WorldWideScience

Sample records for therapeutics discovering virulence-associated

  1. New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics

    Science.gov (United States)

    Pan, Si-Yuan; Zhou, Shu-Feng; Gao, Si-Hua; Yu, Zhi-Ling; Zhang, Shuo-Feng; Tang, Min-Ke; Sun, Jian-Ning; Han, Yi-Fan; Fong, Wang-Fun; Ko, Kam-Ming

    2013-01-01

    With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM) therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is “experience driven,” the search for a therapeutically useful synthetic drug, like “looking for a needle in a haystack,” is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development. PMID:23634172

  2. New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics

    Directory of Open Access Journals (Sweden)

    Si-Yuan Pan

    2013-01-01

    Full Text Available With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is “experience driven,” the search for a therapeutically useful synthetic drug, like “looking for a needle in a haystack,” is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development.

  3. Discovering and Developing Successful Cardiovascular Therapeutics: A Conversation With James N. Topper, MD, PhD.

    Science.gov (United States)

    Topper, James N; Rutherford, John D

    2016-11-15

    Dr James (also known as Jamie) N. Topper, MD, PhD, serves as Managing General Partner at Frazier Healthcare Partners, where he leads the Life Science Venture practice. In 2011, and 2016, he was named to the Midas List of leading venture capitalists, and, in 2013, he was recognized by Forbes as one of the top 10 healthcare investors. He has >25 years of experience working with entrepreneurs to found and build successful therapeutics-focused companies. Dr Topper holds a BS from the University of Michigan. He received an MD and PhD (in biophysics) from Stanford University School of Medicine. He completed postgraduate training in internal medicine and cardiovascular disease at the Brigham and Women's Hospital in Boston and is board certified in both disciplines. © 2016 American Heart Association, Inc.

  4. Virulence-associated gene profiling of Streptococcus suis isolates by PCR

    NARCIS (Netherlands)

    Silva, L.M.G.; Baums, C.G.; Rehm, T.; Wisselink, H.J.; Goethe, R.; Valentin-Weigand, P.

    2006-01-01

    Definition of virulent Streptococcus suis strains is controversial. One successful approach for identification of virulent European strains is differentiation of capsular serotypes (or the corresponding cps types) and subsequent detection of virulence-associated factors, namely the extracellular

  5. Modification of a virulence-associated phenotype after growth of Listeria monocytogenes on food.

    Science.gov (United States)

    Midelet-Bourdin, G; Leleu, G; Copin, S; Roche, S M; Velge, P; Malle, P

    2006-08-01

    To assess the effect of different foods, which have been implicated or not in cases of listeriosis, on the in vitro virulence-associated phenotype level of different Listeria monocytogenes strains. The virulence-associated phenotype level of L. monocytogenes was studied with the in vitro cell test based on a plaque-forming assay with a human adenocarcinoma cell line (HT-29) monolayer. Three strains of L. monocytogenes were grown in preparations (homogenate, 1-mum filtrate or 0.2-mum filtrate) of different food extracts ['rillettes' (potted minced pork), milk, raw salmon and cold-smoked salmon] or in a control medium, brain heart infusion (BHI). The bacterial suspensions grown in food extracts or in BHI at 37 degrees C were diluted with their growth medium (food extract or BHI) or with minimum essential medium before seeding on confluent HT-29 cell monolayers. Filtration of food extracts had no significant effect on the plaque numbers formed by the bacteria. A significant decrease in the plaque numbers was noted for the three strains when they grew in the rillettes extracts, compared with the other food extracts and BHI. The levels of in vitro virulence-associated phenotype of the strains after growth in the rillettes extract were similar to or lower than that of the hypovirulent internal reference strain L. monocytogenes 442. After growth in milk and cold-smoked salmon, the impact on virulence-associated phenotype depended on the strain. In contrast, plaque-forming assay indicated increased virulence-associated phenotype when the strains were switched from a nutrient-rich medium (food extract or BHI) to a minimum essential medium. In vitro virulence-associated phenotype level of the studied strains grown in BHI or cold-smoked salmon was the same as the control virulent strain EGD. In contrast, the nutrients present in rillettes may therefore substantially reduce the number of plaques but not the growth of L. monocytogenes. The utilization of minimum essential

  6. A novel virulence-associated protein, vapE, in Streptococcus suis serotype 2

    National Research Council Canada - National Science Library

    JI, XUE; SUN, YANG; LIU, JUN; ZHU, LINGWEI; GUO, XUEJUN; LANG, XULONG; FENG, SHUZHANG

    2016-01-01

    .... The present study identifies a novel virulence-associated protein E gene (vapE) of SS2. To investigate the importance of vapE in SS2 infection, a vapE knock-out mutant based on SS2 wild-type strain ZY458 was designated 458ΔvapE. 458Δ...

  7. Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Subclasses

    Directory of Open Access Journals (Sweden)

    Siti Zuraidah Mohamad Zobir

    2016-01-01

    Full Text Available Traditional Chinese medicine (TCM still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs of 45 TCM therapeutic action (subclasses from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (subclass. The MOA of a (subclass was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2 and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR, and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, “the foundation of acquired constitution” that includes spleen and stomach. In short, the TCM (subclasses, in many cases share similar targets/pathways despite having different indications.

  8. Profiling of virulence associated genes of Pasteurella multocida isolated from cattle.

    Science.gov (United States)

    Verma, Subhash; Sharma, Mandeep; Katoch, Shailja; Verma, Lovit; Kumar, Sandeep; Dogra, Vishal; Chahota, Rajesh; Dhar, Prasenjit; Singh, Geetanjali

    2013-03-01

    Pasteurella multocida is a causative agent of many major diseases of which haemorrhagic septiciemia (HS) in cattle & a buffalo is responsible for significant losses to livestock sector in India and south Asia. The disease outcome is affected by various host- and pathogen-specific determinants. Several bacterial species-specific putative virulence factors including the capsular and virulence associated genes have been proposed to play a key role in this interaction. A total of 23 isolates of P. multocida were obtained from 335 cases of various clinically healthy and diseased cattle. These isolates were examined for capsule synthesis genes (capA, B, D, E and F) and eleven virulence associated genes (tbpA, pfhA, toxA, hgbB, hgbA, nanH, nanB, sodA, sodC, oma87 and ptfA) by PCR. A total of 19 P. multocida isolates belonging to capsular type B and 4 of capsular type A were isolated. All isolates of capsular type B harboured the virulence associated genes: tbpA, pfhA, hgbA, sodC and nanH, coding for transferrin binding protein, filamentous hemagglutinin, haemoglobin binding protein, superoxide dismutase and neuraminidases, respectively; while isolates belonging to capsular type A also carried tbpA, pfhA, hgbA and nanH genes. Only 50 % of capsular type A isolates contained sodC gene while 100 % of capsular type B isolates had sodC gene. The gene nanB and toxA were absent in all the 23 isolates. In capsular type A isolates, either sodA or sodC gene was present & these genes did not occur concurrently. The presence of virulence associated gene ptfA revealed a positive association with the disease outcome in cattle and could therefore be an important epidemiological marker gene for characterizing P. multocida isolates.

  9. Structure of the virulence-associated protein VapD from the intracellular pathogen Rhodococcus equi

    Energy Technology Data Exchange (ETDEWEB)

    Whittingham, Jean L.; Blagova, Elena V. [University of York, Heslington, York YO10 5DD (United Kingdom); Finn, Ciaran E.; Luo, Haixia; Miranda-CasoLuengo, Raúl [University College Dublin, Dublin (Ireland); Turkenburg, Johan P.; Leech, Andrew P.; Walton, Paul H. [University of York, Heslington, York YO10 5DD (United Kingdom); Murzin, Alexey G. [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom); Meijer, Wim G. [University College Dublin, Dublin (Ireland); Wilkinson, Anthony J., E-mail: tony.wilkinson@york.ac.uk [University of York, Heslington, York YO10 5DD (United Kingdom)

    2014-08-01

    VapD is one of a set of highly homologous virulence-associated proteins from the multi-host pathogen Rhodococcus equi. The crystal structure reveals an eight-stranded β-barrel with a novel fold and a glycine rich ‘bald’ surface. Rhodococcus equi is a multi-host pathogen that infects a range of animals as well as immune-compromised humans. Equine and porcine isolates harbour a virulence plasmid encoding a homologous family of virulence-associated proteins associated with the capacity of R. equi to divert the normal processes of endosomal maturation, enabling bacterial survival and proliferation in alveolar macrophages. To provide a basis for probing the function of the Vap proteins in virulence, the crystal structure of VapD was determined. VapD is a monomer as determined by multi-angle laser light scattering. The structure reveals an elliptical, compact eight-stranded β-barrel with a novel strand topology and pseudo-twofold symmetry, suggesting evolution from an ancestral dimer. Surface-associated octyl-β-d-glucoside molecules may provide clues to function. Circular-dichroism spectroscopic analysis suggests that the β-barrel structure is preceded by a natively disordered region at the N-terminus. Sequence comparisons indicate that the core folds of the other plasmid-encoded virulence-associated proteins from R. equi strains are similar to that of VapD. It is further shown that sequences encoding putative R. equi Vap-like proteins occur in diverse bacterial species. Finally, the functional implications of the structure are discussed in the light of the unique structural features of VapD and its partial structural similarity to other β-barrel proteins.

  10. Discovering Technicolor

    DEFF Research Database (Denmark)

    R. Andersen, J.; Antipin, O.; Azuelos, G.

    2011-01-01

    We provide a pedagogical introduction to extensions of the Standard Model in which the Higgs is composite. These extensions are known as models of dynamical electroweak symmetry breaking or, in brief, Technicolor. Material covered includes: motivations for Technicolor, the construction of underly...... the relevant experimental benchmarks for Vanilla, Running, Walking, and Custodial Technicolor, and a natural fourth family of leptons, by laying out the framework to discover these models at the Large Hadron Collider....

  11. Discovering Wavelets

    CERN Document Server

    Aboufadel, Edward

    1999-01-01

    An accessible and practical introduction to wavelets. With applications in image processing, audio restoration, seismology, and elsewhere, wavelets have been the subject of growing excitement and interest over the past several years. Unfortunately, most books on wavelets are accessible primarily to research mathematicians. Discovering Wavelets presents basic and advanced concepts of wavelets in a way that is accessible to anyone with only a fundamental knowledge of linear algebra. The basic concepts of wavelet theory are introduced in the context of an explanation of how the FBI uses wavelets

  12. Virulence-associated gene pattern of porcine and human Yersinia enterocolitica biotype 4 isolates.

    Science.gov (United States)

    Schneeberger, M; Brodard, I; Overesch, G

    2015-04-02

    Yersinia enterocolitica 4/O:3 is the most important human pathogenic bioserotype in Europe and the predominant pathogenic bioserotype in slaughter pigs. Although many studies on the virulence of Y. enterocolitica strains have showed a broad spectrum of detectable factors in pigs and humans, an analysis based on a strict comparative approach and serving to verify the virulence capability of porcine Y. enterocolitica as a source for human yersiniosis is lacking. Therefore, in the present study, strains of biotype (BT) 4 isolated from Swiss slaughter pig tonsils and feces and isolates from human clinical cases were compared in terms of their spectrum of virulence-associated genes (yadA, virF, ail, inv, rovA, ymoA, ystA, ystB and myfA). An analysis of the associated antimicrobial susceptibility pattern completed the characterization. All analyzed BT 4 strains showed a nearly similar pattern, comprising the known fundamental virulence-associated genes yadA, virF, ail, inv, rovA, ymoA, ystA and myfA. Only ystB was not detectable among all analyzed isolates. Importantly, neither the source of the isolates (porcine tonsils and feces, humans) nor the serotype (ST) had any influence on the gene pattern. From these findings, it can be concluded that the presence of the full complement of virulence genes necessary for human infection is common among porcine BT 4 strains. Swiss porcine BT 4 strains not only showed antimicrobial susceptibility to chloramphenicol, cefotaxime, ceftazidime, ciprofloxacin, colistin, florfenicol, gentamicin, kanamycin, nalidixic acid, sulfamethoxazole, streptomycin, tetracycline and trimethoprim but also showed 100% antibiotic resistance to ampicillin. The human BT 4 strains revealed comparable results. However, in addition to 100% antibiotic resistance to ampicillin, 2 strains were resistant to chloramphenicol and nalidixic acid. Additionally, 1 of these strains was resistant to sulfamethoxazole. The results demonstrated that Y. enterocolitica BT 4

  13. cj0371: a novel virulence-associated gene of Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Xueqing Du

    2016-07-01

    Full Text Available Campylobacter jejuni is the major cause of human bacterial diarrhea worldwide. Its pathogenic mechanism remains poorly understood. cj0371 is a novel gene that was uncovered using immunoscreening. There have been no previous reports regarding its function. In this study, we constructed an insertion mutant and complement of this gene in C. jejuni and examined changes in virulence. We observed that the cj0371 mutant showed significantly increased invasion and colonization ability. We also investigated the role of cj0371 in motility, chemotaxis and growth kinetics to further study its function. We found that the cj0371 mutant displays hypermotility, enhanced chemotaxis and enhanced growth kinetics. In addition, we localized the Cj0371 protein at the poles of C. jejuni by fluorescence microscopy. We present data that collectively significantly proves our hypothesis that cj0371 is a new virulence-associated gene and through the influence of chemotaxis plays a negative role in C. jejuni pathogenicity.

  14. Discovering hidden viral piracy.

    Science.gov (United States)

    Kim, Eddo; Kliger, Yossef

    2005-12-01

    Viruses and developers of anti-inflammatory therapies share a common interest in proteins that manipulate the immune response. Large double-stranded DNA viruses acquire host proteins to evade host defense mechanisms. Hence, viral pirated proteins may have a therapeutic potential. Although dozens of viral piracy events have already been identified, we hypothesized that sequence divergence impedes the discovery of many others. We developed a method to assess the number of viral/human homologs and discovered that at least 917 highly diverged homologs are hidden in low-similarity alignment hits that are usually ignored. However, these low-similarity homologs are masked by many false alignment hits. We therefore applied a filtering method to increase the proportion of viral/human homologous proteins. The homologous proteins we found may facilitate functional annotation of viral and human proteins. Furthermore, some of these proteins play a key role in immune modulation and are therefore therapeutic protein candidates.

  15. Occurrence of virulence-associated genes in Pasteurella multocida isolates obtained from different hosts.

    Science.gov (United States)

    Shirzad Aski, Hesamaddin; Tabatabaei, Mohammad

    2016-07-01

    Pasteurella multocida infects a wide range of animals and the infection may spread to human through animal bites and scratches. Pasteurella multocida isolates, obtained from several clinically healthy and diseased animals (bovine, sheep, goat, poultry, dog and cat), were investigated for capsule biosynthesis (capA, B, D, E and F) and expression of 22 virulence-associated genes using Polymerase Chain Reaction (PCR). Multiplex PCR results revealed expression of capA, capD and capB genes in 81 (61.83%), 30 (22.90%) and 10 isolates (7.29%), respectively. However, neither of the isolates harbored capE or capF genes and ten isolates (7.29%) were negative for all cap genes. The expression of the capB gene was observed in small ruminant isolates. The occurrence of the ompA, ompH, oma87, sodA and sodC genes was noticed in all of the samples. More than 90% of the isolates harbored hgbA (96.18%), ptfA (95.41%), exbBD-tonB (93.12%), nanB (93.12%) and plbB genes (90.83%). The transferrin binding protein encoding gene tbpA was exclusively detected in the ruminant isolates. The limited number of isolates (25.95%) harbored dermonecrotoxin gene (toxA) and the highest occurrence was noted in the small ruminants, and the capsular type D isolates. This study highlights that the toxA, tbpA, and pfhA genes can be considered as important epidemiological markers for the characterization of P. multocida isolates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Triethylene Glycol Up-Regulates Virulence-Associated Genes and Proteins in Streptococcus mutans.

    Science.gov (United States)

    Sadeghinejad, Lida; Cvitkovitch, Dennis G; Siqueira, Walter L; Santerre, J Paul; Finer, Yoav

    2016-01-01

    Triethylene glycol dimethacrylate (TEGDMA) is a diluent monomer used pervasively in dental composite resins. Through hydrolytic degradation of the composites in the oral cavity it yields a hydrophilic biodegradation product, triethylene glycol (TEG), which has been shown to promote the growth of Streptococcus mutans, a dominant cariogenic bacterium. Previously it was shown that TEG up-regulated gtfB, an important gene contributing to polysaccharide synthesis function in biofilms. However, molecular mechanisms related to TEG's effect on bacterial function remained poorly understood. In the present study, S. mutans UA159 was incubated with clinically relevant concentrations of TEG at pH 5.5 and 7.0. Quantitative real-time PCR, proteomics analysis, and glucosyltransferase enzyme (GTF) activity measurements were employed to identify the bacterial phenotypic response to TEG. A S. mutans vicK isogenic mutant (SMΔvicK1) and its associated complemented strain (SMΔvicK1C), an important regulatory gene for biofilm-associated genes, were used to determine if this signaling pathway was involved in modulation of the S. mutans virulence-associated genes. Extracted proteins from S. mutans biofilms grown in the presence and absence of TEG were subjected to mass spectrometry for protein identification, characterization and quantification. TEG up-regulated gtfB/C, gbpB, comC, comD and comE more significantly in biofilms at cariogenic pH (5.5) and defined concentrations. Differential response of the vicK knock-out (SMΔvicK1) and complemented strains (SMΔvicK1C) implicated this signalling pathway in TEG-modulated cellular responses. TEG resulted in increased GTF enzyme activity, responsible for synthesizing insoluble glucans involved in the formation of cariogenic biofilms. As well, TEG increased protein abundance related to biofilm formation, carbohydrate transport, acid tolerance, and stress-response. Proteomics data was consistent with gene expression findings for the selected

  17. Triethylene Glycol Up-Regulates Virulence-Associated Genes and Proteins in Streptococcus mutans.

    Directory of Open Access Journals (Sweden)

    Lida Sadeghinejad

    Full Text Available Triethylene glycol dimethacrylate (TEGDMA is a diluent monomer used pervasively in dental composite resins. Through hydrolytic degradation of the composites in the oral cavity it yields a hydrophilic biodegradation product, triethylene glycol (TEG, which has been shown to promote the growth of Streptococcus mutans, a dominant cariogenic bacterium. Previously it was shown that TEG up-regulated gtfB, an important gene contributing to polysaccharide synthesis function in biofilms. However, molecular mechanisms related to TEG's effect on bacterial function remained poorly understood. In the present study, S. mutans UA159 was incubated with clinically relevant concentrations of TEG at pH 5.5 and 7.0. Quantitative real-time PCR, proteomics analysis, and glucosyltransferase enzyme (GTF activity measurements were employed to identify the bacterial phenotypic response to TEG. A S. mutans vicK isogenic mutant (SMΔvicK1 and its associated complemented strain (SMΔvicK1C, an important regulatory gene for biofilm-associated genes, were used to determine if this signaling pathway was involved in modulation of the S. mutans virulence-associated genes. Extracted proteins from S. mutans biofilms grown in the presence and absence of TEG were subjected to mass spectrometry for protein identification, characterization and quantification. TEG up-regulated gtfB/C, gbpB, comC, comD and comE more significantly in biofilms at cariogenic pH (5.5 and defined concentrations. Differential response of the vicK knock-out (SMΔvicK1 and complemented strains (SMΔvicK1C implicated this signalling pathway in TEG-modulated cellular responses. TEG resulted in increased GTF enzyme activity, responsible for synthesizing insoluble glucans involved in the formation of cariogenic biofilms. As well, TEG increased protein abundance related to biofilm formation, carbohydrate transport, acid tolerance, and stress-response. Proteomics data was consistent with gene expression findings for

  18. The genome of a clinical Klebsiella variicola strain reveals virulence-associated traits and a pl9-like plasmid.

    Science.gov (United States)

    Andrade, Bruno Gabriel N; de Veiga Ramos, Nilceia; Marin, Michel F Abanto; Fonseca, Erica L; Vicente, Ana Carolina P

    2014-11-01

    Klebsiella species frequently cause clinically relevant human infections worldwide. We report the draft genome sequence of a Brazilian clinical isolate (Bz19) of the recently recognized species Klebsiella variicola. The comparison of Bz19 genome content with the At-22 (environmental K. variicola) and several clinical Klebsiella pneumoniae shows that these species share a set of virulence-associated determinants. Of note, this K. variicola strain harbours a plasmid-like element that shares the same backbone present in a multidrug-resistant plasmid found in a clinical K. pneumoniae isolated in USA.

  19. Acquisition and loss of virulence-associated factors during genome evolution and speciation in three clades of Bordetella species.

    Science.gov (United States)

    Linz, Bodo; Ivanov, Yury V; Preston, Andrew; Brinkac, Lauren; Parkhill, Julian; Kim, Maria; Harris, Simon R; Goodfield, Laura L; Fry, Norman K; Gorringe, Andrew R; Nicholson, Tracy L; Register, Karen B; Losada, Liliana; Harvill, Eric T

    2016-09-30

    The genus Bordetella consists of nine species that include important respiratory pathogens such as the 'classical' species B. bronchiseptica, B. pertussis and B. parapertussis and six more distantly related and less extensively studied species. Here we analyze sequence diversity and gene content of 128 genome sequences from all nine species with focus on the evolution of virulence-associated factors. Both genome-wide sequence-based and gene content-based phylogenetic trees divide the genus into three species clades. The phylogenies are congruent between species suggesting genus-wide co-evolution of sequence diversity and gene content, but less correlated within species, mainly because of strain-specific presence of many different prophages. We compared the genomes with focus on virulence-associated genes and identified multiple clade-specific, species-specific and strain-specific events of gene acquisition and gene loss, including genes encoding O-antigens, protein secretion systems and bacterial toxins. Gene loss was more frequent than gene gain throughout the evolution, and loss of hundreds of genes was associated with the origin of several species, including the recently evolved human-restricted B. pertussis and B. holmesii, B. parapertussis and the avian pathogen B. avium. Acquisition and loss of multiple genes drive the evolution and speciation in the genus Bordetella, including large scale gene loss associated with the origin of several species. Recent loss and functional inactivation of genes, including those encoding pertussis vaccine components and bacterial toxins, in individual strains emphasize ongoing evolution.

  20. Adhesion of human and animal escherichia coli strains in association with their virulence-associated genes and phylogenetic origins

    DEFF Research Database (Denmark)

    Fr̈mmel, Ulrike; R̈diger, Stefan; B̈hm, Alexander

    2013-01-01

    VAGs) infection. Moreover, initial evidence indicates that inVAGs and exVAGs support intestinal colonization. We developed new screening tools to genotypically and phenotypically characterize E. coli isolates originating in humans, domestic pigs, and 17 wild mammal and avian species. We analyzed 317 isolates......Intestinal colonization is influenced by the ability of the bacterium to inhabit a niche, which is based on the expression of colonization factors. Escherichia coli carries a broad range of virulence-associated genes (VAGs) which contribute to intestinal (inVAGs) and extraintestinal (ex......) and the European hedgehog (Erinaceus europaeus). The prevalence of exVAGs depended on isolation from a specific host. Human uropathogenic E. coli isolates carried exVAGs with the highest prevalence, followed by badger (Meles meles) and roe deer isolates. Adhesion was found to be very diverse. Adhesion was specific...

  1. Cytokine responses in primary chicken embryo intestinal cells infected with Campylobacter jejuni strains of human and chicken origin and the expression of bacterial virulence-associated genes

    DEFF Research Database (Denmark)

    Li, Yiping; Ingmer, Hanne; Madsen, Mogens

    2008-01-01

    -free media from another co-cultivation experiment also increased the expression of the virulence-associated genes in the C. jejuni chicken isolate, indicating that the expression of bacterial genes is regulated by component(s) secreted upon co-cultivation of bacteria and CEICs. Conclusion We show that under...... in vitro culture condition C. jejuni strains of both human and chicken origins can invade avian host cells with a pro-inflammatory response and that the virulence-associated genes of C. jejuni may play a role in this process....

  2. Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas.

    Science.gov (United States)

    Pandey, Sheo Shankar; Patnana, Pradeep Kumar; Lomada, Santosh Kumar; Tomar, Archana; Chatterjee, Subhadeep

    2016-11-01

    Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named Xanthomonas iron binding regulator) of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc). Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon's involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in Xanthomonads in

  3. Siderophore biosynthesis coordinately modulated the virulence-associated interactive metabolome of uropathogenic Escherichia coli and human urine.

    Science.gov (United States)

    Su, Qiao; Guan, Tianbing; Lv, Haitao

    2016-04-14

    Uropathogenic Escherichia coli (UPEC) growth in women's bladders during urinary tract infection (UTI) incurs substantial chemical exchange, termed the "interactive metabolome", which primarily accounts for the metabolic costs (utilized metabolome) and metabolic donations (excreted metabolome) between UPEC and human urine. Here, we attempted to identify the individualized interactive metabolome between UPEC and human urine. We were able to distinguish UPEC from non-UPEC by employing a combination of metabolomics and genetics. Our results revealed that the interactive metabolome between UPEC and human urine was markedly different from that between non-UPEC and human urine, and that UPEC triggered much stronger perturbations in the interactive metabolome in human urine. Furthermore, siderophore biosynthesis coordinately modulated the individualized interactive metabolome, which we found to be a critical component of UPEC virulence. The individualized virulence-associated interactive metabolome contained 31 different metabolites and 17 central metabolic pathways that were annotated to host these different metabolites, including energetic metabolism, amino acid metabolism, and gut microbe metabolism. Changes in the activities of these pathways mechanistically pinpointed the virulent capability of siderophore biosynthesis. Together, our findings provide novel insights into UPEC virulence, and we propose that siderophores are potential targets for further discovery of drugs to treat UPEC-induced UTI.

  4. Identifying Virulence-Associated Genes Using Transcriptomic and Proteomic Association Analyses of the Plant Parasitic Nematode Bursaphelenchus mucronatus

    Directory of Open Access Journals (Sweden)

    Lifeng Zhou

    2016-09-01

    Full Text Available Bursaphelenchus mucronatus (B. mucronatus isolates that originate from different regions may vary in their virulence, but their virulence-associated genes and proteins are poorly understood. Thus, we conducted an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ to analyse transcriptomic and proteomic data of highly and weakly virulent B. mucronatus isolates during the pathogenic processes. Approximately 40,000 annotated unigenes and 5000 proteins were gained from the isolates. When we matched all of the proteins with their detected transcripts, a low correlation coefficient of r = 0.138 was found, indicating probable post-transcriptional gene regulation involved in the pathogenic processes. A functional analysis showed that five differentially expressed proteins which were all highly expressed in the highly virulent isolate were involved in the pathogenic processes of nematodes. Peroxiredoxin, fatty acid- and retinol-binding protein, and glutathione peroxidase relate to resistance against plant defence responses, while β-1,4-endoglucanase and expansin are associated with the breakdown of plant cell walls. Thus, the pathogenesis of B. mucronatus depends on its successful survival in host plants. Our work adds to the understanding of B. mucronatus’ pathogenesis, and will aid in controlling B. mucronatus and other pinewood nematode species complexes in the future.

  5. Adhesion of Human and Animal Escherichia coli Strains in Association with Their Virulence-Associated Genes and Phylogenetic Origins

    Science.gov (United States)

    Frömmel, Ulrike; Lehmann, Werner; Rödiger, Stefan; Böhm, Alexander; Nitschke, Jörg; Weinreich, Jörg; Groß, Julia; Roggenbuck, Dirk; Zinke, Olaf; Ansorge, Hermann; Vogel, Steffen; Klemm, Per; Wex, Thomas; Schröder, Christian; Wieler, Lothar H.

    2013-01-01

    Intestinal colonization is influenced by the ability of the bacterium to inhabit a niche, which is based on the expression of colonization factors. Escherichia coli carries a broad range of virulence-associated genes (VAGs) which contribute to intestinal (inVAGs) and extraintestinal (exVAGs) infection. Moreover, initial evidence indicates that inVAGs and exVAGs support intestinal colonization. We developed new screening tools to genotypically and phenotypically characterize E. coli isolates originating in humans, domestic pigs, and 17 wild mammal and avian species. We analyzed 317 isolates for the occurrence of 44 VAGs using a novel multiplex PCR microbead assay (MPMA) and for adhesion to four epithelial cell lines using a new adhesion assay. We correlated data for the definition of new adhesion genes. inVAGs were identified only sporadically, particularly in roe deer (Capreolus capreolus) and the European hedgehog ( Erinaceus europaeus). The prevalence of exVAGs depended on isolation from a specific host. Human uropathogenic E. coli isolates carried exVAGs with the highest prevalence, followed by badger (Meles meles) and roe deer isolates. Adhesion was found to be very diverse. Adhesion was specific to cells, host, and tissue, though it was also unspecific. Occurrence of the following VAGs was associated with a higher rate of adhesion to one or more cell lines: afa-dra, daaD, tsh, vat, ibeA, fyuA, mat, sfa-foc, malX, pic, irp2, and papC. In summary, we established new screening methods which enabled us to characterize large numbers of E. coli isolates. We defined reservoirs for potential pathogenic E. coli. We also identified a very broad range of colonization strategies and defined potential new adhesion genes. PMID:23872574

  6. Development of a novel multiplex PCR assay for rapid detection of virulence associated genes of Pasteurella multocida from pigs.

    Science.gov (United States)

    Rajkhowa, S

    2015-09-01

    As the pathogenicity of Pasteurella multocida is associated with various virulence factors (VFs), the aim of the study was to develop a novel multiplex PCR (m-PCR) assay for the rapid detection of important virulence associated genes (VAGs) of P. multocida isolates from pigs. The target recognized VFs used in the study were diverse adhesins (ptfA and pfhA), toxins (toxA), siderophores (tonB and hgbA), sialidases (nanB, nanH) and outer membrane proteins (ompA, ompH, oma87 and plpB). The primers for the genes encoding these VFs were designed by primer3 software (http://bioinfo.ut.ee/primer3-0.4.0/) using gene sequences available in Genbank. The detection limit of the developed assay was 10(2)  CFU ml(-1) . The m-PCR did not produce any nonspecific amplification products when tested against Bordetella bronchiseptica which also commonly infects pigs. We applied m-PCR to the field samples, and the results obtained were the same as the single PCR results. The developed assay would be very useful for veterinary diagnostic laboratories and for others interested in the rapid virulence profiling of porcine P. multocida isolates circulating in the piggeries. The study reports the development and evaluation of a novel multiplex PCR assay for the rapid detection of 11 important VAGs of Pasteurella multocida isolates from pigs. Rapid and simultaneous detection of recognized VFs of the organism are essential to know the virulo-types of P. multocida isolates circulating in the piggeries. The developed novel assay will be very useful for the rapid detection of VAGs of P. multocida isolates from pigs. © 2015 The Society for Applied Microbiology.

  7. The Fungal bZIP Transcription Factor AtfB Controls Virulence-Associated Processes in Aspergillus parasiticus

    Directory of Open Access Journals (Sweden)

    Josephine Wee

    2017-09-01

    Full Text Available Fungal basic leucine zipper (bZIP transcription factors mediate responses to oxidative stress. The ability to regulate stress response pathways in Aspergillus spp. was postulated to be an important virulence-associated cellular process, because it helps establish infection in humans, plants, and animals. Previous studies have demonstrated that the fungal transcription factor AtfB encodes a protein that is associated with resistance to oxidative stress in asexual conidiospores, and AtfB binds to the promoters of several stress response genes. Here, we conducted a gene silencing of AtfB in Aspergillus parasiticus, a well-characterized fungal pathogen of plants, animals, and humans that produces the secondary metabolite and carcinogen aflatoxin, in order to determine the mechanisms by which AtfB contributes to virulence. We show that AtfB silencing results in a decrease in aflatoxin enzyme levels, the down-regulation of aflatoxin accumulation, and impaired conidiospore development in AtfB-silenced strains. This observation is supported by a decrease of AtfB protein levels, and the down-regulation of many genes in the aflatoxin cluster, as well as genes involved in secondary metabolism and conidiospore development. Global expression analysis (RNA Seq demonstrated that AtfB functionally links oxidative stress response pathways to a broader and novel subset of target genes involved in cellular defense, as well as in actin and cytoskeleton arrangement/transport. Thus, AtfB regulates the genes involved in development, stress response, and secondary metabolism in A. parasiticus. We propose that the bZIP regulatory circuit controlled by AtfB provides a large number of excellent cellular targets to reduce fungal virulence. More importantly, understanding key players that are crucial to initiate the cellular response to oxidative stress will enable better control over its detrimental impacts on humans.

  8. Adhesion of human and animal Escherichia coli strains in association with their virulence-associated genes and phylogenetic origins.

    Science.gov (United States)

    Frömmel, Ulrike; Lehmann, Werner; Rödiger, Stefan; Böhm, Alexander; Nitschke, Jörg; Weinreich, Jörg; Groß, Julia; Roggenbuck, Dirk; Zinke, Olaf; Ansorge, Hermann; Vogel, Steffen; Klemm, Per; Wex, Thomas; Schröder, Christian; Wieler, Lothar H; Schierack, Peter

    2013-10-01

    Intestinal colonization is influenced by the ability of the bacterium to inhabit a niche, which is based on the expression of colonization factors. Escherichia coli carries a broad range of virulence-associated genes (VAGs) which contribute to intestinal (inVAGs) and extraintestinal (exVAGs) infection. Moreover, initial evidence indicates that inVAGs and exVAGs support intestinal colonization. We developed new screening tools to genotypically and phenotypically characterize E. coli isolates originating in humans, domestic pigs, and 17 wild mammal and avian species. We analyzed 317 isolates for the occurrence of 44 VAGs using a novel multiplex PCR microbead assay (MPMA) and for adhesion to four epithelial cell lines using a new adhesion assay. We correlated data for the definition of new adhesion genes. inVAGs were identified only sporadically, particularly in roe deer (Capreolus capreolus) and the European hedgehog ( Erinaceus europaeus). The prevalence of exVAGs depended on isolation from a specific host. Human uropathogenic E. coli isolates carried exVAGs with the highest prevalence, followed by badger (Meles meles) and roe deer isolates. Adhesion was found to be very diverse. Adhesion was specific to cells, host, and tissue, though it was also unspecific. Occurrence of the following VAGs was associated with a higher rate of adhesion to one or more cell lines: afa-dra, daaD, tsh, vat, ibeA, fyuA, mat, sfa-foc, malX, pic, irp2, and papC. In summary, we established new screening methods which enabled us to characterize large numbers of E. coli isolates. We defined reservoirs for potential pathogenic E. coli. We also identified a very broad range of colonization strategies and defined potential new adhesion genes.

  9. Discover: Pharmaceutical Information

    OpenAIRE

    Wales, Tim

    1998-01-01

    Discovering user's information needs and expectations is a vitally important step when working in any specialised subject area, none more so than in the field of pharmaceutical information. Adjusting search and sourcing strategies accordingly can save unnecessary time and expense, given the rising cost of subscriptions for periodicals and new media and the inherently expensive nature of niche pharmaceutical monographs and reference tests. The needs of the health professional pharmacist are ge...

  10. Students Discover Unique Planet

    Science.gov (United States)

    2008-12-01

    Three undergraduate students, from Leiden University in the Netherlands, have discovered an extrasolar planet. The extraordinary find, which turned up during their research project, is about five times as massive as Jupiter. This is also the first planet discovered orbiting a fast-rotating hot star. Omega Centauri ESO PR Photo 45a/08 A planet around a hot star The students were testing a method of investigating the light fluctuations of thousands of stars in the OGLE database in an automated way. The brightness of one of the stars was found to decrease for two hours every 2.5 days by about one percent. Follow-up observations, taken with ESO's Very Large Telescope in Chile, confirmed that this phenomenon is caused by a planet passing in front of the star, blocking part of the starlight at regular intervals. According to Ignas Snellen, supervisor of the research project, the discovery was a complete surprise. "The project was actually meant to teach the students how to develop search algorithms. But they did so well that there was time to test their algorithm on a so far unexplored database. At some point they came into my office and showed me this light curve. I was completely taken aback!" The students, Meta de Hoon, Remco van der Burg, and Francis Vuijsje, are very enthusiastic. "It is exciting not just to find a planet, but to find one as unusual as this one; it turns out to be the first planet discovered around a fast rotating star, and it's also the hottest star found with a planet," says Meta. "The computer needed more than a thousand hours to do all the calculations," continues Remco. The planet is given the prosaic name OGLE2-TR-L9b. "But amongst ourselves we call it ReMeFra-1, after Remco, Meta, and myself," says Francis. The planet was discovered by looking at the brightness variations of about 15 700 stars, which had been observed by the OGLE survey once or twice per night for about four years between 1997 and 2000. Because the data had been made public

  11. Discovering Phonemes of Bidayuh

    Directory of Open Access Journals (Sweden)

    Jecky Misieng

    2012-07-01

    Full Text Available There are generally three views of the notion of a phoneme. The structuralist view of the phoneme focuses on this language phenomenon as a phonetic reality. In discovering phonemes of a language, phonologists who hold this view will look for minimal contrasting pairs as a way to determine contrasting sounds of that language. They will also look for allophones or two sounds of the same phoneme which may appear in complementary distribution. This paper will discuss the possible application of the structuralist approach to analyzing the phonemes of a dialect of Bidayuh, one of the Malayo-Polynesian languages spoken in the northern region of Borneo.

  12. Discovering system requirements

    Energy Technology Data Exchange (ETDEWEB)

    Bahill, A.T.; Bentz, B. [Univ. of Arizona, Tucson, AZ (United States). Systems and Industrial Engineering; Dean, F.F. [Sandia National Labs., Albuquerque, NM (United States)

    1996-07-01

    Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirements process. This report provides a high-level overview of the system requirements process, explaining types, sources, and characteristics of good requirements. System requirements, however, are seldom stated by the customer. Therefore, this report shows ways to help you work with your customer to discover the system requirements. It also explains terminology commonly used in the requirements development field, such as verification, validation, technical performance measures, and the various design reviews.

  13. Distribution of antimicrobial resistance determinants, virulence-associated factors and clustered regularly interspaced palindromic repeats loci in isolates of Enterococcus faecalis from various settings and genetic lineages.

    Science.gov (United States)

    Gawryszewska, Iwona; Malinowska, Katarzyna; Kuch, Alicja; Chrobak-Chmiel, Dorota; Trokenheim, Lucja Laniewska-; Hryniewicz, Waleria; Sadowy, Ewa

    2017-03-01

    Enterococcus faecalis represents an important factor of hospital-associated infections (HAIs). The knowledge on its evolution from a commensal to an opportunistic pathogen is still limited; thus, we performed a study to characterise distribution of factors that may contribute to this adaptation. Using a collection obtained from various settings (hospitalised patients, community carriers, animals, fresh food, sewage, water), we investigated differences in antimicrobial susceptibility, distribution of antimicrobial resistance genes, virulence-associated determinants and phenotypes, and CRISPR loci in the context of the clonal relatedness of isolates. Bayesian Analysis of Population Structure revealed the presence of three major groups; two subgroups comprised almost exclusively HAI isolates, belonging to previously proposed enterococcal high-risk clonal complexes (HiRECCs) 6 and 28. Isolates of these two subgroups were significantly enriched in antimicrobial resistance genes, presumably produced a polysaccharide capsule and often carried the aggregation substance asa1; distribution of other virulence-associated genes, such as esp and cyl, formation of a biofilm and gelatinase production were more variable. Moreover, both subgroups showed a low prevalence of CRISPR-Cas 1 and 3 and presence of small CRISPR2 variants. Our study confirms the importance of HiRECCs in the population of E. faecalis and their confinement to the hospital settings. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  15. Chandra Discovers Cosmic Cannonball

    Science.gov (United States)

    2007-11-01

    One of the fastest moving stars ever seen has been discovered with NASA's Chandra X-ray Observatory. This cosmic cannonball is challenging theories to explain its blistering speed. Astronomers used Chandra to observe a neutron star, known as RX J0822-4300, over a period of about five years. During that span, three Chandra observations clearly show the neutron star moving away from the center of the Puppis A supernova remnant. This remnant is the stellar debris field created during the same explosion in which the neutron star was created about 3700 years ago. Chandra X-ray Image of RX J0822-4300 in Puppis A Chandra X-ray Image of RX J0822-4300 in Puppis A By combining how far it has moved across the sky with its distance from Earth, astronomers determined the neutron star is moving at over 3 million miles per hour. At this rate, RX J0822-4300 is destined to escape from the Milky Way after millions of years, even though it has only traveled about 20 light years so far. "This star is moving at 3 million miles an hour, but it's so far away that the apparent motion we see in five years is less than the height of the numerals in the date on a penny, seen from the length of a football field," said Frank Winkler of Middlebury College in Vermont. "It's remarkable, and a real testament to the power of Chandra, that such a tiny motion can be measured." Labeled Image of RX J0822-4300 in Puppis A Labeled Image of RX J0822-4300 in Puppis A "Just after it was born, this neutron star got a one-way ticket out of the Galaxy," said co-author Robert Petre of NASA's Goddard Space Flight Center in Greenbelt, Md. "Astronomers have seen other stars being flung out of the Milky Way, but few as fast as this." So-called hypervelocity stars have been previously discovered shooting out of the Milky Way with speeds around one million miles per hour. One key difference between RX J0822-4300 and these other reported galactic escapees is the source of their speed. The hypervelocity stars are

  16. Lightest exoplanet yet discovered

    Science.gov (United States)

    2009-04-01

    Well-known exoplanet researcher Michel Mayor today announced the discovery of the lightest exoplanet found so far. The planet, "e", in the famous system Gliese 581, is only about twice the mass of our Earth. The team also refined the orbit of the planet Gliese 581 d, first discovered in 2007, placing it well within the habitable zone, where liquid water oceans could exist. These amazing discoveries are the outcome of more than four years of observations using the most successful low-mass-exoplanet hunter in the world, the HARPS spectrograph attached to the 3.6-metre ESO telescope at La Silla, Chile. ESO PR Photo 15a/09 Artist's impression of Gliese 581 e ESO PR Photo 15b/09 A planet in the habitable zone ESO PR Video 15a/09 ESOcast 6 ESO PR Video 15b/09 VNR A-roll ESO PR Video 15c/09 Zoom-in on Gliese 581 e ESO PR Video 15d/09 Artist's impression of Gliese 581 e ESO PR Video 15e/09 Artist's impression of Gliese 581 d ESO PR Video 15f/09 Artist's impression of Gliese 581 system ESO PR Video 15g/09 The radial velocity method ESO PR Video 15h/09 Statement in English ESO PR Video 15i/09 Statement in French ESO PR Video 15j/09 La Silla Observatory "The holy grail of current exoplanet research is the detection of a rocky, Earth-like planet in the ‘habitable zone' -- a region around the host star with the right conditions for water to be liquid on a planet's surface", says Michel Mayor from the Geneva Observatory, who led the European team to this stunning breakthrough. Planet Gliese 581 e orbits its host star - located only 20.5 light-years away in the constellation Libra ("the Scales") -- in just 3.15 days. "With only 1.9 Earth-masses, it is the least massive exoplanet ever detected and is, very likely, a rocky planet", says co-author Xavier Bonfils from Grenoble Observatory. Being so close to its host star, the planet is not in the habitable zone. But another planet in this system appears to be. From previous observations -- also obtained with the HARPS spectrograph

  17. Tracking Listeria monocytogenes contamination and virulence-associated characteristics in the ready-to-eat meat-based food products industry according to the hygiene level.

