, sleep quality and physical and mental well-being of patients, and patients with acute respiratory diseases may have difficulty breathing, anoxia and even life-threatening respiratory failure. Respiratory diseases are generally heterogeneous, with multifaceted causes including smoking, ageing, air pollution, infection and gene mutations. Clinically, a single pulmonary disease can exhibit more than one phenotype or coexist with multiple organ disorders. To correct abnormal function or repair injured respiratory tissues, one of the most promising techniques is to correct mutated genes by gene editing, as some gene mutations have been clearly demonstrated to be associated with genetic or heterogeneous respiratory diseases. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) systems are three innovative gene editing technologies developed recently. In this short review, we have summarised the structure and operating principles of the ZFNs, TALENs and CRISPR/Cas9 systems and their preclinical and clinical applications in respiratory diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Fique Fabric: A Promising Reinforcement for Polymer Composites

    Directory of Open Access Journals (Sweden)

    Sergio Neves Monteiro

    2018-02-01

    Full Text Available A relatively unknown natural fiber extracted from the leaves of the fique plant, native of the South American Andes, has recently shown potential as reinforcement of polymer composites for engineering applications. Preliminary investigations indicated a promising substitute for synthetic fibers, competing with other well-known natural fibers. The fabric made from fique fibers have not yet been investigated as possible composite reinforcement. Therefore, in the present work a more thorough characterization of fique fabric as a reinforcement of composites with a polyester matrix was performed. Thermal mechanical properties of fique fabric composites were determined by dynamic mechanical analysis (DMA. The ballistic performance of plain woven fique fabric-reinforced polyester matrix composites was investigated as a second layer in a multilayered armor system (MAS. The results revealed a sensible improvement in thermal dynamic mechanical behavior. Both viscoelastic stiffness and glass transition temperature were increased with the amount of incorporated fique fabric. In terms of ballistic results, the fique fabric composites present a performance similar to that of the much stronger KevlarTM as an MAS second layer with the same thickness. A cost analysis indicated that armor vests with fique fabric composites as an MAS second layer would be 13 times less expensive than a similar creation made with Kevlar™.

  7. Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application

    Science.gov (United States)

    Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Kim, Hye Hyun; Seo, Hansu; Lee, Kang Dae; Oh, Junghwan

    2017-01-01

    In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications. PMID:29200851

  8. The promise--and peril--of integrated cost systems.

    Science.gov (United States)

    Cooper, R; Kaplan, R S

    1998-01-01

    Recent advances in managerial accounting have helped executives get the information they need to make good strategic decisions. But today's enterprise resource planning systems promise even greater benefits--the chance to integrate activity-based costing, operational-control, and financial reporting systems. But managers need to approach integration very thoughtfully, or they could end up with a system that drives decision making in the wrong direction. Operational-control and ABC systems have fundamentally different purposes. Their requirements for accuracy, timeliness, and aggregation are so different that no single, fully integrated approach can be adequate for both purposes. If an integrated system used real-time cost data instead of standard rates in its ABC subsystem, for example, the result would be dangerously distorted messages about individual product profitability--and that's precisely the problem ABC systems were originally designed to address. Proper linkage and feedback between the two systems is possible, however. Through activity-based budgeting, the ABC system is linked directly to operations control: managers can determine the supply and practical capacity of resources in forthcoming periods. Linking operational control to ABC is also possible. The activity-based portion of an operational control system collects information that, while it mustn't be fed directly into the activity-based strategic cost system, can be extremely useful once it's been properly analyzed. Finally, ABC and operational control can be linked to financial reporting to generate cost of goods sold and inventory valuations--but again, with precautions.

  9. Adult neural stem cells: The promise of the future

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2007-01-01

    Full Text Available Philippe TaupinNational Neuroscience Institute, National University of SingaporeAbstract: Stem cells are self-renewing undifferentiated cells that give rise to multiple types of specialized cells of the body. In the adult, stem cells are multipotents and contribute to homeostasis of the tissues and regeneration after injury. Until recently, it was believed that the adult brain was devoid of stem cells, hence unable to make new neurons and regenerate. With the recent evidences that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS, the adult brain has the potential to regenerate and may be amenable to repair. The function(s of NSCs in the adult CNS remains the source of intense research and debates. The promise of the future of adult NSCs is to redefine the functioning and physiopathology of the CNS, as well as to treat a broad range of CNS diseases and injuries.Keywords: neurogenesis, transdifferentiation, plasticity, cellular therapy

  10. Hydroxychloroquine, a promising choice for coronary artery disease?

    Science.gov (United States)

    Sun, Lizhe; Liu, Mengping; Li, Ruifeng; Zhao, Qiang; Liu, Junhui; Yang, Yanjie; Zhang, Lisha; Bai, Xiaofang; Wei, Yuanyuan; Ma, Qiangqiang; Zhou, Juan; Yuan, Zuyi; Wu, Yue

    2016-08-01

    Coronary artery disease is a common disease that seriously threaten the health of more than 150 million people per year. Atherosclerosis is considered to be the main cause of coronary artery disease which begins with damage or injury to the inner layer of a coronary artery, sometimes as early as childhood. The damage may be caused by various factors, including: smoking, high blood pressure, hypercholesterolemia, sedentary lifestyle, diabetes and insulin resistance. Once a coronary artery disease has developed, all patients need to be treated with long term standard treatment, including heart-healthy lifestyle changes, medicines, and medical procedures or surgery. Hydroxychloroquine, an original antimalarial drug, prevents inflammation caused by lupus erythematosus and rheumatoid arthritis. It is relatively safe and well-tolerated during the treatment. Since atherosclerosis and rheumatoid arthritis have resemble mechanism and increasing clinical researches confirm that hydroxychloroquine has an important role in both anti-rheumatoid arthritis and cardiovascular protection (such as anti-platelet, anti-thrombotic, lipid-regulating, anti-hypertension, hypoglycemia, and so on), we hypothesize that hydroxychloroquine might be a promising choice to coronary artery disease patients for its multiple benefits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Detonation nanodiamonds are promising nontoxic delivery system for urothelial cells.

    Science.gov (United States)

    Zupančič, Daša; Kreft, Mateja Erdani; Grdadolnik, Maja; Mitev, Dimitar; Iglič, Aleš; Veranič, Peter

    2018-01-01

    Detonation nanodiamonds (DNDs) are carbon-based nanomaterials that are among the most promising nanoparticles available for biomedical applications so far. This is due to their biocompatibility, which could be contributed to their inert core and conformable surface nature. However, DNDs cytotoxicity for urothelial cells and the routes of their internalization remains an open question in the aspect of nanodiamond surface. We therefore analyzed four types of DNDs for cytotoxicity and internalization with normal urothelial cells and two types of cancer urothelial cell lines in vitro. Viability of any of the cell types we used was not compromised with any of four DNDs we evaluated after 24-, 48- and 72-h incubation in three different concentrations of DNDs. Transmission electron microscopy revealed that all four types of DNDs were endocytosed into all three types of urothelial cells tested here. We observed DNDs in endosomes, as well as in multivesicular bodies and multilamellar bodies. These results propose using of DNDs as a delivery system for urological applications in human nanomedicine.