    Science.gov (United States)

    Henriques, A R; Gama, L T; Fraqueza, M J

    2017-02-02

    Listeria monocytogenes isolates collected from final products and food contact surfaces of 10 ready-to-eat meat-based food products (RTEMP) producing industries were analyzed to relate their virulence-associated characteristics and genetic profiles with the hygiene assessment of those industries. Together with sample collection, an audit was performed to evaluate the implemented food safety management system and to investigate the specific audit requisites more associated to the occurrence of those L. monocytogenes serogroups frequently related with human disease. L. monocytogenes was present in 18% of the samples. The isolates (n=62) were serogrouped and detection of virulence-associated genes inlA, inlB, inlC and inlJ, and also plcA, hlyA, actA and iap was done by multiplex PCR. After this initial characterization, selected isolates (n=31) were submitted to antibiotic resistance testing by the disk diffusion method for the currently most used human and veterinary antibiotics and resistance was low. These isolates were also subtyped by pulsed-field gel electrophoresis. Genotyping and serogrouping of L. monocytogenes isolates revealed a genetically diverse population. Our data indicate that contamination of final products does not seem to be uniquely related to the sampled food surfaces. The occurrence of those L. monocytogenes serogroups more commonly associated with human disease in industries with a high hygienic audit classification could be the result of a previous identification of the pathogen, with an enforcement of the hygiene program without recognizing the real source of contamination. This reinforces the importance of a conjoined diagnosis using audit data and microbiological testing. Food safety management systems of those industries need improvement, particularly in cleaning and sanitizing operations, analytical control, preventive maintenance, personal hygiene and root cause analysis. Copyright © 2016. Published by Elsevier B.V.

  18. Digimarc Discover on Google Glass

    Science.gov (United States)

    Rogers, Eliot; Rodriguez, Tony; Lord, John; Alattar, Adnan

    2015-03-01

    This paper reports on the implementation of the Digimarc® Discover platform on Google Glass, enabling the reading of a watermark embedded in a printed material or audio. The embedded watermark typically contains a unique code that identifies the containing media or object and a synchronization signal that allows the watermark to be read robustly. The Digimarc Discover smartphone application can read the watermark from a small portion of printed image presented at any orientation or reasonable distance. Likewise, Discover can read the recently introduced Digimarc Barcode to identify and manage consumer packaged goods in the retail channel. The Digimarc Barcode has several advantages over the traditional barcode and is expected to save the retail industry millions of dollars when deployed at scale. Discover can also read an audio watermark from ambient audio captured using a microphone. The Digimarc Discover platform has been widely deployed on the iPad, iPhone and many Android-based devices, but it has not yet been implemented on a head-worn wearable device, such as Google Glass. Implementing Discover on Google Glass is a challenging task due to the current hardware and software limitations of the device. This paper identifies the challenges encountered in porting Discover to the Google Glass and reports on the solutions created to deliver a prototype implementation.

  19. Discover: What Is Public Health?

    Science.gov (United States)

    ... Membership Contact About Membership Contact Discover What is Public Health? Public health protects and improves the health of individuals, families, communities, and populations, locally and globally. Public health is personal. Public health professionals focus on preventing ...

  20. Genetic Diversity and Incidence of Virulence-Associated Genes of Arcobacter butzleri and Arcobacter cryaerophilus Isolates from Pork, Beef, and Chicken Meat in Poland

    Directory of Open Access Journals (Sweden)

    Iwona Zacharow

    2015-01-01

    Full Text Available Incidence of 9 virulence-associated genes and genetic diversity was determined in 79 A. butzleri and 6 A. cryaerophilus isolates from pork, beef, and chicken meat. All A. butzleri isolates harboured the tlyA gene, and most of them carried ciaB, mviN, pldA, cadF, and cj1349 genes. ciaB was found to occur with higher frequency in poultry if compared with pork (p=0.0007, while irgA was more frequent in poultry than in beef (p=0.007. All 6 A. cryaerophilus isolates harboured the ciaB gene, while mviN and tlyA were detected in 3 out of these isolates. Only one isolate carried the cadF gene. All beef-derived A. cryaerophilus isolates carried ciaB, mviN, and tlyA genes. A. cryaerophilus isolates from chicken meat harboured ciaB gene only. The pork-derived isolate harboured ciaB and cadF genes. Seventy-four genotypes were distinguished within 79 A. butzleri isolates. Nineteen from 21 isolates derived from beef and pork were found to be closely related to A. butzleri from chicken meat. Each of the 6 A. cryaerophilus isolates was found to have unique genotype. We demonstrated that closely related genotypes can spread within pork, beef, and chicken meat populations of A. butzleri but not A. cryaerophilus.

  1. Structure of Rhodococcus equi virulence-associated protein B (VapB) reveals an eight-stranded antiparallel β-barrel consisting of two Greek-key motifs

    Energy Technology Data Exchange (ETDEWEB)

    Geerds, Christina [Bielefeld University, Universitaetsstrasse 25, 33615 Bielefeld (Germany); Wohlmann, Jens; Haas, Albert [University of Bonn, Ulrich-Haberland Strasse 61a, 53121 Bonn (Germany); Niemann, Hartmut H., E-mail: hartmut.niemann@uni-bielefeld.de [Bielefeld University, Universitaetsstrasse 25, 33615 Bielefeld (Germany)

    2014-06-18

    The structure of VapB, a member of the Vap protein family that is involved in virulence of the bacterial pathogen R. equi, was determined by SAD phasing and reveals an eight-stranded antiparallel β-barrel similar to avidin, suggestive of a binding function. Made up of two Greek-key motifs, the topology of VapB is unusual or even unique. Members of the virulence-associated protein (Vap) family from the pathogen Rhodococcus equi regulate virulence in an unknown manner. They do not share recognizable sequence homology with any protein of known structure. VapB and VapA are normally associated with isolates from pigs and horses, respectively. To contribute to a molecular understanding of Vap function, the crystal structure of a protease-resistant VapB fragment was determined at 1.4 Å resolution. The structure was solved by SAD phasing employing the anomalous signal of one endogenous S atom and two bound Co ions with low occupancy. VapB is an eight-stranded antiparallel β-barrel with a single helix. Structural similarity to avidins suggests a potential binding function. Unlike other eight- or ten-stranded β-barrels found in avidins, bacterial outer membrane proteins, fatty-acid-binding proteins and lysozyme inhibitors, Vaps do not have a next-neighbour arrangement but consist of two Greek-key motifs with strand order 41238567, suggesting an unusual or even unique topology.

  2. A longitudinal study simultaneously exploring the carriage of APEC virulence associated genes and the molecular epidemiology of faecal and systemic E. coli in commercial broiler chickens.

    Science.gov (United States)

    Kemmett, Kirsty; Humphrey, Tom; Rushton, Steven; Close, Andrew; Wigley, Paul; Williams, Nicola J

    2013-01-01

    Colibacillosis is an economically important syndromic disease of poultry caused by extra-intestinal avian pathogenic Escherichia coli (APEC) but the pathotype remains poorly defined. Combinations of virulence-associated genes (VAGs) have aided APEC identification. The intestinal microbiota is a potential APEC reservoir. Broiler chickens are selectively bred for fast, uniform growth. Here we simultaneously investigate intestinal E. coli VAG carriage in apparently healthy birds and characterise systemic E. coli from diseased broiler chickens from the same flocks. Four flocks were sampled longitudinally from chick placement until slaughter. Phylogrouping, macro-restriction pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed on an isolate subset from one flock to investigate the population structure of faecal and systemic E. coli. Early in production, VAG carriage among chick intestinal E. coli populations was diverse (average Simpson's D value  = 0.73); 24.05% of intestinal E. coli (n = 160) from 1 day old chicks were carrying ≥5 VAGs. Generalised Linear models demonstrated VAG prevalence in potential APEC populations declined with age; 1% of E. coli carrying ≥5 VAGs at slaughter and demonstrated high strain diversity. A variety of VAG profiles and high strain diversity were observed among systemic E. coli. Thirty three new MLST sequence types were identified among 50 isolates and a new sequence type representing 22.2% (ST-2999) of the systemic population was found, differing from the pre-defined pathogenic ST-117 at a single locus. For the first time, this study takes a longitudinal approach to unravelling the APEC paradigm. Our findings, supported by other studies, highlight the difficulty in defining the APEC pathotype. Here we report a high genetic diversity among systemic E. coli between and within diseased broilers, harbouring diverse VAG profiles rather than single and/or highly related pathogenic clones

  3. Campylobacter jejuni infection and virulence-associated genes in children with moderate to severe diarrhoea admitted to emergency rooms in northeastern Brazil.

    Science.gov (United States)

    Quetz, Josiane da S; Lima, Ila F N; Havt, Alexandre; Prata, Mara M G; Cavalcante, Paloma A; Medeiros, Pedro H Q S; Cid, David A C; Moraes, Milena L; Rey, Luís Carlos; Soares, Alberto M; Mota, Rosa M S; Weigl, Bernhard H; Guerrant, Richard L; Lima, Aldo A M

    2012-04-01

    Campylobacter is an important cause of foodborne gastroenteritis. We determined the occurrence of Campylobacter jejuni and Campylobacter coli, using culture-based methods and PCRs targeting virulence-associated genes (VAGs) among children aged ≤14 years who were treated for diarrhoea at emergency rooms in northeastern Brazil. Genomic DNA was extracted directly from stool samples collected from 366 children. A questionnaire was also applied to qualify the clinical conditions presented by each child at the time of admission. C. jejuni and C. coli were detected in 16.4 % (60/366) and 1.4 % (5/366) of the diarrhoeal samples, respectively, by PCR, a much higher proportion than that detected by conventional methods. C. jejuni VAGs were detected in the following proportions of hipO-positive samples: ciaB, 95 % (57/60); dnaJ, 86.7 % (52/60); racR, 98.3 % (59/60); flaA, 80 % (48/60); pldA, 45 % (27/60); cdtABC, 95 % (57/60); and pVir 0 % (0/60). Particular symptoms, such as blood in faeces, vomiting, fever, and/or abdominal pain, were not associated with detection of C. jejuni nor were they associated with any particular VAG or combination of VAGs (P>0.05). C. jejuni and its VAGs were detected in a substantial proportion of the children admitted. Further efforts shall be directed towards elucidating whether these genetic factors or their expressed proteins play a role in Campylobacter pathogenesis.

  4. Detection of virulence-associated genes characteristic of intestinal Escherichia coli pathotypes, including the enterohemorrhagic/enteroaggregative O104:H4, in bovines from Germany and Spain.

    Science.gov (United States)

    Cabal, Adriana; Geue, Lutz; Gómez-Barrero, Susana; Barth, Stefanie; Bárcena, Carmen; Hamm, Katharina; Porrero, M Concepción; Valverde, Aránzazu; Cantón, Rafael; Menge, Christian; Gortázar, Christian; Domínguez, Lucas; Álvarez, Julio

    2015-08-01

    Cattle are reservoirs of enterohemorrhagic Escherichia coli; however, their role in the epidemiology of other pathogenic E. coli remains undefined. A new set of quantitative real-time PCR assays for the direct detection and quantification of nine virulence-associated genes (VAGs) characteristic of the most important human E. coli pathotypes and four serotype-related genes (wzxO104 , fliCH4 , rbfO157 , fliCH7 ) that can be used as a surveillance tool for detection of pathogenic strains was developed. A total of 970 cattle fecal samples were collected in slaughterhouses in Germany and Spain, pooled into 134 samples and analyzed with this tool. stx1, eae and invA were more prevalent in Spanish samples whereas bfpA, stx2, ehxA, elt, est and the rbfO157 /fliCH7 combination were observed in similar proportions in both countries. Genes characteristic of the hybrid O104:H4 strain of the 2011 German outbreak (stx2/aggR/wzxO104 /fliCH4 ) were simultaneously detected in six fecal pools from one German abattoir located near the outbreak epicenter. Although no isolate harboring the full stx2/aggR/wzxO104 /fliCH4 combination was cultured, sequencing of the aggR positive PCR products revealed 100% homology to the aggR from the outbreak strain. Concomitant detection by this direct approach of VAGs from a novel human pathogenic E. coli strain in cattle samples implies that the E. coli gene pool in these animals can be implicated in de novo formation of such highly-virulent strains. The application of this set of qPCRs in surveillance studies could be an efficient early-warning tool for the emergence of zoonotic E. coli in livestock. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  5. Discovering Network Structure Beyond Communities

    OpenAIRE

    Nishikawa, Takashi; Motter, Adilson E.

    2011-01-01

    To understand the formation, evolution, and function of complex systems, it is crucial to understand the internal organization of their interaction networks. Partly due to the impossibility of visualizing large complex networks, resolving network structure remains a challenging problem. Here we overcome this difficulty by combining the visual pattern recognition ability of humans with the high processing speed of computers to develop an exploratory method for discovering groups of nodes chara...

  6. The use of quaternised chitosan-loaded PMMA to inhibit biofilm formation and downregulate the virulence-associated gene expression of antibiotic-resistant staphylococcus.

    Science.gov (United States)

    Tan, Honglue; Peng, Zhaoxiang; Li, Qingtian; Xu, Xiaofen; Guo, Shengrong; Tang, Tingting

    2012-01-01

    also downregulated the expression of MecA, which encodes membrane-bound enzymes known to be penicillin-binding proteins. Our study indicates that 26%HACC-loaded PMMA prevents biofilm formation of Staphylococcus, including antibiotic-resistant strains, on the surface of bone cement, and downregulates the virulence-associated gene expression of antibiotic-resistant staphylococcus, thus providing a promising new strategy for combating implant infections and osteomyelitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Life Stage-specific Proteomes of Legionella pneumophila Reveal a Highly Differential Abundance of Virulence-associated Dot/Icm effectors*

    Science.gov (United States)

    Aurass, Philipp; Gerlach, Thomas; Becher, Dörte; Voigt, Birgit; Karste, Susanne; Bernhardt, Jörg; Riedel, Katharina; Hecker, Michael; Flieger, Antje

    2016-01-01

    Major differences in the transcriptional program underlying the phenotypic switch between exponential and post-exponential growth of Legionella pneumophila were formerly described characterizing important alterations in infection capacity. Additionally, a third state is known where the bacteria transform in a viable but nonculturable state under stress, such as starvation. We here describe phase-related proteomic changes in exponential phase (E), postexponential phase (PE) bacteria, and unculturable microcosms (UNC) containing viable but nonculturable state cells, and identify phase-specific proteins. We present data on different bacterial subproteomes of E and PE, such as soluble whole cell proteins, outer membrane-associated proteins, and extracellular proteins. In total, 1368 different proteins were identified, 922 were quantified and 397 showed differential abundance in E/PE. The quantified subproteomes of soluble whole cell proteins, outer membrane-associated proteins, and extracellular proteins; 841, 55, and 77 proteins, respectively, were visualized in Voronoi treemaps. 95 proteins were quantified exclusively in E, such as cell division proteins MreC, FtsN, FtsA, and ZipA; 33 exclusively in PE, such as motility-related proteins of flagellum biogenesis FlgE, FlgK, and FliA; and 9 exclusively in unculturable microcosms soluble whole cell proteins, such as hypothetical, as well as transport/binding-, and metabolism-related proteins. A high frequency of differentially abundant or phase-exclusive proteins was observed among the 91 quantified effectors of the major virulence-associated protein secretion system Dot/Icm (> 60%). 24 were E-exclusive, such as LepA/B, YlfA, MavG, Lpg2271, and 13 were PE-exclusive, such as RalF, VipD, Lem10. The growth phase-related specific abundance of a subset of Dot/Icm virulence effectors was confirmed by means of Western blotting. We therefore conclude that many effectors are predominantly abundant at either E or PE which suggests

  8. Discovering evolution equations with applications

    CERN Document Server

    McKibben, Mark

    2011-01-01

    Most existing books on evolution equations tend either to cover a particular class of equations in too much depth for beginners or focus on a very specific research direction. Thus, the field can be daunting for newcomers to the field who need access to preliminary material and behind-the-scenes detail. Taking an applications-oriented, conversational approach, Discovering Evolution Equations with Applications: Volume 2-Stochastic Equations provides an introductory understanding of stochastic evolution equations. The text begins with hands-on introductions to the essentials of real and stochast

  9. Discovering network structure beyond communities.

    Science.gov (United States)

    Nishikawa, Takashi; Motter, Adilson E

    2011-01-01

    To understand the formation, evolution, and function of complex systems, it is crucial to understand the internal organization of their interaction networks. Partly due to the impossibility of visualizing large complex networks, resolving network structure remains a challenging problem. Here we overcome this difficulty by combining the visual pattern recognition ability of humans with the high processing speed of computers to develop an exploratory method for discovering groups of nodes characterized by common network properties, including but not limited to communities of densely connected nodes. Without any prior information about the nature of the groups, the method simultaneously identifies the number of groups, the group assignment, and the properties that define these groups. The results of applying our method to real networks suggest the possibility that most group structures lurk undiscovered in the fast-growing inventory of social, biological, and technological networks of scientific interest.

  10. Two newly discovered millisecond pulsars

    Science.gov (United States)

    Nice, D. J.; Taylor, J. H.; Fruchter, A. S.

    1993-01-01

    Two millisecond pulsars have been discovered in the course of systematic surveys being made with the Arecibo radio telescope. PSR J2019 + 2425 has a 3.935 ms period and moves in a nearly circular, 76.5 day orbit around a about 0.3 solar mass companion. PSR J2322 + 2057, with a period of 4.808 ms, is an isolated object. The two pulsars have unusually small period derivatives, corresponding to spin-down time scales of 7.5 +/- 0.5 and 11 +/- 5 Gyr, respectively. Both objects show pulse time-of-arrival residuals no larger than a few microseconds over many months, lending further support to the observation that 'recycled' pulsars have extremely stable rotational behavior. The timing results also confirm that physics related to the rotational dynamics of these strongly self-gravitating stars - in particular, the value of the gravitational coupling constant G - remains essentially constant over time scales comparable to the Hubble time. Dispersion measures of the two pulsars indicate distances of 0.8-0.9 kpc.

  11. Discovering Classes of Strongly Equivalent Logic Programs

    OpenAIRE

    Chen, Y.; Lin, F.

    2011-01-01

    In this paper we apply computer-aided theorem discovery technique to discover theorems about strongly equivalent logic programs under the answer set semantics. Our discovered theorems capture new classes of strongly equivalent logic programs that can lead to new program simplification rules that preserve strong equivalence. Specifically, with the help of computers, we discovered exact conditions that capture the strong equivalence between a rule and the empty set, between two rules, between t...

  12. Discovering Mobile Social Networks by Semantic Technologies

    Science.gov (United States)

    Jung, Jason J.; Choi, Kwang Sun; Park, Sung Hyuk

    It has been important for telecommunication companies to discover social networks from mobile subscribers. They have attempted to provide a number of recommendation services, but they realized that the services were not successful. In this chapter, we present semantic technologies for discovering social networks. The process is mainly composed of two steps; (1) profile identification and (2) context understanding. Through developing a Next generation Contents dElivery (NICE) platform, we were able to generate various services based on the discovered social networks.

  13. In Silico Models for Designing and Discovering Novel Anticancer Peptides

    Science.gov (United States)

    Tyagi, Atul; Kapoor, Pallavi; Kumar, Rahul; Chaudhary, Kumardeep; Gautam, Ankur; Raghava, G. P. S.

    2013-10-01

    Use of therapeutic peptides in cancer therapy has been receiving considerable attention in the recent years. Present study describes the development of computational models for predicting and discovering novel anticancer peptides. Preliminary analysis revealed that Cys, Gly, Ile, Lys, and Trp are dominated at various positions in anticancer peptides. Support vector machine models were developed using amino acid composition and binary profiles as input features on main dataset that contains experimentally validated anticancer peptides and random peptides derived from SwissProt database. In addition, models were developed on alternate dataset that contains antimicrobial peptides instead of random peptides. Binary profiles-based model achieved maximum accuracy 91.44% with MCC 0.83. We have developed a webserver, which would be helpful in: (i) predicting minimum mutations required for improving anticancer potency; (ii) virtual screening of peptides for discovering novel anticancer peptides, and (iii) scanning natural proteins for identification of anticancer peptides (http://crdd.osdd.net/raghava/anticp/).

  14. Scientists Discover Sugar in Space

    Science.gov (United States)

    2000-06-01

    . Glycolaldehyde is a simpler molecular cousin to table sugar, the scientists say. The sugar molecule was detected in a large cloud of gas and dust some 26,000 light-years away, near the center of our Galaxy. Such clouds, often many light-years across, are the material from which new stars are formed. Though very rarified by Earth standards, these interstellar clouds are the sites of complex chemical reactions that occur over hundreds of thousands or millions of years. So far, about 120 different molecules have been discovered in these clouds. Most of these molecules contain a small number of atoms, and only a few molecules with eight or more atoms have been found in interstellar clouds. The 12 Meter Telescope "Finding glycolaldehyde in one of these interstellar clouds means that such molecules can be formed even in very rarified conditions," said Hollis. "We don't yet understand how it could be formed there," he added. "A combination of more astronomical observations and theoretical chemistry work will be required to resolve the mystery of how this molecule is formed in space." "We hope this discovery inspires renewed efforts to find even more kinds of molecules, so that, with a better idea of the total picture, we may be able to deduce the details of the prebiotic chemistry taking place in interstellar clouds," Hollis said. The discovery was made by detecting faint radio emission from the sugar molecules in the interstellar cloud. Molecules rotate end-for-end, and as they change from one rotational energy state to another, they emit radio waves at precise frequencies. The "family" of radio frequencies emitted by a particular molecule forms a unique "fingerprint" that scientists can use to identify that molecule. The scientists identified glycolaldehyde by detecting six frequencies of radio emission in what is termed the millimeter-wavelength region of the electromagnetic spectrum -- a region between more-familiar microwaves and infrared radiation. The NRAO 12 Meter Telescope

  15. Therapeutic vaccine against Streptococcus sobrinus-induced caries.

    Science.gov (United States)

    Dinis, M; Tavares, D; Fonseca, A J M M; Faria, R; Ribeiro, A; Silvério Cabrita, A M; Ferreira, P

    2004-04-01

    Streptococcus sobrinus produces a virulence-associated immunomodulatory protein (VIP) which suppresses the host-specific immune response and induces the early production of IL-10. In this study, we evaluated the effects of therapeutic immunization with this VIP on the incidence of caries in S. sobrinus-infected rats. Groups of Wistar rats were orally infected with S. sobrinus and fed with sucrose-sweetened drinking water ad libitum. Five days later, rats were immunized intranasally with active or heat-inactivated VIP plus alum as adjuvant or PBS plus adjuvant (sham-immunized). After 3 wks, all rats were re-immunized as above. Evaluation of dental caries showed that VIP-immunized animals had significantly fewer enamel sulcal and proximal caries lesions than did the sham-immunized animals (p vaccine against dental caries.

  16. The discovered preference hypothesis - an empirical test

    DEFF Research Database (Denmark)

    Lundhede, Thomas; Ladenburg, Jacob; Olsen, Søren Bøye

    Using stated preference methods for valuation of non-market goods is known to be vulnerable to a range of biases. Some authors claim that these so-called anomalies in effect render the methods useless for the purpose. However, the Discovered Preference Hypothesis, as put forth by Plott [31], offers...... as respondents evaluate more and more choice sets. This finding supports the Discovered Preference Hypothesis interpretation and explanation of starting point bias....

  17. What if Fleming had not discovered penicillin?

    OpenAIRE

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A.; Chinnathambi, Arunachalam

    2014-01-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in...

  18. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  19. Regulatory RNAs discovered in unexpected places.

    Science.gov (United States)

    Pek, Jun Wei; Okamura, Katsutomo

    2015-01-01

    Recent studies have discovered both small and long noncoding RNAs (ncRNAs) encoded in unexpected places. These ncRNA genes were surprises at the time of their discovery, but many quickly became well-accepted families of functional regulatory RNA species. Even after years of extensive gene annotation studies using high-throughput sequencing technologies, new types of ncRNA genes continue to be discovered in unexpected places. We highlight ncRNAs that have atypical structures and that are encoded in what are generally considered 'junk' sequences, such as spacers and introns. We also discuss current bottlenecks in the approaches for identifying novel ncRNAs and the possibility that many remain to be discovered. © 2015 Wiley Periodicals, Inc.

  20. Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

    Science.gov (United States)

    Bode, Nadine J.; Debnath, Irina; Kuan, Lisa; Schulfer, Anjelique; Ty, Maureen

    2015-01-01

    The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections (UTIs). Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for disease progression. Previously, the transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has been shown to repress both swimming and swarming motility. Here we show that MrpJ affects an array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking levels observed during UTIs leads to differential expression of 217 genes related to, among other functions, bacterial virulence, type VI secretion, and metabolism. We probed the molecular mechanism of transcriptional regulation by MrpJ using transcriptional reporters and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence-associated target gene promoters, the promoters of the flagellar master regulator flhDC and mrp itself, appears to be affected by the condensation state of the native chromosome, although both targets share a direct MrpJ binding site proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observed that mrpJ is widely conserved in a collection of recent clinical isolates. Altogether, these findings support a role of MrpJ as a global regulator of P. mirabilis virulence. PMID:25847961

  1. Therapeutic applications of ultrasonography in dentistry

    OpenAIRE

    Jyoti Mago; Soheyl Sheikh; Shambulingappa Pallagatti; Amit Aggarwal

    2014-01-01

    Ultrasonography is one of the most common imaging modality used in dental as well as medical sciences. The use of ultrasonography when discovered was as a therapeutic aid, but in recent times, it has become one of the most common imaging modality next to conventional radiology. Currently, its use as a therapeutic aid has been rediscovered along with its association with other specialized imaging. The aim of this paper is to highlight such advancements in the field of ultrasonography.

  2. Therapeutic applications of ultrasonography in dentistry

    Directory of Open Access Journals (Sweden)

    Jyoti Mago

    2014-01-01

    Full Text Available Ultrasonography is one of the most common imaging modality used in dental as well as medical sciences. The use of ultrasonography when discovered was as a therapeutic aid, but in recent times, it has become one of the most common imaging modality next to conventional radiology. Currently, its use as a therapeutic aid has been rediscovered along with its association with other specialized imaging. The aim of this paper is to highlight such advancements in the field of ultrasonography.

  3. Ultrasound: A Revenant Therapeutic Modality in Dentistry

    OpenAIRE

    Karumuri, Sunil Kumar; Rastogi, Trisha; Beeraka, Kartheeki; Penumatcha, Mohan Raju; Olepu, Sanjeeva Rao

    2016-01-01

    An ultrasound (US) gives a visible image of the organs that are present inside the body. In medicine it serves for diagnosing and also its therapeutic benefits are well established for bone healing, osteointegration and soft tissue healing. In dentistry it is widely used for diagnostic purposes. When it was discovered it was introduced for therapeutic purposes, but due to lack of clinical studies its use as therapy was remittent in dentistry. The aim of the present paper was to establish the ...

  4. Abdominal pregnancy discovered during laparotomy for ...

    African Journals Online (AJOL)

    We report a case of abdominal pregnancy with a dead foetus of 19 gestational weeks and 3 days discovered incidentally during a laparotomy following complications of attempted abortion. Abdominal pregnancy is a rare form of ectopic pregnancy (1% of all ectopic pregnancies) usually diagnosed by ultrasound. In this case ...

  5. Discovering English with the Sketch Engine

    Science.gov (United States)

    Thomas, James

    2014-01-01

    "Discovering English with the Sketch Engine" is the title of a new book (Thomas, 2014) which introduces the use of corpora in language study, teaching, writing and translating. It focuses on using the Sketch Engine to identify patterns of normal usage in many aspects of English ranging from morphology to discourse and pragmatics. This…

  6. Why most discovered true associations are inflated.

    Science.gov (United States)

    Ioannidis, John P A

    2008-09-01

    Newly discovered true (non-null) associations often have inflated effects compared with the true effect sizes. I discuss here the main reasons for this inflation. First, theoretical considerations prove that when true discovery is claimed based on crossing a threshold of statistical significance and the discovery study is underpowered, the observed effects are expected to be inflated. This has been demonstrated in various fields ranging from early stopped clinical trials to genome-wide associations. Second, flexible analyses coupled with selective reporting may inflate the published discovered effects. The vibration ratio (the ratio of the largest vs. smallest effect on the same association approached with different analytic choices) can be very large. Third, effects may be inflated at the stage of interpretation due to diverse conflicts of interest. Discovered effects are not always inflated, and under some circumstances may be deflated-for example, in the setting of late discovery of associations in sequentially accumulated overpowered evidence, in some types of misclassification from measurement error, and in conflicts causing reverse biases. Finally, I discuss potential approaches to this problem. These include being cautious about newly discovered effect sizes, considering some rational down-adjustment, using analytical methods that correct for the anticipated inflation, ignoring the magnitude of the effect (if not necessary), conducting large studies in the discovery phase, using strict protocols for analyses, pursuing complete and transparent reporting of all results, placing emphasis on replication, and being fair with interpretation of results.

  7. Did Viking discover life on Mars?

    Science.gov (United States)

    Klein, H. P.

    1999-01-01

    A major argument in the claim that life had been discovered during the Viking mission to Mars is that the results obtained in the Labeled Release (LR) experiment are analogous to those observed with terrestrial microorganisms. This assertion is critically examined and found to be implausible.

  8. Discovering Sentinel Rules for Business Intelligence

    DEFF Research Database (Denmark)

    Middelfart, Morten; Pedersen, Torben Bach

    2009-01-01

    to absolute data values, we are able to discover strong and useful sentinel rules that would otherwise be hidden when using sequential pattern mining or correlation techniques. We present a method for sentinel rule discovery and an implementation of this method that scales linearly on large data volumes....

  9. Discovering Science through Art-Based Activities

    Science.gov (United States)

    Alberts, Rebecca

    2010-01-01

    Art and science are intrinsically linked; the essence of art and science is discovery. Both artists and scientists work in a systematic but creative way--knowledge and understanding are built up through pieces of art or a series of labs. In the classroom, integrating science and visual art can provide students with the latitude to think, discover,…

  10. Discovering discovery patterns with Predication-based Semantic Indexing.

    Science.gov (United States)

    Cohen, Trevor; Widdows, Dominic; Schvaneveldt, Roger W; Davies, Peter; Rindflesch, Thomas C

    2012-12-01

    In this paper we utilize methods of hyperdimensional computing to mediate the identification of therapeutically useful connections for the purpose of literature-based discovery. Our approach, named Predication-based Semantic Indexing, is utilized to identify empirically sequences of relationships known as "discovery patterns", such as "drug x INHIBITS substance y, substance y CAUSES disease z" that link pharmaceutical substances to diseases they are known to treat. These sequences are derived from semantic predications extracted from the biomedical literature by the SemRep system, and subsequently utilized to direct the search for known treatments for a held out set of diseases. Rapid and efficient inference is accomplished through the application of geometric operators in PSI space, allowing for both the derivation of discovery patterns from a large set of known TREATS relationships, and the application of these discovered patterns to constrain search for therapeutic relationships at scale. Our results include the rediscovery of discovery patterns that have been constructed manually by other authors in previous research, as well as the discovery of a set of previously unrecognized patterns. The application of these patterns to direct search through PSI space results in better recovery of therapeutic relationships than is accomplished with models based on distributional statistics alone. These results demonstrate the utility of efficient approximate inference in geometric space as a means to identify therapeutic relationships, suggesting a role of these methods in drug repurposing efforts. In addition, the results provide strong support for the utility of the discovery pattern approach pioneered by Hristovski and his colleagues. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Discovering phase transitions with unsupervised learning

    Science.gov (United States)

    Wang, Lei

    2016-11-01

    Unsupervised learning is a discipline of machine learning which aims at discovering patterns in large data sets or classifying the data into several categories without being trained explicitly. We show that unsupervised learning techniques can be readily used to identify phases and phases transitions of many-body systems. Starting with raw spin configurations of a prototypical Ising model, we use principal component analysis to extract relevant low-dimensional representations of the original data and use clustering analysis to identify distinct phases in the feature space. This approach successfully finds physical concepts such as the order parameter and structure factor to be indicators of a phase transition. We discuss the future prospects of discovering more complex phases and phase transitions using unsupervised learning techniques.

  12. Discovering Implicit Schemas in JSON Data

    OpenAIRE

    Cánovas, Javier; Cabot, Jordi

    2013-01-01

    International audience; JSON has become a very popular lightweigth format for data exchange. JSON is human readable and easy for computers to parse and use. However, JSON is schemaless. Though this brings some benefits (e.g., flexibility in the representation of the data) it can become a problem when consuming and integrating data from different JSON services since developers need to be aware of the structure of the schemaless data. We believe that a mechanism to discover (and visualize) the ...

  13. What if Fleming had not discovered penicillin?

    Science.gov (United States)

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A; Chinnathambi, Arunachalam

    2014-09-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called "supasulfas", and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents.

  14. African Swine Fever Virus Georgia 2007 with a Deletion of Virulence-Associated Gene 9GL (B119L), when Administered at Low Doses, Leads to Virus Attenuation in Swine and Induces an Effective Protection against Homologous Challenge.

    Science.gov (United States)

    O'Donnell, Vivian; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Carlson, Jolene; Sanford, Brenton; Alfano, Marialexia; Kramer, Edward; Lu, Zhiqiang; Arzt, Jonathan; Reese, Bo; Carrillo, Consuelo; Risatti, Guillermo R; Borca, Manuel V

    2015-08-01

    African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs. Disease control strategies have been hampered by the unavailability of vaccines against ASFV. Since its introduction in the Republic of Georgia, a highly virulent virus, ASFV Georgia 2007 (ASFV-G), has caused an epizootic that spread rapidly into Eastern European countries. Currently no vaccines are available or under development to control ASFV-G. In the past, genetically modified ASFVs harboring deletions of virulence-associated genes have proven attenuated in swine, inducing protective immunity against challenge with homologous parental viruses. Deletion of the gene 9GL (open reading frame [ORF] B119L) in highly virulent ASFV Malawi-Lil-20/1 produced an attenuated phenotype even when administered to pigs at 10(6) 50% hemadsorption doses (HAD50). Here we report the construction of a genetically modified ASFV-G strain (ASFV-G-Δ9GLv) harboring a deletion of the 9GL (B119L) gene. Like Malawi-Lil-20/1-Δ9GL, ASFV-G-Δ9GL showed limited replication in primary swine macrophages. However, intramuscular inoculation of swine with 10(4) HAD50 of ASFV-G-Δ9GL produced a virulent phenotype that, unlike Malawi-Lil-20/1-Δ9GL, induced a lethal disease in swine like parental ASFV-G. Interestingly, lower doses (10(2) to 10(3) HAD50) of ASFV-G-Δ9GL did not induce a virulent phenotype in swine and when challenged protected pigs against disease. A dose of 10(2) HAD50 of ASFV-G-Δ9GLv conferred partial protection when pigs were challenged at either 21 or 28 days postinfection (dpi). An ASFV-G-Δ9GL HAD50 of 10(3) conferred partial and complete protection at 21 and 28 dpi, respectively. The information provided here adds to our recent report on the first attempts toward experimental vaccines against ASFV-G. The main problem for controlling ASF is the lack of vaccines. Studies on ASFV virulence lead to the production of genetically modified attenuated viruses that induce protection

  15. Transcriptional analysis of the MrpJ network: modulation of diverse virulence-associated genes and direct regulation of mrp fimbrial and flhDC flagellar operons in Proteus mirabilis.

    Science.gov (United States)

    Bode, Nadine J; Debnath, Irina; Kuan, Lisa; Schulfer, Anjelique; Ty, Maureen; Pearson, Melanie M

    2015-06-01

    The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections (UTIs). Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for disease progression. Previously, the transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has been shown to repress both swimming and swarming motility. Here we show that MrpJ affects an array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking levels observed during UTIs leads to differential expression of 217 genes related to, among other functions, bacterial virulence, type VI secretion, and metabolism. We probed the molecular mechanism of transcriptional regulation by MrpJ using transcriptional reporters and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence-associated target gene promoters, the promoters of the flagellar master regulator flhDC and mrp itself, appears to be affected by the condensation state of the native chromosome, although both targets share a direct MrpJ binding site proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observed that mrpJ is widely conserved in a collection of recent clinical isolates. Altogether, these findings support a role of MrpJ as a global regulator of P. mirabilis virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Bioengineering lantibiotics for therapeutic success

    Directory of Open Access Journals (Sweden)

    Des eField

    2015-11-01

    Full Text Available Several examples of highly modified antimicrobial peptides have been described. While many such peptides are non-ribosomally synthesized, ribosomally synthesised equivalents are being discovered with increased frequency. Of the latter group, the lantibiotics continue to attract most attention. In the present review, we discuss the implementation of in vivo and in vitro engineering systems to alter, and even enhance, the antimicrobial activity, antibacterial spectrum and physico-chemical properties, including heat stability, solubility, diffusion and protease resistance, of these compounds. Additionally, we discuss the potential applications of these lantibiotics for use as therapeutics.

  17. The Universe for all to discover

    Science.gov (United States)

    Ortiz-Gil, A.; Ballesteros, F.; Espinós, H.; Fernández-Soto, A.; Lanzara, M.; Moya, M. J.; Navarro, J.

    2015-05-01

    In the title of this paper, we have changed the slogan of the International Year of Astronomy, ``The Universe yours to discover" to ``The Universe for all to discover" in order to emphasize the need to think about broader audiences when we plan astronomical activities at school or during outreach events. The strategy we propose follows what is known as the Universal Design for Learning (UDL). UDL allows to reach to the general public as well as to audiences which might be regarded as ``special" because they have some disability. It has been shown that everybody has a preferred style of learning (some remember better what they see, others what they hear or what they touch) and therefore, everybody is more or less able under the different styles of learning. Through this talk I am going to outline some of the principles of the UDL that can be applied in the teaching and communication of Astronomy, along with an example of its implementation in the project ``A Touch of the Universe".

  18. Therapeutic misadventure.

    Science.gov (United States)

    Langford, N J

    2010-10-01

    Therapeutic misadventure can be defined as an injury or an adverse event caused by medical management rather than by an underlying disease. Within the National Health Service there were over 86,000 reported adverse incidents in 2007. In the USA medication errors have been rated as the fourth highest cause of death. Unfortunately one of the greatest contributors to iatrogenic injury is human error. The potential types of misadventure are infinite. Medication errors are a major part of this, being responsible for over 70% of cases that cause serious harm. However, many medication errors caused by slips, lapses, technical errors and mistakes are preventable; intentional violations of safe operating procedures are not. While medication errors were tolerated by society in the past, the readiness to institute criminal proceedings against health-care professionals has increased greatly in the UK over the last decade. The medication process consists of writing prescriptions, dispensing the product, administering it and monitoring its effects. Prescription errors arise owing to incomplete information, lack of appropriate labelling, environmental factors and human blunders. Even with a perfect prescription the right medication must be dispensed and appropriately labelled. Dispensing errors are not uncommon and may be compounded by non-clinical considerations. Administration of a drug by injection is one of the most dangerous aspects of the medication process, especially in inexperienced hands. The final component of medication supply is monitoring the effect of the medication. With short courses of medication such monitoring is easy, but with long-term medication, particularly with potent drugs where the margin between efficacy and toxicity is small, active procedures may be required to ensure toxicity does not ensue. Despite the endeavour of health-care professions to stick to the rule of 'first, do no harm', in reality this is difficult to achieve all of the time. When

  19. Kinetoplastida: new therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Croft S.L.

    2008-09-01

    Full Text Available New formulations and therapeutic switching of the established drugs, amphotericin B and paromomycin, together with the discovery of miltefosine, have significantly improved the opportunities for treatment of visceral leishmaniasis (VL chemotherapy. However, for human African trypanosomiasis (HAT, Chagas disease and cutaneous leishmaniases there has been limited progress. For HAT, a novel diamidine, parfuramidine, is in phase III clinical trial for early-stage disease, but for the treatment of late-stage disease there are no new drugs and combinations of eflornithine with melarsoprol or nifurtimox have been the focus of clinical studies. For Chagas disease, different classes of compounds that have validated biochemical targets, sterol biosynthesis methylases and cysteine proteases, are in various stages of development. The genome sequences that are now available for the pathogens that cause the leishmaniases and trypanosomiases, and new methods for rapid validation of targets, are part of the solution to discover new drugs. The integration of medicinal chemistry, pharmacokinetics, project planning and interaction with the pharma/biotech sector are essential if progress is to be made. Although there are financial constraints, the appearance of new funding sources and not-for-profit product development partnerships offers hope for drug development.

  20. Discovering chemistry with an ab initio nanoreactor

    Science.gov (United States)

    Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert; Liu, Fang; Pande, Vijay S.; Martínez, Todd J.

    2014-12-01

    Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provide detailed physical insight. Although theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor—a highly accelerated first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor, we show new pathways for glycine synthesis from primitive compounds proposed to exist on the early Earth, which provide new insight into the classic Urey-Miller experiment. These results highlight the emergence of theoretical and computational chemistry as a tool for discovery, in addition to its traditional role of interpreting experimental findings.

  1. Discovering the Library with Google Earth

    Directory of Open Access Journals (Sweden)

    Michaela Brenner

    2008-06-01

    Full Text Available Libraries need to provide attractive and exciting discovery tools to draw patrons to the valuable resources in their catalogs. The authors conducted a pilot project to explore the free version of Google Earth as such a discover tool for Portland State Library’s digital collection of urban planning documents. They created eye-catching placemarks with links to parts of this collection, as well as to other pertinent materials like books, images, and historical background information. The detailed how-to-do part of this article is preceded by a discussion about discovery of library materials and followed by possible applications of this Google Earth project.

  2. Discovering New Light States at Neutrino Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Essig, Rouven; /SLAC; Harnik, Roni; /Fermilab; Kaplan, Jared; /SLAC; Toro, Natalia; /Stanford U., Phys. Dept.

    2011-08-11

    Experiments designed to measure neutrino oscillations also provide major opportunities for discovering very weakly coupled states. In order to produce neutrinos, experiments such as LSND collide thousands of Coulombs of protons into fixed targets, while MINOS and MiniBooNE also focus and then dump beams of muons. The neutrino detectors beyond these beam dumps are therefore an excellent arena in which to look for long-lived pseudoscalars or for vector bosons that kinetically mix with the photon. We show that these experiments have significant sensitivity beyond previous beam dumps, and are able to partially close the gap between laboratory experiments and supernovae constraints on pseudoscalars. Future upgrades to the NuMI beamline and Project X will lead to even greater opportunities for discovery. We also discuss thin target experiments with muon beams, such as those available in COMPASS, and show that they constitute a powerful probe for leptophilic PNGBs.

  3. Discovering new information in bibliographic databases

    Directory of Open Access Journals (Sweden)

    Emil Hudomalj

    2005-01-01

    Full Text Available Databases contain information that can usually not be revealed by standard query systems. For that purpose, the methods for knowledge discovery from databases can be applied, which enable the user to browse aggregated data, discover trends, produce online reports, explore possible new associations within the data etc. Such methods are successfully employed in various fields, such as banking, insurance and telecommunications, while they are seldom used in libraries. The article reviews the development of query systems for bibliographic databases, including some early attempts to apply modern knowledge discovery methods. Analytical databases are described in more detail, since they usually serve as the basis for knowledge discovery. Data mining approaches are presented, since they are a central step in the knowledge discovery process. The key role of librarians who can play a key part in developing systems for finding new information in existing bibliographic databases is stressed.

  4. Michael Maier--nine newly discovered letters.

    Science.gov (United States)

    Lenke, Nils; Roudet, Nicolas; Tilton, Hereward

    2014-02-01

    The authors provide a transcription, translation, and evaluation of nine newly discovered letters from the alchemist Michael Maier (1568-1622) to Gebhardt Johann von Alvensleben (1576-1631), a noble landholder in the vicinity of Magdeburg. Stemming from the final year of his life, this correspondence casts new light on Maier's biography, detailing his efforts to secure patronage amid the financial crisis of the early Thirty Years' War. While his ill-fated quest to perfect potable gold continued to form the central focus of his patronage suits, Maier also offered his services in several arts that he had condemned in his printed works, namely astrology and "supernatural" magic. Remarks concerning his previously unknown acquaintance with Heinrich Khunrath call for a re-evaluation of Maier's negotiation of the discursive boundaries between Lutheran orthodoxy and Paracelsianism. The letters also reveal Maier's substantial contribution to a work previously ascribed solely to the English alchemist Francis Anthony.

  5. Discovering relations between indirectly connected biomedical concepts.

    Science.gov (United States)

    Weissenborn, Dirk; Schroeder, Michael; Tsatsaronis, George

    2015-01-01

    The complexity and scale of the knowledge in the biomedical domain has motivated research work towards mining heterogeneous data from both structured and unstructured knowledge bases. Towards this direction, it is necessary to combine facts in order to formulate hypotheses or draw conclusions about the domain concepts. This work addresses this problem by using indirect knowledge connecting two concepts in a knowledge graph to discover hidden relations between them. The graph represents concepts as vertices and relations as edges, stemming from structured (ontologies) and unstructured (textual) data. In this graph, path patterns, i.e. sequences of relations, are mined using distant supervision that potentially characterize a biomedical relation. It is possible to identify characteristic path patterns of biomedical relations from this representation using machine learning. For experimental evaluation two frequent biomedical relations, namely "has target", and "may treat", are chosen. Results suggest that relation discovery using indirect knowledge is possible, with an AUC that can reach up to 0.8, a result which is a great improvement compared to the random classification, and which shows that good predictions can be prioritized by following the suggested approach. Analysis of the results indicates that the models can successfully learn expressive path patterns for the examined relations. Furthermore, this work demonstrates that the constructed graph allows for the easy integration of heterogeneous information and discovery of indirect connections between biomedical concepts.

  6. Imminent science what remains to be discovered

    CERN Document Server

    Bignami, Giovanni F

    2014-01-01

    This is not science fiction. It’s a voyage on the arrow of time to the coming fifty years. The legendary palindromic character Mr. Qfwfq from Italo Calvino’s collection of short stories, The Cosmicomics, will go with us – he who knows all the answers but will give out no hints. He will help us to discover the innovations that will have changed our lives by 2062, when, riding astride Halley’s Comet, our omniscient extraterrestrial will return to visit us.In this book, we shall learn how astronomers will devote themselves to the study of the mysterious force of dark energy, which makes up some three-quarters of the Universe. We shall also delve deeply into the study of our Earth, to exploit the immense thermal energy that lies beneath our feet. We shall solve another enigma in today’s science: the origin of life. We shall come to understand how to develop direct contacts between our brains and the rest of the world. We shall learn about the future of genetics, the reason for the longevity of Methusela...

  7. Astronomers Discover Fastest-Spinning Pulsar

    Science.gov (United States)

    2006-01-01

    Astronomers using the National Science Foundation's Robert C. Byrd Green Bank Telescope have discovered the fastest-spinning neutron star ever found, a 20-mile-diameter superdense pulsar whirling faster than the blades of a kitchen blender. Their work yields important new information about the nature of one of the most exotic forms of matter known in the Universe. Pulsar Graphic Pulsars Are Spinning Neutron Stars CREDIT: Bill Saxton, NRAO/AUI/NSF (Click on image for larger version) "We believe that the matter in neutron stars is denser than an atomic nucleus, but it is unclear by how much. Our observations of such a rapidly rotating star set a hard upper limit on its size, and hence on how dense the star can be.," said Jason Hessels, a graduate student at McGill University in Montreal. Hessels and his colleagues presented their findings to the American Astronomical Society's meeting in Washington, DC. Pulsars are spinning neutron stars that sling "lighthouse beams" of radio waves or light around as they spin. A neutron star is what is left after a massive star explodes at the end of its "normal" life. With no nuclear fuel left to produce energy to offset the stellar remnant's weight, its material is compressed to extreme densities. The pressure squeezes together most of its protons and electrons to form neutrons; hence, the name "neutron star." "Neutron stars are incredible laboratories for learning about the physics of the fundamental particles of nature, and this pulsar has given us an important new limit," explained Scott Ransom, an astronomer at the National Radio Astronomy Observatory and one of Hessels' collaborators on this work. The scientists discovered the pulsar, named PSR J1748-2446ad, in a globular cluster of stars called Terzan 5, located some 28,000 light-years from Earth in the constellation Sagittarius. The newly-discovered pulsar is spinning 716 times per second, or at 716 Hertz (Hz), readily beating the previous record of 642 Hz from a pulsar

  8. Therapeutic Benefits of Cannabis: A Patient Survey

    OpenAIRE

    Webb, Charles W; Webb, Sandra M

    2014-01-01

    Clinical research regarding the therapeutic benefits of cannabis (“marijuana”) has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai‘i.

  9. [Does cannabis have a therapeutic value?].

    Science.gov (United States)

    Lechat, Paul

    2002-01-01

    Among the numerous therapeutic applications claimed for cannabis, many come from anecdotal reports, a few have been subjected to clinical double-blind trials with comparison to a reference treatment. Their results are less than convincing and larger multicentre assays are needed to assess our knowledge. Researches on endogenous cannabinoids as well as on cannabinoids receptors agonists and antagonists may lead to discover new useful drugs devoid of the central nervous system unwanted effects of cannabis.

  10. ROSAT Discovers Unique, Distant Cluster of Galaxies

    Science.gov (United States)

    1995-06-01

    Brightest X-ray Cluster Acts as Strong Gravitational Lens Based on exciting new data obtained with the ROSAT X-ray satellite and a ground-based telescope at the ESO La Silla Observatory, a team of European astronomers [2] has just discovered a very distant cluster of galaxies with unique properties. It emits the strongest X-ray emission of any cluster ever observed by ROSAT and is accompanied by two extraordinarily luminous arcs that represent the gravitationally deflected images of even more distant objects. The combination of these unusual characteristics makes this cluster, now known as RXJ1347.5-1145, a most interesting object for further cosmological studies. DISCOVERY AND FOLLOW-UP OBSERVATIONS This strange cluster of galaxies was discovered during the All Sky Survey with the ROSAT X-ray satellite as a moderately intense X-ray source in the constellation of Virgo. It could not be identified with any already known object and additional ground-based observations were therefore soon after performed with the Max-Planck-Society/ESO 2.2-metre telescope at the La Silla observatory in Chile. These observations took place within a large--scale redshift survey of X-ray clusters of galaxies detected by the ROSAT All Sky Survey, a so-called ``ESO Key Programme'' led by astronomers from the Max-Planck-Institut fur Extraterrestrische Physik and the Osservatorio Astronomico di Brera. The main aim of this programme is to identify cluster X-ray sources, to determine the distance to the X-ray emitting clusters and to investigate their overall properties. These observations permitted to measure the redshift of the RXJ1347.5-1145 cluster as z = 0.45, i.e. it moves away from us with a velocity (about 106,000 km/sec) equal to about one-third of the velocity of light. This is an effect of the general expansion of the universe and it allows to determine the distance as about 5,000 million light-years (assuming a Hubble constant of 75 km/sec/Mpc). In other words, we see these

  11. Discovering biological progression underlying microarray samples.

    Directory of Open Access Journals (Sweden)

    Peng Qiu

    2011-04-01

    Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

  12. Astronomers Discover Spectacular Structure in Distant Galaxy

    Science.gov (United States)

    1999-01-01

    Researchers using the National Science Foundation's Very Large Array (VLA) radio telescope have imaged a "spectacular and complex structure" in a galaxy 50 million light-years away. Their work both resolves a decades-old observational mystery and revises current theories about the origin of X-ray emission coming from gas surrounding the galaxy. The new VLA image is of the galaxy M87, which harbors at its core a supermassive black hole spewing out jets of subatomic particles at nearly the speed of light and also is the central galaxy of the Virgo Cluster of galaxies. The VLA image is the first to show detail of a larger structure that originally was detected by radio astronomers more than a half-century ago. Analysis of the new image indicates that astronomers will have to revise their ideas about the physics of what causes X-ray emission in the cores of many galaxy clusters. Frazer Owen of the National Radio Astronomy Observatory (NRAO) in Socorro, NM; Jean Eilek of the New Mexico Institute of Mining and Technology (NM Tech) in Socorro, NM; and Namir Kassim of the Naval Research Laboratory in Washington, DC, announced their discovery at the American Astronomical Society's meeting today in Austin, TX. The new observations show two large, bubble-like lobes, more than 200,000 light-years across, that emit radio waves. These lobes, which are intricately detailed, apparently are powered by gravitational energy released from the black hole at the galaxy's center. "We think that material is flowing outward from the galaxy's core into these large, bright, radio-emitting 'bubbles,'" Owen said. The newly-discovered "bubbles" sit inside a region of the galaxy known to be emitting X-rays. Theorists have speculated that this X-ray emission arises when gas that originally was part of the Virgo Cluster of galaxies, cools and falls inwards onto M87 itself, at the center of the cluster. Such "cooling flows" are commonly thought to be responsible for strong X-ray emission in many

  13. Discovering Extrasolar Planets with Microlensing Surveys

    Science.gov (United States)

    Wambsganss, J.

    2016-06-01

    An astronomical survey is commonly understood as a mapping of a large region of the sky, either photometrically (possibly in various filters/wavelength ranges) or spectroscopically. Often, catalogs of objects are produced/provided as the main product or a by-product. However, with the advent of large CCD cameras and dedicated telescopes with wide-field imaging capabilities, it became possible in the early 1990s, to map the same region of the sky over and over again. In principle, such data sets could be combined to get very deep stacked images of the regions of interest. However, I will report on a completely different use of such repeated maps: Exploring the time domain for particular kinds of stellar variability, namely microlens-induced magnifications in search of exoplanets. Such a time-domain microlensing survey was originally proposed by Bohdan Paczynski in 1986 in order to search for dark matter objects in the Galactic halo. Only a few years later three teams started this endeavour. I will report on the history and current state of gravitational microlensing surveys. By now, routinely 100 million stars in the Galactic Bulge are monitored a few times per week by so-called survey teams. All stars with constant apparent brightness and those following known variability patterns are filtered out in order to detect the roughly 2000 microlensing events per year which are produced by stellar lenses. These microlensing events are identified "online" while still in their early phases and then monitored with much higher cadence by so-called follow-up teams. The most interesting of such events are those produced by a star-plus-planet lens. By now of order 30 exoplanets have been discovered by these combined microlensing surveys. Microlensing searches for extrasolar planets are complementary to other exoplanet search techniques. There are two particular advantages: The microlensing method is sensitive down to Earth-mass planets even with ground-based telecopes, and it

  14. The Impact of Discovering Life beyond Earth

    Science.gov (United States)

    Dick, Steven J.

    2016-01-01

    Introduction: astrobiology and society Steven J. Dick; Part I. Motivations and Approaches. How Do We Frame the Problems of Discovery and Impact?: Introduction; 1. Current approaches to finding life beyond earth, and what happens if we do Seth Shostak; 2. The philosophy of astrobiology: the Copernican and Darwinian presuppositions Iris Fry; 3. History, discovery, analogy: three approaches to the impact of discovering life beyond earth Steven J. Dick; 4. Silent impact: why the discovery of extraterrestrial life should be silent Clément Vidal; Part II. Transcending Anthropocentrism. How Do We Move beyond our Own Preconceptions of Life, Intelligence and Culture?: Introduction; 5. The landscape of life Dirk Schulze-Makuch; 6. The landscape of intelligence Lori Marino; 7. Universal biology: assessing universality from a single example Carlos Mariscal; 8. Equating culture, civilization, and moral development in imagining extraterrestrial intelligence: anthropocentric assumptions? John Traphagan; 9. Communicating with the other: infinity, geometry, and universal math and science Douglas Vakoch; Part III. Philosophical, Theological, and Moral Impact. How Do We Comprehend the Cultural Challenges Raised by Discovery?: Introduction; 10. Life, intelligence and the pursuit of value in cosmic evolution Mark Lupisella; 11. 'Klaatu barada nikto' - or, do they really think like us? Michael Ruse; 12. Alien minds Susan Schneider; 13. The moral subject of astrobiology: guideposts for exploring our ethical and political responsibilities towards extraterrestrial life Elspeth Wilson and Carol Cleland; 14. Astrobiology and theology Robin Lovin; 15. Would you baptize an extraterrestrial? Guy Consolmagno, SJ; Part IV. Practical Considerations: How Should Society Prepare for Discovery - and Non-Discovery?: Introduction; 16. Is there anything new about astrobiology and society? Jane Maienschein; 17. Evaluating preparedness for the discovery of extraterrestrial life: considering potential

  15. Scientix in our school- discovering STEM

    Science.gov (United States)

    Melcu, Cornelia

    2017-04-01

    My name is Cornelia Melcu and I am a primary school teacher in Brasov. Additionally, I am a teacher trainer of Preparatory Class Curriculum, Google Application in Education Course and European Projects Course and a mentor to new teachers and students in university. I am an eTwinning, Scientix and ESERO ambassador too. During the last three school years my school was involved in several STEM projects, part of Scientix community. The main goal of those projects was to develop basic STEM skills of our students based on project work integrated into the curriculum. Open the Gates to the Universe (http://gatestotheuniverse.blogspot.ro; https://twinspace.etwinning.net/12520/home) is an eTwinning project for primary school students started on September 2015 and finished on September 2016. Some of our partners were from the Mediterranean area. The students discovered different aspects of space science and astronomy working on international groups. They explored some aspects of Science included in their curriculum using resources from ESERO, ROEDUSEIS and Space Awareness (e.g. Calculate with Rosetta, Writing the travel diary, Build Rosetta, How to become an astronaut, etc.) The project was a great opportunity to apply integrated learning methods for developing competencies which are a part of the primary school curriculum in Romania. In Language and Communication classes the students talked about their partners living places and their traditions and habits. They learnt some basic words in their partners language related to the weather. They created stories- both in Romanian and English; they described life in space and astronomical phenomena. They talked to the other partners during the several online meetings we organized and wrote short stories in English. In Mathematics and Science they found out about the Milky Way, the Solar System, the weather, famous astronauts and astronomers. They calculated, solved problems, made experiments and explained specific natural phenomena

  16. Astronomers Discover Six-Image Gravitational Lens

    Science.gov (United States)

    2001-08-01

    An international team of astronomers has used the National Science Foundation's Very Long Baseline Array (VLBA) radio telescope and NASA's Hubble Space Telescope (HST) to discover the first gravitational lens in which the single image of a very distant galaxy has been split into six different images. The unique configuration is produced by the gravitational effect of three galaxies along the line of sight between the more-distant galaxy and Earth. Optical and Radio Images of Gravitational Lens "This is the first gravitational lens with more than four images of the background object that is produced by a small group of galaxies rather than a large cluster of galaxies," said David Rusin, who just received his Ph.D. from the University of Pennsylvania. "Such systems are expected to be extremely rare, so this discovery is an important stepping stone. Because this is an intermediate case between gravitational lenses produced by single galaxies and lenses produced by large clusters of galaxies, it will give us insights we can't get from other types of lenses," Rusin added. The gravitational lens, called CLASS B1359+154, consists of a galaxy more than 11 billion light-years away in the constellation Bootes, with a trio of galaxies more than 7 billion light-years away along the same line of sight. The more-distant galaxy shows signs that it contains a massive black hole at its core and also has regions in which new stars are forming. The gravitational effect of the intervening galaxies has caused the light and radio waves from the single, more-distant galaxy to be "bent" to form six images as seen from Earth. Four of these images appear outside the triangle formed by the three intermediate galaxies and two appear inside that triangle. "This lens system is a very interesting case to study because it is more complicated than lenses produced by single galaxies, and yet simpler than lenses produced by clusters of numerous galaxies," said Chris Kochanek of the Harvard

  17. Carbon Atmosphere Discovered On Neutron Star

    Science.gov (United States)

    2009-11-01

    without pulsations would require a tiny size, consistent only with exotic stars made of strange quark matter. "Our carbon veil solves one of the big questions about the neutron star in Cas A," said Craig Heinke. "People have been willing to consider some weird explanations, so it's a relief to discover a less peculiar solution." Unlike most astronomical objects, neutron stars are small enough to understand on a human scale. For example, neutron stars typically have a diameter of about 14 miles, only slightly longer than a half-marathon. The atmosphere of a neutron star is on an even smaller scale. The researchers calculate that the carbon atmosphere is only about 4 inches thick, because it has been compressed by a surface gravity that is 100 billion times stronger than on Earth. "For people who are used to hearing about immense sizes of things in space, it might be a surprise that we can study something so small," said Ho. "It's also funny to think that such a thin veil over this star played a key role in frustrating researchers." In Earth's time frame, the estimated age of the neutron star in Cas A is only several hundred years, making it about ten times younger than other neutron stars with detected surface emission. Therefore, the Cas A neutron star gives a unique window into the early life of a cooling neutron star. The carbon itself comes from a combination of material that has fallen back after the supernova, and nuclear reactions on the hot surface of the neutron star which convert hydrogen and helium into carbon. The X-ray spectrum and lack of pulsar activity suggest that the magnetic field on the surface of this neutron star is relatively weak. Similarly low magnetic fields are implied for several other young neutron stars by study of their weak X-ray pulsations. It is not known whether these neutron stars will have low magnetic fields for their entire lives, and never become radio pulsars, or whether processes in their interior will lead to the development of

  18. 76 FR 4393 - Discover Financial Services Negotiated Service Agreement

    Science.gov (United States)

    2011-01-25

    ... Discover Financial Services Negotiated Service Agreement AGENCY: Postal Regulatory Commission. ACTION... Financial Services negotiated service agreement to the market dominant product list. This notice addresses... 3020, et seq., to add a Discover Financial Services (DFS) negotiated service agreement to the market...

  19. Youngest Stellar Explosion in Our Galaxy Discovered

    Science.gov (United States)

    2008-05-01

    Astronomers have found the remains of the youngest supernova, or exploded star, in our Galaxy. The supernova remnant, hidden behind a thick veil of gas and dust, was revealed by the National Science Foundation's Very Large Array (VLA) and NASA's Chandra X-Ray Observatory, which could see through the murk. The object is the first example of a "missing population" of young supernova remnants. 1985 and 2008 VLA Images Move cursor over image to blink. VLA Images of G1.9+0.3 in 1985 and 2008: Circle for size comparison. CREDIT: Green, et al., NRAO/AUI/NSF From observing supernovae in other galaxies, astronomers have estimated that about three such stellar explosions should occur in our Milky Way every century. However, the most recent one known until now occurred around 1680, creating the remnant called Cassiopeia A. The newly-discovered object is the remnant of an explosion only about 140 years ago. "If the supernova rate estimates are correct, there should be the remnants of about 10 supernova explosions in the Milky Way that are younger than Cassiopeia A," said David Green of the University of Cambridge in the UK, who led the VLA study. "It's great to finally track one of them down." Supernova explosions, which mark the violent death of a star, release tremendous amounts of energy and spew heavy elements such as calcium and iron into interstellar space. They thus seed the clouds of gas and dust from which new stars and planets are formed and, through their blast shocks, can even trigger such formation. The lack of evidence for young supernova remnants in the Milky Way had caused astronomers to wonder if our Galaxy, which appears otherwise normal, differed in some unknown way from others. Alternatively, scientists thought that the "missing" Milky Way supernovae perhaps indicated that their understanding of the relationship between supernovae and other galactic processes was in error. The astronomers made their discovery by measuring the expansion of the debris from

  20. Medicinal benefits of marine invertebrates: sources for discovering natural drug candidates.

    Science.gov (United States)

    De Zoysa, Mahanama

    2012-01-01

    Marine invertebrates are one of the major groups of organisms, which could be diversified under the major taxonomic groups of Porifera, Cnidaria, Mollusca, Arthropoda, Echinodermata, and many other minor phyla. To date, range of medicinal benefits and a significant number of marine natural products (MNPs) have been discovered from marine invertebrates. Seafood diet from edible marine invertebrates such as mollusks and crustaceans has been linked with various medicinal benefits to improve human health. Among marine invertebrates, spongers from phylum Porifera is the most dominant group responsible for discovering large number of MNPs, which have been used as template to develop therapeutic drugs. MNPs isolated from invertebrates have shown wide range of therapeutic properties including antimicrobial, antioxidant, antihypertensive, anticoagulant, anticancer, anti-inflammatory, wound healing and immune modulator, and other medicinal effects. Therefore, marine invertebrates are rich sources of chemical diversity and health benefits for developing drug candidates, cosmetics, nutritional supplements, and molecular probes that can be supported to increase the healthy life span of human. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Spectroscopic Classifications with Magellan of 7 Supernovae Discovered by DES

    Science.gov (United States)

    Blanchard, P. K.; Challis, P.; Drout, M.; Kirshner, R.; Brown, P. J.; Krisciunas, K.; Suntzeff, N.; D'Andrea, C.; Nichol, R.; Papadopoulos, A.; Smith, M.; Sullivan, M.; Maartens, R.; Gupta, R.; Kovacs, E.; Kuhlmann, S.; Spinka, H.; Ahn, E.; Finley, D. A.; Frieman, J.; Marriner, J.; Wester, W.; Aldering, G.; Kim, A. G.; Thomas, R. C.; Barbary, K.; Bloom, J. S.; Goldstein, D.; Nugent, P.; Perlmutter, S.; Foley, R. J.; Castander, F. J.; Desai, S.; Paech, K.; Smith, R. C.; Schubnell, M.; Kessler, R.; Scolnic, D.; Covarrubias, R. A.; Brout, D. J.; Fischer, J. A.; Gladney, L.; March, M.; Sako, M.; Wolf, R. C.

    2015-01-01

    We report optical spectroscopy of supernova candidates discovered by the Dark Energy Survey. The spectra (425-945 nm) were obtained using IMACS on the 6.5m Baade telescope at the Las Campanas Observatory on Dec 19, 2014.

  2. Hidden Abilities Discovered Among Multiply Handicapped Blind Children

    Science.gov (United States)

    Klineman, Janet

    1975-01-01

    The effectiveness of an objective, systematic assessment and individualized programing approach for discovering new channels of learning is illustrated with case study evaluations of multiply handicapped visually impaired children with complex learning and behavioral problems. (SB)

  3. Gerekenariseerde loopbaanvoorligting : 'n evaluering van die DISCOVER-stelsel

    OpenAIRE

    2014-01-01

    D.Litt. et Phil. (Psychology) Career planning is a developmental process that can be facilitated by career development programmes. One of the recent developments in these programmes was the introduction of computerized career counselling which enables the user to explore career activities independently. An experimental investigation in which the DISCOVER computerized system was used, was conducted at two universities in an attempt to determine whether DISCOVER could be a useful aid for car...

  4. Therapeutic use exemption

    Science.gov (United States)

    Dvorak, J; Kirkendall, D; Vouillamoz, M

    2006-01-01

    Football players who have either physical symptoms or disease after injury may need to be treated with specific medicines that are on the list of prohibited substances. Therapeutic use exemption may be granted to such players, in accordance with strictly defined criteria—these are presented in this article. Procedures of how to request for an abbreviated or a standard therapeutic use exemption are explained, and data on therapeutic use exemptions (UEFA and FIFA, 2004 and 2005) are also presented. PMID:16799102

  5. Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study.

    Science.gov (United States)

    Dewey, Frederick E; Murray, Michael F; Overton, John D; Habegger, Lukas; Leader, Joseph B; Fetterolf, Samantha N; O'Dushlaine, Colm; Van Hout, Cristopher V; Staples, Jeffrey; Gonzaga-Jauregui, Claudia; Metpally, Raghu; Pendergrass, Sarah A; Giovanni, Monica A; Kirchner, H Lester; Balasubramanian, Suganthi; Abul-Husn, Noura S; Hartzel, Dustin N; Lavage, Daniel R; Kost, Korey A; Packer, Jonathan S; Lopez, Alexander E; Penn, John; Mukherjee, Semanti; Gosalia, Nehal; Kanagaraj, Manoj; Li, Alexander H; Mitnaul, Lyndon J; Adams, Lance J; Person, Thomas N; Praveen, Kavita; Marcketta, Anthony; Lebo, Matthew S; Austin-Tse, Christina A; Mason-Suares, Heather M; Bruse, Shannon; Mellis, Scott; Phillips, Robert; Stahl, Neil; Murphy, Andrew; Economides, Aris; Skelding, Kimberly A; Still, Christopher D; Elmore, James R; Borecki, Ingrid B; Yancopoulos, George D; Davis, F Daniel; Faucett, William A; Gottesman, Omri; Ritchie, Marylyn D; Shuldiner, Alan R; Reid, Jeffrey G; Ledbetter, David H; Baras, Aris; Carey, David J

    2016-12-23

    The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery. Copyright © 2016, American Association for the Advancement of Science.

  6. Chicanoizing the Therapeutic Community

    Science.gov (United States)

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  7. Therapeutic Crisis Intervention.

    Science.gov (United States)

    Holden, Martha J.; Powers, Jane Levine

    1993-01-01

    Describes Therapeutic Crisis Intervention (TCI) program as providing staff with skills, knowledge, and confidence to manage child in crisis to bring about a "maximum amount of lasting response." Contends that, by applying principles of TCI training, direct care worker can attain therapeutic control and maintain dignity of both adult and child…

  8. Trends in Therapeutic Recreation.

    Science.gov (United States)

    Smith, Ralph W.

    1995-01-01

    Discusses the implications of the rapid, dramatic changes taking place in therapeutic recreation for individuals with physical disabilities. The article notes the impact of changes in managed care, examines programming trends in therapeutic recreation (adventure/outdoor education, competitive sports, handcycling, health enhancement activities, and…

  9. Reporting therapeutic discourse in a therapeutic community.

    Science.gov (United States)

    Chapman, G E

    1988-03-01

    Research in nurses' communications has concentrated on nurse to patient interactions. Those few studies which focus on nurse to nurse communications seem to be generated by a pragmatic and normative concern with effective information sharing. In this paper, which describes one aspect of a larger case study of a hospital-based therapeutic community, the description and analysis of nurses' reports flows not from a normative model of professional practice, but rather an exploration of how professional practice is articulated as discourse in nurses' written accounts. Foucault's ideas about therapeutic discourse inform the theoretical framework of the research. Ethnomethodological concerns with the importance of documentary analysis provide the methodological rationale for examining nurses' 24-hour report documents, as official discourse, reflecting therapeutic practice in this setting. A content analysis of nurses' reports, collected over a period of 4 months, demonstrated the importance of domesticity and ordinary everyday activities in nurses' accounts of hospital life. Disruption to the 'life as usual' domesticity in the community seemed to be associated with admission to and discharge from the hospital when interpersonal and interactional changes between patients occur. It is suggested that nurses in general hospital wards and more orthodox psychiatric settings might usefully consider the impact of admissions and discharges on the group of patients they manage, and make this a discursive focus of their work.

  10. Discovering Glaser: My Experience of Doing Grounded Theory

    OpenAIRE

    Lesley Margaret Piko

    2014-01-01

    For my investigation into how general practitioners (GPs) experience their medical careers, I used a grounded theory methodology based on the early work of Glaser and Strauss (1967) and Glaser’s subsequent work (Glaser, 1978, 1998). Glaser (1998) suggested you need to do grounded theory in order to understand the methodology. I found as I engaged in the process I began to understand the meaning of Glaser’s teachings and to discover Glaser. In this article, I share my experience of discovering...

  11. The Magic of Mathematics Discovering the Spell of Mathematics

    CERN Document Server

    Pappas, Theoni

    2011-01-01

    Delves into the world of ideas, explores the spell mathematics casts on our lives, and helps you discover mathematics where you least expect it. Be spellbound by the mathematical designs found in nature. Learn how knots may untie the mysteries of life. Be mesmerized by the computer revolution. Discover how the hidden forces of mathematics hold architectural structures together connect your telephone calls help airplanes get off the ground solve the mysteries of the living cell. See how some artists use a mathematical palette in their works and how many writers draw upon the wealth of its ideas

  12. [PLURAL THERAPEUTIC ITINERARIES].

    Science.gov (United States)

    Iorio, Silvia

    2015-01-01

    This article addresses the strategies employed by Nahua community of Mexixo to deal with health problems. Drawing on qualitative research, it discusses the choice of plural therapeutic itineraries, including the use of informal and formal healthcare.

  13. Discovering Theorems in Abstract Algebra Using the Software "GAP"

    Science.gov (United States)

    Blyth, Russell D.; Rainbolt, Julianne G.

    2010-01-01

    A traditional abstract algebra course typically consists of the professor stating and then proving a sequence of theorems. As an alternative to this classical structure, the students could be expected to discover some of the theorems even before they are motivated by classroom examples. This can be done by using a software system to explore a…

  14. Discovering How a Communicative Notion Is Expressed in English.

    Science.gov (United States)

    Kennedy, Graeme D.

    A study to develop a methodology for discovering how one important notion or semantic category, "frequency of occurrence," is expressed in words, phrases, or other linguistic devices in academic English began with a search for devices expressing that notion, by analyzing text from a news magazine, a New Zealand geography textbook, and a…

  15. Bioinformatic analysis to discover putative drug targets against ...

    African Journals Online (AJOL)

    /

    2012-01-26

    Jan 26, 2012 ... Bioinformatic analysis to discover putative drug targets against diarrheal causative agents. Muhammad Shakil Khan, Sana Zahra and Hamid Rashid*. Department of Bioinformatics, Mohammad Ali Jinnah University, Islamabad, Pakistan. Accepted 23 September, 2011. Availability of genome sequences of ...

  16. Levels of Glycosylated Haemoglobin in newly discovered Sudanese ...

    African Journals Online (AJOL)

    ... random blood glucose, body mass index, hypertension, or the duration of symptoms. Conclusion: HbA1c levels in newly discovered diabetics was found to be elevated, with significant difference between diabetics of less than forty, and above forty years of age. Key wards: Diabetes, HbA1c, Ketoacidosis, Hypertension.

  17. Discover 4-H Clubs: The Essential Resource for 4-H

    Science.gov (United States)

    MacArthur, Stacey; Nelson, Cindy; Brower, Naomi; Memmott, Margie; Peterson, Gaelynn

    2016-01-01

    Obstacles facing new 4-H volunteers include time constraints and difficulty finding project-specific information, resources, and opportunities available for club members. As a solution to these obstacles and an aid for assisting volunteers in becoming confident in delivering information to youth, content experts produced Discover 4-H Clubs, a…

  18. The Spy VI child : A newly discovered Neandertal infant

    NARCIS (Netherlands)

    Crevecoeur, Isabelle; Bayle, Priscilla; Rougier, Helene; Maureille, Bruno; Higham, Thomas; van der Plicht, Johannes; De Clerck, Nora; Semal, Patrick

    2010-01-01

    Spy cave (Jemeppe-sur-Sambre Belgium) is reputed for the two adult Neandertal individuals discovered in situ in 1886 Recent reassessment of the Spy collections has allowed direct radiocarbon dating of these individuals The sorting of all of the faunal collections has also led to the discovery of the

  19. Re-Discovering Mendel: The Case of Carl Correns

    Science.gov (United States)

    Rheinberger, Hans-Jörg

    2015-01-01

    Carl Erich Correns (1864-1933) is remembered in the annals of science as one of the three botanists who re-discovered Mendel's laws. He can also, however, be regarded as one of the founding figures of classical genetics in Germany. Between 1894 and 1899 he carried out the crossing experiments with corn and peas that led to the re-statement of…

  20. US NSF: scientists discover planetary system similar to our own

    CERN Multimedia

    2003-01-01

    An international team of scientists has discovered a planet and star that may share the same relationship as Jupiter and our Sun, the closest comparison that researchers have found since they began their search for extra-solar planets nearly a decade ago (1 page).

  1. Scientists discover planetary system similar to our own

    CERN Multimedia

    2003-01-01

    'An international team of scientists has discovered a planet and star that may share the same relationship as Jupiter and our Sun, the closest comparison that researchers have found since they began their search for extra-solar planets nearly a decade ago' (1 page).

  2. How Einstein Discovered the Special Theory of Relativity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 2. How Einstein Discovered the Special Theory of Relativity. Sriranjan Banerji. General Article Volume 11 Issue 2 February 2006 pp 27-42. Fulltext. Click here to view fulltext PDF. Permanent link:

  3. A new screening method for discovering antibacterial agents from ...

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-04-26

    Apr 26, 2012 ... orchids that increased the isolation efficiency of previously uncultivable fungi. Given the appropriate culture conditions, the MAPC technique can be employed to discover novel antibiotics produced by common, rare and “uncultivable” species from different ecological niches of soil, water, plants, etc (Warcup ...

  4. Re-discovering indigenous knowledge – Ulwazi Lwemveli for ...

    African Journals Online (AJOL)

    Application of this knowledge in specific different areas continues to be part of practices in these communities, albeit with challenges imposed by systems of colonial education and religion, apartheid and the emerging global knowledge economy. Therefore, the imperative to re-discover and re-store IK cannot be ...

  5. New Pulsars Discovered in Arecibo Drift-Scan Searches

    OpenAIRE

    McLaughlin, M. A.; Lorimer, D. R.; Champion, D.J.; Xilouris, K.; Arzoumanian, Z.; Backer, D. C.; Cordes, J. M.; Lommen, A. N.; Fruchter, A. S.

    2003-01-01

    We report on new pulsars discovered in Arecibo drift-scan data. Processing of 2200 square degrees of data has resulted in the detection of 41 known and 12 new pulsars. New pulsars include two millisecond pulsars, one solitary and one binary recycled pulsar, and one pulsar with very unusual pulse profile morphology and complex drifting subpulse behavior.

  6. How did Cantor Discover Set Theory and Topology?

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 11. How did Cantor Discover Set Theory and Topology? S M Srivastava. General Article Volume 19 Issue 11 November 2014 pp 977-999 ... Author Affiliations. S M Srivastava1. Indian Statistical Institute 203 B T Road Kolkata 700108, India.

  7. A new screening method for discovering antibacterial agents from ...

    African Journals Online (AJOL)

    Since high-throughput screening (HTS) that selects antibacterial agents according to targets in vitro rather than whole-cell have not proven effective in the discovery of new antibiotics; new approaches for discovering the next generation of antibiotics are urgently needed. Filamentous fungi are an important source for many ...

  8. Annular pancreas intra operatively discovered: a case report

    Directory of Open Access Journals (Sweden)

    Zeineb Mzoughi

    2011-10-01

    Full Text Available Annular pancreas is a rare congenital abnormality. This entity can rarely be symptomatic. Patients can present with gastrointestinal obstruction or acute pancreatitis. We report a case with a rich iconography, of an annular pancreas discovered intraoperatively. A 46- year-old woman was operated with the diagnosis of acute cholecystitis with common bile duct stones. At operation, a strip of pancreatic tissue (2 cm completely encircled the second duodenum. Open cholecytectomy with choledocotomy and stones extractionwas done. Postoperatively, she developed an acute pancreatitis. The post-operative cholangiography showed the annular duct surrounding the second duodenum. Annular pancreas is rare. Symptoms may occur in newborn children. In adults, annular pancreas discovering is radiological or intra operatively.

  9. Discovering Glaser: My Experience of Doing Grounded Theory

    Directory of Open Access Journals (Sweden)

    Lesley Margaret Piko

    2014-12-01

    Full Text Available For my investigation into how general practitioners (GPs experience their medical careers, I used a grounded theory methodology based on the early work of Glaser and Strauss (1967 and Glaser’s subsequent work (Glaser, 1978, 1998. Glaser (1998 suggested you need to do grounded theory in order to understand the methodology. I found as I engaged in the process I began to understand the meaning of Glaser’s teachings and to discover Glaser. In this article, I share my experience of discovering my theory of optimising professional life. This theory explains how GPs develop their professional life in response to their need for sustainment—a need that encapsulates self-care to sustain wellbeing, work interest to sustain motivation and income to sustain lifestyle.

  10. Metagenomic approach for discovering new pathogens in infection disease outbreaks

    Directory of Open Access Journals (Sweden)

    Emanuela Giombini

    2011-09-01

    Full Text Available Viruses represent the most abundant biological components on earth.They can be found in every environment, from deep layers of oceans to animal bodies.Although several viruses have been isolated and sequenced, in each environment there are millions of different types of viruses that have not been identified yet.The advent of nextgeneration sequencing technologies with their high throughput capabilities make possible to study in a single experiment all the community of microorganisms present in a particular sample “microbioma”.They made more feasible the application of the metagenomic approach, by which it is also possible to discover and identify new pathogens, that may pose a threat to public health.This paper summarizes the most recent applications of nextgeneration sequencing to discover new viral pathogens during the occurrence of infection disease outbreaks.