  12. Case series in cognitive neuropsychology: promise, perils, and proper perspective.

    Science.gov (United States)

    Rapp, Brenda

    2011-10-01

    Schwartz and Dell (2010) advocated for a major role for case series investigations in cognitive neuropsychology. They defined the key features of this approach and presented a number of arguments and examples illustrating the benefits of case series studies and their contribution to computational cognitive neuropsychology. In the Special Issue on "Case Series in Cognitive Neuropsychology" there are six commentaries on Schwartz and Dell as well as a response to the six commentaries by Dell and Schwartz (2011 this issue). In this paper, I provide a brief summary of the key points made in Schwartz and Dell, and I review the promise and perils of case series design as revealed by the six commentaries. I conclude by placing the set of papers within a broader perspective, providing some clarification of the historical record on case series and single-case approaches, raising some cautionary notes for case series studies and situating both case series and single-case approaches within the larger context of theory development in the cognitive sciences.

  13. Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

    Science.gov (United States)

    Grant, Igor; Cahn, B. Rael

    2008-01-01

    The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control. PMID:18806886

  14. Acetylcholinesterase inhibition by somes promising Brazilian medicinal plants.

    Science.gov (United States)

    Feitosa, C M; Freitas, R M; Luz, N N N; Bezerra, M Z B; Trevisan, M T S

    2011-08-01

    A microplate assay and a thin-layer chromatography (TLC) "in situ" assay based on the Ellman assay was used to screen for acetylcholinesterase inhibitors from ethyl acetate and methanol extracts of Brazilian medicinal plants of families that, according to the literature, have traditional uses that might be connected with acetylcholinesterase inhibition. Eighteen species belonging to Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae, Nyctaginaceae and Rutaceae families were tested. The most active plants were Ipomoea asarifolia (IC50 = 0.12 mg/mL), Jatropha curcas (IC50 = 0.25 mg/mL), Jatropha gossypiifolia (IC50 = 0.05 mg/mL), Kalanchoe brasiliensis (IC50 = 0.16 mg/mL) and Senna alata (IC50 = 0.08 mg/mL). The most promising extracts were the Jatropha gossypiifolia and Senna alata species assuming there were compounds with a similar activity to galanthamine, which should contain about 1% of an active compound, or if present at lower levels even more active compounds than galanthamine (IC50 = 0.37 x 10-3 mg/mL) should be present.

  15. IMPLEMENTING AN ISO 10001-BASED PROMISE IN INPATIENTS CARE

    Directory of Open Access Journals (Sweden)

    Mohammad Ashiqur Rahman Khan

    2013-09-01

    Full Text Available This paper presents the implementation of a Customer Satisfaction Promise (CSP that requires nurses to introduce themselves and explain the care plan to the patients of a hospital unit in Canada. The CSP implementation, maintenance and improvement activities were based on ISO 10001:2007. Qualitative and quantitative performance data were collected from nurses, the unit manager and patients, and improvement suggestions were made. During the implementation, nurses introduced themselves 95% of the time and explained the care plan 86% of the time. When interviewed, some nurses stated that the CSP was a good reinforcement of a practice already expected of them, which made patients happy, satisfied and more comfortable. Data from a small sample of patients was not adequate in clearly indicating the CSP's performance or improvement, but was useful in validating the survey and the feedback form. To our knowledge, applications of ISO 10001:2007 in health care have not been studied. Furthermore, this paper may be the first example of the integrated use of ISO 10001 and ISO 10002 in health care.

  16. Microencapsulation: A promising technique for controlled drug delivery.

    Science.gov (United States)

    Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

    2010-07-01

    MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

  17. Murgabskaya Oblast, a promising gas region of Central Asia

    Energy Technology Data Exchange (ETDEWEB)

    Amanniyazov, K.N.; Abdyyev, A.A.

    1981-01-01

    Gas fields of the Murgabskiy region are multiple-bed. The industrial gas content is associated with the sandy-terrigenous formations of the Shatlyk productive level of the lower Goterivskiy stage. The gas formation is anticlinal, occasionally floating. A map is compiled for the dispersal of the Shatlyk level which isolates the lithological composition, thickness, zones of dispersal of sandstone, etc. A description is provided for the map plan of the Shatlyk level. Alternation of sandy-argillaceous and carbonate rocks created favorable prerequisites for the development in the deposits of the Neocomian of lithological-physical pairs of ''collectors-mantles'', the basis for trap formation in structures and zones of lithological substitution. Within the Murgabskiy region, the greatest outlook for discovering new gas fields is confined to the Shatlyk level. It is associated with the central part of the Murgabskiy Basin where major deposits have already been discovered. A group of structures in the eastern submersion of the Kopetdag trough at the junction of the Murgabskiy Basin is important. The structures at the junction of East Kopetdag and the Murgabskiy Basin may be promising. The outlook for possible gas is associated with deposits of the lower cretaceous and Sharaplinksiy level. The main task must be comprehensive in investigation of the suprasaline apt-Neocomian and Kimmeridgian-Tithonian deposits as possible multiple-bed gas and oil containing masses.

  18. Para rubber seed oil: new promising unconventional oil for cosmetics.

    Science.gov (United States)

    Lourith, Nattaya; Kanlayavattanakul, Mayuree; Sucontphunt, Apirada; Ondee, Thunnicha

    2014-01-01

    Para rubber seed was macerated in petroleum ether and n-hexane, individually, for 30 min. The extraction was additionally performed by reflux and soxhlet for 6 h with the same solvent and proportion. Soxhlet extraction by petroleum ether afforded the greatest extractive yield (22.90 ± 0.92%). Although antioxidant activity by means of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay was insignificantly differed in soxhleted (8.90 ± 1.15%) and refluxed (9.02 ± 0.71%) by n-hexane, soxhlet extraction by n-hexane was significantly (p < 0.05) potent scavenged 2,2'-azino-bis(3-ethylbenzothaiazoline)-6-sulfonic acid) or ABTS radical with trolox equivalent antioxidant capacity (TEAC) of 66.54 ± 6.88 mg/100 g oil. This extract was non cytotoxic towards normal human fibroblast cells. In addition, oleic acid and palmitic acid were determined at a greater content than in the seed of para rubber cultivated in Malaysia, although linoleic and stearic acid contents were not differed. This bright yellow extract was further evaluated on other physicochemical characters. The determined specific gravity, refractive index, iodine value, peroxide value and saponification value were in the range of commercialized vegetable oils used as cosmetic raw material. Therefore, Para rubber seed oil is highlighted as the promising ecological ingredient appraisal for cosmetics. Transforming of the seed that is by-product of the important industrial crop of Thailand into cosmetics is encouraged accordingly.

  19. Promising oncolytic agents for metastatic breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Cody JJ

    2015-06-01

    Full Text Available James J Cody,1 Douglas R Hurst2 1ImQuest BioSciences, Frederick, MD, 2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: New therapies for metastatic breast cancer patients are urgently needed. The long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. In addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. Oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. A number of different viruses have been used to develop oncolytic agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia virus, measles virus, reovirus, and others. In general, clinical trials for several cancers have demonstrated excellent safety records and evidence of efficacy. However, the impressive tumor responses often observed in preclinical studies have yet to be realized in the clinic. In order for the promise of oncolytic virotherapy to be fully realized for breast cancer patients, effectiveness must be demonstrated in metastatic disease. This review provides a summary of oncolytic virotherapy strategies being developed to target metastatic breast cancer. Keywords: oncolytic virus, virotherapy, breast cancer, metastasis 

  20. Promising new vaccine candidates against Campylobacter in broilers.

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    Marine Meunier

    Full Text Available Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1 significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features.