  11. Kant and therapeutic privilege.

    Science.gov (United States)

    Brown, Chris

    2008-08-01

    Given Kant's exceptionless moral prohibition on lying, one might suspect that he is committed to a similar prohibition on withholding diagnostic and prognostic information from patients. I confirm this suspicion by adapting arguments against therapeutic privilege from his arguments against lying. However, I show that all these arguments are importantly flawed and submit that they should be rejected. A more compelling Kantian take on informed consent and therapeutic privilege is achievable, I argue, by focusing on Kant's duty of beneficence, which requires us to aim at furthering others' ends. But I show that there are some cases in which furthering a patient's ends requires withholding material medical information from her. Although I concede that these cases are probably quite rare, I conclude that the best Kantian thinking agrees with that of therapeutic privilege's advocates.

  12. A new hard X-ray transient discovered by INTEGRAL

    DEFF Research Database (Denmark)

    Gibaud, L.; Bazzano, A.; Bozzo, E.

    2011-01-01

    INTEGRAL discovered a new hard X-ray transient, IGR J17498-2921, during the observations performed from 2011-08-11 22:45 to 2011-08-12 05:54 UTC. The source is detected in the IBIS/ISGRI mosaic at a preliminary significance level of 11 and 9 sigma in the 20-40 keV and 40-80 keV energy bands, resp...

  13. Discovering patterns of activity in unstructured incident reports at scale

    Science.gov (United States)

    2015-05-12

    problematic activity by a particular reporter. • Taken en masse, we use the tickets as as a statistical sample of observations to learn about the threat and...information • DHS informational website • MD5 • 3 phishing email addresses • Filename • File paths • IPs 12Discovering patterns of activity in incident... statistical patterns in indicators across tickets and reporters to estimate similarity metrics and indicator communities. • Communities can be more

  14. Inner solar system material discovered in the Oort cloud

    OpenAIRE

    Meech, Karen J.; Yang, Bin; Kleyna, Jan; Hainaut, Olivier R.; Berdyugina, Svetlana; Keane, Jacqueline V.; Micheli, Marco; Morbidelli, Alessandro; Wainscoat, Richard J.

    2016-01-01

    We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system...

  15. Discovering the quantum universe the role of particle colliders

    CERN Document Server

    2006-01-01

    What does "Quantum Universe" mean? To discover what the universe is made of and how it works is the challenge of particle physics. "Quantum Universe" defines the quest to explain the universe in terms of quantum physics, which governs the behavior of the microscopic, subatomic world. It describes a revolution in particle physics and a quantum leap in our understanding of the mystery and beauty of the universe.

  16. Genetic Architect: Discovering Genomic Structure with Learned Neural Architectures

    OpenAIRE

    Deming, Laura; Targ, Sasha; Sauder, Nate; Almeida, Diogo; Ye, Chun Jimmie

    2016-01-01

    Each human genome is a 3 billion base pair set of encoding instructions. Decoding the genome using deep learning fundamentally differs from most tasks, as we do not know the full structure of the data and therefore cannot design architectures to suit it. As such, architectures that fit the structure of genomics should be learned not prescribed. Here, we develop a novel search algorithm, applicable across domains, that discovers an optimal architecture which simultaneously learns general genom...

  17. Discovering health topics in social media using topic models.

    Science.gov (United States)

    Paul, Michael J; Dredze, Mark

    2014-01-01

    By aggregating self-reported health statuses across millions of users, we seek to characterize the variety of health information discussed in Twitter. We describe a topic modeling framework for discovering health topics in Twitter, a social media website. This is an exploratory approach with the goal of understanding what health topics are commonly discussed in social media. This paper describes in detail a statistical topic model created for this purpose, the Ailment Topic Aspect Model (ATAM), as well as our system for filtering general Twitter data based on health keywords and supervised classification. We show how ATAM and other topic models can automatically infer health topics in 144 million Twitter messages from 2011 to 2013. ATAM discovered 13 coherent clusters of Twitter messages, some of which correlate with seasonal influenza (r = 0.689) and allergies (r = 0.810) temporal surveillance data, as well as exercise (r =  .534) and obesity (r =  -.631) related geographic survey data in the United States. These results demonstrate that it is possible to automatically discover topics that attain statistically significant correlations with ground truth data, despite using minimal human supervision and no historical data to train the model, in contrast to prior work. Additionally, these results demonstrate that a single general-purpose model can identify many different health topics in social media.

  18. Discovering health topics in social media using topic models.

    Directory of Open Access Journals (Sweden)

    Michael J Paul

    Full Text Available By aggregating self-reported health statuses across millions of users, we seek to characterize the variety of health information discussed in Twitter. We describe a topic modeling framework for discovering health topics in Twitter, a social media website. This is an exploratory approach with the goal of understanding what health topics are commonly discussed in social media. This paper describes in detail a statistical topic model created for this purpose, the Ailment Topic Aspect Model (ATAM, as well as our system for filtering general Twitter data based on health keywords and supervised classification. We show how ATAM and other topic models can automatically infer health topics in 144 million Twitter messages from 2011 to 2013. ATAM discovered 13 coherent clusters of Twitter messages, some of which correlate with seasonal influenza (r = 0.689 and allergies (r = 0.810 temporal surveillance data, as well as exercise (r =  .534 and obesity (r =  -.631 related geographic survey data in the United States. These results demonstrate that it is possible to automatically discover topics that attain statistically significant correlations with ground truth data, despite using minimal human supervision and no historical data to train the model, in contrast to prior work. Additionally, these results demonstrate that a single general-purpose model can identify many different health topics in social media.

  19. Discovering System Health Anomalies Using Data Mining Techniques

    Science.gov (United States)

    Sriastava, Ashok, N.

    2005-01-01

    We present a data mining framework for the analysis and discovery of anomalies in high-dimensional time series of sensor measurements that would be found in an Integrated System Health Monitoring system. We specifically treat the problem of discovering anomalous features in the time series that may be indicative of a system anomaly, or in the case of a manned system, an anomaly due to the human. Identification of these anomalies is crucial to building stable, reusable, and cost-efficient systems. The framework consists of an analysis platform and new algorithms that can scale to thousands of sensor streams to discovers temporal anomalies. We discuss the mathematical framework that underlies the system and also describe in detail how this framework is general enough to encompass both discrete and continuous sensor measurements. We also describe a new set of data mining algorithms based on kernel methods and hidden Markov models that allow for the rapid assimilation, analysis, and discovery of system anomalies. We then describe the performance of the system on a real-world problem in the aircraft domain where we analyze the cockpit data from aircraft as well as data from the aircraft propulsion, control, and guidance systems. These data are discrete and continuous sensor measurements and are dealt with seamlessly in order to discover anomalous flights. We conclude with recommendations that describe the tradeoffs in building an integrated scalable platform for robust anomaly detection in ISHM applications.

  20. UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry.

    Science.gov (United States)

    Zhao, Ying-Yong; Cheng, Xian-Long; Vaziri, Nosratola D; Liu, Shuman; Lin, Rui-Chao

    2014-10-01

    Metabonomics is a powerful and promising analytic tool that allows assessment of global low-molecular-weight metabolites in biological systems. It has a great potential for identifying useful biomarkers for early diagnosis, prognosis and assessment of therapeutic interventions in clinical practice. The aim of this review is to provide a brief summary of the recent advances in UPLC-based metabonomic approach for biomarker discovery in a variety of diseases, and to discuss their significance in clinical chemistry. All the available information on UPLC-based metabonomic applications for discovering biomarkers of diseases were collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Springer, Google Scholar, etc.). Metabonomics has been used in clinical chemistry to identify and evaluate potential biomarkers and therapeutic targets in various diseases affecting the liver (hepatocarcinoma and liver cirrhosis), lung (lung cancer and pneumonia), gastrointestinal tract (colorectal cancer) and urogenital tract (prostate cancer, ovarian cancer and chronic kidney disease), as well as metabolic diseases (diabetes) and neuropsychiatric disorders (Alzheimer's disease and schizophrenia), etc. The information provided highlights the potential value of determination of endogenous low-molecular-weight metabolites and the advantages and potential drawbacks of the application of UPLC-based metabonomics in clinical setting. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  1. Lymphedema and Therapeutic Lymphangiogenesis

    Directory of Open Access Journals (Sweden)

    Yukihiro Saito

    2013-01-01

    Full Text Available Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor.

  2. Therapeutic development in psoriasis.

    Science.gov (United States)

    Sobell, Jeffrey M; Leonardi, Craig L

    2014-06-01

    Advances in molecular biology have provided the basis for development of new therapeutic approaches to psoriasis. New, more effective therapies target specific molecules in the inflammatory cascade involved in the pathogenesis of psoriasis.The biologic era of psoriasis therapy began with inhibitors of T-cell activation, tumor necrosis factor-α, and interleukin (IL)-12/23. Continued investigation has led to therapies and therapeutic candidates that target IL-17, IL-23, phosphodiesterase-4, and isomers of Janus kinase. 2014 by Frontline Medical Communications Inc.

  3. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  4. 77 FR 27785 - Request for Information Regarding the NIH-Industry Program To Discover New Therapeutic Uses for...

    Science.gov (United States)

    2012-05-11

    ... the public sector has new ideas and the wherewithal to advance new applications, public-private... the most significant challenges for public-private partnerships that foster drug rescue between... carried out through collaborations between pharmaceutical companies and the biomedical research community...

  5. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  6. Therapeutic HPV DNA vaccines

    Science.gov (United States)

    Lin, Ken; Roosinovich, Elena; Ma, Barbara; Hung, Chien-Fu

    2010-01-01

    It is now well established that most cervical cancers are causally associated with HPV infection. This realization has led to efforts to control HPV-associated malignancy through prevention or treatment of HPV infection. Currently, commercially available HPV vaccines are not designed to control established HPV infection and associated premalignant and malignant lesions. To treat and eradicate pre-existing HPV infections and associated lesions which remain prevalent in the U.S. and worldwide, effective therapeutic HPV vaccines are needed. DNA vaccination has emerged as a particularly promising form of therapeutic HPV vaccines due to its safety, stability and ability to induce antigen-specific immunity. This review focuses on improving the potency of therapeutic HPV vaccines through modification of dendritic cells (DCs) by [1] increasing the number of antigen-expressing/antigen-loaded DCs, [2] improving HPV antigen expression, processing and presentation in DCs, and [3] enhancing DC and T cell interaction. Continued improvement in therapeutic HPV DNA vaccines may ultimately lead to an effective DNA vaccine for the treatment of HPV-associated malignancies. PMID:20066511

  7. Discovering Astronomy: An Astro 101 e-book

    Science.gov (United States)

    Shawl, Stephen J.; Byrd, Gene; Deustua, Susana E.; LoPresto, Michael C.

    2016-01-01

    Discovering Astronomy, now available in its 6th edition as an eText, has many advantages and features for your students. We have partnered with etextink.com and WebAssign.net to produce an affordable set of cost-saving options for your students. Also available is the Discovering Astronomy Activity Manual, which provides students with an active-learning experience.Our etext is device independent and thus accessible through any web browser. Americans with Disabilities Act compatibility provides access for all students. Hotlinks to outside sites provide further information for interested students. Lecture demonstration videos of important concepts, made specifically for this new edition, are embedded within the text as appropriate. Students can highlight text, take notes, and bookmark locations within the text. Important terms are linked to the glossary. Search capabilities allow students to easily find what they want.Instructors can interact with their students directly through the etext once the class roster has been provided. For example, instructors can embed assignments into their students' etext and add their own notes and updates, which are immediately visible to their students.Updates can be quickly made by us as new findings become available. For example, updates from New Horizons were added at the time of the closest approach to Pluto, and an update on the recent announcement of current water on Mars was added the day of the announcement.We will present results of our own experience with college and high school students' use of Discovering Astronomy in online courses.Details of the book, a sample chapter, and other information are available at discoveringastronomy.weebly.com.

  8. Sir Alexander Fleming: Scottish researcher who discovered penicillin.

    Science.gov (United States)

    Ligon, B Lee

    2004-01-01

    The discovery and development of penicillin changed the entire direction of approaches to treating infectious diseases and saved the lives of millions of people. Indeed, the development of penicillin was a watershed event in the battle against infectious diseases, and the individual who discovered it, Sir Alexander Fleming, remains a prominent individual in the annals of medical history. This article focuses primarily on the personal life of Alexander Fleming, an individual who had a remarkable diversity of interests and who made many contributions to science and medicine.

  9. An approach for discovering keywords from Spanish tweets using Wikipedia

    Directory of Open Access Journals (Sweden)

    Daniel AYALA

    2016-05-01

    Full Text Available Most approaches to keywords discovery when analyzing microblogging messages (among them those from Twitter are based on statistical and lexical information about the words that compose the text. The lack of context in the short messages can be problematic due to the low co-occurrence of words. In this paper, we present a new approach for keywords discovering from Spanish tweets based on the addition of context information using Wikipedia as a knowledge base. We present four different ways to use Wikipedia and two ways to rank the new keywords. We have tested these strategies using more than 60000 Spanish tweets, measuring performance and analyzing particularities of each strategy.

  10. Discovering timing feature interactions with timed UML 2 interactions

    DEFF Research Database (Denmark)

    Störrle, Harald; Knapp, Alexander

    2016-01-01

    patterns of timing specifications and show how they can be translated into UML 2 interactions with time constraints. We define a semantics that allows us to define and check coherence and consistency conditions of timing specifications. RESULTS: We provide a systematic process for mapping timing...... requirements into timed UML interactions and algorithms for checking their coherence and consistency. CONCLUSIONS: With our approach, it becomes easier to check and validate timing specifications. It is not our ambition to achieve complete coverage, i.e., discovering all timing specification defects. Instead...

  11. Knots and surfaces a guide to discovering mathematics

    CERN Document Server

    Farmer, David W

    1995-01-01

    In most mathematics textbooks, the most exciting part of mathematics-the process of invention and discovery-is completely hidden from the reader. The aim of Knots and Surfaces is to change all that. By means of a series of carefully selected tasks, this book leads readers to discover some real mathematics. There are no formulas to memorize; no procedures to follow. The book is a guide: its job is to start you in the right direction and to bring you back if you stray too far. Discovery is left to you. Suitable for a one-semester course at the beginning undergraduate level, there are no prerequi

  12. Marquette Island: A Distinct Mafic Lithology Discovered by Opportunity

    Science.gov (United States)

    Mittlefehldt, David W.; Gellert, R.; Herkenhoff, K. E.; Clark, B. C.; Cohen, B. A.; Fleischer, I.; Jolliff, B. L.; Klingelhoefer, G.; Ming, D. W.; Yingst, R. A.

    2010-01-01

    While rolling over the Meridiani Planum sedimentary terrane, the rover Opportunity has occasionally discovered large, > 10 cm erratics. Most of these have proven to be meteorites [1], but one - Bounce Rock - is a martian basaltic rock similar in composition to the meteorite EETA79001 lithology B [2]. Presently, Opportunity is intensively investigating an --30 cm tall rock named Marquette Island that may be a distinct type of martian mafic lithology. We report the results of its continuing investigation using the Microscopic Imager (MI); Mossbauer Spectrometer (MB) and Alpha Particle X-ray Spectrometer (APXS). A companion abstract discusses the results of Panoramic Camera (Pancam) imaging of the rock [3].

  13. Growing Self-Estemm and Discovering Intelligences through Oral Production

    Directory of Open Access Journals (Sweden)

    Ochoa Dora Liliana

    2002-08-01

    Full Text Available After having applied a needs analysis in an eleventh grade course of English, I could notice that there was a big lack of security and self-confidence in the students. They expressed in different data-gathering instruments their fear when speaking in front of the class. Also, they talked about their insecurity when pronouncing English and the need for more opportunities for developing speaking. Therefore, the implementation of an innovation in class was carried out in order to respond to the students¿ needs and make them discover their talents. The implementation was successful and students improved some areas of their communicative competence.

  14. Aplicación del modelo Discovering Hands en Argentina

    OpenAIRE

    Infante Rasch, Oriana; Urbina Hueso, Jhoan Sebastian

    2016-01-01

    Discovering Hands (DH) es un proyecto que nace en Alemania en el 2006, liderado por el doctor Frank Hoffmann. El programa se desarrolla pensando en el importante problema de salud pública en el cual se ha convertido en el cáncer de mama, pues según la Organización Mundial de la Salud es el mayor causal de muerte en mujeres, tanto en países desarrollados como en vía de desarrollo, y en Alemania esta enfermedad acaba con la vida de aproximadamente 18.000 mujeres cada año. (The Global Journal, ...

  15. Critical perspective: named reactions discovered and developed by women.

    Science.gov (United States)

    Olson, Julie A; Shea, Kevin M

    2011-05-17

    Named organic reactions. As chemists, we're all familiar with them: who can forget the Diels-Alder reaction? But how much do we know about the people behind the names? For example, can you identify a reaction named for a woman? How about a reaction discovered or developed by a woman but named for her male adviser? Our attempts to answer these simple questions started us on the journey that led to this Account. We introduce you to four reactions named for women and nine reactions discovered or developed by women. Using information obtained from the literature and, whenever possible, through interviews with the chemists themselves, their associates, and their advisers, we paint a more detailed picture of these remarkable women and their outstanding accomplishments. Some of the women you meet in this Account include Irma Goldberg, the only woman unambiguously recognized with her own named reaction. Gertrude Maud Robinson, the wife of Robert Robinson, who collaborated with him on several projects including the Piloty-Robinson pyrrole synthesis. Elizabeth Hardy, the Bryn Mawr graduate student who discovered the Cope rearrangement. Dorothee Felix, a critical member of Albert Eschenmoser's research lab for over forty years who helped develop both the Eschenmoser-Claisen rearrangement and the Eschenmoser-Tanabe fragmentation. Jennifer Loebach, the University of Illinois undergraduate who was part of the team in Eric Jacobsen's lab that discovered the Jacobsen-Katsuki epoxidation. Keiko Noda, a graduate student in Tsutomu Katsuki's lab who also played a key role in the development of the Jacobsen-Katsuki epoxidation. Lydia McKinstry, a postdoc in Andrew Myers's lab who helped develop the Myers asymmetric alkylation. Rosa Lockwood, a graduate student at Boston College whose sole publication is the discovery of the Nicholas reaction. Kaori Ando, a successful professor in Japan who helped develop the Roush asymmetric alkylation as a postdoc at MIT. Bianka Tchoubar, a

  16. Multistage vector (MSV) therapeutics

    Science.gov (United States)

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-01-01

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  17. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    Oral administration of therapeutic peptides could benefit millions of chronically ill people worldwide, through easier and less stigmatized therapy, and likely improve the long-term effects of currently widespread disease mismanagement. However, oral peptide delivery is a formidable task due......, but it is not widely studied in an oral context. As acylation furthermore increases interactions with the lipid membranes of mammalian cells, it offers several potential benefits for oral delivery of therapeutic peptides, and we hypothesize that tailoring the acylation may be used to optimize intestinal translocation...... to the harsh and selective gastrointestinal system, and development has lacked far behind injection therapy. Peptide acylation is a powerful tool to alter the pharmacokinetics, biophysical properties and chemical stability of injectable peptide drugs, primarily used to prolong blood circulation...

  18. Therapeutic use of cannabis.

    Science.gov (United States)

    de Vries, Kay; Green, Anita J

    Therapeutic cannabis use raises a number of dilemmas for nurses. This article examines the legal, political and ethical challenges raised by the use of cannabis by people with life-limiting or terminal illnesses in their own homes. (Throughout this paper, the term cannabis refers to illegal cannabis unless specified.) A literature review of databases from 1996 was conducted and internet material was also examined. Evidence on the therapeutic use of cannabis suggests it may produce improvements in quality of life, which has led to increased use among people with life-limiting illnesses. The cannabis used is usually obtained illegally, which can have consequences for both those who use it and nurses who provide treatment in the community.

  19. Leech Therapeutic Applications

    OpenAIRE

    Abdualkader, A. M.; A M Ghawi; Alaama, M.; M. Awang; A Merzouk

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproduct...

  20. Identification of immunogenic and virulence-associated Campylobacter jejuni proteins.

    Science.gov (United States)

    Nielsen, Lene N; Luijkx, Thomas A; Vegge, Christina S; Johnsen, Christina Kofoed; Nuijten, Piet; Wren, Brendan W; Ingmer, Hanne; Krogfelt, Karen A

    2012-02-01

    With the aim of identifying proteins important for host interaction and virulence, we have screened an expression library of NCTC 11168 Campylobacter jejuni genes for highly immunogenic proteins. A commercial C. jejuni open reading frame (ORF) library consisting of more than 1,600 genes was transformed into the Escherichia coli expression strain BL21(DE3), resulting in 2,304 clones. This library was subsequently screened for immunogenic proteins using antibodies raised in rabbit against a clinical isolate of C. jejuni; this resulted in 52 highly reactive clones representing 25 different genes after sequencing. Selected candidate genes were inactivated in C. jejuni NCTC 11168, and the virulence was examined using INT 407 epithelial cell line and motility, biofilm, autoagglutination, and serum resistance assays. These investigations revealed C. jejuni antigen 0034c (Cj0034c) to be a novel virulence factor and support the usefulness of the method. Further, several antigens were tested as vaccine candidates in two mouse models, in which Cj0034c, Cj0404, and Cj0525c resulted in a reduction of invasion in spleen and liver after challenge.

  1. High throughput techniques for discovering new glycine receptor modulators and their binding sites

    Directory of Open Access Journals (Sweden)

    Daniel F Gilbert

    2009-10-01

    Full Text Available The inhibitory glycine receptor (GlyR is a member of the Cys-loop receptor family that mediates inhibitory neurotransmission in the central nervous system. These receptors are emerging as potential drug targets for inflammatory pain, immunomodulation, spasticity and epilepsy. Antagonists that specifically inhibit particular GlyR isoforms are also required as pharmacological probes for elucidating the roles of particular GlyR isoforms in health and disease. Although a substantial number of both positive and negative GlyR modulators have been identified, very few of these are specific for the GlyR over other receptor types. Thus, the potential of known compounds as either therapeutic leads or pharmacological probes is limited. It is therefore surprising that there have been few published studies describing attempts to discover novel GlyR isoform-specific compounds. The first aim of this review is to consider various methods for efficiently screening compounds against these receptors. We conclude that an anion sensitive yellow fluorescent protein is optimal for primary screening and that automated electrophysiology of cells stably expressing GlyRs is useful for confirming hits and quantitating the actions of identified compounds. The second aim of this review is to demonstrate how these techniques are used in our laboratory for the purpose of both discovering novel GlyR-active compounds and characterizing their binding sites. We also describe a reliable, cost effective method for transfecting HEK293 cells in single wells of a 384 well plate using nanogram quantities of cDNA.

  2. Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy.

    Directory of Open Access Journals (Sweden)

    Zhiwei Huang

    Full Text Available Chloroquine (CQ and other quinoline-containing antimalarials are important drugs with many therapeutic benefits as well as adverse effects. However, the molecular targets underlying most such effects are largely unknown. By taking a novel functional genomics strategy, which employs a unique combination of genome-wide drug-gene synthetic lethality (DGSL, gene-gene synthetic lethality (GGSL, and dosage suppression (DS screens in the model organism Saccharomyces cerevisiae and is thus termed SL/DS for simplicity, we found that CQ inhibits the thiamine transporters Thi7, Nrt1, and Thi72 in yeast. We first discovered a thi3Δ mutant as hypersensitive to CQ using a genome-wide DGSL analysis. Using genome-wide GGSL and DS screens, we then found that a thi7Δ mutation confers severe growth defect in the thi3Δ mutant and that THI7 overexpression suppresses CQ-hypersensitivity of this mutant. We subsequently showed that CQ inhibits the functions of Thi7 and its homologues Nrt1 and Thi72. In particular, the transporter activity of wild-type Thi7 but not a CQ-resistant mutant (Thi7(T287N was completely inhibited by the drug. Similar effects were also observed with other quinoline-containing antimalarials. In addition, CQ completely inhibited a human thiamine transporter (SLC19A3 expressed in yeast and significantly inhibited thiamine uptake in cultured human cell lines. Therefore, inhibition of thiamine uptake is a conserved mechanism of action of CQ. This study also demonstrated SL/DS as a uniquely effective methodology for discovering drug targets.

  3. Learning Faster by Discovering and Exploiting Object Similarities

    Directory of Open Access Journals (Sweden)

    Tadej Janež

    2013-03-01

    Full Text Available In this paper we explore the question: “Is it possible to speed up the learning process of an autonomous agent by performing experiments in a more complex environment (i.e., an environment with a greater number of different objects?” To this end, we use a simple robotic domain, where the robot has to learn a qualitative model predicting the change in the robot's distance to an object. To quantify the environment's complexity, we defined cardinal complexity as the number of objects in the robot's world, and behavioural complexity as the number of objects' distinct behaviours. We propose Error reduction merging (ERM, a new learning method that automatically discovers similarities in the structure of the agent's environment. ERM identifies different types of objects solely from the data measured and merges the observations of objects that behave in the same or similar way in order to speed up the agent's learning. We performed a series of experiments in worlds of increasing complexity. The results in our simple domain indicate that ERM was capable of discovering structural similarities in the data which indeed made the learning faster, clearly superior to conventional learning. This observed trend occurred with various machine learning algorithms used inside the ERM method.

  4. Discovering Congested Routes Using Vehicle Trajectories in Road Networks

    Directory of Open Access Journals (Sweden)

    Kyoung Soo Bok

    2015-01-01

    Full Text Available The popular route recommendation and traffic monitoring over the road networks have become important in the location-based services. The schemes to find out the congested routes were proposed by considering the number of vehicles in a road segment. However, the existing schemes do not consider the features of each road segment such as width, length, and direction in a road network. Furthermore, the existing schemes fail to consider the average moving speed of vehicles. Therefore, they can detect the incorrect density routes. To overcome such problems, we propose a new discovering scheme of congested routes through the analysis of vehicle trajectories in a road network. The proposed scheme divides each road into segments with different width and length in a road network. And then, the congested road segment is detected through the saturation degree of the road segment and the average moving speed of vehicles in the road segment. Finally, we compute the final congested routes by using a clustering scheme. The experimental results have shown that the proposed scheme can efficiently discover the congested routes in the different directions of the roads.

  5. Discovering the cosmos with small spacecraft the American explorer program

    CERN Document Server

    Harvey, Brian

    2018-01-01

    Explorer was the original American space program and Explorer 1 its first satellite, launched in 1958. Sixty years later, it is the longest continuously running space program in the world, demonstrating to the world how we can explore the cosmos with small spacecraft. Almost a hundred Explorers have already been launched.  Explorers have made some of the fundamental discoveries of the Space Age.Explorer 1 discovered Earth’s radiation belts. Later Explorers surveyed the Sun, the X-ray and ultraviolet universes, black holes, magnetars and gamma ray bursts. An Explorer found the remnant of the Big Bang. One Explorer chased and was the first to intercept a comet. The program went through a period of few launches during the crisis of funding for space science in the 1980s. However, with the era of ‘faster, cheaper, better,’ the program was reinvented, and new exiting missions began to take shape, like Swift and the asteroid hunter WISE.  Discovering the Cosmos with Small Spacecraft gives an account of ...

  6. Novel virophages discovered in a freshwater lake in China

    Directory of Open Access Journals (Sweden)

    Chaowen eGong

    2016-01-01

    Full Text Available Virophages are small double-stranded DNA viruses that are parasites of giant DNA viruses that infect unicellular eukaryotes. Here we identify a novel group of virophages, named Dishui Lake virophages (DSLVs that were discovered in Dishui Lake (DSL: an artificial freshwater lake in Shanghai, China. Based on PCR and metagenomic analysis, the complete genome of DSLV1 was found to be circular and 28,788 base pairs in length, with a G+C content 43.2%, and 28 predicted open reading frames (ORFs. Fifteen of the DSLV1 ORFs have sequence similarity to known virophages. Two DSLV1 ORFs exhibited sequence similarity to that of prasinoviruses (Phycodnaviridae and chloroviruses (Phycodnaviridae, respectively, suggesting horizontal gene transfer occurred between these large algal DNA viruses and DSLV1. 46 other virophages-related contigs were also obtained, including six homologous major capsid protein (MCP gene. Phylogenetic analysis of these MCPs showed that DSLVs are closely related to OLV (Organic Lake virophage and YSLVs (Yellowstone Lake virophages, especially to YSLV3, except for YSLV7. These results indicate that freshwater ecotopes are the hotbed for discovering novel virophages as well as understanding their diversity and properties.

  7. Ongoing therapeutic trials and outcome measures for Duchenne muscular dystrophy.

    Science.gov (United States)

    Govoni, Alessandra; Magri, Francesca; Brajkovic, Simona; Zanetta, Chiara; Faravelli, Irene; Corti, Stefania; Bresolin, Nereo; Comi, Giacomo P

    2013-12-01

    Muscular dystrophy is a heterogeneous group of genetic disorders characterised by progressive muscle tissue degeneration. No effective treatment has been discovered for these diseases. Preclinical and clinical studies aimed at the development of new therapeutic approaches have been carried out, primarily in subjects affected with dystrophinopathies (Duchenne and Becker muscular dystrophy). In this review, we outline the current therapeutic approaches and past and ongoing clinical trials, highlighting both the advantages and limits of each one. The experimental designs of these trials were based on different rationales, including immunomodulation, readthrough strategies, exon skipping, gene therapy, and cell therapy. We also provide an overview of available outcome measures, focusing on their reliability in estimating meaningful clinical improvement in order to aid in the design of future trials. This perspective is extremely relevant to the field considering the recent development of novel therapeutic approaches that will result in an increasing number of clinical studies over the next few years.

  8. [Therapeutic measures in tardive dyskinesia].

    Science.gov (United States)

    Tegeler, J; Wöller, W

    1983-06-01

    Studies on the treatments for neuroleptic-induced tardive dyskinesia published in the literature are reviewed. The great number of different treatments and the controversial results of most studies show that there is as yet no specific and safe treatment for tardive dyskinesia. Suggestions for well-designed treatment studies are given: Placebo-controlled double-blind design, larger patient populations, clear diagnostic and standard observing and rating conditions using different assessment methods and videotapes, withdrawal of neuroleptics and antiparkinsonian drugs to discover reversible tardive dyskinesia. If this procedure is not feasible, neuroleptics and other drugs should be maintained at a stable dose level. Longer term studies of some months are necessary to study the prolonged efficacy of different drugs. The effect of dopamine-antagonists such as neuroleptics and of dopamine-depleting agents such as reserpine and oxypertine is of limited duration. Dopamine-agonists such as L-Dopa, bromocriptine and amantadine help only few patients and may even aggravate the symptoms of tardive dyskinesia. In some double-blind studies cholinergic drugs such as lecithin and deanol have improved tardive dyskinesia, but further controlled studies are needed. Anticholinergic drugs such as antiparkinsonian agents should not be prescribed because they may aggravate tardive dyskinesia. Some patients respond to GABA-ergic agents such as baclofen, sodium valproate and the benzodiazepines, but further studies are needed before the value of GABA-ergic agents in the treatment of tardive dyskinesia can be properly assessed. After withdrawal of neuroleptics the average of remission rates within a year is 20%-30%. Elderly patients are more likely to have persistent dyskinesias. A progressive stepwise diminution of the neuroleptic dose and of the antiparkinsonian agents is recommended. When a patient's psychosis is exacerbated after withdrawal of the neuroleptics and tardive dyskinesia

  9. Discovering metric temporal constraint networks on temporal databases.

    Science.gov (United States)

    Álvarez, Miguel R; Félix, Paulo; Cariñena, Purificación

    2013-07-01

    In this paper, we propose the ASTPminer algorithm for mining collections of time-stamped sequences to discover frequent temporal patterns, as represented in the simple temporal problem (STP) formalism: a representation of temporal knowledge as a set of event types and a set of metric temporal constraints among them. To focus the mining process, some initial knowledge can be provided by the user, also expressed as an STP, that acts as a seed pattern for the searching procedure. In this manner, the mining algorithm will search for those frequent temporal patterns consistent with the initial knowledge. Health organisations demand, for multiple areas of activity, new computational tools that will obtain new knowledge from huge collections of data. Temporal data mining has arisen as an active research field that provides new algorithms for discovering new temporal knowledge. An important point in defining different proposals is the expressiveness of the resulting temporal knowledge, which is commonly found in the bibliography in a qualitative form. ASTPminer develops an Apriori-like strategy in an iterative algorithm where, as a result of each iteration i, a set of frequent temporal patterns of size i is found that incorporates three distinctive mechanisms: (1) use of a clustering procedure over distributions of temporal distances between events to recognise similar occurrences as temporal patterns; (2) consistency checking of every combination of temporal patterns, which ensures the soundness of the resultant patterns; and (3) use of seed patterns to allow the user to drive the mining process. To validate our proposal, several experiments were conducted over a database of time-stamped sequences obtained from polysomnography tests in patients with sleep apnea-hypopnea syndrome. ASTPminer was able to extract well-known temporal patterns corresponding to different manifestations of the syndrome. Furthermore, the use of seed patterns resulted in a reduction in the size of

  10. Frankincense--therapeutic properties.

    Science.gov (United States)

    Al-Yasiry, Ali Ridha Mustafa; Kiczorowska, Bożena

    2016-01-04

    Recently, increasing interest in natural dietary and therapeutic preparations used as dietary supplements has been observed. One of them is frankincense. This traditional medicine of the East is believed to have anti-inflammatory, expectorant, antiseptic, and even anxiolytic and anti-neurotic effects. The present study aims to verify the reported therapeutic properties of Boswellia resin and describe its chemical composition based on available scientific studies. The main component of frankincense is oil (60%). It contains mono- (13%) and diterpenes (40%) as well as ethyl acetate (21.4%), octyl acetate (13.4%) and methylanisole (7.6%). The highest biological activity among terpenes is characteristic of 11-keto-ß-acetyl-beta-boswellic acid, acetyl-11-keto-ß-boswellic acid and acetyl-α-boswellic acid. Contemporary studies have shown that resin indeed has an analgesic, tranquilising and anti-bacterial effects. From the point of view of therapeutic properties, extracts from Boswellia serrata and Boswellia carterii are reported to be particularly useful. They reduce inflammatory conditions in the course of rheumatism by inhibiting leukocyte elastase and degrading glycosaminoglycans. Boswellia preparations inhibit 5-lipoxygenase and prevent the release of leukotrienes, thus having an anti-inflammatory effect in ulcerative colitis, irritable bowel syndrome, bronchitis and sinusitis. Inhalation and consumption of Boswellia olibanum reduces the risk of asthma. In addition, boswellic acids have an antiproliferative effect on tumours. They inhibit proliferation of tumour cells of the leukaemia and glioblastoma subset. They have an anti-tumour effect since they inhibit topoisomerase I and II-alpha and stimulate programmed cell death (apoptosis).

  11. Frankincense – therapeutic properties

    Directory of Open Access Journals (Sweden)

    Ali Ridha Mustafa Al-Yasiry

    2016-01-01

    Full Text Available Recently, increasing interest in natural dietary and therapeutic preparations used as dietary supplements has been observed. One of them is frankincense. This traditional medicine of the East is believed to have anti-inflammatory, expectorant, antiseptic, and even anxiolytic and anti-neurotic effects. The present study aims to verify the reported therapeutic properties of Boswellia resin and describe its chemical composition based on available scientific studies. The main component of frankincense is oil (60%. It contains mono- (13% and diterpenes (40% as well as ethyl acetate (21.4%, octyl acetate (13.4% and methylanisole (7.6%. The highest biological activity among terpenes is characteristic of 11-keto-ß-acetyl-beta-boswellic acid, acetyl-11-keto-ß-boswellic acid and acetyl-α-boswellic acid. Contemporary studies have shown that resin indeed has an analgesic, tranquilising and anti-bacterial effects. From the point of view of therapeutic properties, extracts from Boswellia serrata and Boswellia carterii are reported to be particularly useful. They reduce inflammatory conditions in the course of rheumatism by inhibiting leukocyte elastase and degrading glycosaminoglycans. Boswellia preparations inhibit 5-lipoxygenase and prevent the release of leukotrienes, thus having an anti-inflammatory effect in ulcerative colitis, irritable bowel syndrome, bronchitis and sinusitis. Inhalation and consumption of Boswellia olibanum reduces the risk of asthma. In addition, boswellic acids have an antiproliferative effect on tumours. They inhibit proliferation of tumour cells of the leukaemia and glioblastoma subset. They have an anti-tumour effect since they inhibit topoisomerase I and II-alpha and stimulate programmed cell death (apoptosis.

  12. Therapeutic nanomedicine surmounts the limitations of pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Odiba Arome

    2017-09-01

    Full Text Available Science always strives to find an improved way of doing things and nanoscience is one such approach. Nanomaterials are suitable for pharmaceutical applications mostly because of their size which facilitates absorption, distribution, metabolism and excretion of the nanoparticles. Whether labile or insoluble nanoparticles, their cytotoxic effect on malignant cells has moved the use of nanomedicine into focus. Since nanomedicine can be described as the science and technology of diagnosing, treating and preventing diseases towards ultimately improving human health, a lot of nanotechnology options have received approval by various regulatory agencies. Nanodrugs also have been discovered to be more precise in targeting the desired site, hence maximizing the therapeutic effects, while minimizing side-effects on the rest of the body. This unique property and more has made nanomedicine popular in therapeutic medicine employing nanotechnology in genetic therapy, drug encapsulation, enzyme manipulation and control, tissue engineering, target drug delivery, pharmacogenomics, stem cell and cloning, and even virus-based hybrids. This review highlights nanoproducts that are in development and have gained approval through one clinical trial stage or the other.

  13. [Therapeutic applications of digestive endoscopy].

    Science.gov (United States)

    Ortega, J A; Pérez, L; Madureri, V

    1976-01-01

    Endoscopy has proven useful as a diagnostic tool and recently many useful therapeutic possibilities have been proposed. The authors discuss their experience with therapeutic endoscopic procedures and present new ones for treatment of Acalasia and small sliding hiatal hernia.

  14. Therapeutic approaches to cellulite.

    Science.gov (United States)

    Green, Jeremy B; Cohen, Joel L; Kaufman, Joely; Metelitsa, Andrei I; Kaminer, Michael S

    2015-09-01

    Cellulite is a condition that affects the vast majority of women. Although it is of no danger to one's overall health, cellulite can be psychosocially debilitating. Consequently, much research has been devoted to understanding cellulite and its etiopathogenesis. With additional insights into the underlying causes of its clinical presentation, therapeutic modalities have been developed that offer hope to cellulite sufferers. This review examines evidence for topical treatments, noninvasive energy-based devices, and recently developed minimally invasive interventions that may finally provide a solution. ©2015 Frontline Medical Communications.

  15. [Achievement of therapeutic objectives].

    Science.gov (United States)

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.

  16. [Is therapeutic deadlock inevitable?].

    Science.gov (United States)

    Vignat, Jean-Pierre

    2016-01-01

    Many long-term treatments appear to be an expression of therapeutic deadlock. The situation leads to a questioning of the concept of chronicity and the identification of the determining factors of situations which are apparently blocked, marked by the search for solutions taking a back seat to the taking of action. The interaction between patients' mental apparatus and the care apparatus lies at the heart of the question, interpreted from an institutional, collective and individual perspective, supported by the clinical and psychopathological approach, and the return to the prioritisation of the thought. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Current approaches to discover marine antileishmanial natural products.

    Science.gov (United States)

    Tempone, André G; Martins de Oliveira, Camila; Berlinck, Roberto G S

    2011-04-01

    Leishmaniasis is a neglected infectious disease caused by kinetoplastid protozoans. An urgent need for novel chemotherapeutics exists. The current approaches to discover new antileishmanial compounds present many drawbacks, including high-cost and time-consuming bioassays. Thus, advances in leishmaniasis treatment are limited, and the development of screening assays is hindered. The combination of multidisciplinary approaches using standardised methods and synchronous projects could be an alternative to develop novel drugs for leishmaniasis treatment. In this review, we discuss the current status of leishmaniasis occurrence and treatment. In addition, we address the advantages and limitations of in vitro leishmaniasis bioassays and discuss the findings of drug discovery research using natural products. Finally, we comprehensively review the marine natural products that are active against Leishmania spp., including their natural sources and bioactivity profile. © Georg Thieme Verlag KG Stuttgart · New York.

  18. [Recently discovered hormones with a role in energy homeostasis].

    Science.gov (United States)

    Krykorková, I; Nedvídková, J

    2003-02-01

    Adipocytal hormones resistin and adiponectin and gastric peptide ghrelin are recently discovered hormones, which are considered to take part in energy metabolism regulation. Resistin is expressed in adipose tissue only and its increased levels could cause insulin resistance and thus link obesity with type 2 diabetes. Adiponectin, as well as resistin, are products of genes, expressed in adipose tissue. Adiponectin could prevent development of aterosclerosis and it could play a role in anti-inflammatory reactions. Ghrelin is produced mainly in the stomach. Beside its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. Main roles of resistin, adiponectin and ghrelin are summarised in the presented overview.

  19. Communication Boot Camp: Discover the Speaker in You!

    Directory of Open Access Journals (Sweden)

    Zuraidah Binti Ali

    2013-07-01

    Full Text Available Learning can take place almost anywhere, and this is especially true for our undergraduates who wish to become public speakers. Besides university course and public speaking workshops on campus grounds, undergraduates are now looking for a different learning environment – communication boot camps!! This study presents a compilation of learners’ experience, fun-filled activities, insightful feedback and memorable boot camp moments as captured in camp photos and feedback surveys. It involves a total of thirty seven undergraduates who enrolled in a Communication Boot Camp at Janda Baik, Pahang. Results show that Communication Boot Camp is a successful strategy to groom public speakers with a positive correlation between camp success and camp objectives, particularly in reducing shyness, motivating participants to become public speakers and discovering their talent and skills. In short, the study adds to the promise of zest and delight in public speaking.

  20. Cassini discovers a kinematic spiral ring around Saturn.

    Science.gov (United States)

    Charnoz, S; Porco, C C; Déau, E; Brahic, A; Spitale, J N; Bacques, G; Baillie, K

    2005-11-25

    Since the time of the Voyager flybys of Saturn in 1980-1981, Saturn's eccentric F ring has been known to be accompanied on either side by faint strands of material. New Cassini observations show that these strands, initially interpreted as concentric ring segments, are in fact connected and form a single one-arm trailing spiral winding at least three times around Saturn. The spiral rotates around Saturn with the orbital motion of its constituent particles. This structure is likely the result of differential orbital motion stretching an initial cloud of particles scattered from the dense core of the F ring. Different scenarios of formation, implying ringlet-satellite interactions, are explored. A recently discovered moon candidate, S/2004 S6, is on an orbit that crosses the F-ring core at the intersection of the spiral with the ring, which suggests a dynamical connection between S/2004 S6 and the spiral.

  1. A systematic approach to discover and characterize natural plant biostimulants

    Directory of Open Access Journals (Sweden)

    Giovanni ePovero

    2016-04-01

    Full Text Available The use of natural plant biostimulants is proposed as an innovative solution to address the challenges to sustainable agriculture, to ensure optimal nutrient uptake, crop yield, quality, and tolerance to abiotic stress. However, the process of selection and characterization of plant biostimulant matrices is complex and involves a series of rigorous evaluations customized to the needs of the plant.Here, we propose a highly differentiated plant biostimulant development and production platform, which involves a combination of technology, processes, and know-how. Chemistry, biology and omic concepts are combined/integrated to investigate and understand the specific mode(s of action of bioactive ingredients. The proposed approach allows to predict and characterize the function of natural compounds as biostimulants. By managing and analyzing massive amounts of complex data, it is therefore possible to discover, evaluate and validate new product candidates, thus expanding the uses of existing products to meet the emerging needs of agriculture.

  2. A Systematic Approach to Discover and Characterize Natural Plant Biostimulants.

    Science.gov (United States)

    Povero, Giovanni; Mejia, Juan F; Di Tommaso, Donata; Piaggesi, Alberto; Warrior, Prem

    2016-01-01

    The use of natural plant biostimulants is proposed as an innovative solution to address the challenges to sustainable agriculture, to ensure optimal nutrient uptake, crop yield, quality, and tolerance to abiotic stress. However, the process of selection and characterization of plant biostimulant matrices is complex and involves a series of rigorous evaluations customized to the needs of the plant. Here, we propose a highly differentiated plant biostimulant development and production platform, which involves a combination of technology, processes, and know-how. Chemistry, biology and omic concepts are combined/integrated to investigate and understand the specific mode(s) of action of bioactive ingredients. The proposed approach allows to predict and characterize the function of natural compounds as biostimulants. By managing and analyzing massive amounts of complex data, it is therefore possible to discover, evaluate and validate new product candidates, thus expanding the uses of existing products to meet the emerging needs of agriculture.

  3. Quantify spatial relations to discover handwritten graphical symbols

    Science.gov (United States)

    Li, Jinpeng; Mouchère, Harold; Viard-Gaudin, Christian

    2012-01-01

    To model a handwritten graphical language, spatial relations describe how the strokes are positioned in the 2-dimensional space. Most of existing handwriting recognition systems make use of some predefined spatial relations. However, considering a complex graphical language, it is hard to express manually all the spatial relations. Another possibility would be to use a clustering technique to discover the spatial relations. In this paper, we discuss how to create a relational graph between strokes (nodes) labeled with graphemes in a graphical language. Then we vectorize spatial relations (edges) for clustering and quantization. As the targeted application, we extract the repetitive sub-graphs (graphical symbols) composed of graphemes and learned spatial relations. On two handwriting databases, a simple mathematical expression database and a complex flowchart database, the unsupervised spatial relations outperform the predefined spatial relations. In addition, we visualize the frequent patterns on two text-lines containing Chinese characters.

  4. Discovering Related Clinical Concepts Using Large Amounts of Clinical Notes

    Directory of Open Access Journals (Sweden)

    Kavita Ganesan

    2016-01-01

    Full Text Available The ability to find highly related clinical concepts is essential for many applications such as for hypothesis generation, query expansion for medical literature search, search results filtering, ICD-10 code filtering and many other applications. While manually constructed medical terminologies such as SNOMED CT can surface certain related concepts, these terminologies are inadequate as they depend on expertise of several subject matter experts making the terminology curation process open to geographic and language bias. In addition, these terminologies also provide no quantifiable evidence on how related the concepts are. In this work, we explore an unsupervised graphical approach to mine related concepts by leveraging the volume within large amounts of clinical notes. Our evaluation shows that we are able to use a data driven approach to discovering highly related concepts for various search terms including medications, symptoms and diseases.

  5. Re-discovering Mendel: The Case of Carl Correns

    Science.gov (United States)

    Rheinberger, Hans-Jörg

    2015-01-01

    Carl Erich Correns (1864-1933) is remembered in the annals of science as one of the three botanists who re-discovered Mendel's laws. He can also, however, be regarded as one of the founding figures of classical genetics in Germany. Between 1894 and 1899 he carried out the crossing experiments with corn and peas that led to the re-statement of Gregor Mendel's (1822-1884) results. Between 1900 and 1910, he explored the complications of these laws, including the coupling of factors due to their chromosomal location and the inheritance of sex, in a great number of plant species. In later years Correns became interested in and experimented on phenomena of extra-nuclear inheritance.

  6. Discovering opinion leaders for medical topics using news articles.

    Science.gov (United States)

    Jonnalagadda, Siddhartha; Peeler, Ryan; Topham, Philip

    2012-03-15

    Rapid identification of subject experts for medical topics helps in improving the implementation of discoveries by speeding the time to market drugs and aiding in clinical trial recruitment, etc. Identifying such people who influence opinion through social network analysis is gaining prominence. In this work, we explore how to combine named entity recognition from unstructured news articles with social network analysis to discover opinion leaders for a given medical topic. We employed a Conditional Random Field algorithm to extract three categories of entities from health-related new articles: Person, Organization and Location. We used the latter two to disambiguate polysemy and synonymy for the person names, used simple rules to identify the subject experts, and then applied social network analysis techniques to discover the opinion leaders among them based on their media presence. A network was created by linking each pair of subject experts who are mentioned together in an article. The social network analysis metrics (including centrality metrics such as Betweenness, Closeness, Degree and Eigenvector) are used for ranking the subject experts based on their power in information flow. We extracted 734,204 person mentions from 147,528 news articles related to obesity from January 1, 2007 through July 22, 2010. Of these, 147,879 mentions have been marked as subject experts. The F-score of extracting person names is 88.5%. More than 80% of the subject experts who rank among top 20 in at least one of the metrics could be considered as opinion leaders in obesity. The analysis of the network of subject experts with media presence revealed that an opinion leader might have fewer mentions in the news articles, but a high network centrality measure and vice-versa. Betweenness, Closeness and Degree centrality measures were shown to supplement frequency counts in the task of finding subject experts. Further, opinion leaders missed in scientific publication network analysis

  7. Discovering the plates boundaries in the Mediterranean sea

    Science.gov (United States)

    Marinelli, Maurizio

    2017-04-01

    During the 8th class the students learn geology. We analyze the earth's layers, the earthquakes, the volcanoes and other natural phenomena like subduction and orogeny. We start with a global study but our goal is to focus on the crust to discover the plates boundaries, particularly the boundary between Eurasian and African Plate in the Mediterranean sea. It's very simple for the students to discover all the information using the Internet or the science book, but I want to make with them an exploration of earth science with the help of the natural phenomena we studied during the year. We connect with Istituto Nazionale di Geofisica e Vulcanologia ( http://www.ingv.it/en/ ) where we can find a map with the earthquakes happened in the last years in Italy and in the Mediterranean sea and the list of the main volcanoes. In this way we can draw a map of the mediterranean plates and we can talk about the past and the future of the Mediterranean sea, Europe and Africa based on our maps and on the Alps orogeny. Using youtube we can have a confirm of our hypothesis about the future of the Mediterranean sea (https://www.youtube.com/watch?v=uGcDed4xVD4 ). A good observation for the students is given by the fact that we live in Europe but actually we stay on the African plate. The boundary is 5 km north of our school and we can go and visit the place where it is possible to see the different height of the two plates.

  8. Risk of appendicitis in patients with incidentally discovered appendicoliths.

    Science.gov (United States)

    Khan, Muhammad Sohaib; Chaudhry, Mustafa Belal Hafeez; Shahzad, Noman; Tariq, Marvi; Memon, Wasim Ahmed; Alvi, Abdul Rehman

    2018-01-01

    An appendicolith-related appendiceal obstruction leading to appendicitis is a commonly encountered surgical emergency that has clear evidence-based management plans. However, there is no consensus on management of asymptomatic patients when appendicoliths are found incidentally. The objective of this study was to determine the risk of appendicitis in patients with an incidental finding of the appendicolith. A retrospective matched cohort study of patients with appendicolith discovered incidentally on computed tomographic scan from January 2008 to December 2014 at our institution was completed. The size and position of the appendicolith were ascertained. The study group was matched by age and gender to a control group. Both groups were contacted and interviewed regarding development of appendicitis. In total, 111 patients with appendicolith were successfully contacted and included in the study. Mean age was found to be 38 ± 15 y with 36 (32%) of the study population being females. Mean length of appendix was 66 ± 16 mm, and mean width was 5.8 ± 0.9 mm. Mean size of the appendicolith was 3.6 ± 1.1 mm (1.4-7.8 mm). Fifty-eight percent of appendicoliths was located at the proximal end or whole of appendix, 31% at mid area, and 11% at the distal end of appendix. All patients of the study and control groups were contacted, and at a mean follow-up of 4.0 ± 1.7 y, there was no occurrence of acute appendicitis in either group. Patients with incidentally discovered appendicolith on radiological imaging did not develop appendicitis. Hence, the risk of developing acute appendicitis for these patients does not seem higher than the general population. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Discovering Tradeoffs, Vulnerabilities, and Dependencies within Water Resources Systems

    Science.gov (United States)

    Reed, P. M.

    2015-12-01

    There is a growing recognition and interest in using emerging computational tools for discovering the tradeoffs that emerge across complex combinations infrastructure options, adaptive operations, and sign posts. As a field concerned with "deep uncertainties", it is logically consistent to include a more direct acknowledgement that our choices for dealing with computationally demanding simulations, advanced search algorithms, and sensitivity analysis tools are themselves subject to failures that could adversely bias our understanding of how systems' vulnerabilities change with proposed actions. Balancing simplicity versus complexity in our computational frameworks is nontrivial given that we are often exploring high impact irreversible decisions. It is not always clear that accepted models even encompass important failure modes. Moreover as they become more complex and computationally demanding the benefits and consequences of simplifications are often untested. This presentation discusses our efforts to address these challenges through our "many-objective robust decision making" (MORDM) framework for the design and management water resources systems. The MORDM framework has four core components: (1) elicited problem conception and formulation, (2) parallel many-objective search, (3) interactive visual analytics, and (4) negotiated selection of robust alternatives. Problem conception and formulation is the process of abstracting a practical design problem into a mathematical representation. We build on the emerging work in visual analytics to exploit interactive visualization of both the design space and the objective space in multiple heterogeneous linked views that permit exploration and discovery. Many-objective search produces tradeoff solutions from potentially competing problem formulations that can each consider up to ten conflicting objectives based on current computational search capabilities. Negotiated design selection uses interactive visualization

  10. Discovering opinion leaders for medical topics using news articles

    Directory of Open Access Journals (Sweden)

    Jonnalagadda Siddhartha

    2012-03-01

    Full Text Available Abstract Background Rapid identification of subject experts for medical topics helps in improving the implementation of discoveries by speeding the time to market drugs and aiding in clinical trial recruitment, etc. Identifying such people who influence opinion through social network analysis is gaining prominence. In this work, we explore how to combine named entity recognition from unstructured news articles with social network analysis to discover opinion leaders for a given medical topic. Methods We employed a Conditional Random Field algorithm to extract three categories of entities from health-related new articles: Person, Organization and Location. We used the latter two to disambiguate polysemy and synonymy for the person names, used simple rules to identify the subject experts, and then applied social network analysis techniques to discover the opinion leaders among them based on their media presence. A network was created by linking each pair of subject experts who are mentioned together in an article. The social network analysis metrics (including centrality metrics such as Betweenness, Closeness, Degree and Eigenvector are used for ranking the subject experts based on their power in information flow. Results We extracted 734,204 person mentions from 147,528 news articles related to obesity from January 1, 2007 through July 22, 2010. Of these, 147,879 mentions have been marked as subject experts. The F-score of extracting person names is 88.5%. More than 80% of the subject experts who rank among top 20 in at least one of the metrics could be considered as opinion leaders in obesity. Conclusion The analysis of the network of subject experts with media presence revealed that an opinion leader might have fewer mentions in the news articles, but a high network centrality measure and vice-versa. Betweenness, Closeness and Degree centrality measures were shown to supplement frequency counts in the task of finding subject experts. Further

  11. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  12. Therapeutic Uses of Exosomes

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2013-01-01

    Full Text Available Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigen-specific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.

  13. Engineering therapeutic protein disaggregases.

    Science.gov (United States)

    Shorter, James

    2016-05-15

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. © 2016 Shorter. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

    Science.gov (United States)

    Jiang, Binghu; Wang, Jichen; Ni, Yicheng; Chen, Feng

    2013-01-01

    Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin. PMID:24052807

  15. Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

    Science.gov (United States)

    Kalid, Ori; Mense, Martin; Fischman, Sharon; Shitrit, Alina; Bihler, Hermann; Ben-Zeev, Efrat; Schutz, Nili; Pedemonte, Nicoletta; Thomas, Philip J.; Bridges, Robert J.; Wetmore, Diana R.; Marantz, Yael; Senderowitz, Hanoch

    2010-12-01

    Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability. In silico structure-based screening was performed at the putative binding-sites and a total of 496 candidate compounds from all three sites were tested in functional assays. A total of 15 compounds, representing diverse chemotypes, were identified as F508del folding correctors. This corresponds to a 3% hit rate, tenfold higher than hit rates obtained in corresponding high-throughput screening campaigns. The same binding sites also yielded potentiators and, most notably, compounds with a dual corrector-potentiator activity (dual-acting). Compounds harboring both activity types may prove to be better leads for the development of CF therapeutics than either pure correctors or pure potentiators. To the best of our knowledge this is the first report of structure-based discovery of CFTR modulators.

  16. Therapeutic and diagnostic nanomaterials

    CERN Document Server

    Devasena T

    2017-01-01

    This brief highlights nanoparticles used in the diagnosis and treatment of prominent diseases and toxic conditions. Ecofriendly methods which are ideal for the synthesis of medicinally valued nanoparticles are explained and the characteristic features of these particles projected. The role of these particles in the therapeutic field, and the induced biological changes in some diseases are discussed. The main focus is on inflammation, oxidative stress and cellular membrane integrity alterations. The effect of nanoparticles on these changes produced by various agents are highlighted using in vitro and in vivo models. The mechanism of nanoparticles in ameliorating the biological changes is supported by relevant images and data. Finally, the brief demonstrates recent developments on the use of nanoparticles in diagnosis or sensing of some biological materials and biologically hazardous environmental materials.

  17. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  18. Therapeutic applications of melatonin

    Science.gov (United States)

    2013-01-01

    Melatonin is a methoxyindole synthesized within the pineal gland. The hormone is secreted during the night and appears to play multiple roles within the human organism. The hormone contributes to the regulation of biological rhythms, may induce sleep, has strong antioxidant action and appears to contribute to the protection of the organism from carcinogenesis and neurodegenerative disorders. At a therapeutic level as well as in prevention, melatonin is used for the management of sleep disorders and jet lag, for the resynchronization of circadian rhythms in situations such as blindness and shift work, for its preventive action in the development of cancer, as additive therapy in cancer and as therapy for preventing the progression of Alzheimer’s disease and other neurodegenerative disorders. PMID:23515203

  19. Microfabricated therapeutic actuators

    Science.gov (United States)

    Lee, Abraham P.; Northrup, M. Allen; Ciarlo, Dino R.; Krulevitch, Peter A.; Benett, William J.

    1999-01-01

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

  20. Therapeutic effects of reading

    Directory of Open Access Journals (Sweden)

    Agustín HIDALGO

    2017-06-01

    Full Text Available Reading is an act that requires isolation and loneliness, which allows rewriting the narratives through the identification between the reader and the character, the involvement in the fact narrated and singular recreation by every single reader. The act of reading allows stepping aside from reality. The reading as well as the writing perform the therapeutic effect of helping to understand the illness and to know experiences of others patients that can be useful for the accompaniment, overcoming and/or making decisions. There is not a concrete literary that could be universally recommend to every patient, but all the genre can be useful to some patient. However, poetry, novel and autobiographies are frequently referred as the manuscripts that provide help and consolation.

  1. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    polymerized in a controlled manner with carrier monomers of historically proven biocompatible polymers. The carrier polymers, the loading of ribavirin as well as the size of the polymer were varied systematically with the aid of an automated synthesis platform. These polymers were tested in a cellular assay...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein......The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...

  2. Discovering the first microRNA-targeted drug

    DEFF Research Database (Denmark)

    Lindow, Morten; Kauppinen, Sakari

    2012-01-01

    MicroRNAs (miRNAs) are important post-transcriptional regulators of nearly every biological process in the cell and play key roles in the pathogenesis of human disease. As a result, there are many drug discovery programs that focus on developing miRNA-based therapeutics. The most advanced...... of these programs targets the liver-expressed miRNA-122 using the locked nucleic acid (LNA)–modified antisense oligonucleotide miravirsen. Here, we describe the discovery of miravirsen, which is currently in phase 2 clinical trials for treatment of hepatitis C virus (HCV) infection....

  3. Therapeutic Approaches in CLIPPERS.

    Science.gov (United States)

    Taieb, Guillaume; Allou, Thibaut; Labauge, Pierre

    2017-05-01

    CLIPPERS for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a steroid-sensitive and steroid-dependent brainstem inflammatory disease of unknown origin. Since its first description in 2010, about 60 cases have been reported throughout the world. The mean age at onset is 50 years and men seem to be more frequently affected. In patients without chronic corticosteroid therapy or immunosuppressive agents, the disease had a relapsing remitting course, and the mean annualized relapse rate was 0.5. During attacks, although clinical and radiological improvement after high doses of corticosteroids was systematically observed, patients could display subsequent disability and hindbrain atrophy. Since no progressive course was observed, clinical and radiological sequelae were correlated with previous severe attacks. Therefore, maintaining the disease in remission may prevent the accumulation of disability. In the literature, no relapse occurred when chronic corticosteroid therapy was maintained above 20 mg per day. However, steroids side effects led to propose corticosteroid-sparing therapies. Unfortunately, no controlled therapy studies for CLIPPERS have been performed yet, and no therapeutic recommendations exist. Using the PubMed database, all articles having the following keywords "chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids" and "CLIPPERS" have been analysed. Considering that the mean annual relapse rate was 0.5, and that no relapse occurred when corticosteroid therapy was maintained above 20 mg per day, the therapeutic efficiency of corticosteroid-sparing agents was considered as "probable" when patients had a relapse-free period ≥24 months, in the absence of concomitant corticosteroid therapy. Corticosteroid-sparing agents whose efficiency is "probable" are methotrexate in two cases, cyclophosphamide in one case and hydroxychloroquine in one case. Considering the

  4. Faint Carbon Stars Discovered by the Sloan Digital Sky Survey

    Science.gov (United States)

    Margon, B.; Anderson, S. F.; Deutsch, E. W.; Harris, H. C.; SDSS Collaboration

    1999-12-01

    Although faint high latitude carbon (FHLC) stars range in luminosity by up to factors of 105, both the high and low luminosity versions are interesting. The apparently faintest of the luminous giants are located at >100 kpc, and aside from raising issues of stellar evolution, are also excellent probes of the dynamics of the distant halo, at a distance which encompasses all of the dark matter. The intrinsically faint dwarf carbon stars constitute a class of objects just recognized a decade ago, yet now understood to be the numerical majority of all stars with C2 in their spectra. The faintest of the FHLC (R>16) have thus far been discovered either serendipitously, or in very small numbers by heterogeneous techniques. We have long hoped that the Sloan Digital Sky Survey (SDSS) might provide a large, homogeneously-selected sample of FHLCs via color-selection from the 5-color imaging data base, and followup fiber spectroscopy as an adjunct to other SDSS primary programs. However this is a challenging task, as these rare objects are expected to be only slightly separated from the 108 normal stars in SDSS photometry, even in 5-color space. In particular, most FHLCs are not terribly red. Here we report initial successful results on the search for FHLC stars in SDSS commissioning data. Two such objects have thus far been discovered in a very informal search of a small fraction of the data. The fainter object, at R 19, is one of the faintest FHLC yet known, boding well for the prospect of a respectable number (>102) of new objects in the entire Survey. The brighter object (R 17) is most certainly a dwarf: it displays proper motion of 0.24'' yr-1, one of the highest motions known for any dC star. Curiously, the faint object also shows evidence for a small but significant proper motion, and thus dwarf classification. It now appears likely that SDSS will fulfill long-standing hopes as a source of a large number of uniformly-selected and well-characterized FHLCs. In a metaphor

  5. Plasmid composition and virulence-associated factors of Yersinia pestis isolates from a plague outbreak at the Paraíba State, Brazil Composição plasmidial e fatores associados à virulência em cepas de Yersinia pestis de um surto de peste no Estado da Paraíba, Brasil

    Directory of Open Access Journals (Sweden)

    Nilma Cintra Leal

    1989-10-01

    Full Text Available Pathogenic Yersinia pestis isolates were collected during a plague outbreak at the Paraiba State in 1986. The Y. pestis isolates were investigated for the presence of virulence-associated factors and plasmid content. All strains analysed were proficient in the expression of the VW and fraction 1 antigens, pigment adsorption and pesticin-fibronolysin-coagulase production. A similar plasmid profile composed by four plasmid with molecular weight of 60, 44, 14.9, and 6.4 Megadaltons (MD was found in all strains. DNA cleavage with EcoRI restriction enzyme further demonstrated the uniform plasmid content of the Y. pestis isolates. Seven additional Y. pestis strains, previously isolated in the same region but in an endemic state, showed the same plasmid fingerprint. The lack of any detectable difference between epidemic and endemic isolates as well as the value of plasmid fingerprints in epidemiology of Y. pestis is discussed.Cepas patogênicas de Yersinia pestis foram coletadas durante um surto de peste no Estado da Paraíba em 1986. Os isolados de Y. pestis foram analisados quanto a presença de fatores associados à virulência e conteúdo plasmidial. Todas as linhagens analisadas foram proficientes na expressão dos antígenos VW e fração 1, além de possuírem capacidade de adsorção de pigmentos e produção de pesticina-fibrinolisina-coagulase. Um perfil plasmidial semelhante composto por quatro plasmídeos com peso molecular de 60, 44, 14.9, e 6.4 MD foi encontrado em todas as linhagens. A clivagem do DNA plasmidial com a enzima de restrição EcoRI demonstrou o conteúdo plasmidial uniforme dos isolados de Y. pestis. Sete outras linhagens de Y. pestis, isoladas previamente no mesmo local mas em condição endêmica, mostraram o mesmo perfil plasmidial. A falta de diferenças entre os isolados epidêmicos e endêmicos assim como o uso do perfil plasmidial na epidemiologic de Y. pestis e discutida.

  6. Discovering vesicle traffic network constraints by model checking.

    Science.gov (United States)

    Shukla, Ankit; Bhattacharyya, Arnab; Kuppusamy, Lakshmanan; Srivas, Mandayam; Thattai, Mukund

    2017-01-01

    A eukaryotic cell contains multiple membrane-bound compartments. Transport vesicles move cargo between these compartments, just as trucks move cargo between warehouses. These processes are regulated by specific molecular interactions, as summarized in the Rothman-Schekman-Sudhof model of vesicle traffic. The whole structure can be represented as a transport graph: each organelle is a node, and each vesicle route is a directed edge. What constraints must such a graph satisfy, if it is to represent a biologically realizable vesicle traffic network? Graph connectedness is an informative feature: 2-connectedness is necessary and sufficient for mass balance, but stronger conditions are required to ensure correct molecular specificity. Here we use Boolean satisfiability (SAT) and model checking as a framework to discover and verify graph constraints. The poor scalability of SAT model checkers often prevents their broad application. By exploiting the special structure of the problem, we scale our model checker to vesicle traffic systems with reasonably large numbers of molecules and compartments. This allows us to test a range of hypotheses about graph connectivity, which can later be proved in full generality by other methods.

  7. Cellular Metabolic Network Analysis: Discovering Important Reactions in Treponema pallidum

    Science.gov (United States)

    Chen, Xueying; Zhao, Min; Qu, Hong

    2015-01-01

    T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis. PMID:26495292

  8. Cellular metabolic network analysis: discovering important reactions in Treponema pallidum.

    Science.gov (United States)

    Chen, Xueying; Zhao, Min; Qu, Hong

    2015-01-01

    T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis.

  9. Discovering geothermal supercritical fluids: a new frontier for seismic exploration.

    Science.gov (United States)

    Piana Agostinetti, Nicola; Licciardi, Andrea; Piccinini, Davide; Mazzarini, Francesco; Musumeci, Giovanni; Saccorotti, Gilberto; Chiarabba, Claudio

    2017-11-06

    Exploiting supercritical geothermal resources represents a frontier for the next generation of geothermal electrical power plant, as the heat capacity of supercritical fluids (SCF),which directly impacts on energy production, is much higher than that of fluids at subcritical conditions. Reconnaissance and location of intensively permeable and productive horizons at depth is the present limit for the development of SCF geothermal plants. We use, for the first time, teleseismic converted waves (i.e. receiver function) for discovering those horizons in the crust. Thanks to the capability of receiver function to map buried anisotropic materials, the SCF-bearing horizon is seen as the 4km-depth abrupt termination of a shallow, thick, ultra-high (>30%) anisotropic rock volume, in the center of the Larderello geothermal field. The SCF-bearing horizon develops within the granites of the geothermal field, bounding at depth the vapor-filled heavily-fractured rock matrix that hosts the shallow steam-dominated geothermal reservoirs. The sharp termination at depth of the anisotropic behavior of granites, coinciding with a 2 km-thick stripe of seismicity and diffuse fracturing, points out the sudden change in compressibility of the fluid filling the fractures and is a key-evidence of deep fluids that locally traversed the supercritical conditions. The presence of SCF and fracture permeability in nominally ductile granitic rocks open new scenarios for the understanding of magmatic systems and for geothermal exploitation.

  10. Children's strategies for discovering cause-effect relationships

    Science.gov (United States)

    Rudnitsky, Alan N.; Hunt, Charles R.

    This study describes strategies children use to solve a complex problem. The problem asked children to figure out how to control a vehicle that they drove by pressing particular keys on a computer. The problem can be viewed as scientific in that variables must be identified and hypotheses formulated and tested to discover cause-effect relationships. Subjects were fifth and sixth graders sampled from public and private schools. The primary purpose of the study was to examine the transition between implicit, immature problem-solving strategies and explicit, mature theorizing characteristic of scientific problem solving. The study manipulated the problem perspective subjects were given and the number of cause-effect relationships in the problem. The study's description of children's problem solving highlights focusing, problem-solving behavior that is aimed at forming a mental representation, model, or theory about the problem, as a key link between mature and immature reasoning. Subject's school and school X perspective interaction was found to affect problem-solving performance.

  11. Timing of Five PALFA-discovered Millisecond Pulsars

    Science.gov (United States)

    Stovall, K.; Allen, B.; Bogdanov, S.; Brazier, A.; Camilo, F.; Cardoso, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Ferdman, R.; Freire, P. C. C.; Hessels, J. W. T.; Jenet, F.; Kaplan, D. L.; Karako-Argaman, C.; Kaspi, V. M.; Knispel, B.; Kotulla, R.; Lazarus, P.; Lee, K. J.; van Leeuwen, J.; Lynch, R.; Lyne, A. G.; Madsen, E.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Scholz, P.; Siemens, X.; Stairs, I. H.; Stappers, B. W.; Swiggum, J.; Zhu, W. W.; Venkataraman, A.

    2016-12-01

    We report the discovery and timing results for five millisecond pulsars (MSPs) from the Arecibo PALFA survey: PSRs J1906+0055, J1914+0659, J1933+1726, J1938+2516, and J1957+2516. Timing observations of the five pulsars were conducted with the Arecibo and Lovell telescopes for time spans ranging from 1.5 to 3.3 years. All of the MSPs except one (PSR J1914+0659) are in binary systems with low eccentricities. PSR J1957+2516 is likely a redback pulsar, with a ˜ 0.1 {M}⊙ companion and possible eclipses that last ˜10% of the orbit. The position of PSR J1957+2516 is also coincident with a near-infrared source. All five MSPs are distant (\\gt 3.1 kpc) as determined from their dispersion measures, and none of them show evidence of γ-ray pulsations in a fold of Fermi Gamma-Ray Space Telescope data. These five MSPs bring the total number of MSPs discovered by the PALFA survey to 26 and further demonstrate the power of this survey in finding distant, highly dispersed MSPs deep in the Galactic plane.

  12. Inner solar system material discovered in the Oort cloud.

    Science.gov (United States)

    Meech, Karen J; Yang, Bin; Kleyna, Jan; Hainaut, Olivier R; Berdyugina, Svetlana; Keane, Jacqueline V; Micheli, Marco; Morbidelli, Alessandro; Wainscoat, Richard J

    2016-04-01

    We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system in the Oort cloud. C/2014 S3 could be the key to verifying these predictions of the migration-based dynamical models. Furthermore, this object displays a very faint, weak level of comet-like activity, five to six orders of magnitude less than that of typical ice-rich comets on similar Orbits coming from the Oort cloud. For the nearly tailless appearance, we are calling C/2014 S3 a Manx object. Various arguments convince us that this activity is produced by sublimation of volatile ice, that is, normal cometary activity. The activity implies that C/2014 S3 has retained a tiny fraction of the water that is expected to be present at its formation distance in the inner solar system. We may be looking at fresh inner solar system Earth-forming material that was ejected from the inner solar system and preserved for billions of years in the Oort cloud.

  13. Discovering market basket patterns using hierarchical association rules

    Directory of Open Access Journals (Sweden)

    Marijana Zekić-Sušac

    2015-10-01

    Full Text Available Association rules are a data mining method for discovering patterns of frequent item sets, such as products in a store that are frequently purchased at the same time by a customer (market basket analysis. A number of interestingness measures for association rules have been developed to date, but research has shown that there a dominant measure does not exist. Authors have mostly used objective measures, whereas subjective measures have rarely been investigated. This paper aims to combine objective measures such as support, confidence and lift with a subjective approach based on human expert selection in order to extract interesting rules from a real dataset collected from a large Croatian retail chain. Hierarchical association rules were used to enhance the efficiency of the extraction rule. The results show that rules that are more interesting were extracted using the hierarchical method, and that a hybrid approach of combining objective and subjective measures succeeds in extracting certain unexpected and actionable rules. The research can be useful for retail and marketing managers in planning marketing strategies, as well as for researchers investigating this field.

  14. Discovering Psychological Principles by Mining Naturally Occurring Data Sets.

    Science.gov (United States)

    Goldstone, Robert L; Lupyan, Gary

    2016-07-01

    The very expertise with which psychologists wield their tools for achieving laboratory control may have had the unwelcome effect of blinding psychologists to the possibilities of discovering principles of behavior without conducting experiments. When creatively interrogated, a diverse range of large, real-world data sets provides powerful diagnostic tools for revealing principles of human judgment, perception, categorization, decision-making, language use, inference, problem solving, and representation. Examples of these data sets include patterns of website links, dictionaries, logs of group interactions, collections of images and image tags, text corpora, history of financial transactions, trends in twitter tag usage and propagation, patents, consumer product sales, performance in high-stakes sporting events, dialect maps, and scientific citations. The goal of this issue is to present some exemplary case studies of mining naturally existing data sets to reveal important principles and phenomena in cognitive science, and to discuss some of the underlying issues involved with conducting traditional experiments, analyses of naturally occurring data, computational modeling, and the synthesis of all three methods. Copyright © 2016 Cognitive Science Society, Inc.

  15. Decision Tree Approach to Discovering Fraud in Leasing Agreements

    Directory of Open Access Journals (Sweden)

    Horvat Ivan

    2014-09-01

    Full Text Available Background: Fraud attempts create large losses for financing subjects in modern economies. At the same time, leasing agreements have become more and more popular as a means of financing objects such as machinery and vehicles, but are more vulnerable to fraud attempts. Objectives: The goal of the paper is to estimate the usability of the data mining approach in discovering fraud in leasing agreements. Methods/Approach: Real-world data from one Croatian leasing firm was used for creating tow models for fraud detection in leasing. The decision tree method was used for creating a classification model, and the CHAID algorithm was deployed. Results: The decision tree model has indicated that the object of the leasing agreement had the strongest impact on the probability of fraud. Conclusions: In order to enhance the probability of the developed model, it would be necessary to develop software that would enable automated, quick and transparent retrieval of data from the system, processing according to the rules and displaying the results in multiple categories.

  16. Discovering large network motifs from a complex biological network

    Science.gov (United States)

    Terada, Aika; Sese, Jun

    2009-12-01

    Graph structures representing relationships between entries have been studied in statistical analysis, and the results of these studies have been applied to biological networks, whose nodes and edges represent proteins and the relationships between them, respectively. Most of the studies have focused on only graph structures such as scale-free properties and cliques, but the relationships between nodes are also important features since most of the proteins perform their functions by connecting to other proteins. In order to determine such relationships, the problem of network motif discovery has been addressed; network motifs are frequently appearing graph structures in a given graph. However, the methods for network motif discovery are highly restrictive for the application to biological network because they can only be used to find small network motifs or they do not consider noise and uncertainty in observations. In this study, we introduce a new index to measure network motifs called AR index and develop a novel algorithm called ARIANA for finding large motifs even when the network has noise. Experiments using a synthetic network verify that our method can find better network motifs than an existing algorithm. By applying ARIANA to a real complex biological network, we find network motifs associated with regulations of start time of cell functions and generation of cell energies and discover that the cell cycle proteins can be categorized into two different groups.

  17. [Nuclear transfer and therapeutic cloning].

    Science.gov (United States)

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  18. Therapeutic vaccines for leishmaniasis.

    Science.gov (United States)

    Khamesipour, Ali

    2014-11-01

    Numerous therapeutic strategies are used to treat leishmaniasis. The treatment of cutaneous leishmaniasis (CL) is solely depends on antimonate derivatives with safety issues and questionable efficacy and there is no fully effective modality to treat CL caused by Leishmania tropica and Leishmania braziliensis. There is no prophylactic vaccine available against any form of leishmaniasis. Immunotherapy for CL has a long history; immunotherapy trials of first and second generation vaccines showed promising results. The current article briefly covers the prophylactic vaccines and explains different immunotherapy strategies that have been used to treat leishmaniasis. This paper does not include experimental vaccines and only lays emphasis on human trials and those vaccines which reached human trials. Immunotherapy is currently used to successfully treat several disorders; Low cost, limited side effects and no possibility to develop resistance make immunotherapy a valuable choice especially for infectious disease with chemotherapy problems. Efforts are needed to explore the immunological surrogate marker(s) of cure and protection in leishmaniasis and overcome the difficulties in standardization of crude Leishmania vaccines. One of the reasons for anti-leishmaniasis vaccine failure is lack of an appropriate adjuvant. So far, not enough attention has been paid to develop vaccines for immunotherapy of leishmaniasis.

  19. Therapeutic uses of magnesium.

    Science.gov (United States)

    Guerrera, Mary P; Volpe, Stella Lucia; Mao, Jun James

    2009-07-15

    Magnesium is an essential mineral for optimal metabolic function. Research has shown that the mineral content of magnesium in food sources is declining, and that magnesium depletion has been detected in persons with some chronic diseases. This has led to an increased awareness of proper magnesium intake and its potential therapeutic role in a number of medical conditions. Studies have shown the effectiveness of magnesium in eclampsia and preeclampsia, arrhythmia, severe asthma, and migraine. Other areas that have shown promising results include lowering the risk of metabolic syndrome, improving glucose and insulin metabolism, relieving symptoms of dysmenorrhea, and alleviating leg cramps in women who are pregnant. The use of magnesium for constipation and dyspepsia are accepted as standard care despite limited evidence. Although it is safe in selected patients at appropriate dosages, magnesium may cause adverse effects or death at high dosages. Because magnesium is excreted renally, it should be used with caution in patients with kidney disease. Food sources of magnesium include green leafy vegetables, nuts, legumes, and whole grains.

  20. Leech Therapeutic Applications

    Science.gov (United States)

    Abdualkader, A. M.; Ghawi, A. M.; Alaama, M.; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  1. Prostate cancer heterogeneity: Discovering novel molecular targets for therapy.

    Science.gov (United States)

    Ciccarese, Chiara; Massari, Francesco; Iacovelli, Roberto; Fiorentino, Michelangelo; Montironi, Rodolfo; Di Nunno, Vincenzo; Giunchi, Francesca; Brunelli, Matteo; Tortora, Giampaolo

    2017-03-01

    Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies. In the future, the identification of driver mutations present at a specific stage of the disease, the classification PCa based on specific molecular alterations, and the selection of the most appropriate therapy based on biomarkers predictors of response represent the foundations for an increasingly more accurate personalized medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Therapeutic cloning in the mouse

    Science.gov (United States)

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  3. Talkoot Portals: Discover, Tag, Share, and Reuse Collaborative Science Workflows

    Science.gov (United States)

    Wilson, B. D.; Ramachandran, R.; Lynnes, C.

    2009-05-01

    A small but growing number of scientists are beginning to harness Web 2.0 technologies, such as wikis, blogs, and social tagging, as a transformative way of doing science. These technologies provide researchers easy mechanisms to critique, suggest and share ideas, data and algorithms. At the same time, large suites of algorithms for science analysis are being made available as remotely-invokable Web Services, which can be chained together to create analysis workflows. This provides the research community an unprecedented opportunity to collaborate by sharing their workflows with one another, reproducing and analyzing research results, and leveraging colleagues' expertise to expedite the process of scientific discovery. However, wikis and similar technologies are limited to text, static images and hyperlinks, providing little support for collaborative data analysis. A team of information technology and Earth science researchers from multiple institutions have come together to improve community collaboration in science analysis by developing a customizable "software appliance" to build collaborative portals for Earth Science services and analysis workflows. The critical requirement is that researchers (not just information technologists) be able to build collaborative sites around service workflows within a few hours. We envision online communities coming together, much like Finnish "talkoot" (a barn raising), to build a shared research space. Talkoot extends a freely available, open source content management framework with a series of modules specific to Earth Science for registering, creating, managing, discovering, tagging and sharing Earth Science web services and workflows for science data processing, analysis and visualization. Users will be able to author a "science story" in shareable web notebooks, including plots or animations, backed up by an executable workflow that directly reproduces the science analysis. New services and workflows of interest will be

  4. Discovering the Role of Grain Boundary Complexions in Materials

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, Martin P. [Lehigh Univ., Bethlehem, PA (United States)

    2015-03-19

    in a range of materials systems, and to characterize their structures, range of stability and selected physical properties. First, an Au-based bilayer interfacial phase was discovered at a bicrystal boundary in the Si-Au system. This bilayer transitioned abruptly to an intrinsic (“clean”) grain boundary phase, suggesting first-order phase behavior. This study represents the discovery of grain boundary complexions in a completely new system, i.e., a semiconductor-metal system, giving further support to the expectation that grain boundary complexions are a general phenomenon not limited to any particular class of materials. The TiO2-CuO system exhibited four grain boundary interfacial phases: a monolayer, disordered bilayer, disordered trilayer, and non-wetting nanoscale amorphous drop (which likely resulted from dewetting of a nanoscale IGF). SiO2 contamination was discovered in the TiO2-CuO samples, and we hypothesize that this impurity may have caused an “order-disorder” transition to occur. In other words, we expect that pure TiO2-CuO may have a higher tendency to exhibit ordered bilayer and trilayer complexions, which may also exhibit a well-defined order-disorder transition temperature. In this effort we have also identified unique complexion transitions in yttria and strontium titanate.

  5. A new population of protostars discovered by Herschel

    Science.gov (United States)

    Stutz, A. M.; Tobin, J.; Fischer, W.; S. T. Megeath; Stanke, T.; Ali, B.; Henning, T.