  1. Survey of Promising Technologies for 5G Networks

    Directory of Open Access Journals (Sweden)

    Nam Tuan Le

    2016-01-01

    Full Text Available As an enhancement of cellular networks, the future-generation 5G network can be considered an ultra-high-speed technology. The proposed 5G network might include all types of advanced dominant technologies to provide remarkable services. Consequently, new architectures and service management schemes for different applications of the emerging technologies need to be recommended to solve issues related to data traffic capacity, high data rate, and reliability for ensuring QoS. Cloud computing, Internet of things (IoT, and software-defined networking (SDN have become some of the core technologies for the 5G network. Cloud-based services provide flexible and efficient solutions for information and communications technology by reducing the cost of investing in and managing information technology infrastructure. In terms of functionality, SDN is a promising architecture that decouples control planes and data planes to support programmability, adaptability, and flexibility in ever-changing network architectures. However, IoT combines cloud computing and SDN to achieve greater productivity for evolving technologies in 5G by facilitating interaction between the physical and human world. The major objective of this study provides a lawless vision on comprehensive works related to enabling technologies for the next generation of mobile systems and networks, mainly focusing on 5G mobile communications.

  2. Neuroimaging in psychiatric pharmacogenetics research: the promise and pitfalls.

    Science.gov (United States)

    Falcone, Mary; Smith, Ryan M; Chenoweth, Meghan J; Bhattacharjee, Abesh Kumar; Kelsoe, John R; Tyndale, Rachel F; Lerman, Caryn

    2013-11-01

    The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.

  3. Vernonia condensata Baker (Asteraceae): A Promising Source of Antioxidants

    Science.gov (United States)

    da Silva, Jucélia Barbosa; Temponi, Vanessa dos Santos; Gasparetto, Carolina Miranda; Fabri, Rodrigo Luiz; Aragão, Danielle Maria de Oliveira; Pinto, Nícolas de Castro Campos; Ribeiro, Antônia; Scio, Elita; Del-Vechio-Vieira, Glauciemar; de Sousa, Orlando Vieira

    2013-01-01

    The present study evaluated the antioxidant potential of Vernonia condensata Baker (Asteraceae). Dried and powdered leaves were exhaustively extracted with ethanol by static maceration followed by partition to obtain the hexane, dichloromethane, ethyl acetate, and butanol fractions. Total phenols and flavonoids contents were determined through spectrophotometry and flavonoids were identified by HPLC-DAD system. The antioxidant activity was assessed by DPPH radical scavenging activity, TLC-bioautography, reducing power of Fe+3, phosphomolybdenum, and TBA assays. The total phenolic content and total flavonoids ranged from 0.19 to 23.11 g/100 g and from 0.13 to 4.10 g/100 g, respectively. The flavonoids apigenin and luteolin were identified in the ethyl acetate fraction. The IC50 of DPPH assay varied from 4.28 to 75.10 µg/mL and TLC-bioautography detected the antioxidant compounds. The reducing power of Fe+3 was 19.98 to 336.48 μg/mL, while the reaction with phosphomolybdenum ranged from 13.54% to 32.63% and 56.02% to 135.00% considering ascorbic acid and rutin as reference, respectively. At 30 mg/mL, the ethanolic extract and fractions revealed significant effect against lipid peroxidation. All these data sustain that V. condensata is an important and promising source of bioactive substances with antioxidant activity. PMID:24489987

  4. Nanocellulose: a promising nanomaterial for advanced electrochemical energy storage.

    Science.gov (United States)

    Chen, Wenshuai; Yu, Haipeng; Lee, Sang-Young; Wei, Tong; Li, Jian; Fan, Zhuangjun

    2018-04-23

    Nanocellulose has emerged as a sustainable and promising nanomaterial owing to its unique structures, superb properties, and natural abundance. Here, we present a comprehensive review of the current research activities that center on the development of nanocellulose for advanced electrochemical energy storage. We begin with a brief introduction of the structural features of cellulose nanofibers within the cell walls of cellulose resources. We then focus on a variety of processes that have been explored to fabricate nanocellulose with various structures and surface chemical properties. Next, we highlight a number of energy storage systems that utilize nanocellulose-derived materials, including supercapacitors, lithium-ion batteries, lithium-sulfur batteries, and sodium-ion batteries. In this section, the main focus is on the integration of nanocellulose with other active materials, developing films/aerogel as flexible substrates, and the pyrolyzation of nanocellulose to carbon materials and their functionalization by activation, heteroatom-doping, and hybridization with other active materials. Finally, we present our perspectives on several issues that need further exploration in this active research field in the future.

  5. Case Series in Cognitive Neuropsychology: Promise, Perils and Proper Perspective

    Science.gov (United States)

    Rapp, Brenda

    2012-01-01

    Schwartz & Dell (2010) advocated for a major role for case series investigations in cognitive neuropsychology. They defined the key features of this approach and presented a number of arguments and examples illustrating the benefits of case series studies and their contribution to computational cognitive neuropsychology. In the Special Issue on “Case Series in Cognitive Neuropsychology” there are six commentaries on Schwartz and Dell (2010) as well as a response to the six commentaries by Dell and Schwartz. In this paper, I provide a brief summary of the key points made in Schwartz and Dell (2010) and I review the promise and perils of case series design as revealed by the six commentaries. I conclude by placing the set of papers within a broader perspective, providing some clarification of the historical record on case series and single case approaches, raising some cautionary notes for case series studies and situating both case series and single case approaches within the larger context of theory development in the cognitive sciences. PMID:22746685

  6. Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application.

    Science.gov (United States)

    Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Kim, Hye Hyun; Seo, Hansu; Lee, Kang Dae; Oh, Junghwan

    2017-01-01

    In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications.

  7. Visualizing Chemistry: The Progess and Promise of Advanced Chemical Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Committee on Revealing Chemistry Through Advanced Chemical Imaging

    2006-09-01

    The field of chemical imaging can provide detailed structural, functional, and applicable information about chemistry and chemical engineering phenomena that have enormous impacts on medicine, materials, and technology. In recognizing the potential for more research development in the field of chemical imaging, the National Academies was asked by the National Science Foundation, Department of Energy, U.S. Army, and National Cancer Institute to complete a study that would review the current state of molecular imaging technology, point to promising future developments and their applications, and suggest a research and educational agenda to enable breakthrough improvements in the ability to image molecular processes simultaneously in multiple physical dimensions as well as time. The study resulted in a consensus report that provides guidance for a focused research and development program in chemical imaging and identifies research needs and possible applications of imaging technologies that can provide the breakthrough knowledge in chemistry, materials science, biology, and engineering for which we should strive. Public release of this report is expected in early October.