    2012-03-01

    We present a newly discovered Herschel--detected class of very red protostars found in the Herschel Orion Protostar Survey (HOPS). In contrast to the known Orion protostars targeted with HOPS, the new sources are undetected or very faint in the Spitzer 24 μm imaging. A subset of these sources is redder than any of the known Orion Class 0 protostars, and appear similar in their 70 μm to 24 μm colors to the most extreme Class 0 objects known. These new Orion protostars are likely to be in a very early and short lived stage of protostellar evolution. As a sample of extremely red sources at a common distance, they represent an important new population of protostars. The majority of these reddest sources exhibit associated IRAC 4.5, and 5.8 μm extended emission that suggests the presence of an outflow, confirming their protostellar nature. In addition, many of these sources are located within classical filaments as traced by Spitzer absorption features and APEX 870 μm dust emission maps. Fits of the broad--band SEDs to radiative transfer models of protostars suggest that the extremely red 70 μm to 24 μm colors result from a combination of nearly edge--on viewing angles and high envelope infall rates. We analyze the properties of the filaments from which these sources form using sub--mm and IRAM 30 m N_2H^+ measurements. Finally, we present the initial results of a search for outflows using IRAM 30 m CO maps. As a population of cold protostars detected by Herschel but not Spitzer, the PBRS extend the Spitzer--identified sample to earlier stages of envelope evolution, allowing the most complete census yet of the Orion protostellar population.

  6. Discovering structure and evolution within the coronae of Seyfert galaxies

    Science.gov (United States)

    Wilkins, Daniel; Gallo, Luigi C.; Silva, Catia; Costantini, Elisa

    2017-08-01

    Detailed analysis of the reflection and reverberation of X-rays from the innermost regions of AGN accretion discs reveals the structure and processes that produce the intense continuum emission and the extreme variability we see, right down to the innermost stable orbit and event horizon of the black hole. Observations of Seyfert galaxies spanning more than a decade have enabled measurement of the geometry of the corona and how it evolves, leading to orders of magnitude in variability. They reveal processes the corona undergoes during transient events, notably the collimation and ejection of the corona during X-ray flares, reminiscent of the aborted launching of a jet.Recent reverberation studies, of the Seyfert galaxy I Zwicky 1 with XMM-Newton, are revealing structures within the corona for the very first time. A persistent collimated core is discovered, akin to the base of a jet embedded in the innermost regions alongside an extended corona related to the accretion disc. The detection of the flare in the X-ray emission enables the evolution of both the collimated and extended portions of the corona to be tracked. The flare is seen originating as an increase in activity above the accretion disc before propagating inwards, energising the collimated core at a later time, leading to a second sharp increase in the X-ray luminosity.This gives us important constraints on the processes by which energy is liberated from black hole accretion flows, how they are governed over time and how jets are launched, giving us the deepest insight to date of how these extreme objects are powered.

  7. [Search for natural substances with therapeutic activity: George R. Pettit].

    Science.gov (United States)

    Da Silva, Pierre P J; Bendjeddou, Lyamin Z; Meijer, Laurent

    2014-03-01

    This series of brief reviews covers the "life and work" of famous and iconic researchers who discovered major therapeutics from natural products: their life history, the circumstances of their discoveries, the molecules and their molecular, cellular and physiological mechanisms of action, and their biomedical applications. Dedicated to George R. Pettit, the second article reviews the life of the famous researcher, his worldwide exploration of natural products, especially of marine origin, in search of promising anticancer leads, his discovery and structural elucidation of very potent drug candidates, their synthesis and the launch of some of them on the pharmaceutical market. An extraordinary scientific career which lead George R. Pettit from exploration of Nature to state-of-the-art analytical and synthetic chemistry and from clinical trials to therapeutic successes. © 2014 médecine/sciences – Inserm.

  8. Terpenoids as Potential Anti-Alzheimer’s Disease Therapeutics

    Directory of Open Access Journals (Sweden)

    So-Young Park

    2012-03-01

    Full Text Available Alzheimer’s disease (AD is one of the most well-known neurodegenerative diseases and explains 50–60% of dementia in patients. The prevalence rate of AD is positively correlated with age and AD affects ≥ 40% of those over 85 years old. The major AD therapeutics available on the market are acetylcholinesterase inhibitors, such as tacrine and donepezil. New therapeutic agents that can block the disease-inducing mechanisms are essential. Diverse efforts have been made to discover anti-AD agents from natural sources. In this review article, we describe some representative terpenoids such as ginsenosides, gingkolides, and canabinoids as potential anti-AD agents. These compounds exhibit promising in vitro and in vivo biological activities, but are still waiting clinical trials. Additionally, we also discuss some terpenoids including cornel iridoid glycoside, oleanolic acid, tenuifolin, cryptotanshinone, and ursolic acid, which are under investigation for their in vitro and in vivo animal studies.

  9. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  10. Therapeutical aspect of trichomoniasis

    Directory of Open Access Journals (Sweden)

    Vukićević Jelica

    2003-01-01

    Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

  11. Discovering aptamers by cell-SELEX against human soluble growth factors ectopically expressed on yeast cell surface.

    Directory of Open Access Journals (Sweden)

    Hsien-Wei Meng

    Full Text Available SELEX, the process of selecting aptamers, is often hampered by the difficulty of preparing target molecules in their native forms and by a lack of a simple yet quantitative assay for monitoring enrichment and affinity of reactive aptamers. In this study, we sought to discover DNA aptamers against human serum markers for potential therapeutic and diagnostic applications. To circumvent soluble expression and immobilization for performing SELEX, we ectopically expressed soluble growth factors on the surface of yeast cells to enable cell-SELEX and devised a flow cytometry-based method to quantitatively monitor progressive enrichment of specific aptamers. High-throughput sequencing of selected pools revealed that the emergence of highly enriched sequences concurred with the increase in the percentage of reactive aptamers shown by flow cytometry. Particularly, selected DNA aptamers against VEGF were specific and of high affinity (K(D  = ∼ 1 nM and demonstrated a potent inhibition of capillary tube formation of endothelial cells, comparable to the effect of a clinically approved anti-VEGF antibody drug, bevacizumab. Considering the fact that many mammalian secretory proteins have been functionally expressed in yeast, the strategy of implementing cell-SELEX and quantitative binding assay can be extended to discover aptamers against a broad array of soluble antigens.

  12. READING PHILEMON AS THERAPEUTIC NARRATIVE

    African Journals Online (AJOL)

    2010-03-29

    Mar 29, 2010 ... Contrary to an initial impression, the narrative therapeutic approach does not emerge from a completely psychological ... Furthermore, a narrative therapeutic reading does not exist in a vacuum, therefore this investigation ..... converted to Christianity, Philemon supported other believers in various ways ...

  13. Discovering motifs in ranked lists of DNA sequences.

    Directory of Open Access Journals (Sweden)

    Eran Eden

    2007-03-01

    Full Text Available Computational methods for discovery of sequence elements that are enriched in a target set compared with a background set are fundamental in molecular biology research. One example is the discovery of transcription factor binding motifs that are inferred from ChIP-chip (chromatin immuno-precipitation on a microarray measurements. Several major challenges in sequence motif discovery still require consideration: (i the need for a principled approach to partitioning the data into target and background sets; (ii the lack of rigorous models and of an exact p-value for measuring motif enrichment; (iii the need for an appropriate framework for accounting for motif multiplicity; (iv the tendency, in many of the existing methods, to report presumably significant motifs even when applied to randomly generated data. In this paper we present a statistical framework for discovering enriched sequence elements in ranked lists that resolves these four issues. We demonstrate the implementation of this framework in a software application, termed DRIM (discovery of rank imbalanced motifs, which identifies sequence motifs in lists of ranked DNA sequences. We applied DRIM to ChIP-chip and CpG methylation data and obtained the following results. (i Identification of 50 novel putative transcription factor (TF binding sites in yeast ChIP-chip data. The biological function of some of them was further investigated to gain new insights on transcription regulation networks in yeast. For example, our discoveries enable the elucidation of the network of the TF ARO80. Another finding concerns a systematic TF binding enhancement to sequences containing CA repeats. (ii Discovery of novel motifs in human cancer CpG methylation data. Remarkably, most of these motifs are similar to DNA sequence elements bound by the Polycomb complex that promotes histone methylation. Our findings thus support a model in which histone methylation and CpG methylation are mechanistically linked

  14. Three novel virophage genomes discovered from Yellowstone Lake metagenomes.

    Science.gov (United States)

    Zhou, Jinglie; Sun, Dawei; Childers, Alyson; McDermott, Timothy R; Wang, Yongjie; Liles, Mark R

    2015-01-15

    Virophages are a unique group of circular double-stranded DNA viruses that are considered parasites of giant DNA viruses, which in turn are known to infect eukaryotic hosts. In this study, the genomes of three novel Yellowstone Lake virophages (YSLVs)--YSLV5, YSLV6, and YSLV7--were identified from Yellowstone Lake through metagenomic analyses. The relative abundance of these three novel virophages and previously identified Yellowstone Lake virophages YSLV1 to -4 were determined in different locations of the lake, revealing that most of the sampled locations in the lake, including both mesophilic and thermophilic habitats, had multiple virophage genotypes. This likely reflects the diverse habitats or diversity of the eukaryotic hosts and their associated giant viruses that serve as putative hosts for these virophages. YSLV5 has a 29,767-bp genome with 32 predicted open reading frames (ORFs), YSLV6 has a 24,837-bp genome with 29 predicted ORFs, and YSLV7 has a 23,193-bp genome with 26 predicted ORFs. Based on multilocus phylogenetic analysis, YSLV6 shows a close evolutionary relationship with YSLV1 to -4, whereas YSLV5 and YSLV7 are distantly related to the others, and YSLV7 represents the fourth novel virophage lineage. In addition, the genome of YSLV5 has a G+C content of 51.1% that is much higher than all other known virophages, indicating a unique host range for YSLV5. These results suggest that virophages are abundant and have diverse genotypes that likely mirror diverse giant viral and eukaryotic hosts within the Yellowstone Lake ecosystem. This study discovered novel virophages present within the Yellowstone Lake ecosystem using a conserved major capsid protein as a phylogenetic anchor for assembly of sequence reads from Yellowstone Lake metagenomic samples. The three novel virophage genomes (YSLV5 to -7) were completed by identifying specific environmental samples containing these respective virophages, and closing gaps by targeted PCR and sequencing. Most of

  15. Clinical applications of therapeutic phlebotomy

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-07-01

    Full Text Available Kyung Hee Kim,1 Ki Young Oh,2 1Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, 2Department of Physical Medicine and Rehabilitation, Soonchunhyang University, Cheonan Hospital, Cheonan, South Korea Abstract: Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. Keywords: therapeutic phlebotomy, hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, nonalcoholic fatty liver disease

  16. Rethinking Therapeutic Misconception in Biobanking

    DEFF Research Database (Denmark)

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... evaluating biobanks. We present four examples taken from recent developments in biobanking to argue why the notion of therapeutic misconception is problematic in that biobanking practices are increasingly seeking to bridge research and treatment in diff erent ways. In this article we explore examples where...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  17. Lipidomics applications for discovering biomarkers of diseases in clinical chemistry.

    Science.gov (United States)

    Zhao, Ying-Yong; Cheng, Xian-long; Lin, Rui-Chao

    2014-01-01

    Lipids are the fundamental components of biological membranes as well as the metabolites of organisms. Lipids play diverse and important roles in biologicals. The lipid imbalance is closely associated with numerous human lifestyle-related diseases, such as atherosclerosis, obesity, diabetes, and Alzheimer's disease. Lipidomics or lipid profiling is a system-based study of all lipids aiming at comprehensive analysis of lipids in the biological system. Lipidomics has been accepted as a lipid-related research tool in lipid biochemistry, clinical biomarker discovery, disease diagnosis, and in understanding disease pathology. Lipidomics will not only provide insights into the specific functions of lipid species in health and disease, but will also identify potential biomarkers for establishing preventive or therapeutic programs for human diseases. This review presents an overview of lipidomics followed by in-depth discussion of its application to the study of human diseases, including extraction methods of lipids, analytical technologies, data analysis, and clinical research in cancer, neuropsychiatric disease, cardiovascular disease, kidney disease, and respiratory disease. We describe the current status of the identification of metabolic biomarkers in different diseases. We also discuss the lipidomics for the future perspectives and their potential problems. The application of lipidomics in clinical studies may provide new insights into lipid profiling and pathophysiological mechanisms.

  18. Targeting hepatocellular carcinoma: what did we discover so far?

    Directory of Open Access Journals (Sweden)

    Ana Filipa Brito

    2016-10-01

    Full Text Available Hepatocellular carcinoma (HCC is increasingly considered an issue of global importance. Its rates of incidence and mortality have been markedly increasing over the last decades. Among risk factors, some should be highlighted, namely the infections by hepatitis B and C virus, as well as clinical cases of cirrhosis. HCC is characterized as asymptomatic disease in the initial stages which most often leads to a late diagnosis. At molecular and genetic level HCC represents a highly complex tumor entity, including a wide variety of mutations, thus accounting for different mechanisms of resistance towards therapeutic approaches. In particular, mutations of the TP53 gene, as well as a deregulation between the expression of pro- and anti-apoptotic proteins of the BCL-2 family are observed. Regarding treatment modalities, surgical procedures offer the best chance of cure, however, due to a late diagnosis, most of concerned patients cannot be subjected to them. Chemotherapy and radiotherapy are also ineffective, and currently, the treatment with sorafenib is the most commonly used systemic therapy although it can only increase the patient survival for some months. In this sense, a quick and accurate investigation is of utmost importance in order to develop ways of early diagnosis as well as new therapies for HCC.

  19. Despite Appearances, Cosmic Explosions Have Common Origin, Astronomers Discover

    Science.gov (United States)

    2003-11-01

    A Fourth of July fireworks display features bright explosions that light the sky with different colors, yet all have the same cause. They just put their explosive energy into different colors of light. Similarly, astronomers have discovered, a variety of bright cosmic explosions all have the same origin and the same amount of total energy. This is the conclusion of an international team of astronomers that used the National Science Foundation's Very Large Array (VLA) radio telescope to study the closest known gamma-ray burst earlier this year. Artist's conception of burst Artist's Conception of Twin Jets in Energetic Cosmic Explosion CREDIT: Dana Berry, SkyWorks Digital (Click on Image for Larger Version) "For some reason we don't yet understand, these explosions put greatly varying percentages of their explosive energy into the gamma-ray portion of their output," said Dale Frail, of the National Radio Astronomy Observatory (NRAO) in Socorro, NM. That means, he said, that both strong and weak gamma-ray bursts, along with X-ray flashes, which emit almost no gamma rays, are just different forms of the same cosmic beast. The research team reported their results in the November 13 issue of the scientific journal Nature. The scientists trained the VLA on a gamma-ray burst discovered using NASA's HETE-2 satellite last March 29. This burst, dubbed GRB 030329, was the closest such burst yet seen, about 2.6 billion light-years from Earth. Because of this relative proximity, the burst was bright, with visible light from its explosion reaching a level that could be seen in amateur telescopes. As the burst faded, astronomers noted an underlying distinctive signature of a supernova explosion, confirming that the event was associated with the death of a massive star. Since 1999, astronomers have known that the strong outbursts of gamma rays, X-rays, visible light and radio waves from these bursts form beams, like those from a flashlight, rather than spreading in all directions

  20. The Most Distant Object Yet Discovered in the Universe

    Science.gov (United States)

    2009-04-01

    ESO's Very Large Telescope has shown that a faint gamma-ray burst detected last Thursday is the signature of the explosion of the earliest, most distant known object in the Universe (a redshift of 8.2). The explosion apparently took place more than 13 billion years ago, only about 600 million years after the Big Bang. ESO PR Photo 17a/09 Artist's impression of a gamma-ray burst Gamma-ray bursts (GRBs) are powerful flashes of energetic gamma-rays lasting from less than a second to several minutes. They release a tremendous amount of energy in this short time making them the most powerful events in the Universe. They are thought to be mostly associated with the explosion of stars that collapse into black holes. The gamma-ray burst GRB 090423 was detected by the NASA/STFC/ASI Swift satellite during the morning (CEST) of Thursday 23 April 2009. The 10 second burst was located in the constellation of Leo (the Lion). It was soon being followed by a whole range of telescopes on the ground, including the 2.2-metre ESO/MPG telescope at La Silla and ESO's Very Large Telescope (VLT) at Paranal, both in Chile. VLT infrared observations, made 17 hours after the burst detection, allowed astronomers to establish the distance to the explosion. "We find that the light coming from the explosion has been stretched, or redshifted, considerably by the expansion of the Universe", says Nial Tanvir, the leader of the team who made the VLT observations. "With a redshift of 8.2 this is the most remote gamma-ray burst ever detected, and also the most distant object ever discovered -- by some way." Because light moves at a finite speed, looking farther into the Universe means looking back in time. The explosion occurred when the Universe was about 600 million years old, less than 5 percent of its current age. It is believed that the very first stars only formed when the Universe was between 200 and 400 million years old. "This discovery proves the importance of gamma-ray bursts in probing the

  1. Nitroproteins in Human Astrocytomas Discovered by Gel Electrophoresis and Tandem Mass Spectrometry

    Science.gov (United States)

    Peng, Fang; Li, Jianglin; Guo, Tianyao; Yang, Haiyan; Li, Maoyu; Sang, Shushan; Li, Xuejun; Desiderio, Dominic M.; Zhan, Xianquan

    2015-12-01

    Protein tyrosine nitration is involved in the pathogenesis of highly fatal astrocytomas, a type of brain cancer. To understand the molecular mechanisms of astrocytomas and to discover new biomarkers/therapeutic targets, we sought to identify nitroproteins in human astrocytoma tissue. Anti-nitrotyrosine immunoreaction-positive proteins from a high-grade astrocytoma tissue were detected with two-dimensional gel electrophoresis (2DGE)-based nitrotyrosine immunoblots, and identified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fifty-seven nitrotyrosine immunopositive protein spots were detected. A total of 870 proteins (nitrated and non-nitrated) in nitrotyrosine-immunopositive 2D gel spots were identified, and 18 nitroproteins and their 20 nitrotyrosine sites were identified with MS/MS analysis. These nitroproteins participate in multiple processes, including drug-resistance, signal transduction, cytoskeleton, transcription and translation, cell proliferation and apoptosis, immune response, phenotypic dedifferentiation, cell migration, and metastasis. Among those nitroproteins that might play a role in astrocytomas was nitro-sorcin, which is involved in drug resistance and metastasis and might play a role in the spread and treatment of an astrocytoma. Semiquantitative immune-based measurements of different sorcin expressions were found among different grades of astrocytomas relative to controls, and a semiquantitative increased nitration level in high-grade astrocytoma relative to control. Nitro-β-tubulin functions in cytoskeleton and cell migration. Semiquantitative immunoreactivity of β-tubulin showed increased expression among different grades of astrocytomas relative to controls and semiquantitatively increased nitration level in high-grade astrocytoma relative to control. Each nitroprotein was rationalized and related to the corresponding functional system to provide new insights into tyrosine nitration and its potential role in the

  2. Therapeutic benefits of cannabis: a patient survey.

    Science.gov (United States)

    Webb, Charles W; Webb, Sandra M

    2014-04-01

    Clinical research regarding the therapeutic benefits of cannabis ("marijuana") has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai'i. The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0-10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai'i. No serious adverse effects were reported. These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety. Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.

  3. The therapeutic potential of cannabis and cannabinoids.

    Science.gov (United States)

    Grotenhermen, Franjo; Müller-Vahl, Kirsten

    2012-07-01

    Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany. Selective literature review. Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.

  4. Neutrophils: potential therapeutic targets in tularemia?

    Directory of Open Access Journals (Sweden)

    Lee-Ann H Allen

    2013-12-01

    Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

  5. Therapeutic interaction with an older personality disordered patient.

    Science.gov (United States)

    Josephs, Lawrence; Sanders, Avihay; Gorman, Bernard S

    2014-06-01

    This study reflects an assessment of the relationship between change in defensive functioning and change in the therapeutic interaction during an eight-year treatment episode of an older personality disordered woman. The patient, Ms. Q, possessed schizoid, avoidant, and depressive personality disorders as well as major depression as assessed by the Millon Clinical Multiaxial Inventory-III (MCMI-III). At the end of the treatment episode, Ms. Q still possessed an avoidant personality disorder and significant depressive personality traits but no longer possessed clinically significant schizoid traits or major depression. Ms. Q made significant positive change in her adaptive defensive functioning as assessed by the Defense Mechanism Rating Scale (DMRS). Through time-series analysis it was discovered that positive change in adaptive defenses was predicted by increases in a specific type of therapeutic interaction as assessed by the Psychotherapy Q Sort (PQS). In this therapeutic interaction the therapist in a didactic and advice-giving manner highlighted the patient's role in a problem in a clear and coherent way that could be perceived as tactless. Time-series analysis revealed a reciprocal relationship in which positive changes in adaptive defenses predicted further increases in that particular quality of therapeutic interaction.

  6. Therapeutics for filovirus infection: traditional approaches and progress towards in silico drug design.

    Science.gov (United States)

    Shurtleff, Amy C; Nguyen, Tam L; Kingery, David A; Bavari, Sina

    2012-10-01

    Ebolaviruses and marburgviruses cause severe and often lethal human hemorrhagic fevers. As no FDA-approved therapeutics are available for these infections, efforts to discover new therapeutics are important, especially because these pathogens are considered biothreats and emerging infectious diseases. All methods for discovering new therapeutics should be considered, including compound library screening in vitro against virus and in silico structure-based drug design, where possible, if sufficient biochemical and structural information is available. This review covers the structure and function of filovirus proteins, as they have been reported to date, as well as some of the current antiviral screening approaches. The authors discuss key studies mapping small-molecule modulators that were found through library and in silico screens to potential sites on viral proteins or host proteins involved in virus trafficking and pathogenesis. A description of ebolavirus and marburgvirus diseases and available animal models is also presented. To discover novel therapeutics with potent efficacy using sophisticated computational methods, more high-resolution crystal structures of filovirus proteins and more details about the protein functions and host interaction will be required. Current compound screening efforts are finding active antiviral compounds, but an emphasis on discovery research to investigate protein structures and functions enabling in silico drug design would provide another avenue for finding antiviral molecules. Additionally, targeting of protein-protein interactions may be a future avenue for drug discovery since disrupting catalytic sites may not be possible for all proteins.

  7. Cell-penetrating peptides transport therapeutics into cells.

    Science.gov (United States)

    Ramsey, Joshua D; Flynn, Nicholas H

    2015-10-01

    Nearly 30years ago, certain small, relatively nontoxic peptides were discovered to be capable of traversing the cell membrane. These cell-penetrating peptides, as they are now called, have been shown to not only be capable of crossing the cell membrane themselves but can also carry many different therapeutic agents into cells, including small molecules, plasmid DNA, siRNA, therapeutic proteins, viruses, imaging agents, and other various nanoparticles. Many cell-penetrating peptides have been derived from natural proteins, but several other cell-penetrating peptides have been developed that are either chimeric or completely synthetic. How cell-penetrating peptides are internalized into cells has been a topic of debate, with some peptides seemingly entering cells through an endocytic mechanism and others by directly penetrating the cell membrane. Although the entry mechanism is still not entirely understood, it seems to be dependent on the peptide type, the peptide concentration, the cargo the peptide transports, and the cell type tested. With new intracellular disease targets being discovered, cell-penetrating peptides offer an exciting approach for delivering drugs to these intracellular targets. There are hundreds of cell-penetrating peptides being studied for drug delivery, and ongoing studies are demonstrating their success both in vitro and in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Isolated Star-Forming Cloud Discovered in Intracluster Space

    Science.gov (United States)

    2003-01-01

    Subaru and VLT Join Forces in New Study of Virgo Galaxy Cluster [1] Summary At a distance of some 50 million light-years, the Virgo Cluster is the nearest galaxy cluster. It is located in the zodiacal constellation of the same name (The Virgin) and is a large and dense assembly of hundreds of galaxies. The "intracluster" space between the Virgo galaxies is permeated by hot X-ray emitting gas and, as has become clear recently, by a sparse "intracluster population of stars". So far, stars have been observed to form in the luminous parts of galaxies. The most massive young stars are often visible indirectly by the strong emission from surrounding cocoons of hot gas, which is heated by the intense radiation from the embedded stars. These "HII regions" (pronounced "Eitch-Two" and so named because of their content of ionized hydrogen) may be very bright and they often trace the beautiful spiral arms seen in disk galaxies like our own Milky Way. New observations by the Japanese 8-m Subaru telescope and the ESO Very Large Telescope (VLT) have now shown that massive stars can also form in isolation, far from the luminous parts of galaxies. During a most productive co-operation between astronomers working at these two world-class telescopes, a compact HII region has been discovered at the very boundary between the outer halo of a Virgo cluster galaxy and Virgo intracluster space. This cloud is illuminated and heated by a few hot and massive young stars. The estimated total mass of the stars in the cloud is only a few hundred times that of the Sun. Such an object is rare at the present epoch. However, there may have been more in the past, at which time they were perhaps responsible for the formation of a fraction of the intracluster stellar population in clusters of galaxies. Massive stars in such isolated HII regions will explode as supernovae at the end of their short lives, and enrich the intracluster medium with heavy elements. Observations of two other Virgo cluster

  9. Therapeutic hypothermia for acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  10. Frontiers in nano-therapeutics

    CERN Document Server

    Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

    2017-01-01

    This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

  11. [Therapeutic management of neurodermatitis atopica].

    Science.gov (United States)

    Kägi, M K

    1998-08-01

    The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens. During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended. Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations. Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis.

  12. [Current Therapeutic Approaches to Sarcoidosis].

    Science.gov (United States)

    Pizarro, Carmen; Skowasch, Dirk; Grohé, Christian

    2017-01-01

    Sarcoidosis represents a non-caseating, granulomatous disorder of unknown aetiology whose clinical manifestation is heterogeneous and frequently multisystemic. The portion of patients needing systemic treatment varies: though many patients may undergo spontaneous remission, organ-threatening courses demand systemic therapy. Corticosteroids are the first-line treatment option; however, disease´s progression and/or major corticosteroid side effects may require second- and third-line therapeutics. A current stepwise therapeutic algorithm to sarcoidosis that characterizes additive and alternative therapeutic agents is given in the following review. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Extrasolar Planet in Double Star System Discovered from La Silla

    Science.gov (United States)

    1998-11-01

    Early Success With New Swiss Telescope During the past three years, about fifteen planetary companions have been discovered in orbits around dwarf stars. They have revealed to astrophysicists a broad diversity of planetary systems at other stars. Giant planets with masses ranging from half to several times the mass of Jupiter, the largest planet in our own solar system, have been detected with various telescopes. The orbital periods range from 3.1 to 1650 days; while some of the orbits are of circular shape, others are very elongated. The observed diversity naturally raises questions about how these exoplanets are formed. Now, following only a few months of observations, a Swiss team of astronomers [1], working with a new Swiss astronomical facility at the ESO La Silla Observatory mainly dedicated to the search for exoplanets, has made its first planetary detection. It is a massive planet moving in an almost circular orbit around a nearby star that is itself the primary component of a double star system. The Geneva southern extrasolar planet search programme ESO PR Photo 45a/98 ESO PR Photo 45a/98 [Preview - JPEG: 800 x 640 pix - 456k] [High-Res - JPEG: 3000 x 2400 pix - 2.7Mb] ESO PR Photo 45b/98 ESO PR Photo 45b/98 [Preview - JPEG: 800 x 953 pix - 296k] [High-Res - JPEG: 3000 x 3572 pix - 2.3Mb] PR Photo 45a/98 (left) is a view of the dome with the 1.2-m Swiss Leonard Euler Telescope at the ESO La Silla Observatory. The telescope itself is shown in Photo 45b/98 (right). In June 1998, the CORALIE echelle spectrograph was mounted at the 1.2-m Swiss telescope at La Silla and the commissioning phase was begun, during which the telescope and the spectrograph would be trimmed to perfection. This facility is specifically designed for high-precision radial-velocity measurements and it will mostly be used for an ambitious search for large extrasolar planets around stars in the southern celestial hemisphere. Over 1000 stars will be investigated. Such a vast observational

  14. [Therapeutic drug monitoring of antimicrobials

    NARCIS (Netherlands)

    Mouton, J.W.; Aarnoutse, R.E.

    2014-01-01

    The importance of dose adjustments of antimicrobials based on measured concentrations in an individual ('therapeutic drug monitoring', TDM) is increasingly recognized. There are several reasons for this. First, there is a better understanding of the relationships between doses administered,

  15. Therapeutic Vaccines for Chronic Infections

    Science.gov (United States)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  16. Neutron Star Discovered Where a Black Hole Was Expected

    Science.gov (United States)

    2005-11-01

    stars and black holes are the end stages in the evolution of a star, so their progenitors must have been among the most massive stars in the cluster. Muno and colleagues discovered a pulsing neutron star in a cluster of stars known as Westerlund 1. This cluster contains a hundred thousand or more stars in a region only 30 light years across, which suggests that all the stars were born in a single episode of star formation. Based on optical properties such as brightness and color some of the normal stars in the cluster are known to have masses of about 40 suns. Since the progenitor of the neutron star has already exploded as a supernova, its mass must have been more than 40 solar masses. 2MASS Infrared Image of Westerlund 1 2MASS Infrared Image of Westerlund 1 Introductory astronomy courses sometimes teach that stars with more than 25 solar masses become black holes -- a concept that until recently had no observational evidence to test it. However, some theories allow such massive stars to avoid becoming black holes. For example, theoretical calculations by Alexander Heger of the University of Chicago and colleagues indicate that extremely massive stars blow off mass so effectively during their lives that they leave neutron stars when they go supernovae. Assuming that the neutron star in Westerlund 1 is one of these, it raises the question of where the black holes observed in the Milky Way and other galaxies come from. Other factors, such as the chemical composition of the star, how rapidly it is rotating, or the strength of its magnetic field might dictate whether a massive star leaves behind a neutron star or a black hole. The theory for stars of normal chemical composition leaves a small window of initial masses - between about 25 and somewhat less than 40 solar masses - for the formation of black holes from the evolution of single massive stars. The identification of additional neutron stars or the discovery of black holes in young star clusters should further

  17. Scientists discover massive jet streams flowing inside the sun

    Science.gov (United States)

    1997-08-01

    the Earth. The Stanford research team has been viewing the Sun's surface with one of these instruments called a Michelson Doppler Imager that can measure the vertical motion of the Sun's surface at one million different points once per minute. The measurements show the effects of sound waves that permeate the interior. The researchers then apply techniques similar to Earth based seismology and computer aided tomography to infer and map the flow patterns and temperature beneath the Sun's roiling surface. "These techniques allow us to peer inside the Sun using sound waves, much like a doctor can look inside a pregnant woman with a sonogram," said Dr. Schou. Currently, the Stanford scientists have both identified new structures in the interior of the Sun and clarified the form of previously discovered ones. Understanding their relationship to solar activity will require more observations and time for analysis. "At this point, we do not know whether the plasma streams snake around like the jet stream on Earth, or whether it is a less dynamic feature," said Dr. Douglas Gough, of Cambridge University, UK. "It is intriguing to speculate that these streams may affect solar weather like the terrestrial jetstream impacts weather patterns on Earth, but this is completely unclear right now. The same speculation may apply to the other flows we've observed, or they may act in concert. It will be especially helpful to make observations as the Sun enters its next active cycle, expected to peak around the year 2001." NOTE TO EDITORS: Images to support this story and further information are available from : ESA Public Relations Division Tel: +33.1(0)53.69.7155 Fax: +33.1(0)53.69.7690 The images also can be found at the following Internet address: http://www.gsfc.nasa.gov/

  18. Chandra Discovers "Rivers Of Gravity" That Define Cosmic Landscape

    Science.gov (United States)

    2002-07-01

    NASA’s Chandra X-ray Observatory has discovered part of an intergalactic web of hot gas and dark matter that contains most of the material in the universe. The hot gas, which appears to lie like a fog in channels carved by rivers of gravity, has been hidden from view since the time galaxies formed. “The Chandra observations, together with ultraviolet observations, are a major advance in our understanding of how the universe evolved over the last 10 billion years,” said Fabrizio Nicastro of the Harvard-Smithsonian Center for Astrophysics (CfA) in Cambridge, Mass. and head of one of the teams of scientists involved in the discovery. Four independent teams of scientists, whose results appear as separate papers in The Astrophysical Journal, used Chandra to detect intergalactic gas with temperatures ranging from 300,000 to 5 million degrees Celsius. This gas forms part of a gigantic system of hot gas and dark matter that defines the cosmic landscape. The gaseous component alone contains more material than all the stars in the universe. “We had strong suspicions from the Big Bang theory and observations of the early universe that this gas exists in the present era, but like a stealth aircraft it had eluded our detection,” said Claude Canizares of the Massachusetts Institute of Technology (MIT), who along with Taotao Fang, led of one of the teams. The hot gas detected by Chandra can be used to trace the presence of the more massive dark matter component. The discovery of the hot gas may eventually enable astronomers to map of the distribution of dark matter in the universe and perhaps understand its origin. Ultraviolet telescopes had detected cooler components of the hot gas system, but because of its high temperatures most of it is detectable only with an extremely sensitive X-ray telescope. The various groups used two techniques to probe the intergalactic gas. One method uses the absorbing effects of the gas on X-rays from distant galaxies. On their way to

  19. Astronomers Discover Most Massive Neutron Star Yet Known

    Science.gov (United States)

    2010-10-01

    Astronomers using the National Science Foundation's Green Bank Telescope (GBT) have discovered the most massive neutron star yet found, a discovery with strong and wide-ranging impacts across several fields of physics and astrophysics. "This neutron star is twice as massive as our Sun. This is surprising, and that much mass means that several theoretical models for the internal composition of neutron stars now are ruled out," said Paul Demorest, of the National Radio Astronomy Observatory (NRAO). "This mass measurement also has implications for our understanding of all matter at extremely high densities and many details of nuclear physics," he added. Neutron stars are the superdense "corpses" of massive stars that have exploded as supernovae. With all their mass packed into a sphere the size of a small city, their protons and electrons are crushed together into neutrons. A neutron star can be several times more dense than an atomic nucleus, and a thimbleful of neutron-star material would weigh more than 500 million tons. This tremendous density makes neutron stars an ideal natural "laboratory" for studying the most dense and exotic states of matter known to physics. The scientists used an effect of Albert Einstein's theory of General Relativity to measure the mass of the neutron star and its orbiting companion, a white dwarf star. The neutron star is a pulsar, emitting lighthouse-like beams of radio waves that sweep through space as it rotates. This pulsar, called PSR J1614-2230, spins 317 times per second, and the companion completes an orbit in just under nine days. The pair, some 3,000 light-years distant, are in an orbit seen almost exactly edge-on from Earth. That orientation was the key to making the mass measurement. As the orbit carries the white dwarf directly in front of the pulsar, the radio waves from the pulsar that reach Earth must travel very close to the white dwarf. This close passage causes them to be delayed in their arrival by the distortion of

  20. 32 CFR 644.533 - Contamination discovered after return of land to owner, or sale.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Contamination discovered after return of land to owner, or sale. 644.533 Section 644.533 National Defense Department of Defense (Continued) DEPARTMENT OF... Other Contamination from Proposed Excess Land and Improvements § 644.533 Contamination discovered after...

  1. Distant World in Peril Discovered from La Silla

    Science.gov (United States)

    2003-01-01

    Giant Exoplanet Orbits Giant Star Summary When, in a distant future, the Sun begins to expand and evolves into a "giant" star, the surface temperature on the Earth will rise dramatically and our home planet will eventually be incinerated by that central body. Fortunately for us, this dramatic event is several billion years away. However, that sad fate will befall another planet, just discovered in orbit about the giant star HD 47536, already within a few tens of millions of years. At a distance of nearly 400 light-years from us, it is the second-remotest planetary system discovered to date [1]. This is an interesting side-result of a major research project, now carried out by a European-Brazilian team of astronomers [2]. In the course of a three-year spectroscopic survey, they have observed about 80 giant stars in the southern sky with the advanced FEROS spectrograph on the 1.52-m telescope installed at the ESO La Silla Observatory (Chile). It is one of these stars that has just been found to host a giant planet. This is only the fourth such case known and with a diameter of about 33 million km (or 23.5 times that of our Sun), HD 47536 is by far the largest of those giant stars [1]. The distance of the planet from the star is still of the order of 300 million km (or twice the distance of the Earth from the Sun), a safe margin now, but this will not always be so. The orbital period is 712 days, i.e., somewhat less than two Earth years, and the planet's mass is 5 - 10 times that of Jupiter. The presence of exoplanets in orbit around giant stars, some of which will eventually perish into their central star (be "cannibalized"), provides a possible explanation of the anomalous abundance of certain chemical elements that is observed in the atmospheres of some stars, cf. ESO PR 10/01. This interesting discovery bodes well for coming observations of exoplanetary systems with new, more powerful instruments, like HARPS to be installed next year at the ESO 3.6-m telescope on

  2. LIGO Discovers the Merger of Two Black Holes

    Science.gov (United States)

    Kohler, Susanna

    2016-02-01

    is: how do binary black holes form? Two primary mechanisms have been proposed:A binary star system contains two stars that are each massive enough to individually collapse into a black hole. If the binary isnt disrupted during the two collapse events, this forms an isolated black-hole binary.Single black holes form in dense cluster environments and then because they are the most massive objects sink to the center of the cluster. There they form pairs through dynamical interactions.Now that were able to observe black-hole binaries through gravitational-wave detections, one way we could distinguish between the two formation mechanisms is from spin measurements. If we discover a clear preference for the misalignment of the two black holes spins, this would favor formation in clusters, where theres no reason for the original spins to be aligned.The current, single detection is not enough to provide constraints, but if we can compile a large enough sample of events, we can start to present a statistical case favoring one channel over the other.What does GW150914 mean for the future of gravitational-wave detection?The fact that Advanced LIGO detected an event even before the start of its first official observing run is certainly promising! The LIGO team estimates that the volume the detectors can probe will still increase by at least a factor of ~10 as the observing runs become more sensitive and of longer duration.Aerial view of the Virgo interferometer near Pisa, Italy. [Virgo Collaboration]In addition, LIGO is not alone in the gravitational-wave game. LIGOs counterpart in Europe, Virgo, is also undergoing design upgrades to increase its sensitivity. Within this year, Virgo should be able to take data simultaneously with LIGO, allowing for better localization of sources. And the launch of (e)LISA, ESAs planned space-based interferometer, will grant us access to a new frequency range, opening a further window to the gravitational-wave sky.The detection of GW150914 marks

  3. The History of Therapeutic Aerosols: A Chronological Review

    Science.gov (United States)

    Thiel, Charles G.

    2017-01-01

    Abstract In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the

  4. The History of Therapeutic Aerosols: A Chronological Review.

    Science.gov (United States)

    Stein, Stephen W; Thiel, Charles G

    2017-02-01

    In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We

  5. ADONIS Discovers Dust Disk around a Star with a Planet

    Science.gov (United States)

    2000-10-01

    and a planet, that combination may indeed be comparatively common among solar-type stars. Our own Solar system also contains dust. When the dust scatters the sunlight, this can be observed as "zodiacal light" , a cone of faint light extending above the western horizon soon after sunset or the eastern just before sunrise. The same phenomenon should thus be observable from the planet orbiting iota Horologii . PR Photo 27/00 : The disk at iota Horologii . The exoplanet at iota Horologii Last year, the star iota Horologii was found to have a planetary companion, at least twice as heavy as Jupiter, the largest planet in the Solar System. It was the first exoplanet to be discovered in an almost earth-like orbit, cf. ESO PR 12/99 ). This discovery was based on long-term measurements of the radial velocity of iota Horologii by means of the 1.4-m Coudé Auxiliary Telescope (CAT) at La Silla. The extremely accurate observations were made with the Coude-Echelle-Spectrometer (CES) which is now connected to the ESO 3.6-m telescope. With the combination of spectroscopic (CES) and high-angular resolution (ADONIS) observational facilities at one telescope, the 3.6-m is uniquely suited for this type of front-line research. Dust disks and planets around stars Dust disks around stars still retain information about the formation processes of the exoplanetary systems as they are formed by collisions of planetesimals or proto-planets. However, it is still a somewhat controversial issue exactly how the presence of giant planets influences these collisions or whether the existence of a planetary system can be inferred from observed structures in dust disks. To cast more light on this fundamental issue, it is necessary to search for systems which have both a planet and a dust disk. Our own Solar System contains a significant amount of dust particles which can be seen during very clear evenings and nights by naked eye as a diffuse band of light in the sky - the "zodiacal light". Observations

  6. Bone-seeking therapeutic radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Srivastava Suresh C.

    2002-01-01

    Full Text Available Bone-seeking therapeutic radiopharmaceuticals are utilized on the basis of the radionuclide?s particulate emissions (primarily low to intermediate beta emission. The requirements therefore are different from those of bone imaging agents that consist mainly of short-lived single photon emitters. Lately, the therapeutic bone seeking radiopharmaceuticals have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients, for the treatment of joint pain resulting from inflamed synovium (radiosynoviorthesis, or radiosynovectomy, or from various other forms of arthritic disease. There is, however, a paucity of published data on the bio-pharmacokinetics of these agents when used following intravenous administration for bone pain palliation. This paper will briefly review and summarize the presently available chemical and biopharmacokinetic information on the various clinically approved as well as experimental bone-localizing therapeutic radiopharmaceuticals, and make projections on their clinical application for the treatment of primary/metastatic cancer in bone.