  8. Acetylcholinesterase inhibition by somes promising Brazilian medicinal plants

    Directory of Open Access Journals (Sweden)

    CM. Feitosa

    Full Text Available A microplate assay and a thin-layer chromatography (TLC "in situ" assay based on the Ellman assay was used to screen for acetylcholinesterase inhibitors from ethyl acetate and methanol extracts of Brazilian medicinal plants of families that, according to the literature, have traditional uses that might be connected with acetylcholinesterase inhibition. Eighteen species belonging to Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae, Nyctaginaceae and Rutaceae families were tested. The most active plants were Ipomoea asarifolia (IC50 = 0.12 mg/mL, Jatropha curcas (IC50 = 0.25 mg/mL, Jatropha gossypiifolia (IC50 = 0.05 mg/mL, Kalanchoe brasiliensis (IC50 = 0.16 mg/mL and Senna alata (IC50 = 0.08 mg/mL. The most promising extracts were the Jatropha gossypiifolia and Senna alata species assuming there were compounds with a similar activity to galanthamine, which should contain about 1% of an active compound, or if present at lower levels even more active compounds than galanthamine (IC50 = 0.37 x 10-3 mg/mL should be present.

  9. Mesenchymal stem cell-derived microparticles: a promising therapeutic strategy.

    Science.gov (United States)

    Tan, Xi; Gong, Yong-Zhen; Wu, Ping; Liao, Duan-Fang; Zheng, Xi-Long

    2014-08-18

    Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.

  10. Tasty THC: Promises and Challenges of Cannabis Edibles

    Science.gov (United States)

    Barrus, Daniel G.; Capogrossi, Kristen L.; Cates, Sheryl C.; Gourdet, Camille K.; Peiper, Nicholas C.; Novak, Scott P.; Lefever, Timothy W.; Wiley, Jenny L.

    2016-01-01

    Food products containing cannabis extract (edibles) have emerged as a popular and lucrative facet of the legalized market for both recreational and medicinal cannabis. The many formulations of cannabis extracts used in edibles present a unique regulatory challenge for policy makers. Though edibles are often considered a safe, discreet, and effective means of attaining the therapeutic and/or intoxicating effects of cannabis without exposure to the potentially harmful risks of cannabis smoking, little research has evaluated how ingestion differs from other methods of cannabis administration in terms of therapeutic efficacy, subjective effects, and safety. The most prominent difference between ingestion and inhalation of cannabis extracts is the delayed onset of drug effect with ingestion. Consumers often do not understand this aspect of edible use and may consume a greater than intended amount of drug before the drug has taken effect, often resulting in profoundly adverse effects. Written for the educated layperson and for policy makers, this paper explores the current state of research regarding edibles, highlighting the promises and challenges that edibles present to both users and policy makers, and describes the approaches that four states in which recreational cannabis use is legal have taken regarding regulating edibles. PMID:28127591

  11. Volatile aldehydes are promising broad-spectrum postharvest insecticides.

    Science.gov (United States)

    Hammond, D G; Rangel, S; Kubo, I

    2000-09-01

    A variety of naturally occurring aldehydes common in plants have been evaluated for their insecticidal activity and for phytotoxicity to postharvest fruits, vegetables, and grains. Twenty-nine compounds were initially screened for their activity against aphids on fava bean leaf disks. Application under reduced pressure (partial vacuum) for the first quarter of fumigation increased insecticidal activity severalfold. The 11 best aldehydes were assayed against aphids placed under the third leaf of whole heads of iceberg lettuce using the same two-tier reduced-pressure regime, which caused no additional detriment to the commodity over fumigation at atmospheric pressure. Phytotoxicity to naked and wrapped iceburg lettuce, green and red table grapes, lemon, grapefruit, orange, broccoli, avocado, cabbage, pinto bean, and rice at doses that killed 100% of aphids was recorded for three promising fumigants: propanal, (E)-2-pentenal, and 2-methyl-(E)-2-butenal. These three compounds have excellent potential as affordable postharvest insect control agents, killing 100% of the aphids with little or no detectable harm to a majority of the commodities tested. Preliminary assays indicate that similar doses are also effective against mealybugs, thrips, and whitefly.

  12. Best in show but not best shape: a photographic assessment of show dog body condition.

    Science.gov (United States)

    Such, Z R; German, A J

    2015-08-01

    Previous studies suggest that owners often wrongly perceive overweight dogs to be in normal condition. The body shape of dogs attending shows might influence owners' perceptions, with online images of overweight show winners having a negative effect. This was an observational in silico study of canine body condition. 14 obese-prone breeds and 14 matched non-obese-probe breeds were first selected, and one operator then used an online search engine to identify 40 images, per breed, of dogs that had appeared at a major national UK show (Crufts). After images were anonymised and coded, a second observer subjectively assessed body condition, in a single sitting, using a previously validated method. Of 1120 photographs initially identified, 960 were suitable for assessing body condition, with all unsuitable images being from longhaired breeds. None of the dogs (0 per cent) were underweight, 708 (74 per cent) were in ideal condition and 252 (26 per cent) were overweight. Pugs, basset hounds and Labrador retrievers were most likely to be overweight, while standard poodles, Rhodesian ridgebacks, Hungarian vizslas and Dobermanns were least likely to be overweight. Given the proportion of show dogs from some breeds that are overweight, breed standards should be redefined to be consistent with a dog in optimal body condition. British Veterinary Association.

  13. Digital dentistry: promise, reality and the role of software standards

    NARCIS (Netherlands)

    Benalouane, A.; Bakker, Q.; Wismeijer, D.; Genuchten, M.

    2011-01-01

    Up until now, dentistry was mostly carried out in the "analogue" world: X-rays were examined on film, patient information was recorded on paper, impressions were poured in plaster to create models, models were waxed and physical dental articulators were used. Today, certain steps of the process can

  14. Synthesis, characterization and in vitro biocompatibility assessment of a novel tripeptide hydrogelator, as a promising scaffold for tissue engineering applications.

    Science.gov (United States)

    Pospišil, Tihomir; Ferhatović Hamzić, Lejla; Brkić Ahmed, Lada; Lovrić, Marija; Gajović, Srećko; Frkanec, Leo

    2016-10-20

    We have synthesized and characterized a self-assembling tripeptide hydrogelator Ac-l-Phe-l-Phe-l-Ala-NH2. A series of experiments showed that the hydrogel material could serve as a stabile and biocompatible physical support as it improves the survival of HEK293T cells in vitro, thus being a promising biomaterial for use in tissue engineering applications.

  15. Identification of Promising Remediation Technologies for Iodine in the UP-1 Operable Unit

    Energy Technology Data Exchange (ETDEWEB)

    Strickland, Christopher E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Johnson, Christian D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lee, Brady D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Qafoku, Nikolla [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Szecsody, James E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Truex, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Vermeul, Vincent R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2017-09-01

    Iodine-129 (129I) generated at the U.S. Department of Energy (DOE) Hanford Site during plutonium production was released to the subsurface, resulting in several large, though dilute, plumes in the groundwater, including the plume in the 200-UP-1 operable unit (OU). Because 129I is an uncommon contaminant, relevant remediation experience and scientific literature are limited, though work is under way to better understand the fate and transport of 129I in the environment and the effectiveness of potential remediation technologies. The recent UP-1 Evaluation Plan for Iodine and report on the Conceptual Model of Iodine Behavior in the Subsurface at the Hanford Site provide information on the history of contamination in the 200-UP-1 OU, relevant controlling processes (biological and geochemical), risk, the conceptual site model, and potential remedial options, which provided a foundation for this study. In this study, available information was compiled and used to categorize potential remediation technologies, culminating in a recommendation of promising technologies for further evaluation. Approaches to improve the technical information about promising technologies are also recommended in this study so that a subsequent evaluation of potential remediation alternatives can assess these technologies.

  16. Problem-solving versus cognitive restructuring of medically ill seniors with depression (PROMISE-D trial: study protocol and design

    Directory of Open Access Journals (Sweden)

    Sharpe Louise

    2012-11-01

    Full Text Available Abstract Background With an ageing population in most Western countries, people are living longer but often with one or more chronic physical health problems. Older people in physically poor health are at greater risk of developing clinical depression. Cognitive Behavioural Therapy (CBT and Problem Solving Therapy (PST have both been found to be efficacious in treating late-life depression, however patients with “multi-morbidity” (i.e. more than one chronic condition are often excluded from these trials. The aim of this study is to compare the efficacy of CBT and PST in treating older adults who have one or more chronic physical health conditions and a diagnosable depressive disorder. This study will be the first to explicitly target the treatment of depression in older people in primary care settings presenting with a range of health problems using behavioural interventions. Methods/design The PROMISE-D study is a randomised controlled trial of two evidence-based treatments for late-life major or minor depression for patients who also have at least one co-morbid chronic health problem. Participants will be randomised to two active interventions (PST or CBT or enhanced treatment-as-usual (E-TAU. Primary outcomes will be depression diagnostic status and severity of depression (according to the Hamilton Depression Rating Scale and the Geriatric Depression Scale. Secondary outcomes will be anxiety severity, quality of life and health care utilisation. Assessments will be conducted by a researcher who remains blind to the patient’s treatment allocation and will be conducted pre and post-treatment and at six and 12 months follow-up. Health care utilisation will be assessed throughout a two year period following entry to the trial. Executive function, rumination and emotion regulation will also be measured to determine the impact of these factors on treatment response in two treatment groups. Discussion Multi-morbidity, the experience of two or

  17. Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

    Science.gov (United States)

    Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

    2017-01-01

    Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries

  18. Centrosome – a promising anti-cancer target

    Directory of Open Access Journals (Sweden)

    Rivera-Rivera Y

    2016-12-01

    Full Text Available Yainyrette Rivera-Rivera, Harold I Saavedra Department of Pharmacology, Ponce Health Sciences University-School of Medicine, Ponce Research Institute, Ponce, Puerto Rico Abstract: The centrosome, an organelle discovered >100 years ago, is the main microtubule-organizing center in mammalian organisms. The centrosome is composed of a pair of centrioles surrounded by the pericentriolar material (PMC and plays a major role in the regulation of cell cycle transitions (G1-S, G2-M, and metaphase-anaphase, ensuring the normality of cell division. Hundreds of proteins found in the centrosome exert a variety of roles, including microtubule dynamics, nucleation, and kinetochore–microtubule attachments that allow correct chromosome alignment and segregation. Errors in these processes lead to structural (shape, size, number, position, and composition, functional (abnormal microtubule nucleation and disorganized spindles, and numerical (centrosome amplification [CA] centrosome aberrations causing aneuploidy and genomic instability. Compelling data demonstrate that centrosomes are implicated in cancer, because there are important oncogenic and tumor suppressor proteins that are localized in this organelle and drive centrosome aberrations. Centrosome defects have been found in pre-neoplasias and tumors from breast, ovaries, prostate, head and neck, lung, liver, and bladder among many others. Several drugs/compounds against centrosomal proteins have shown promising results. Other drugs have higher toxicity with modest or no benefits, and there are more recently developed agents being tested in clinical trials. All of this emerging evidence suggests that targeting centrosome aberrations may be a future avenue for therapeutic intervention in cancer research. Keywords: centrosomes, cell cycle, mitosis, CA, CIN, cancer therapy

  19. Adjacent segment disease and C-ADR: promises fulfilled?

    Science.gov (United States)

    Riew, K Daniel; Schenk-Kisser, Jeannette M.; Skelly, Andrea C.

    2012-01-01

    Study design: Systematic review. Clinical question: Do the rates and timing of adjacent segment disease (ASD) differ between cervical total disc arthroplasty (C-ADR) and anterior cervical discectomy and fusion (ACDF) in patients treated for cervical degenerative disc disease? Methods: A systematic search of MEDLINE/PubMed and bibliographies of key articles was done to identify studies with long-term follow-up for symptomatic and/or radiographic ASD comparing C-ADR with fusion for degenerative disc disease of the cervical spine. The focus was on studies with longer follow-up (48–60 months) of primary US Food and Drug Administration trials of Prestige ST, Prodisc-C, and Bryan devices as available. Trials of other discs with a minimum of 24 months follow-up were considered for inclusion. Studies evaluating lordosis/angle changes at adjacent segments and case series were excluded. Results: From 14 citations identified, four reports from three randomized controlled trials and four nonrandomized studies are summarized. Risk differences between C-ADR and ACF for symptomatic ASD were 1.5%–2.3% and were not significant across RCT reports. Time to development of ASD did not significantly differ between treatments. Rates of radiographic ASD were variable. No meaningful comparison of ASD rates based on disc design was possible. No statistical differences in adjacent segment range of motion were noted between treatment groups. Conclusion: Our analysis reveals that, to date, there is no evidence that arthroplasty decreases ASD compared with ACDF; the promise of arthroplasty decreasing ASD has not been fulfilled. PMID:23236312

  20. A promising microbiological test for the diagnosis of drowning.

    Science.gov (United States)

    Lucci, Arturo; Campobasso, Carlo P; Cirnelli, Antonello; Lorenzini, Giulio

    2008-11-20

    A number of biological and chemical tests have been developed over the years to determine whether a person was drowned. This study focuses on the potential of a microbiological test for detecting common bacterial markers of water faecal pollution such as faecal coliforms (FC) and faecal streptococci (FS) as possible indicators of drowning. A promising previous study was carried out on central and peripheral blood samples of 42 drowned victims (20 cases in saltwater and 22 cases in freshwater) and 30 not-drowned bodies. To improve the accuracy of our previous results and also in order to investigate a possible cause of a false positive due to pulmonary passive diffusion and subsequently endogenous or exogenous bacterial invasion of the blood in the post-mortem interval (PMI), the FC and FS test was applied to bodies submerged in water but died from causes other than drowning. In the present study, blood samples collected from the left ventricle (LV), right ventricle (RV), femoral artery (FA) and, femoral vein (FV) of 10 drowned victims (5 cases in freshwater and 5 cases in seawater) and 3 not-drowned individuals with bodies submerged in water for a while after death have been analysed. Preliminary results are in agreement with other reports dealing with diatoms and marine bacteria that suggest to exclude the hypothesis of a passive penetration of sufficient quantities of drowning medium into circulation after death or during the agonal period. Based on our results there is also no evidence of a relevant dissemination of endogenous micro-flora from the gastrointestinal tract affecting the FS and FC test. There are still several other factors that could influence the applicability of post-mortem FS and FC cultures for the diagnosis of drowning and they need further investigations. The present article provides only a glimpse of the potential of the FS and FC test as bacteriological method for the diagnosis of drowning.

  1. Phytoremediation of Polychlorinated Biphenyls: New Trends and Promises

    Science.gov (United States)

    Van Aken, Benoit; Correa, Paola A.; Schnoor, Jerald L.