  7. Therapeutic hypothermia for acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... is directly related to stroke severity and outcome, and fever after stroke is associated with substantial increases in morbidity and mortality. Normalisation of temperature in acute stroke by antipyretics is generally recommended, although there is no direct evidence to support this treatment. Despite its...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  8. Conflicts in the therapeutic field

    Directory of Open Access Journals (Sweden)

    Antonino Aprea

    2012-06-01

    Full Text Available How the analytical knowledge that compare human consciousness with that, even more disturbing, moving behind his fifth can be said to be “for peace”? It can be - and this will be the contribution of the proposal - the same tortuous and enigmatic of therapeutic practice, with its hesitations and his impulses, to outline a path crossing and overcoming the conflict? May, finally, peace, in the sense of feasibility of intra-and interpersonal dialectic instead of tearing and hostileconfrontation with oneself and with the other, to be a reference in some crucial pivot of ethical therapeutic work? To these questions the intervention seeks to answer retracing some of the highlights of almost three years of therapeutic work with a young woman and her family.

  9. Oligonucleotide conjugates for therapeutic applications.

    Science.gov (United States)

    Winkler, Johannes

    2013-07-01

    Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake mechanisms and pharmacokinetic properties.

  10. An Update on the Therapeutic Approach to Vernal Keratoconjunctivitis.

    Science.gov (United States)

    Esposito, Susanna; Fior, Giulia; Mori, Alessandro; Osnaghi, Silvia; Ghiglioni, Daniele

    2016-10-01

    Vernal keratoconjunctivitis (VKC) is an inflammatory disease of the ocular surface. It commonly occurs in the first decade of life, has a wide geographical distribution, and usually occurs in warm, dry areas. The pathogenesis of VKC seems to have an immune, nervous, and endocrine basis. The most common eye symptoms are itching, discharge, tearing, eye irritation, redness of the eyes, and photophobia. Although VKC generally has a good prognosis, the lack of clarity regarding the origin of the disease makes treatment a challenge for pediatricians and ophthalmologists. The purpose of this review is to discuss the pathogenesis, clinical features, and diagnostic criteria in VKC, with a focus on its therapeutic management. The selection of a therapeutic scheme from the many available options is based on clinical features and the personal preferences of both physicians and patients. Due to the lack of uniform grading of disease severity, there is no worldwide consensus on first-line and second-line therapeutic approaches. The choice of treatment for long-term moderate to severe VKC includes topical cyclosporine or tacrolimus. Further data are needed to define the minimal effective concentration and the safety of these drugs in eye drops and to clarify the diagnosis of VKC in patients who require these drugs. Finally, while promising newly discovered drugs are expected to enter into clinical practice, further studies on their efficacy and safety are required.

  11. [Therapeutic touch and anorexia nervosa].

    Science.gov (United States)

    Satori, Nadine

    2016-01-01

    An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. Copyright © 2016. Published by Elsevier Masson SAS.

  12. Therapeutic options for visceral leishmaniasis.

    Science.gov (United States)

    Monge-Maillo, Begoña; López-Vélez, Rogelio

    2013-11-01

    Visceral leishmaniasis (VL), also known as Kala-Azar, is a disseminated protozoal infection caused principally by Leishmania donovani and Leishmania infantum (known as Leishmania chagasi in South America). The therapeutic options for VL are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, HIV co-infection, malnourishment and other concomitant infections. This article provides an exhaustive review of the literature regarding studies published on the treatment of VL, and gives therapeutic recommendations stratified according to their level of evidence, the species of Leishmania implicated and the geographical location of the infection.

  13. Therapeutic Adherence in Smoking Therapy

    Directory of Open Access Journals (Sweden)

    María Salvador Manzano

    2010-02-01

    Full Text Available Therapeutic adherence is a complex and multidimensional concept. The percentage of adherence to treatments involving a change in lifestyle, such as quitting smoking, is lower than in other disorders, a fact which has relevant clinical, psychological and economic consequences. This paper aims to review the associated factors with adherence to therapy in smoking treatment. Strategies to enhance therapeutic adherence involve the adequate choice of treatment, to know the smoker´s characteristics, breaking down organizational barriers in health system and the training of health professionals in communication skills with patients.

  14. Therapeutics for Equine Endocrine Disorders.

    Science.gov (United States)

    Durham, Andy E

    2017-04-01

    Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Computer Assistance for "Discovering" Formulas in System Engineering and Operator Theory

    National Research Council Canada - National Science Library

    Helton J.W; Foias M.C

    1999-01-01

    The objective of this paper is two-fold. First we present a methodology for using a combination of computer assistance and human intervention to discover highly algebraic theorems in operator, matrix, and linear systems engineering theory...

  16. Building on the International Polar Year: Discovering Interdisciplinary Data Through Federated Search

    National Research Council Canada - National Science Library

    Yarmey, L; Khalsa, S L

    2014-01-01

    ... of expertise in community data repositories. Federated search enables specialized data holdings to be discovered by broader audiences and complements the role of metadata registries such as the Global Change Master Directory, providing...

  17. Accelerated approach of discovering plant-derived drug leads for treatment of tuberculosis

    CSIR Research Space (South Africa)

    Naidoo, D

    2010-09-01

    Full Text Available The bioprospecting research group at CSIR biosciences undertakes research that taps into South Africa’s plant biodiversity with the aim of discovering natural products that can be used to develop new medicines effective against tuberculosis (TB...

  18. Strategic Sustainability Performance Plan. Discovering Sustainable Solutions to Power and Secure America’s Future

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2010-09-01

    Sustainability is fundamental to the Department of Energy’s research mission and operations as reflected in the Department’s Strategic Plan. Our overarching mission is to discover the solutions to power and secure America’s future.

  19. ISLSCP II IGBP DISCover and SiB Land Cover, 1992-1993

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set describes the geographic distributions of 17 classes of land cover based on the International Geosphere-Biosphere DISCover land cover legend (Loveland...

  20. Mining literatures to discover novel multiple biological associations in a disease context.

    Science.gov (United States)

    Faro, Alberto; Giordano, Daniela; Maiorana, Francesco

    2015-01-01

    The text mining methods proposed to discover associations between pairs of biological entities by mining a scientific literature often extract associations already existing in the literature, whereas their extensions supervise too much the discovery process with heuristics and ontologies that limit the research space. On the other hand, the methods that search novel associations applying the text mining methods to two literatures do not avoid the risk of discovering syllogisms based on faulty premises. For this reason, the paper proposes a method that helps the users to discover associations among biological entities by mining the literature using an unsupervised clustering approach. The discovered multiple associations are derived from binary associations to limit the computational load without compromising the methodology accuracy. A case study demonstrates how the tool derived from the methodology works in practice. A comparison between this tool and other tools available in the literature points out the methodology effectiveness.

  1. The renaissance of complement therapeutics.

    Science.gov (United States)

    Ricklin, Daniel; Mastellos, Dimitrios C; Reis, Edimara S; Lambris, John D

    2018-01-01

    The increasing number of clinical conditions that involve a pathological contribution from the complement system - many of which affect the kidneys - has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond.

  2. READING PHILEMON AS THERAPEUTIC NARRATIVE

    African Journals Online (AJOL)

    2010-03-29

    Mar 29, 2010 ... harsh treatment of slaves in the early Christian environment) and a challenging narrative (a more humane conduct of ... therapeutic, it has also proved to be a useful perspective from which to conduct a literary analysis, because it can ...... The Cambridge companion to postmodern theology, pp. 186−202,.

  3. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    Although prevention is the ideal goal for genetic disorders, various types of therapeutic management are available. Such management approaches depend on the nature of the defect, how well it is understood at the genetic and bio- chemical levels and the practical feasibility of correction. In some conditions.

  4. Therapeutic balloon-assisted enteroscopy

    NARCIS (Netherlands)

    H. Aktas (Huseyin); P.B.F. Mensink (Peter)

    2009-01-01

    textabstractSince the introduction of the first balloon-based enteroscopic technique in 2001, therapeutic balloon-assisted enteroscopy (BAE) using either the single or double balloon enteroscopy technique (respectively SBE and DBE) has evolved rapidly. Argon plasma coagulation (APC), polypectomy,

  5. The renaissance of complement therapeutics

    Science.gov (United States)

    Ricklin, Daniel; Mastellos, Dimitrios C.; Reis, Edimara S.; Lambris, John D.

    2018-01-01

    The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond. PMID:29199277

  6. Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Sabrina Lusvarghi

    2016-10-01

    Full Text Available Griffithsin (GRFT, an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.

  7. Ligands of Therapeutic Utility for the Liver X Receptors

    Directory of Open Access Journals (Sweden)

    Rajesh Komati

    2017-01-01

    Full Text Available Liver X receptors (LXRs have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain.

  8. Regulators of innate immunity as novel targets for panviral therapeutics.

    Science.gov (United States)

    Es-Saad, Salwa; Tremblay, Nicolas; Baril, Martin; Lamarre, Daniel

    2012-10-01

    Interferons (IFNs) have long been used as an immunomodulatory therapy for a large array of acute and chronic viral infections. However, IFN therapies have been plagued by severe side effects. The discovery of pathogen recognition receptors (PRR) rejuvenated the interest for immunomodulatory therapies. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. The potential therapeutic effects of THC on Alzheimer's disease.

    Science.gov (United States)

    Cao, Chuanhai; Li, Yaqiong; Liu, Hui; Bai, Ge; Mayl, Jonathan; Lin, Xiaoyang; Sutherland, Kyle; Nabar, Neel; Cai, Jianfeng

    2014-01-01

    The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways.

  10. Discovering Mozart.

    Science.gov (United States)

    Rusk, Nicole

    2010-06-01

    High-throughput imaging of genome-wide RNA interference screens and systematic analysis of protein complexes involved in mitosis yield valuable resources and reveal new subunits of well-characterized complexes.

  11. Discovering Diversity.

    Science.gov (United States)

    Manner, Barbara M.; Hattler, Jean Anne

    2000-01-01

    Introduces a preservice teacher field trip to the rain forests and coastal areas. This experience develops an awareness for different cultures among preservice teachers by experiencing biological and cultural diversity in Costa Rica. Presents students' own ideas on this experience. (YDS)

  12. Therapeutic approaches for celiac disease

    Science.gov (United States)

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  13. Therapeutic Dancing for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Lorenna Pryscia Carvalho Aguiar

    2016-06-01

    Full Text Available Therapeutic dancing has been advocated as an effective adjunct to conventional physical therapies for people living with Parkinson's disease (PD. This systematic review evaluates studies on the outcomes of different dance genres on mobility and quality of life in PD. We searched databases including CINHAL (1982–2015, Medline (1922–2015, Scopus (1996–2015, Web of Science (2002–2015, Embase (2007–2015, PEDro (1999–2015 and the Cochrane Library (1996–2015. The key words were: Parkinson's disease, Parkinson*, Parkinsonism, dance, dance therapy, dance genres, safety, feasibility, and quality of life. Two independent investigators reviewed the texts. Only randomized controlled trials, quasirandomized controlled trials, and case series studies were included. There was emerging evidence that therapeutic dance can be safe and feasible for people with mild to moderately severe PD, with beneficial effects on walking, freezing of gait, and health related quality of life.

  14. Therapeutic drug monitoring: antiarrhythmic drugs

    OpenAIRE

    Campbell, T. J.; Williams, K. M.(Virginia Polytechnic Institute and State University, 24061, Blacksburg, VA, USA)

    1998-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class ...

  15. Potential Therapeutic Effects of Psilocybin.

    Science.gov (United States)

    Johnson, Matthew W; Griffiths, Roland R

    2017-07-01

    Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

  16. Thermodynamic aspects of therapeutic hypothermia.

    Science.gov (United States)

    Vanlandingham, Sean C; Kurz, Michael C; Wang, Henry E

    2015-01-01

    Therapeutic hypothermia (TH) is an important treatment for post-cardiac arrest syndrome. Despite its widespread practice, only limited data describe the thermodynamic aspects of heat transfer during TH. This paper reviews the principles of human body heat balance and provides a conceptual model for characterizing heat exchange during TH. The model may provide a framework for computer simulation for improving training in or clinical methods of TH. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Therapeutic advances in muscular dystrophy

    OpenAIRE

    Leung, Doris G; Wagner, Kathryn R

    2013-01-01

    The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystr...

  18. Conotoxins that Confer Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    John A. C. Archer

    2012-06-01

    Full Text Available Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA approved pharmaceutical drug, Ziconotide (Prialt®; Elan Pharmaceuticals, Inc. that is the synthetic equivalent of the naturally occurring ω-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD was also inferred.

  19. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  20. Therapeutic Applications of Carbon Monoxide

    Science.gov (United States)

    Knauert, Melissa; Vangala, Sandeep; Haslip, Maria; Lee, Patty J.

    2013-01-01

    Heme oxygenase-1 (HO-1) is a regulated enzyme induced in multiple stress states. Carbon monoxide (CO) is a product of HO catalysis of heme. In many circumstances, CO appears to functionally replace HO-1, and CO is known to have endogenous anti-inflammatory, anti-apoptotic, and antiproliferative effects. CO is well studied in anoxia-reoxygenation and ischemia-reperfusion models and has advanced to phase II trials for treatment of several clinical entities. In alternative injury models, laboratories have used sepsis, acute lung injury, and systemic inflammatory challenges to assess the ability of CO to rescue cells, organs, and organisms. Hopefully, the research supporting the protective effects of CO in animal models will translate into therapeutic benefits for patients. Preclinical studies of CO are now moving towards more complex damage models that reflect polymicrobial sepsis or two-step injuries, such as sepsis complicated by acute respiratory distress syndrome. Furthermore, co-treatment and post-treatment with CO are being explored in which the insult occurs before there is an opportunity to intervene therapeutically. The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models. PMID:24648866

  1. Conotoxins that confer therapeutic possibilities

    KAUST Repository

    Essack, Magbubah

    2012-06-04

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

  2. Conotoxins: Therapeutic Potential and Application

    Directory of Open Access Journals (Sweden)

    Richard T. Layer

    2006-04-01

    Full Text Available The pharmacological variety of conotoxins, diverse peptides found in the venoms of marine cone snails, is well recognized. Venoms from each of the estimated 500 species of cone snails contain 50 to 200 distinct biologically active peptides. Most conotoxins characterized to date target receptors and ion channels of excitable tissues, such as ligandgated nicotinic acetylcholine, N-methyl-D-aspartate, and type 3 serotonin receptors, as well as voltage-gated calcium, sodium, and potassium channels, and G-protein-coupled receptors including α-adrenergic, neurotensin, and vasopressin receptors, and the norepinephrine transporter. Several conotoxins have shown promise in preclinical models of pain, convulsive disorders, stroke, neuromuscular block, and cardioprotection. The pharmacological selectivity of the conotoxins, coupled with the safety and efficacy demonstrated in preclinical models, has led to their investigation as human therapeutic agents. In the following review, we will survey the pharmacology and therapeutic rationale of those conotoxins with potential clinical application, and discuss the unique challenges that each will face in the course of their transition from venom component to human therapeutic.

  3. Murine depression model and its potential applications for discovering foods and farm products with antidepressant-like effects

    Directory of Open Access Journals (Sweden)

    Tatsuhiko eGoto

    2016-03-01

    Full Text Available Advanced societies face increased health problems related to various stresses. Chronic psychological stress is a major risk factor for psychiatric disorders such as depression. Although therapeutic agents reduce several symptoms of depression, most have side effects in a broad range of the population. Furthermore, some victims of depression do not show significant improvement with any drugs, so alternative approaches are needed. Good dietary habits may potentially reduce depressive symptoms, but there is little scientific evidence thus far. Murine depression models are useful to test nutritional approaches in vivo. Our model mice subjected to a subchronic mild social defeat stress (sCSDS paradigm show several alterations in physiological parameters and social behavior. These stress-induced symptoms in sCSDS mice can be used as cues to identify antidepressant-like natural resources including foods and farm products. We previously discovered that sCSDS mice show more vulnerability to social stress by changing dietary condition. In addition, we developed a more objective system for analyzing mouse behavior using a 3D depth-sensing camera to understand relationships between diet and behavior. The combination of sCSDS mice with 3D behavioral analysis is a powerful method for screening ingredients in foods and farm products for antidepressant-like effects.

  4. Dynamical complex network theory applied to the therapeutics of brain malignancies

    Science.gov (United States)

    Meyer-Bäse, Anke; Fratte, Daniel; Barbu, Adrian; Pinker-Domenig, Katja

    2015-05-01

    An important problem in modern therapeutics at the metabolomic, transcriptomic or phosphoproteomic level remains to identify therapeutic targets in a plentitude of high-throughput data from experiments relevant to a variety of diseases. This paper presents the application of novel graph algorithms and modern control solutions applied to the graph networks resulting from specific experiments to discover disease-related pathways and drug targets in glioma cancer stem cells (GSCs). The theoretical frameworks provides us with the minimal number of "driver nodes" necessary to determine the full control over the obtained graph network in order to provide a change in the network's dynamics from an initial state (disease) to a desired state (non-disease). The achieved results will provide biochemists with techniques to identify more metabolic regions and biological pathways for complex diseases, and design and test novel therapeutic solutions.

  5. DISCOVERING HABITABLE EARTHS, HOT JUPITERS, AND OTHER CLOSE PLANETS WITH MICROLENSING

    Energy Technology Data Exchange (ETDEWEB)

    Di Stefano, R. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

    2012-06-20

    Searches for planets via gravitational lensing have focused on cases in which the projected separation, a, between planet and star is comparable to the Einstein radius, R{sub E} . This paper considers smaller orbital separations and demonstrates that evidence of close-orbit planets can be found in the low-magnification portion of the light curves generated by the central star. We develop a protocol for discovering hot Jupiters as well as Neptune-mass and Earth-mass planets in the stellar habitable zone. When planets are not discovered, our method can be used to quantify the probability that the lens star does not have planets within specified ranges of the orbital separation and mass ratio. Nearby close-orbit planets discovered by lensing can be subject to follow-up observations to study the newly discovered planets or to discover other planets orbiting the same star. Careful study of the low-magnification portions of lensing light curves should produce, in addition to the discoveries of close-orbit planets, definite detections of wide-orbit planets through the discovery of 'repeating' lensing events. We show that events exhibiting extremely high magnification can effectively be probed for planets in close, intermediate, and wide distance regimes simply by adding several-time-per-night monitoring in the low-magnification wings, possibly leading to gravitational lensing discoveries of multiple planets occupying a broad range of orbits, from close to wide, in a single planetary system.

  6. DISCOVER: A Service Oriented Approach to Managing Earth Science Data Across Distributed Project-specific Repositories

    Science.gov (United States)

    Keiser, K.; Conover, H.; Hawkins, L.; Beaumont, B.; He, M.; Drewry, M.; Nair, M.

    2008-12-01

    The Global Hydrology Resource Center (GHRC), a NASA Earth Science data center managed by the University of Alabama in Huntsville, is one of twelve data centers that make up the Distributed Active Archive Centers (DAAC) Alliance. Over the years, GHRC staff have developed and evolved a production information management infrastructure to ingest, inventory, archive and distribute a variety of data products to our users. The GHRC has also collaborated with Remote Sensing Systems (RSS) over the course of three NASA Earth Science programs (ESIP, REaSON, and now MEaSURES) to develop valuable Earth science products and services, specifically for passive microwave sensors. This continued effort, known as the DISCOVER (Distributed Information Services for Climate and Ocean products and Visualizations for Earth Research) project, has been able to explore more experimental data services. A result of this collaboration is that services developed and hardened in the DISCOVER service oriented architecture may be integrated into the baseline GHRC infrastructure. For example, the GHRC Data Pool was originally developed for DISCOVER and is now supporting the inventory, search and distribution of science data products across multiple GHRC and DISCOVER data repositories. Distributed services for harvesting metadata and packaging data orders interoperate with two complementary search/access/order user interfaces through a central metadata and order tracking database. This presentation will discuss the science data tools and services developed by DISCOVER and the GHRC, with a focus on integration of new services into an established data management infrastructure.

  7. Individualised cancer therapeutics: dream or reality? Therapeutics construction.

    Science.gov (United States)

    Shen, Yuqiao; Senzer, Neil; Nemunaitis, John

    2005-11-01

    The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi.

  8. Multi-Objective Optimization Algorithm to Discover Condition-Specific Modules in Multiple Networks

    Directory of Open Access Journals (Sweden)

    Xiaoke Ma

    2017-12-01

    Full Text Available The advances in biological technologies make it possible to generate data for multiple conditions simultaneously. Discovering the condition-specific modules in multiple networks has great merit in understanding the underlying molecular mechanisms of cells. The available algorithms transform the multiple networks into a single objective optimization problem, which is criticized for its low accuracy. To address this issue, a multi-objective genetic algorithm for condition-specific modules in multiple networks (MOGA-CSM is developed to discover the condition-specific modules. By using the artificial networks, we demonstrate that the MOGA-CSM outperforms state-of-the-art methods in terms of accuracy. Furthermore, MOGA-CSM discovers stage-specific modules in breast cancer networks based on The Cancer Genome Atlas (TCGA data, and these modules serve as biomarkers to predict stages of breast cancer. The proposed model and algorithm provide an effective way to analyze multiple networks.

  9. The VESPA Survey: 100 New Variable Stars Discovered in Two Years

    Science.gov (United States)

    Quadri, U.; Strabla, L.; Girelli, R.

    2017-06-01

    We describe the VESPA project made at IAU station 565, Astronomical Observatory in Bassano Bresciano (BS), Italy. It is one photometric survey of the northern hemisphere which has the aim of discovering and investigating new variable stars. In the first two years of activity we have discovered 100 new variable stars in the course of observations carried out from August 2014 to September 2016. The newly discovered stars comprise 80 eclipsing binary stars (66 of them classified as W Ursae Majoris, 11 as beta Lyrae, and 3 beta Persei), one rotating (ROT), one ellipsoidal variable (ELL), and 18 pulsating variables (5 of them classified as RRAB, 7 RRC, 3 HADS, 2 delta Scuti and one Cepheid). Variability classification is based on the properties of the optical light curves that we obtained using our 255 mm F/4.7 Newton robotic telescope.

  10. FAST SS-ILM: A COMPUTATIONALLY EFFICIENT ALGORITHM TO DISCOVER SOCIALLY IMPORTANT LOCATIONS

    Directory of Open Access Journals (Sweden)

    A. S. Dokuz

    2017-11-01

    Full Text Available Socially important locations are places which are frequently visited by social media users in their social media lifetime. Discovering socially important locations provide several valuable information about user behaviours on social media networking sites. However, discovering socially important locations are challenging due to data volume and dimensions, spatial and temporal calculations, location sparseness in social media datasets, and inefficiency of current algorithms. In the literature, several studies are conducted to discover important locations, however, the proposed approaches do not work in computationally efficient manner. In this study, we propose Fast SS-ILM algorithm by modifying the algorithm of SS-ILM to mine socially important locations efficiently. Experimental results show that proposed Fast SS-ILM algorithm decreases execution time of socially important locations discovery process up to 20 %.

  11. Fast Ss-Ilm a Computationally Efficient Algorithm to Discover Socially Important Locations

    Science.gov (United States)

    Dokuz, A. S.; Celik, M.

    2017-11-01

    Socially important locations are places which are frequently visited by social media users in their social media lifetime. Discovering socially important locations provide several valuable information about user behaviours on social media networking sites. However, discovering socially important locations are challenging due to data volume and dimensions, spatial and temporal calculations, location sparseness in social media datasets, and inefficiency of current algorithms. In the literature, several studies are conducted to discover important locations, however, the proposed approaches do not work in computationally efficient manner. In this study, we propose Fast SS-ILM algorithm by modifying the algorithm of SS-ILM to mine socially important locations efficiently. Experimental results show that proposed Fast SS-ILM algorithm decreases execution time of socially important locations discovery process up to 20 %.

  12. [Therapeutic possibilities after traumatic experiences].

    Science.gov (United States)

    Kapfhammer, Hans-Peter

    2008-12-01

    Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) are frequent, but not obligatory psychological sequelae following trauma. A major subgroup of patients face a chronic course of illness associated with an increased psychiatric comorbidity and significant impairments in psychosocial adaptation. The typical psychopathological symptoms of ASD and PTSD are best described within a multifactorial model integrating both neurobiological and psychosocial influences. The complex etiopathogenesis of acute and posttraumatic stress disorder favours multimodal approaches in the treatment. Differential psychotherapeutic and pharmacological strategies are available. In a critical survey on empirical studies, psychological debriefing cannot be considered as a positive approach to be recommended as general preventive measure during the immediate posttraumatic phase. Positive effects of cognitive-behavioral interventions can be established for ASD. Psychodynamic psychotherapy, cognitive-behavioral therapy and EMDR show promising results in the treatment of PTSD. Major clinical restrictions of patient sampling within special research facilities, however, do not allow an unconditional generalization of these data to psychiatric routine care. In an empirical analysis the SSRIs are the most and best studied medications for ASD and PTSD. In comparison to tricyclic antidepressants SSRIs demonstrate a broader spectrum of therapeutic effects and are better tolerated. The substance classes of SSNRI, DAS, SARI and NaSSA are to be considered as drugs of second choice. They promise a therapeutic efficacy equivalent to the SSRIs, being investigated so far only in open studies. MAO-inhibitors may dispose of a positive therapeutic potential, their profile of side effects must be respected, however. Mood stabilizers and atypical neuroleptics may be used first and foremost in add-on strategies. Benzodiazepines should be used only with increased caution for a short time in states of

  13. Therapeutic applications of circadian rhythms for the cardiovascular system

    Science.gov (United States)

    Tsimakouridze, Elena V.; Alibhai, Faisal J.; Martino, Tami A.

    2015-01-01

    The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for example the diurnal variation of heart rate, blood pressure, and timing of onset of adverse cardiovascular events such as heart attack and sudden cardiac death. Over the past decade, the circadian clock mechanism has emerged as a crucial factor regulating these daily fluctuations. Most recently, these studies have led to a growing clinical appreciation that targeting circadian biology offers a novel therapeutic approach toward cardiovascular (and other) diseases. Here we describe leading-edge therapeutic applications of circadian biology including (1) timing of therapy to maximize efficacy in treating heart disease (chronotherapy); (2) novel biomarkers discovered by testing for genomic, proteomic, metabolomic, or other factors at different times of day and night (chronobiomarkers); and (3) novel pharmacologic compounds that target the circadian mechanism with potential clinical applications (new chronobiology drugs). Cardiovascular disease remains a leading cause of death worldwide and new approaches in the management and treatment of heart disease are clearly warranted and can benefit patients clinically. PMID:25941487

  14. Therapeutical approaches under investigation for treatment of Chagas disease.

    Science.gov (United States)

    Bahia, Maria Terezinha; Diniz, Lívia de Figueiredo; Mosqueira, Vanessa Carla Furtado

    2014-09-01

    A century after its discovery, American trypanosomiasis or Chagas disease remains a serious health problem in Latin America, where it affects around 7 - 8 million people. The prevalence of Chagas disease in the poorer parts of the world has meant that it has largely been neglected with limited progress that made in identifying new drugs for the treatment. The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available for Chagas disease with limitations that include variable efficacy, long treatment courses and toxicity. This review focuses on different therapeutic strategies that have been used for the discovery of new treatments for Chagas disease. These include combination chemotherapy, drug repositioning, re-dosing regimens for current drugs and the identification of new drugs with specified target profiles. There are currently several reasons for a more optimistic view about chemotherapy with Chagas disease. However, despite some progress being made in preclinical studies, there is yet to be an ideal drug or formulation for human treatment. One major drawback in the evaluation of potential Chagas disease therapeutics is the lack of tools available to perform the said evaluation. Indeed, there is a great need to discover a better biomarker that could determine the efficacy of potential chemotherapeutics in treated patients.

  15. Cannabinoids: mechanisms and therapeutic applications in the CNS.

    Science.gov (United States)

    Drysdale, Alison J; Platt, Bettina

    2003-12-01

    Cannabinoids comprise three classes of compounds, the active components of marijuana (Cannabis sativa), as well as endogenous and synthetic derivatives. To date, two distinct cannabinoid receptors (CB1 and CB2) have been discovered, but evidence for further receptor types has been brought forward. The potential use of cannabinoids for medicinal purposes has long been known, but the mechanisms of action of both exogenously applied and endogenous cannabinoids are only partly established. For nervous system disorders, cannabinoids may be useful by modulating neurotransmission and calcium homeostasis as well as by anti-inflammatory and anti-oxidant actions. Some cannabinoids can also trigger cell death, which may be of therapeutic benefit in the treatment of malignant tumours. A number of both in vitro and in vivo models have provided promising but diverse evidence for cannabinoid protection in glutamate-mediated excitotoxicity, hypoxia and glucose deprivation, brain trauma, epilepsy and MS. Subsequent to many preclinical investigations, clinical trials are now underway in a variety of the above applications. Overall, the understanding of the therapeutic relevance of cannabinoids will rely on further investigations into the neuroprotective and neurotoxic potency of cannabinoids in animal models and humans, as much as on a further advancement of our general understanding of the endocannabinoid system and the development of specific compounds devoid of unwanted psychoactive side effects.

  16. Enactments in Psychoanalysis: Therapeutic Benefits.

    Science.gov (United States)

    Stern, Stanley

    The therapeutic benefits of enactments are addressed. Relevant literature reveals disparate conceptions about the nature and use of enactments. Clarification of the term is discussed. This analyst's theoretical and technical evolution is addressed; it is inextricably related to using enactments. How can it not be? A taxonomy of enactments is presented. The article considers that enactments may be fundamental in the evolution from orthodox to contemporary analytic technique. Assumptions underlying enactments are explored, as are guidelines for using enactments. Finally, the article posits that enactments have widened the scope of analysis and contributed to its vitality.

  17. Imaging of prehospital stroke therapeutics

    Science.gov (United States)

    Lin, Michelle P; Sanossian, Nerses; Liebeskind, David S

    2016-01-01

    Despite significant quality improvement efforts to streamline in-hospital acute stroke care in the conventional model, there remain inherent layers of treatment delays, which could be eliminated with prehospital diagnostics and therapeutics administered in a mobile stroke unit. Early diagnosis using Telestroke and neuroimaging while in the ambulance may enable targeted routing to hospitals with specialized care, which will likely improve patient outcomes. Key clinical trials in Telestroke, mobile stroke units with prehospital neuroimaging capability, prehospital ultrasound and co-administration of various classes of neuroprotectives, antiplatelets and antithrombin agents with intravenous thrombolysis are discussed in this article. PMID:26308602

  18. PubMed on Tap: discovering design principles for online information delivery to handheld computers.

    Science.gov (United States)

    Hauser, Susan E; Demner-Fushman, Dina; Ford, Glenn; Thoma, George R

    2004-01-01

    Online access to biomedical information from handheld computers will be a valuable adjunct to other popular medical applications if information delivery systems are designed with handheld computers in mind. The goal of this project is to discover design principles to facilitate practitioners' access to online medical information at the point-of-care. A prototype system was developed to serve as a testbed for this research. Using the testbed, an initial evaluation has yielded several user interface design principles. Continued research is expected to discover additional user interface design principles as well as guidelines for results organization and system performance

  19. IGBP-DIS global 1 km land cover data set, DISCover: First results

    Science.gov (United States)

    Loveland, T.R.; Belward, A.S.

    1997-01-01

    The International Geosphere-Biosphere Programme Data and Information System (IGBP-DIS) is co-ordinating the development of global land data sets from Advanced Very High Resolution Radiometer (AVHRR) data. The first is a 1 km spatial resolution land cover product `DISCover', based on monthly Normalized Difference Vegetation Index composites from 1992 and 1993. DISCover is a 17 class land cover dataset based on the science requirements of IGBP elements. Mapping uses unsupervised classification with post-classification refinement using ancillary data. Draft Africa, North America and South America products are now available for peer review.

  20. The IGBP-DIS global 1km land cover data set, DISCover: First results

    Science.gov (United States)

    Loveland, Thomas R.; Belward, A.S.

    1997-01-01

    The International Geosphere-Biosphere Programme Data and Information System (IGBP-DIS) is co-ordinating the development of global land data sets from Advanced Very High Resolution Radiometer (AVHRR) data. The first is a 1 km spatial resolution land cover product 'DISCover', based on monthly Normalized Difference Vegetation Index composites from 1992 and 1993. DISCover is a 17 class land cover dataset based on the science requirements of IGBP elements. Mapping uses unsupervised classification with post-classification refinement using ancillary data. Draft Africa, North America and South America products are now available for peer review.

  1. Starlight detectives how astronomers, inventors, and eccentrics discovered the modern universe

    CERN Document Server

    Hirshfeld, Alan

    2014-01-01

    NBC News “Top Science and Tech Books of the Year" selectionScientific American/FSG “Favorite Science Books of the Year" selectionNature.com “Top Reads of the Year" selectionKirkus Reviews “Best Books of the Year" selectionDiscover magazine “Top 5 Summer Read"“A masterful balance of science, history and rich narrative." —Discover magazine“Hirshfeld tells this climactic discovery of the expanding universe with great verve and sweep, as befits a story whose scope, characters and import leave

  2. Therapeutic modality: rehabilitation of the injured athlete.

    Science.gov (United States)

    Nyland, John; Nolan, Michael F

    2004-04-01

    Traditional therapeutic modalities include cryotherapy, sonotherapy, pulsed electrical stimulation, transcutaneous electrical nerve stimulation, high-volt pulsed current, and iotopheresis. Alternative modalities include acupuncture, magnetic field therapy, biofeedback,and massage. All therapeutic modalities should be considered adjuncts to progressive functional exercise. Controlled studies rarely reach consensus regarding the efficacy of therapeutic modalities,so their use should be individualized to the patient.

  3. Therapeutic drug monitoring, a practical application

    NARCIS (Netherlands)

    Kees Neef, C.; Touw, D.J.

    Therapeutic Drug Monitoring (TDM) is an indispensable tool in therapeutic handling and medication safety. A definition of TDM is: Therapeutic drug monitoring is a system of quality assurance of a drug management system, aiming that the right drug is given tot the right patient in the right dose in

  4. Therapeutic Robotics: A Technology Push

    Science.gov (United States)

    Krebs, Hermano Igo; Hogan, Neville

    2009-01-01

    In this paper, we present a retrospective and chronological review of our efforts to revolutionize the way physical medicine is practiced by developing and deploying therapeutic robots. We present a sample of our clinical results with well over 300 stroke patients, both inpatients and outpatients, proving that movement therapy has a measurable and significant impact on recovery following brain injury. Bolstered by this result, we embarked on a two-pronged approach: 1) to determine what constitutes best therapy practice and 2) to develop additional therapeutic robots. We review our robots developed over the past 15 years and their unique characteristics. All are configured both to deliver reproducible therapy but also to measure outcomes with minimal encumbrance, thus providing critical measurement tools to help unravel the key question posed under the first prong: what constitutes “best practice”? We believe that a “gym” of robots like these will become a central feature of physical medicine and the rehabilitation clinic within the next ten years. PMID:19779587

  5. [Therapeutic Aggressiveness and Liquid Oncology].

    Science.gov (United States)

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  6. Clinical results in cachexia therapeutics.

    Science.gov (United States)

    Crawford, Jeffrey

    2016-05-01

    This article highlights recent developments in the area of cancer cachexia and therapeutic interventions. Therapeutic interventions in cancer cachexia have been guided by clinical studies focused on the central role of muscle and the increased use of CT imaging to measure the impact of skeletal muscle loss on clinical outcomes. At the translational level, a number of different model systems have emphasized the importance of blockade of tumor-induced inflammation and its potential impact on reversing the cachexia phenotype, including FN14, a receptor in the TNF pathway, as well as the parathyroid hormone-related protein. Clinical studies continue to demonstrate the importance of nutrition and exercise as part of a multimodality approach. Although a number of promising agents are being evaluated, both enobosarm, a selected androgen receptor modulator, and anamorelin, a ghrelin agonist have completed phase III trials. Both agents have shown significant impact on reversal of skeletal muscle loss, but inconsistent effect on physical function improvement. Anamorelin also has a positive effect on appetite and weight gain. Further analysis of these studies, along with regulatory guidance, will be critical in the further development of these and other promising agents in the clinical management of patients with cancer cachexia.

  7. Neonatal Encephalopathy: Update on Therapeutic Hypothermia and Other Novel Therapeutics.

    Science.gov (United States)

    McAdams, Ryan M; Juul, Sandra E

    2016-09-01

    Neonatal encephalopathy (NE) is a major cause of neonatal mortality and morbidity. Therapeutic hypothermia (TH) is standard treatment for newborns at 36 weeks of gestation or greater with intrapartum hypoxia-related NE. Term and late preterm infants with moderate to severe encephalopathy show improved survival and neurodevelopmental outcomes at 18 months of age after TH. TH can increase survival without increasing major disability, rates of an IQ less than 70, or cerebral palsy. Neonates with severe NE remain at risk of death or severe neurodevelopmental impairment. This review discusses the evidence supporting TH for term or near term neonates with NE. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Piperazine derivatives for therapeutic use: a patent review (2010-present).

    Science.gov (United States)

    Rathi, Anuj K; Syed, Riyaz; Shin, Han-Seung; Patel, Rahul V

    2016-07-01

    Piperazine, a six membered nitrogen containing heterocycle, is of great significance to the rational design of drugs. This moiety can be found in a plethora of well-known drugs with various therapeutic uses, such as antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardio protectors, anti-inflammatory, and imaging agents. Slight modification to the substitution pattern on the piperazine nucleus facilitates a recognizable difference in the medicinal potential of the resultant molecules. Scifinder was the main source used to search for patents containing piperazine compounds with therapeutic uses. The article describes a variety of molecular designs bearing piperazine entity furnishing CNS agents, anticancer, cardio-protective agents, antiviral, anti-tuberculosis, anti-inflammatory, antidiabetic, and antihistamine profiles, as well as agents relieving pain and useful in imaging applications. The great interest gathered to explore piperazine based molecules in relatively few years reflects the broad potential of the entity. Earlier, this scaffold was considered to express CNS activity only. However, a significant increase in research covering studies of several different activities of piperazine ring suggest a successful emergence of the pharmacophore. Certain patents outlined in the present article recommend that piperazines can be a flexible building block to discover drug-like elements and modification of substituents present on the piperazine ring may have a significant impact on the pharmacokinetic and pharmacodynamics factors of the resulting molecules. This article aims to provide insights to piperazine based molecular fragments that would assist drug discoverers to rationally design molecules for various diseases. We anticipate, and highly recommend, further therapeutic investigations on this motif.

  9. Discovering the Art of Mathematics: Using String Art to Investigate Calculus

    Science.gov (United States)

    von Renesse, Christine; Ecke, Volker

    2016-01-01

    One goal of our Discovering the Art of Mathematics project is to empower students in the liberal arts to become confident creators of art and imaginative creators of mathematics. In this paper, we describe our experience with using string art to guide liberal arts students in exploring ideas of calculus. We provide excerpts from our inquiry-based…

  10. Non-imaged pulmonary nodules discovered during thoracotomy for metastasectomy by lung palpation

    National Research Council Canada - National Science Library

    Cerfolio, Robert James; McCarty, Todd; Bryant, Ayesha S

    2009-01-01

    ... for VATS for metastasectomy is missing small metastatic lesions due to a lack of intraoperative palpation. Several series have shown that when the lung is carefully palpated via a bi-manual technique (which is only possible via a thoracotomy), many lung nodules are discovered that were not imaged preoperatively and some are malignant. P...

  11. INTEGRAL discovered a new hard X-ray source: IGRJ17511-3057

    NARCIS (Netherlands)

    Baldovin, C.; Kuulkers, E.; Ferrigno, C.; Bozzo, E.; Chenevez, J.; Brandt, S.; Beckmann, V.; Bird, A.; Domingo, A.; Ebisawa, K.; Jonker, P.; Kretschmar, P.; Markwardt, C.; Oosterbroek, T.; Paizis, A.; Risquez, D.; Sanchez-Fernandez, C.; Shaw, S.; Wijnands, R.

    2009-01-01

    During the latest observations of the Galactic Bulge monitoring (see ATel #438), carried out between 2009-09-12 03:21:34 and 2009-09-12 05:27:22 (UTC), INTEGRAL discovered a new bright hard X-ray source, which we designate IGRJ17511-3057. The source is detected in the INTEGRAL/IBIS mosaic image with

  12. When Two Circles Determine a Triangle. Discovering and Proving a Geometrical Condition in a Computer Environment

    Science.gov (United States)

    Metaxas, Nikolaos; Karagiannidou, Andromachi

    2010-01-01

    Visualization of mathematical relationships enables students to formulate conjectures as well as to search for mathematical arguments to support these conjectures. In this project students are asked to discover the sufficient and necessary condition so that two circles form the circumscribed and inscribed circle of a triangle and investigate how…

  13. Examining Pre-K Professional Development Programs: Discovering the Road to Exceptional Instructional Practices

    Science.gov (United States)

    Williams, Sheila D.

    2016-01-01

    The purpose of this qualitative research study was to discover and interpret the experiences of pre-k teachers in an urban school district located in a Northeastern region of the United States. Using a basic qualitative research design, fifteen participants were recruited by a purposeful sampling method to be interviewed after the implementation…

  14. Ochthebius ( s.str .) capicola (Coleoptera) re-discovered in the Cape ...

    African Journals Online (AJOL)

    New distributional records and ecological observations are presented for the Cape endemic hydraenid Ochthebius capicola. Considered extinct on the Cape Peninsula, the species has been re-discovered at two adjacent locations as well as at a new site in Tsitsikamma National Park, Eastern Cape. New species ...