    2011-01-01

    Transgenic plants and associated bacteria constitute a new generation of genetically modified organisms for efficient and environmental-friendly treatment of soil and water contaminated with polychlorinated biphenyls (PCBs). This review focuses on recent advances in phytoremediation for the treatment of PCBs, including the development of transgenic plants and associated bacteria. Phytoremediation, or the use of higher plants for rehabilitation of soil and groundwater, is a promising strategy for cost-effective treatment of sites contaminated by toxic compounds, including toxic PCBs. Plants can help mitigate environmental pollution by PCBs through a range of mechanisms: besides uptake from soil (phytoextraction), plants are capable of enzymatic transformation of PCBs (phytotransformation); by releasing a variety of secondary metabolites, plants also enhance the microbial activity in the root zone, improving biodegradation of PCBs (rhizoremediation). However, because of their hydrophobicity and chemical stability, PCBs are only slowly taken up and degraded by plants and associated bacteria, resulting in incomplete treatment and potential release of toxic metabolites into the environment. Moreover, naturally occurring plant-associated bacteria may not possess the enzymatic machinery necessary for PCB degradation. In order to overcome these limitations, bacterial genes involved in the metabolism of PCBs, such as biphenyl dioxygenases, have been introduced into higher plants, following a strategy similar to the development of transgenic crops. Similarly, bacteria have then been genetically modified that exhibit improved biodegradation capabilities and are able to maintain stable relationships with plants. Transgenic plants and associated bacteria bring hope for a broader and more efficient application of phytoremediation for the treatment of PCBs. PMID:20384372

  2. Indium antimonide nanowires arrays for promising thermoelectric converters

    Directory of Open Access Journals (Sweden)

    Gorokh G. G.

    2015-02-01

    Full Text Available The authors have theoretically substantiated the possibility to create promising thermoelectric converters based on quantum wires. The calculations have shown that the use of quantum wires with lateral dimensions smaller than quantum confinement values and high concentration and mobility of electrons, can lead to a substantial cooling of one of the contacts up to tens of degrees and to the heating of the other. The technological methods of manufacturing of indium antimonide nanowires arrays with high aspect ratio of the nanowire diameters to their length in the modified nanoporous anodic alumina matrixes were developed and tested. The microstructure and composition of the formed nanostructures were investigated. The electron microscopy allowed establishing that within each pore nanowires are formed with diameters of 35 nm and a length of 35 microns (equal to the matrix thickness. The electron probe x-ray microanalysis has shown that the atomic ratio of indium and antimony in the semiconductor nanostructures amounted to 38,26% and 61,74%, respectively. The current-voltage measurement between the upper and lower contacts of Cu/InSb/Cu structure (1 mm2 has shown that at 2.82 V negative voltage at the emitter contact, current density is 129,8 A/cм2, and the collector contact is heated up to 75 degrees during 150 sec. Thus, the experimental results confirmed the theoretical findings that the quantum wire systems can be used to create thermoelectric devices, which can be widely applied in electronics, in particular, for cooling integrated circuits (processors, thermal controlling of the electrical circuits by changing voltage value.

  3. Anti-chemokine small molecule drugs: a promising future?

    Science.gov (United States)

    Proudfoot, Amanda E I; Power, Christine A; Schwarz, Matthias K

    2010-03-01

    Chemokines have principally been associated with inflammation due to their role in the control of leukocyte migration, but just over a decade ago chemokine receptors were also identified as playing a pivotal role in the entry of the HIV virus into cells. Chemokines activate seven transmembrane G protein-coupled receptors, making them extremely attractive therapeutic targets for the pharmaceutical industry. Although there are now a large number of molecules targeting chemokines and chemokine receptors including neutralizing antibodies in clinical trials for inflammatory diseases, the results to date have not always been positive, which has been disappointing for the field. These failures have often been attributed to redundancy in the chemokine system. However, other difficulties have been encountered in drug discovery processes targeting the chemokine system, and these will be addressed in this review. In this review, the reader will get an insight into the hurdles that have to be overcome, learn about some of the pitfalls that may explain the lack of success, and get a glimpse of the outlook for the future. In 2007, the FDA approved maraviroc, an inhibitor of CCR5 for the prevention of HIV infection, the first triumph for a small-molecule drug acting on the chemokine system. The time to market, 11 years from discovery of CCR5, was fast by industry standards. A second small-molecule drug, a CXCR4 antagonist for hematopoietic stem cell mobilization, was approved by the FDA at the end of 2008. The results of a Phase III trial with a CCR9 inhibitor for Crohn's disease are also promising. This could herald the first success for a chemokine receptor antagonist as an anti-inflammatory therapeutic and confirms the importance of chemokine receptors as a target class for anti-inflammatory and autoimmune diseases.

  4. Alginate hydrogel as a promising scaffold for dental-derived stem cells: an in vitro study.

    Science.gov (United States)

    Moshaverinia, Alireza; Chen, Chider; Akiyama, Kentaro; Ansari, Sahar; Xu, Xingtian; Chee, Winston W; Schricker, Scott R; Shi, Songtao

    2012-12-01

    The objectives of this study were to: (1) develop an injectable and biodegradable scaffold based on oxidized alginate microbeads encapsulating periodontal ligament (PDLSCs) and gingival mesenchymal stem cells (GMSCs); and (2) investigate the stem cell viability, and osteogenic differentiation of the stem cells in vitro. Stem cells were encapsulated using alginate hydrogel. The stem cell viability, proliferation and differentiation to adipogenic and osteogenic tissues were studied. To investigate the expression of both adipogenesis and ontogenesis related genes, the RNA was extracted and RT-PCR was performed. The degradation behavior of hydrogel based on oxidized sodium alginate with different degrees of oxidation was studied in PBS at 37 °C as a function of time by monitoring the changes in weight loss. The swelling kinetics of alginate hydrogel was also investigated. The results showed that alginate is a promising candidate as a non-toxic scaffold for PDLSCs and GMSCs. It also has the ability to direct the differentiation of these stem cells to osteogenic and adipogenic tissues as compared to the control group in vitro. The encapsulated stem cells remained viable in vitro and both osteo-differentiated and adipo-differentiated after 4 weeks of culturing in the induction media. It was found that the degradation profile and swelling kinetics of alginate hydrogel strongly depends on the degree of oxidation showing its tunable chemistry and degradation rate. These findings demonstrate for the first time that immobilization of PDLSCs and GMSCs in the alginate microspheres provides a promising strategy for bone tissue engineering.

  5. The promises and pitfalls of retrieval-extinction procedures in preventing relapse to drug seeking

    Directory of Open Access Journals (Sweden)

    Gavan P McNally

    2013-03-01

    Full Text Available Relapse to drug seeking after treatment or a period of abstinence remains a fundamental challenge for drug users. The retrieval – extinction procedure offers promise in augmenting the efficacy of exposure based treatment for drug use and for protecting against relapse to drug seeking. Preceding extinction training with a brief retrieval or reminder trial, retrieval – extinction training, has been shown to reduce reinstatement of extinguished drug seeking in animal models and also to produce profound and long lasting decrements in cue-induced craving in human heroin users. However, the mechanisms that mediate these effects of retrieval - extinction training are unclear. Moreover, under some circumstances, the retrieval – extinction procedure can significantly increase vulnerability to reinstatement in animal models.

  6. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG ADDICTION: PRECLINICAL EVIDENCE

    Science.gov (United States)

    Foll, Bernard Le; Ciano, Patricia Di; Panlilio, Leigh V.; Goldberg, Steven R.; Ciccocioppo, Roberto

    2013-01-01

    This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-α and PPAR-γ. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-α agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-γ agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together this preclinical data indicates that PPAR agonists are promising new medications for drug addiction treatment. PMID:23614675

  7. An Overview of Metallic Nanowire Networks, Promising Building Blocks for Next Generation Transparent Conductors: Emergence, Fundamentals and Challenges

    Science.gov (United States)

    Pirsalami, Sedigheh; Zebarjad, Seyed Mojtaba; Daneshmanesh, Habib

    2017-08-01

    Transparent conductors (TCs) have a wide range of applications in numerous electronic and optoelectronic devices. This review provides an overview of the emergence of metallic nanowire networks (MNNs) as promising building blocks for the next generation transparent conductors. The fundamental aspects, structure-property relations, fabrication techniques and the corresponding challenges are reviewed. Theoretical and experimental researches suggest that nanowires with smaller diameter, longer length and higher aspect ratio have higher performance. Yet, the development of an efficient synthesis technique for the production of MNNs has remained a challenge. The synthesis method is also crucial to the scalability and the commercial potential of these emerging TCs. The most promising techniques for the synthesis together with their advantages, limitations and the recent findings are here discussed. Finally, we will try to show the promising future research trends in MNNs to have an approach to design the next generation TCs.

  8. Humic derivatives as promising hormone-like materials

    Science.gov (United States)

    Koroleva, R. P.; Khudaibergenova, E. M.; Kydralieva, K. A.; Jorobekova, Sh. J.

    2009-04-01

    The aim of this research is to prepare novel bio-inoculants derived from coal humic substances (HS) using bio-solubilization technique. This approach can be considered to some extent as model for supply plants with available nutrients throw the mineralisation of organic matter in soils by bacteria and fungi. Screening for the stable and active microorganisms' strains possessing ability to degrade humic substances was performed. The following subjects were examined using different isolation methods: natural microbial population from city soil, wood rot of Ulmis Pamila and biohumus of vermiculture of Eisenia foetida. Approaches for monitoring the humics-solubilizing fungi growth under liquid surface conditions in the presence of HS, proper conditions of bio-solubilization technique were elaborated. Coal humic acids (HA) from oxidized brown coal (Kyrgyz deposits) were isolated and added to a Czapek nutrient broth which was used either in full strength or without nitrogen source. The individual flasks were inoculated with natural microbial populations of corresponding cultivated soil, biohumus and wood rot samples for 12 months. Evaluation of phyto-hormonal activity of the produced HS and their derivatives in respect to higher plants with auxine and gibberellic tests was performed. To characterize structure of the biopreparations obtained, an experimental approach was undertaken that implies application of different complementary techniques for the structural analysis of biopreparations. As those were used: elemental and functional analysis, FTIR and 1H, 13C NMR spectroscopy and size-exclusion chromatography. According to the elemental composition of HS recovered from microbial cultures, a decrease in carbon and a significant increase of nitrogen in HS reisolated from the full strength broth inoculated with wood-decay microorganisms has been found. If biohumus microorganisms were used as inoculum, only minor changes were detected in the elemental composition of HS. A

  9. Cytokines and therapy in COPD: a promising combination?

    NARCIS (Netherlands)

    W.I. de Boer (Pim)

    2002-01-01

    textabstractCOPD is a major health problem, with patients showing a progressively declining, largely irreversible, change in lung function. This is associated with chronic airways inflammation and structural remodeling, including loss of alveolar walls, and goblet cell metaplasia

  10. Exploring the promises of intersectionality for advancing women's health research.

    Science.gov (United States)

    Hankivsky, Olena; Reid, Colleen; Cormier, Renee; Varcoe, Colleen; Clark, Natalie; Benoit, Cecilia; Brotman, Shari

    2010-02-11

    Women's health research strives to make change. It seeks to produce knowledge that promotes action on the variety of factors that affect women's lives and their health. As part of this general movement, important strides have been made to raise awareness of the health effects of sex and gender. The resultant base of knowledge has been used to inform health research, policy, and practice. Increasingly, however, the need to pay better attention to the inequities among women that are caused by racism, colonialism, ethnocentrism, heterosexism, and able-bodism, is confronting feminist health researchers and activists. Researchers are seeking new conceptual frameworks that can transform the design of research to produce knowledge that captures how systems of discrimination or subordination overlap and "articulate" with one another. An emerging paradigm for women's health research is intersectionality. Intersectionality places an explicit focus on differences among groups and seeks to illuminate various interacting social factors that affect human lives, including social locations, health status, and quality of life. This paper will draw on recently emerging intersectionality research in the Canadian women's health context in order to explore the promises and practical challenges of the processes involved in applying an intersectionality paradigm. We begin with a brief overview of why the need for an intersectionality approach has emerged within the context of women's health research and introduce current thinking about how intersectionality can inform and transform health research more broadly. We then highlight novel Canadian research that is grappling with the challenges in addressing issues of difference and diversity. In the analysis of these examples, we focus on a largely uninvestigated aspect of intersectionality research - the challenges involved in the process of initiating and developing such projects and, in particular, the meaning and significance of social

  11. Exploring the promises of intersectionality for advancing women's health research

    Directory of Open Access Journals (Sweden)

    Clark Natalie

    2010-02-01

    Full Text Available Abstract Women's health research strives to make change. It seeks to produce knowledge that promotes action on the variety of factors that affect women's lives and their health. As part of this general movement, important strides have been made to raise awareness of the health effects of sex and gender. The resultant base of knowledge has been used to inform health research, policy, and practice. Increasingly, however, the need to pay better attention to the inequities among women that are caused by racism, colonialism, ethnocentrism, heterosexism, and able-bodism, is confronting feminist health researchers and activists. Researchers are seeking new conceptual frameworks that can transform the design of research to produce knowledge that captures how systems of discrimination or subordination overlap and "articulate" with one another. An emerging paradigm for women's health research is intersectionality. Intersectionality places an explicit focus on differences among groups and seeks to illuminate various interacting social factors that affect human lives, including social locations, health status, and quality of life. This paper will draw on recently emerging intersectionality research in the Canadian women's health context in order to explore the promises and practical challenges of the processes involved in applying an intersectionality paradigm. We begin with a brief overview of why the need for an intersectionality approach has emerged within the context of women's health research and introduce current thinking about how intersectionality can inform and transform health research more broadly. We then highlight novel Canadian research that is grappling with the challenges in addressing issues of difference and diversity. In the analysis of these examples, we focus on a largely uninvestigated aspect of intersectionality research - the challenges involved in the process of initiating and developing such projects and, in particular, the meaning

  12. Korea's promise - a tale of two cities

    Energy Technology Data Exchange (ETDEWEB)

    Suh, K.Y., E-mail: kysuh@snu.ac.kr [Seoul National Univ., Seoul (Korea, Republic of)

    2014-07-01

    Korea is the fifth largest producer of nuclear power in the world. Regrettably, though, Seoul has bumped against huge public pressure to reduce the country's use of nuclear power after the Fukushima accident and the safety scandal, and has had to lower the share of nuclear power from 41% of all power by 2030 to 29% by 2035. This will nonetheless allow doubling its nuclear capacity within the next two decades on account of plans to build at least 16 new plants without increasing fossil fuel footprints. Korea currently has 23 NPPs operating to generate 30% of all electricity. Shin-Kori Units 5 & 6 are to be built on top of five NPPs currently under construction, and another four in the planning stage. Each will have a generation capacity of 1,400 MWe and be completed by 2020. An antinuclear activist has complained that these plans to build two new NPPs attest that the government is discounting the public concerns over safety. Korea has nonetheless learned the lessons the hard way from the fleet of reactors on her east and west coasts. Nuclear is making it back with the people, by the people, and for the people. Changes and challenges prevail in the global marketplace, waiting to be resolved and responded sooner rather than later. The debate on nuclear power and global warming needs to be about technology, cost, location and speed. There linger concerns about a probable accident at the Yongbyon nuclear complex given their inexperience with reactors, international isolation and domestic poverty. The latest mishap should be a wakeup call for the Pacific Rim in general, and Northeast Asia in particular. Korea promises to rewrite a tale of the two cities that has yet to be proudly told the story about nuclear beyond changes and challenges in the peninsula championing peaceful use and assuring global acceptance. Safety first and foremost - not a single accident will take place on the peninsula. Public opinion is usually based on what people have experienced through

  13. Periostin: a promising target of therapeutical intervention for prostate cancer

    Directory of Open Access Journals (Sweden)

    Ding Weihong

    2011-06-01

    RNA-Periostin LNCap cells growed slowly in vitro and in vivo. The tissues of xenografts as PCa were verificated by HE staining. Additionally, the weak positive Periostin expressed tumor cells could be seen in the tissues of 6 xenografts from the group of down-regulated Periostin LNCap cells which had a significant decrease of the amount of Periostin compared to the other two group. Furthermore, our results demonstrated that sliencing Periostin could inhibit migration of LNCap cells in vitro. Conclusions Our data indicates that Periostin as an up-regulated protein in PCa may be a promising target of therapeutical intervention for PCa in future.

  14. Korea's promise - a tale of two cities

    International Nuclear Information System (INIS)

    Suh, K.Y.

    2014-01-01

    Korea is the fifth largest producer of nuclear power in the world. Regrettably, though, Seoul has bumped against huge public pressure to reduce the country's use of nuclear power after the Fukushima accident and the safety scandal, and has had to lower the share of nuclear power from 41% of all power by 2030 to 29% by 2035. This will nonetheless allow doubling its nuclear capacity within the next two decades on account of plans to build at least 16 new plants without increasing fossil fuel footprints. Korea currently has 23 NPPs operating to generate 30% of all electricity. Shin-Kori Units 5 & 6 are to be built on top of five NPPs currently under construction, and another four in the planning stage. Each will have a generation capacity of 1,400 MWe and be completed by 2020. An antinuclear activist has complained that these plans to build two new NPPs attest that the government is discounting the public concerns over safety. Korea has nonetheless learned the lessons the hard way from the fleet of reactors on her east and west coasts. Nuclear is making it back with the people, by the people, and for the people. Changes and challenges prevail in the global marketplace, waiting to be resolved and responded sooner rather than later. The debate on nuclear power and global warming needs to be about technology, cost, location and speed. There linger concerns about a probable accident at the Yongbyon nuclear complex given their inexperience with reactors, international isolation and domestic poverty. The latest mishap should be a wakeup call for the Pacific Rim in general, and Northeast Asia in particular. Korea promises to rewrite a tale of the two cities that has yet to be proudly told the story about nuclear beyond changes and challenges in the peninsula championing peaceful use and assuring global acceptance. Safety first and foremost - not a single accident will take place on the peninsula. Public opinion is usually based on what people have experienced through

  15. Perspectives of the lobster-eye telescope: The promising types of cosmic X-ray sources

    Science.gov (United States)

    Šimon, V.

    2017-07-01

    We show the astrophysical aspects of observing the X-ray sky with the planned lobster-eye telescope. This instrument is important because it is able to provide wide-field X-ray imaging. For the testing observations, we propose to include also X-ray binaries in which matter transfers onto the compact object (mostly the neutron star). We show the typical features of the long-term X-ray activity of such objects. Observing in the soft X-ray band is the most promising because their X-ray intensity is the highest in this band. Since these X-ray sources tend to concentrate toward the center of our Galaxy, several of them can be present in the field of view of the tested instrument.

  16. The Forgotten Promise of E-government Maturity

    DEFF Research Database (Denmark)

    Andersen, Kim Normann; Medaglia, Rony; Vatrapu, Ravi

    2011-01-01

    Assessing e-government responsiveness is one of the major gaps in the currently dominant e-government maturity models. While we have a relatively large pool of models focusing on technological and organizational integration from a supply side perspective, measures of responsiveness of e-government...... that one third of central government agencies did not respond at all, and close to 80% of the ministries provided none or incomplete answers. Local government responds faster and provides answers that are more complete and accurate than those provided by central government. Implications for e-government...

  17. Promising applications of graphene and graphene-based nanostructures

    Science.gov (United States)

    Nguyen, Bich Ha; Hieu Nguyen, Van

    2016-06-01

    The present article is a review of research works on promising applications of graphene and graphene-based nanostructures. It contains five main scientific subjects. The first one is the research on graphene-based transparent and flexible conductive films for displays and electrodes: efficient method ensuring uniform and controllable deposition of reduced graphene oxide thin films over large areas, large-scale pattern growth of graphene films for stretchble transparent electrodes, utilization of graphene-based transparent conducting films and graphene oxide-based ones in many photonic and optoelectronic devices and equipments such as the window electrodes of inorganic, organic and dye-sensitized solar cells, organic light-emitting diodes, light-emitting electrochemical cells, touch screens, flexible smart windows, graphene-based saturated absorbers in laser cavities for ultrafast generations, graphene-based flexible, transparent heaters in automobile defogging/deicing systems, heatable smart windows, graphene electrodes for high-performance organic field-effect transistors, flexible and transparent acoustic actuators and nanogenerators etc. The second scientific subject is the research on conductive inks for printed electronics to revolutionize the electronic industry by producing cost-effective electronic circuits and sensors in very large quantities: preparing high mobility printable semiconductors, low sintering temperature conducting inks, graphene-based ink by liquid phase exfoliation of graphite in organic solutions, and developing inkjet printing technique for mass production of high-quality graphene patterns with high resolution and for fabricating a variety of good-performance electronic devices, including transparent conductors, embedded resistors, thin-film transistors and micro supercapacitors. The third scientific subject is the research on graphene-based separation membranes: molecular dynamics simulation study on the mechanisms of the transport of

  18. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability

    NARCIS (Netherlands)

    Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo

    2017-01-01

    The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and

  19. People's Education (for People's Power)--A Promise Unfulfilled

    Science.gov (United States)

    Mathebula, Thokozani

    2013-01-01

    The central feature of Athenian citizens' rights, that is, people's participation in government, is also enshrined in the South African Constitution. This article argues for the Athenian style of participatory democracy as a viable model of participation in governing South African schools. The author claims that "people's education",…

  20. Promising in vitro performances of nickel-free nitrogen containing ...

    Indian Academy of Sciences (India)

    Administrator

    studies after bone implantation in the sheep tibia of steel,. P558, indicate that P558 .... from Super Religare. Laboratory (SRL), Mumbai, India, or HiMedia, Mumbai, ..... with the model of a two-layer structure for the passive film. The values of the ...