  15. DiscoTect: A System for Discovering the Architectures of Running Programs using Colored Petri Nets

    Science.gov (United States)

    2006-03-01

    Logging Error Reporting Publish/ Subscribe Simulation Component Support Com- ponent Event Local Call Legend: User Envt Scheduler Task...connectors. Two of the components—User and Envt (Environment)—recorded in the document do not show up in the discov- ered architecture. To confirm

  16. Using Appreciative Inquiry to Discover and Deliver Change for Surgical Technology Students

    Science.gov (United States)

    Cabai, Katherine A.

    2012-01-01

    The purpose of this study was to examine efficacious teaching-learning strategies that community college stakeholders employ that enhance surgical technology student outcomes. Knowles's adult learning theory, constructivist theory, and appreciative inquiry served as the theoretical foundation for this study. Discovering effective aspects and…

  17. Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance

    NARCIS (Netherlands)

    Pitsiladis, Y.P.; Tanaka, M.; Eynon, N.; Bouchard, C.; North, K.N.; Williams, A.G.; Collins, M.; Moran, C.N.; Britton, S.L.; Fuku, N.; Ashley, E.A.; Klissouras, V.; Lucia, A.; Ahmetov, I.I.; de Geus, E.J.C.; Alsayrafi, M.

    2016-01-01

    Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of

  18. Protocols for Teaching Students How to Search for, Discover, and Evaluate Innovations

    Science.gov (United States)

    Norton, William I., Jr.; Hale, Dena H.

    2011-01-01

    The authors introduce and develop protocols to guide aspiring entrepreneurs' behaviors in searching for and discovering innovative ideas that may have commercial potential. Systematic search has emerged as a theory-based, prescriptive framework to guide innovative behavior. Grounded in Fiet's theory of search and discovery, this article provides…

  19. The pearls of using real-world evidence to discover social groups

    Science.gov (United States)

    Cardillo, Raymond A.; Salerno, John J.

    2005-03-01

    In previous work, we introduced a new paradigm called Uni-Party Data Community Generation (UDCG) and a new methodology to discover social groups (a.k.a., community models) called Link Discovery based on Correlation Analysis (LDCA). We further advanced this work by experimenting with a corpus of evidence obtained from a Ponzi scheme investigation. That work identified several UDCG algorithms, developed what we called "Importance Measures" to compare the accuracy of the algorithms based on ground truth, and presented a Concept of Operations (CONOPS) that criminal investigators could use to discover social groups. However, that work used a rather small random sample of manually edited documents because the evidence contained far too many OCR and other extraction errors. Deferring the evidence extraction errors allowed us to continue experimenting with UDCG algorithms, but only used a small fraction of the available evidence. In attempt to discover techniques that are more practical in the near-term, our most recent work focuses on being able to use an entire corpus of real-world evidence to discover social groups. This paper discusses the complications of extracting evidence, suggests a method of performing name resolution, presents a new UDCG algorithm, and discusses our future direction in this area.

  20. 48 CFR 752.209-71 - Organizational conflicts of interest discovered after award.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Organizational conflicts... CLAUSES Texts of Provisions and Clauses 752.209-71 Organizational conflicts of interest discovered after..., establishing a restraint on the contractor's eligibility for future contracts. Organizational Conflicts of...

  1. Discovering and explaining work-family strategies of parents in Luxembourg

    NARCIS (Netherlands)

    Zhelyazkova, Nevena

    2014-01-01

    The presented analysis discovers and explains typical patterns of work-family reconciliation for parents who had a child in the same period (2003) and in the same country (Luxembourg), thus facing the same macroeconomic and institutional conditions. Work-family trajectories are reconstructed as

  2. John Ellis, theoretical physicists: Are we close to discovering the Higgs Boson?

    CERN Multimedia

    CERN Video Productions; Silvano de Gennaro

    2012-01-01

    John Ellis, theoretical physicists, answers the question "Are we close to discovering the Higgs Boson and why is it so difficult to find it?" in preparation of the Press Conference following the scientific seminar announcing results of the searches for the Higgs boson on July 4 2012.

  3. KEGS Transients Discovered by a Pan-STARRS1 Search of the Kepler Campaign 16 Field

    Science.gov (United States)

    Smith, K. W.; Rest, A.; Tucker, B. E.; Garnavich, P. M.; Margheim, S.; Kasen, D.; Olling, R.; Shaya, E.; Narayan, G.; Villar, A.; Forster, F.; Mushotzky, R.; Zenteno, A.; James, D.; Smith, R. Chris; Dotson, J. L.; Barentsen, G.; Gully-Santiago, M.; Smartt, S. J.; Wright, D. E.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Schultz, A.; Magnier, E.; Waters, C.; Bulger, J.; Wainscoat, R. J.

    2018-01-01

    We report the following transients discovered by Pan-STARRS1 during a targeted search of the Kepler Campaign 16 field as part of the K2 Extragalactic Survey (KEGS) for Transients (see http://www.mso.anu.edu.au/kegs/).

  4. Discovering Inexpensive, Effective Catalysts for Solar Energy Conversion: An Authentic Research Laboratory Experience

    Science.gov (United States)

    Shaner, Sarah E.; Hooker, Paul D.; Nickel, Anne-Marie; Leichtfuss, Amanda R.; Adams, Carissa S.; de la Cerda, Dionisia; She, Yuqi; Gerken, James B.; Pokhrel, Ravi; Ambrose, Nicholas J.; Khaliqi, David; Stahl, Shannon S.; Schuttlefield Christus, Jennifer D.

    2016-01-01

    Electrochemical water oxidation is a major focus of solar energy conversion efforts. A new laboratory experiment has been developed that utilizes real-time, hands-on research to discover catalysts for solar energy conversion. The HARPOON, or Heterogeneous Anodes Rapidly Perused for Oxygen Overpotential Neutralization, experiment allows an array of…

  5. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes

    NARCIS (Netherlands)

    Dutilh, Bas E|info:eu-repo/dai/nl/304546313; Cassman, Noriko; McNair, Katelyn; Sanchez, Savannah E; Silva, Genivaldo G Z; Boling, Lance; Barr, Jeremy J; Speth, Daan R; Seguritan, Victor; Aziz, Ramy K; Felts, Ben; Dinsdale, Elizabeth A; Mokili, John L; Edwards, Robert A

    2014-01-01

    Metagenomics, or sequencing of the genetic material from a complete microbial community, is a promising tool to discover novel microbes and viruses. Viral metagenomes typically contain many unknown sequences. Here we describe the discovery of a previously unidentified bacteriophage present in the

  6. Discovering relational-based association rules with multiple minimum supports on microarray datasets.

    Science.gov (United States)

    Liu, Yu-Cheng; Cheng, Chun-Pei; Tseng, Vincent S

    2011-11-15

    Association rule analysis methods are important techniques applied to gene expression data for finding expression relationships between genes. However, previous methods implicitly assume that all genes have similar importance, or they ignore the individual importance of each gene. The relation intensity between any two items has never been taken into consideration. Therefore, we proposed a technique named REMMAR (RElational-based Multiple Minimum supports Association Rules) algorithm to tackle this problem. This method adjusts the minimum relation support (MRS) for each gene pair depending on the regulatory relation intensity to discover more important association rules with stronger biological meaning. In the actual case study of this research, REMMAR utilized the shortest distance between any two genes in the Saccharomyces cerevisiae gene regulatory network (GRN) as the relation intensity to discover the association rules from two S.cerevisiae gene expression datasets. Under experimental evaluation, REMMAR can generate more rules with stronger relation intensity, and filter out rules without biological meaning in the protein-protein interaction network (PPIN). Furthermore, the proposed method has a higher precision (100%) than the precision of reference Apriori method (87.5%) for the discovered rules use a literature survey. Therefore, the proposed REMMAR algorithm can discover stronger association rules in biological relationships dissimilated by traditional methods to assist biologists in complicated genetic exploration.

  7. VizieR Online Data Catalog: newly discovered planets from WASP-South (Turner+, 2016)

    Science.gov (United States)

    Turner, O. D.; Anderson, D. R.; Cameron, A. Collier; Delrez, L.; Evans, D. F.; Gillon, M.; Hellier, C.; Jehin, E.; Lendl, M.; Maxted, P. F. L.; Pepe, F.; Pollacco, D.; Queloz, D.; Segransan, D.; Smalley, B.; Smith, A. M. S.; Triaud, A. H. M. J.; Udry, S.; West, R. G.

    2017-02-01

    Lightcurves and radial velocity data of three newly discovered planets from the WASP-South survey. Discovery data come from the WASP-South telescope (SAAO, South Africa) with follow-up lightcurves from the TRAPPIST telescope and EulerCam on the Swiss telescope (La Silla, Chile). Radial velocity data are from the CORALIE spectrograph on the Swiss telescope. (6 data files).

  8. 7 CFR 1901.259 - Actions to be taken when archeological properties are discovered during construction.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Actions to be taken when archeological properties are... Procedures for the Protection of Historical and Archeological Properties § 1901.259 Actions to be taken when archeological properties are discovered during construction. (a) When properties of significant HA value are...

  9. EPIC 201585823, a rare triple-mode RR Lyrae star discovered in K2 mission data

    DEFF Research Database (Denmark)

    Kurtz, Donald W.; Bowman, Dominic M.; Ebo, Simon J.

    2016-01-01

    We have discovered a new, rare triple-mode RR Lyr star, EPIC 201585823, in the Kepler K2 mission Campaign 1 data. This star pulsates primarily in the fundamental and first-overtone radial modes, and, in addition, a third non-radial mode. The ratio of the period of the non-radial mode to that of t...

  10. First records of Nocomis biguttatus (Hornyhead Chub) from West Virginia discovered in museum voucher specimens

    Science.gov (United States)

    Welsh, Stuart A.; Cincotta, Daniel A.; Starnes, Wayne C.

    2013-01-01

    Specimens of Nocomis biguttatus (Hornyhead Chub) from South Fork Hughes River (Little Kanawha River drainage, WV) were discovered in two museum lots at the North Carolina Museum of Natural Sciences. These accessions, collected in 1960 and 1966, represent an addition to the state fauna and are the first distribution records for this species from the Appalachian Plateau, WV

  11. Communication between the right and circumflex coronary arteries discovered incidentally by multidetector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Se Hwan; Kim, Eui Jong; Woo, Jong Shin; Kim, Soo Joong; Youn, Hyo Chul; Oh, Joo Hyeong [College of Medicine, Kyung Hee University, Seoul (Korea, Republic of)

    2016-09-15

    Intercoronary communication is a rare congenital coronary anomaly. We present a case of a 48-year-old man with an incidentally discovered communication between the right and circumflex coronary arteries, who was admitted with chest tightness and exertional dyspnea. The initial diagnosis was made using electrocardiogram-gated multidetector computed tomography.

  12. Incidence of and sequels to medical problems discovered in medical students during study-related activities

    NARCIS (Netherlands)

    Pols, J; Boendermaker, PM; Muntinghe, H

    2003-01-01

    Purpose Students often act as subjects during practical and clinical skills training sessions. This routine seems to be quite acceptable for them but may present side-effects. Disorders, sometimes of a serious nature, have been discovered in medical students during clinical skills training. Because

  13. CWI cryptanalyst discovers new cryptographic attack variant in Flame spy malware

    NARCIS (Netherlands)

    M.M.J. Stevens (Marc); R.J.F. Cramer (Ronald)

    2012-01-01

    htmlabstractCryptanalyst Marc Stevens from the Centrum Wiskunde & Informatica (CWI) in Amsterdam, known for breaking the https security in 2008 using a cryptanalytic attack on MD5, analyzed the recent Flame virus this week. He discovered that for this spy malware an as yet unknown cryptographic

  14. Novel RNA Virus Genome Discovered in Ghost Ants (Tapinoma melanocephalum) from Hawaii.

    Science.gov (United States)

    Brettell, Laura E; Mordecai, Gideon J; Pachori, Purnima; Martin, Stephen J

    2017-07-27

    Here, we report the full-genome sequence of Milolii virus, a novel single-stranded (positive-sense) RNA virus discovered from Tapinoma melanocephalum ants in Hawaii. The genome is 10,475 nucleotides long, encoding a polyprotein of 3,304 amino acids. Copyright © 2017 Brettell et al.

  15. Timing and Interstellar Scattering of 35 Distant Pulsars Discovered in the PALFA Survey

    NARCIS (Netherlands)

    Nice, D.J.; Altiere, A.; Bogdanov, S.; Cordes, J.M.; Farrington, D.; Hessels, J.W.T.; Kaspi, V.M.; Lyne, A.G.; Popa, L.; Ransom, S.M.; Sanpa-Arsa, S.; Stappers, B.W.; Wang, Y.; Allen, B.; Bhat, N.D.R.; Brazier, A.; Camilo, F.; Champion, D.J.; Chatterjee, S.; Crawford, F.; Deneva, J.S.; Desvignes, G.; Freire, P.C.C.; Jenet, F.A.; Knispel, B.; Lazarus, P.; Lee, K.J.; van Leeuwen, J.; Lorimer, D.R.; Lynch, R.; McLaughlin, M.A.; Scholz, P.; Siemens, X.; Stairs, I.H.; Stovall, K.; Venkataraman, A.; Zhu, W.

    2013-01-01

    We have made extensive observations of 35 distant slow (non-recycled) pulsars discovered in the ongoing Arecibo PALFA pulsar survey. Timing observations of these pulsars over several years at Arecibo Observatory and Jodrell Bank Observatory have yielded high-precision positions and measurements of

  16. "Discovering the Cell": An Educational Game about Cell and Molecular Biology

    Science.gov (United States)

    Spiegel, Carolina N.; Alves, Gutemberg G.; Cardona, Tania da S.; Melim, Leandra M. C.; Luz, Mauricio R. M. P.; Araujo-Jorge, Tania C.; Henriques-Pons, Andrea

    2008-01-01

    The role of games within education becomes clearer as students become more active and are able to take decisions, solve problems and react to the results of those decisions. The educational board game "Discovering the Cell" ("Celula Adentro"), is based on problem-solving learning. This investigative game attempts to stimulate…

  17. A non-parametric hierarchical model to discover behavior dynamics from tracks

    NARCIS (Netherlands)

    Kooij, J.F.P.; Englebienne, G.; Gavrila, D.M.

    2012-01-01

    We present a novel non-parametric Bayesian model to jointly discover the dynamics of low-level actions and high-level behaviors of tracked people in open environments. Our model represents behaviors as Markov chains of actions which capture high-level temporal dynamics. Actions may be shared by

  18. Exploring National Parks & Monuments: Students Can Discover National Monuments, National Parks & Natural Wonders

    Science.gov (United States)

    Curriculum Review, 2009

    2009-01-01

    This article presents an interview with Cynthia Light Brown, author of "Discover National Monuments, National Parks: Natural Wonders," a book that introduces readers ages 8-12 to the history and science behind some of the amazing natural sites in the United States. In this interview, Cynthia Light Brown describes how she became interested in…

  19. Discovering frequently recurring movement sequences in team-sport athlete spatiotemporal data.

    Science.gov (United States)

    Sweeting, Alice J; Aughey, Robert J; Cormack, Stuart J; Morgan, Stuart

    2017-12-01

    Athlete external load is typically analysed from predetermined movement thresholds. The combination of movement sequences and differences in these movements between playing positions is also currently unknown. This study developed a method to discover the frequently recurring movement sequences across playing position during matches. The external load of 12 international female netball athletes was collected by a local positioning system during four national-level matches. Velocity, acceleration and angular velocity were calculated from positional (X, Y) data, clustered via one-dimensional k-means and assigned a unique alphabetic label. Combinations of velocity, acceleration and angular velocity movement were compared using the Levenshtein distance and similarities computed by the longest common substring problem. The contribution of each movement sequence, according to playing position and relative to the wider data set, was then calculated via the Minkowski distance. A total of 10 frequently recurring combinations of movement were discovered, regardless of playing position. Only the wing attack, goal attack and goal defence playing positions are closely related. We developed a technique to discover the movement sequences, according to playing position, performed by elite netballers. This methodology can be extended to discover the frequently recurring movements within other team sports and across levels of competition.

  20. The therapeutic relationship after psychiatric admission.

    LENUS (Irish Health Repository)

    Roche, Eric

    2014-03-01

    The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

  1. Therapeutic Plasmapheresis in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Zeynep Kendi Celebi

    2013-02-01

    Full Text Available In 1960's, with succesfully renal transplantations, acute rejection became to be a serious problem for graft survival. From 1965 to 2010, with the introduction of new immunosuppressant agents such as cyclosporine, mycophenolate mofetile and tacrolimus, the acute rejection rates declined from 80% to 10% . There is an ongoing gradual improvement in allograft survival. Use of Therapeutic plasma exchange (TPE is not evidence based treatment, but TPE is necessary for pre- and also post transplantation in patients with DSA. TPE is also a main treatment for antibody mediated rejection (AMR , but in clinical practice the duration and frequency of TPE and individual difference of antibody production is unclear. There is a requirement for more specific antibody elimination. Further randomised controlled studies are needed to elucidate TPE use before and after kidney transplantation. [Dis Mol Med 2013; 1(1.000: 8-10

  2. Angiogenesis and Its Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2013-01-01

    Full Text Available Angiogenesis plays critical roles in human physiology that range from reproduction and fetal growth to wound healing and tissue repair. The sophisticated multistep process is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis may lead to several angiogenic disorders, including vascular insufficiency (myocardial or critical limb ischemia and vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies. Thus, numerous therapeutic opportunities can be envisaged through the successful understanding and subsequent manipulation of angiogenesis. Here, we review the clinical implications of angiogenesis and discuss pro- and antiangiogenic agents that offer potential therapy for cancer and other angiogenic diseases.

  3. [New therapeutic options in obesity].

    Science.gov (United States)

    Heufelder, A E

    2003-10-16

    The basis for a therapeutic concept for obesity comprises specific measures aimed at changing inappropriate lifestyle habits (overeating, unsuitable diet, sedentary lifestyle) and psychological counseling (identification of bad eating habits, motivation, intensive coaching). Education by a physician on an individual or small-group basis, with emphasis on the practical implementation of fitness training (endurance and muscle building!), together with modification of the diet, has proved successful. In parallel with this, supportive anti-obesity medication makes a useful contribution to weight reduction and the control of risk factors. Evidence-based anti-obesity drugs such as sibutramine and orlistat facilitate the start of weight reduction, thus providing additional motivation of success, and support the long-term effect by stabilizing the weight loss. Health insurance carriers should, in future, selectively support evaluated and approved medication-based and non-medication-based weight-reduction programs, and reimburse the patient who has successfully participated in one.

  4. Therapeutic Drug Monitoring of Lithium

    DEFF Research Database (Denmark)

    Mose, Tina; Damkier, Per; Petersen, Magnus

    2015-01-01

    BACKGROUND: Serum lithium is monitored to ensure levels within the narrow therapeutic window. This study examines the interlaboratory variation and inaccuracy of lithium monitoring in Denmark. METHODS: In 16 samples consisting of (1) control materials (n = 4), (2) pooled patient serum (n = 5......), and (3) serum from individual patients (n = 7), lithium was measured in 19 laboratories using 20 different instruments. The lithium concentrations were targeted by a reference laboratory. Ion-selective electrode (n = 5), reflective spectrophotometric (RSM, n = 5), and spectrophotometric (n = 10) methods...... of >12%. Seven of these instruments had a systematic positive or negative bias and more so at lower lithium concentrations. Three poorly calibrated instruments were found in the ion-selective electrode group, 3 in the spectrophotometric group, and 2 in the RSM group. The instruments using reflectance...

  5. Brain plasticity-based therapeutics

    Science.gov (United States)

    Merzenich, Michael M.; Van Vleet, Thomas M.; Nahum, Mor

    2014-01-01

    The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from (a) the more-behavioral, traditional clinical strategies of professional therapy practitioners, and (b) an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine. PMID:25018719

  6. Therapeutic interventions in cerebral palsy.

    Science.gov (United States)

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

  7. Novel therapeutic approaches in chondrosarcoma.

    Science.gov (United States)

    Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

    2017-03-01

    Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

  8. Host modulation by therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sugumari Elavarasu

    2012-01-01

    Full Text Available Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs, bisphosphonates, nitrous oxide (NO synthase inhibitors, recombinant human interleukin-11 (rhIL-11, omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA, mitogen-activated protein kinase (MAPK inhibitors, nuclear factor-kappa B (NF-kb inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α are some of the therapeutic agents that have host modulation properties.

  9. Brain Plasticity-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Michael eMerzenich

    2014-06-01

    Full Text Available The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from a the more-behavioral, traditional clinical strategies of professional therapy practitioners, and b an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine.

  10. Guidelines for Rational Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Byunghee Yoo

    2017-12-01

    Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

  11. Harsh humour: a therapeutic discourse.

    Science.gov (United States)

    McCreaddie, May

    2010-11-01

    Humour research in healthcare has tended to focus on rehearsed as opposed to spontaneous humour. This paper reports an empirical example of spontaneous humour in healthcare interactions: a negative case analysis from a constructivist grounded theory study. Twenty Clinical Nurse Specialist (CNS)-patient interactions and CNS pre- and postinteraction audio diaries provided the baseline data corpus. Follow-up interviews, field notes, focus groups and observations serviced theory generation with a constant comparison approach to data collection and analyses. Interpretative and illustrative frameworks incorporating humour theories, non-laughter humour support, discursive features and prosodical features of speech were applied to all data. This paper is based upon the negative case comprising a 90-minute follow-up interview and 10 hours of field note observations. The negative case - a CNS working with female drug users' sexual and reproductive health needs - contradicted emerging findings from the baseline data corpus. First, the negative case had greater awareness of humour, deliberately initiated humour and recognised parameters and exclusion zones. Second, a good patient personal was evident in the baseline data corpus but the negative case worked with 'bad' patients. Accordingly, a specific type of humour - harsh humour - was evident in the negative case. Harsh humour used areas of potential discord (e.g. drug use) as a focus of humour creation and maintenance. The deliberate initiation of harsh humour enabled the negative case and her colleagues to achieve their aims by engaging effectively with unpredictable, reluctant and recalcitrant patients. The negative case demonstrates how humour can be used to therapeutically enhance healthcare interactions with disenfranchised individuals. Humour is not superficial but integral to the accomplishment of key aspects of interactions. Health and social care workers should consider the potential for therapeutic humour to engage

  12. Discovering Land Cover Web Map Services from the Deep Web with JavaScript Invocation Rules

    Directory of Open Access Journals (Sweden)

    Dongyang Hou

    2016-06-01

    Full Text Available Automatic discovery of isolated land cover web map services (LCWMSs can potentially help in sharing land cover data. Currently, various search engine-based and crawler-based approaches have been developed for finding services dispersed throughout the surface web. In fact, with the prevalence of geospatial web applications, a considerable number of LCWMSs are hidden in JavaScript code, which belongs to the deep web. However, discovering LCWMSs from JavaScript code remains an open challenge. This paper aims to solve this challenge by proposing a focused deep web crawler for finding more LCWMSs from deep web JavaScript code and the surface web. First, the names of a group of JavaScript links are abstracted as initial judgements. Through name matching, these judgements are utilized to judge whether or not the fetched webpages contain predefined JavaScript links that may prompt JavaScript code to invoke WMSs. Secondly, some JavaScript invocation functions and URL formats for WMS are summarized as JavaScript invocation rules from prior knowledge of how WMSs are employed and coded in JavaScript. These invocation rules are used to identify the JavaScript code for extracting candidate WMSs through rule matching. The above two operations are incorporated into a traditional focused crawling strategy situated between the tasks of fetching webpages and parsing webpages. Thirdly, LCWMSs are selected by matching services with a set of land cover keywords. Moreover, a search engine for LCWMSs is implemented that uses the focused deep web crawler to retrieve and integrate the LCWMSs it discovers. In the first experiment, eight online geospatial web applications serve as seed URLs (Uniform Resource Locators and crawling scopes; the proposed crawler addresses only the JavaScript code in these eight applications. All 32 available WMSs hidden in JavaScript code were found using the proposed crawler, while not one WMS was discovered through the focused crawler

  13. Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller Medication Using Machine Learning.

    Science.gov (United States)

    Ross, Mindy K; Yoon, Jinsung; van der Schaar, Auke; van der Schaar, Mihaela

    2018-01-01

    Pediatric asthma has variable underlying inflammation and symptom control. Approaches to addressing this heterogeneity, such as clustering methods to find phenotypes and predict outcomes, have been investigated. However, clustering based on the relationship between treatment and clinical outcome has not been performed, and machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth. Our objectives were to use our novel machine learning algorithm, predictor pursuit (PP), to discover pediatric asthma phenotypes on the basis of asthma control in response to controller medications, to predict longitudinal asthma control among children with asthma, and to identify features associated with asthma control within each discovered pediatric phenotype. We applied PP to the Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes on the basis of asthma control between assigned controller therapy groups (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes using the Asthma Clinical Research Network/Childhood Asthma Research and Education network data. We next predicted children's asthma control over time and compared PP's performance with that of traditional prediction methods. Last, we identified clinical features most correlated with asthma control in the discovered phenotypes. Four phenotypes were discovered in both datasets: allergic not obese (A + /O - ), obese not allergic (A - /O + ), allergic and obese (A + /O + ), and not allergic not obese (A - /O - ). Of the children with well-controlled asthma in the Childhood Asthma Management Program dataset, we found more nonobese children treated with budesonide than with nedocromil (P = 0.015) and more obese children treated with nedocromil than with budesonide (P = 0.008). Within the obese group, more A + /O + children's asthma was well controlled with nedocromil than with budesonide (P = 0.022) or with placebo

  14. Translational nanomedicine--through the therapeutic window.

    Science.gov (United States)

    Pierce, Robin L

    2015-01-01

    Translational nanomedicine occurs only through the successful integration of multiple inputs and iterative modifications. The therapeutic window plays a pivotal role in the trajectory of translational nanomedicine. Often defined in terms of the range of dosage for safe and effective therapeutic effect, a second definition of the therapeutic window refers to the often narrow temporal window in which a therapeutic effect can be obtained. Expanding the second definition to explicitly include the spatial dimension, this article explores aspects of the therapeutic spaces created by nanomedicine that shift the traditional dimensions of symptom, sign and pathology. This article analyzes three aspects of the therapeutic window in nanomedicine - temporal, spatial and manner of construction and their impact on the dimensions of modern medicine.

  15. Therapeutic strategies in Sickle Cell Anemia: The past present and future.

    Science.gov (United States)

    Fernandes, Queenie

    2017-06-01

    Sickle Cell Anemia (SCA) was one of the first hemoglobinopathies to be discovered. It is distinguished by the mutation-induced expression of a sickle cell variant of hemoglobin (HbS) that triggers erythrocytes to take a characteristic sickled conformation. The complex physiopathology of the disease and its associated clinical complications has initiated multi-disciplinary research within its field. This review attempts to lay emphasis on the evolution, current standpoint and future scope of therapeutic strategies in SCA. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. An Application of Improved Gap-BIDE Algorithm for Discovering Access Patterns

    Directory of Open Access Journals (Sweden)

    Xiuming Yu

    2012-01-01

    Full Text Available Discovering access patterns from web log data is a typical sequential pattern mining application, and a lot of access pattern mining algorithms have been proposed. In this paper, we propose an improved approach of Gap-BIDE algorithm to extract user access patterns from web log data. Compared with the previous Gap-BIDE algorithm, a process of getting a large event set is proposed in the provided algorithm; the proposed approach can find out the frequent events by discarding the infrequent events which do not occur continuously in an accessing time before generating candidate patterns. In the experiment, we compare the previous access pattern mining algorithm with the proposed one, which shows that our approach is very efficient in discovering access patterns in large database.

  17. Discovering Words in Fluent Speech: The Contribution of Two Kinds of Statistical Information

    Science.gov (United States)

    Thiessen, Erik D.; Erickson, Lucy C.

    2013-01-01

    To efficiently segment fluent speech, infants must discover the predominant phonological form of words in the native language. In English, for example, content words typically begin with a stressed syllable. To discover this regularity, infants need to identify a set of words. We propose that statistical learning plays two roles in this process. First, it provides a cue that allows infants to segment words from fluent speech, even without language-specific phonological knowledge. Second, once infants have identified a set of lexical forms, they can learn from the distribution of acoustic features across those word forms. The current experiments demonstrate both processes are available to 5-month-old infants. This demonstration of sensitivity to statistical structure in speech, weighted more heavily than phonological cues to segmentation at an early age, is consistent with theoretical accounts that claim statistical learning plays a role in helping infants to adapt to the structure of their native language from very early in life. PMID:23335903

  18. Discovering Words in Fluent Speech: The Contribution of Two Kinds of Statistical Information

    Directory of Open Access Journals (Sweden)

    Erik D Thiessen

    2013-01-01

    Full Text Available To efficiently segment fluent speech, infants must discover the predominant phonological form of words in the native language. In English, for example, content words typically begin with a stressed syllable. To discover this regularity, infants need to identify a set of words. We propose that statistical learning plays two roles in this process. First, it provides a cue that allows infants to segment words from fluent speech, even without language-specific phonological knowledge. Second, once infants have identified a set of lexical forms, they can learn from the distribution of acoustic features across those word forms. The current experiments demonstrate both processes are available to 5-month-old infants. This is an earlier age than prior demonstration of sensitivity to statistical structure in speech, and consistent with theoretical accounts that claim statistical learning plays a role in helping infants to adapt to the structure of their native language from very early in life.

  19. An early sophisticated East Polynesian voyaging canoe discovered on New Zealand's coast.

    Science.gov (United States)

    Johns, Dilys A; Irwin, Geoffrey J; Sung, Yun K

    2014-10-14

    The colonization of the islands of East Polynesia was a remarkable episode in the history of human migration and seafaring. We report on an ocean-sailing canoe dating from close to that time. A large section of a complex composite canoe was discovered recently at Anaweka on the New Zealand coast. The canoe dates to approximately A.D. 1400 and was contemporary with continuing interisland voyaging. It was built in New Zealand as an early adaptation to a new environment, and a sea turtle carved on its hull makes symbolic connections with wider Polynesian culture and art. We describe the find and identify and radiocarbon date the construction materials. We present a reconstruction of the whole canoe and compare it to another early canoe previously discovered in the Society Islands.

  20. Incidentally found and unexpected tumors discovered by MRI examination for temporomandibular joint arthrosis

    Energy Technology Data Exchange (ETDEWEB)

    Yanagi, Yoshinobu; Asaumi, Jun-ichi E-mail: asaumi@md.okayama-u.ac.jp; Maki, Yuu; Murakami, Jun; Hisatomi, Miki; Matsuzaki, Hidenobu; Konouchi, Hironobu; Honda, Yosutoshi; Kishi, Kanji

    2003-07-01

    We examined the frequency of incidentally found or unexpected tumors discovered at the time of magnetic resonance imaging (MRI) examinations in the temporomandibular joint (TMJ) region for patients with suspicion of TMJ arthrosis. Five MR images (T1-weighted transverse scout image and proton density and T2-weighted oblique sagittal images at the open and closed mouth) were acquired. In 2776 MRI examinations of TMJ arthrosis, two tumors were discovered. They consisted of an adenoid cystic carcinoma in the deep portion of the parotid gland, and a malignant tumor extending from the infratemporal fossa to the parapharyngeal space. The rate of incidentally founded or unexpected tumors in TMJ examinations was low (0.072%), but the two tumors found were malignant tumors, and therefore, scout image should be carefully examined, not only used for positing the slice.

  1. Discovering novel neuroactive drugs through high-throughput behavior-based chemical screening in the zebrafish

    Directory of Open Access Journals (Sweden)

    Giancarlo eBruni

    2014-07-01

    Full Text Available Most neuroactive drugs were discovered through unexpected behavioral observations. Systematic behavioral screening is inefficient in most model organisms. But, automated technologies are enabling a new phase of discovery-based research in central nervous system (CNS pharmacology. Researchers are using large-scale behavior based chemical screens in zebrafish to discover compounds with new structures, targets and functions. These compounds are powerful tools for understanding CNS signaling pathways. Substantial differences between human and zebrafish biology will make it difficult to translate these discoveries to clinical medicine. However, given the molecular genetic similarities between humans and zebrafish, it is likely that some of these compounds will have translational utility. We predict that the greatest new successes in CNS drug discovery will leverage many model systems, including in vitro assays, cells, rodents, and zebrafish.

  2. Fitting a mixture model by expectation maximization to discover motifs in biopolymers

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, T.L.; Elkan, C. [Univ. of California, La Jolla, CA (United States)

    1994-12-31

    The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences. Multiple motifs are found by fitting a mixture model to the data, probabilistically erasing the occurrences of the motif thus found, and repeating the process to find successive motifs. The algorithm requires only a set of unaligned sequences and a number specifying the width of the motifs as input. It returns a model of each motif and a threshold which together can be used as a Bayes-optimal classifier for searching for occurrences of the motif in other databases. The algorithm estimates how many times each motif occurs in each sequence in the dataset and outputs an alignment of the occurrences of the motif. The algorithm is capable of discovering several different motifs with differing numbers of occurrences in a single dataset.

  3. Chemical Abundance Measurements of Ultra-Faint Dwarf Galaxies Discovered by the Dark Energy Survey

    Science.gov (United States)

    Nagasawa, Daniel; Marshall, Jennifer L.; Simon, Joshua D.; Hansen, Terese; Li, Ting; Bernstein, Rebecca; Balbinot, Eduardo; Drlica-Wagner, Alex; Pace, Andrew; Strigari, Louis; Pellegrino, Craig; DePoy, Darren L.; Suntzeff, Nicholas; Bechtol, Keith; Dark Energy Suvey

    2018-01-01

    We present chemical abundance analysis results derived from high-resolution spectroscopy of ultra-faint dwarfs discovered by the Dark Energy Survey. Ultra-faint dwarf galaxies preserve a fossil record of the chemical abundance patterns imprinted by the first stars in the Universe. High-resolution spectroscopic observations of member stars in several recently discovered Milky Way satellites reveal a range of abundance patterns among ultra-faint dwarfs suggesting that star formation processes in the early Universe were quite diverse. The chemical content provides a glimpse not only of the varied nucleosynthetic processes and chemical history of the dwarfs themselves, but also the environment in which they were formed. We present the chemical abundance analysis of these objects and discuss possible explanations for the observed abundance patterns.

  4. Selective flower abortion maintains moth cooperation in a newly discovered pollination mutualism.

    Science.gov (United States)

    Goto, Ryutaro; Okamoto, Tomoko; Kiers, E Toby; Kawakita, Atsushi; Kato, Makoto

    2010-03-01

    The evolutionary stability of mutualisms is enhanced when partners possess mechanisms to prevent overexploitation by one another. In obligate pollination-seed consumption mutualisms, selective abortion of flowers containing excessive eggs represents one such mechanism, but empirical tests have long been limited to the yucca-yucca moth mutualism. We present evidence for selective abortion in the recently discovered mutualism between Glochidion trees and Epicephala moths. In Glochidion acuminatum, proportion of aborted flowers progressively increased both with higher egg load and increased ovule damage. Selective abortion resulted in a 16% seed production increase compared with expectations under random abortion, and moths suffered fitness losses as high as 62% when ovipositing into pre-infested flowers. Moth eggs were laid singly more often than expected under random oviposition, thus avoiding potential disadvantages from multiple infestations. As new pollination mutualisms are being discovered, selective abortion mechanisms may prove to be more widespread than previously thought.

  5. A Trip to the Cataclysmic Binary Zoo: Detailed Follow-up of 35 Recently Discovered Systems

    Science.gov (United States)

    Thorstensen, John R.; Alper, Erek H.; Weil, Kathryn E.

    2016-12-01

    We report follow-up studies of 35 recently discovered cataclysmic variables (CVs), 32 of which were found in large, automated synoptic sky surveys. The objects were selected for observational tractability. For 34 of the objects, we present mean spectra and spectroscopic orbital periods, and for one more we give an eclipse-based period. Thirty-two of the period determinations are new, and three of these refine published estimates based on superhump periods. The remaining three of our determinations confirm previously published periods. Twenty of the stars are confirmed or suspected dwarf novae with periods shorter than 3 hr, but we also find three apparent polars (AM Her stars) and six systems with P\\gt 5 {hr}. Five of these systems have secondary stars visible in their spectra, from which we estimate distances when possible. The orbital period distribution of this sample is very similar to that of previously discovered CVs.

  6. Novel therapeutics for Stargardt disease.

    Science.gov (United States)

    Lu, Louise J; Liu, Ji; Adelman, Ron A

    2017-06-01

    Stargardt disease, an inherited macular dystrophy caused by mutations in the ABCA4 gene encoding a retinal transporter protein, is the most prevalent form of macular degeneration in children. Patients with Stargardt disease develop severe vision loss within their first or second decades of life, which progresses to irreversible decreased visual acuity in almost all cases. Presently, there are no standard treatments for Stargardt disease. However, encouraging progress has been made in the development of innovative approaches to preventing vision loss in Stargardt patients. Among the promising treatment candidates include ALK-001, fenretinide, and A1120 as pharmacological agents to modulate the visual cycle, StarGen(TM) as a vector for supplementation of a functional ABCA4 gene, and stem-cell transplantation of hESC-RPE cells for regeneration of the retinal pigment epithelium. This study aims to systematically review and summarize evidence concerning the most up-to-date developments in pharmacologic, gene, and stem-cell therapies as novel therapeutic strategies to improve vision for patients with Stargardt disease.

  7. Therapeutic plasma exchange in Casablanca.

    Science.gov (United States)

    Tazi, I; Merimi, F; Majd, A; Benchemsi, N

    2008-08-01

    Therapeutic plasma exchange (TPE) is an extracorporeal blood purification method for the treatment of diseases in which pathological proteins have to be eliminated. In the aim to demonstrate our single center activity, we analyzed our data since 2 years. Between years 2002 and 2005, 104 TPE procedures were performed on 42 patients. Median age and male/female ratio were 32 (range, 17-56) and 24/18, respectively. Departments those referred the majority of the TPE were neurology (n=32), nephrology (n=5) and intensive care unit (n=5). The most common indications were: polyradiculoneuropathies (53%), myasthenia gravis (17%) and Guillain-Barré syndrome (12%). The median TPE procedure per patient was 2.3 (range, 1-10). In the majority of patients, vascular access was provided by puncture of two large, durable peripheral antecubital veins. The procedures were performed with the "Haemonetic Ultralight" discontinuous flow cell separator devices. Citrate solution was used as an anticoagulant in all cases. The substitution fluids most often used in our unit are Albumin 20% solution (92 times), Albumin 4% (10 times) and fresh frozen plasma (twice). Seventy five percent of the patients showed improvement, 7% remained the same and 18% worsened. Thirteen adverse reactions were recorded. The creation of a national registry by the local society is a vital move to improve TPE practice in our country.

  8. Therapeutic drug monitoring: antiarrhythmic drugs

    Science.gov (United States)

    Campbell, T J; Williams, K M

    1998-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the β-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:9803978

  9. Therapeutic outcomes of retinal hemangioblastomas.

    Science.gov (United States)

    Kim, Hyesun; Yi, Jeong H; Kwon, Hee J; Lee, Christopher S; Lee, Sung C

    2014-12-01

    To report the results of treatments and therapeutic complications of retinal hemangioblastomas (RH). Retrospective consecutive case series. Data from 32 patients (37 eyes) with RH were reviewed for characteristics of RH and treatment outcomes. Among 32 patients, we identified 73 RHs in 37 eyes. At baseline, 24 of 37 eyes (65%) had 20/50 visual acuity or better, 8 eyes (22%) had intermediate vision (20/400-20/50), and 5 eyes (13%) had poor vision (≤20/400). Seven RHs (9.6%) were located in the juxtapapillary area, and 66 RHs (90.4%) were located in peripheral area. Small RHs (54.8%; thermotherapy, and large RHs (20.5%; >3.0 mm in size) were treated with a combination of transpupillary thermotherapy and cryotherapy. After treatment, 90% of small RHs regressed, whereas only 67% of large RHs regressed (P = 0.044). Peripheral RHs showed better response to treatment than juxtapapillary RHs (P = 0.010). Treatment-related complications occurred in 5 eyes (14%), and 1-step combination therapy was applied more frequently in the complication group (P = 0.048). Small RHs in peripheral areas may require aggressive treatment because they respond well to treatment. In larger RHs, staged treatment could reduce treatment-related complications. Transpupillary thermotherapy could be an effective method in tumor regression for moderate-to-large-sized RHs showing tumor regression rate of 70%.

  10. [Probiotics and their therapeutic properties].

    Science.gov (United States)

    Ochmański, W; Barabasz, W

    1999-01-01

    Probiotics are specific products of microorganisms, and by being biologically active positively act on stabilizing the bacteriological flora of the gastrointestinal tract. They are live or lyophilized bacterial cultures, especially those derived from lactic fermentation (Lactobacillacea and Streptococcacea). The first to use the term probiotics were Lilly and Stillwell in 1965 when referring to substances produced by protozoa, which in turn stimulated the growth of other organisms. Probiotics are devoid of side affects and do not cause accumulation of toxic substances in the body. They are administered for therapeutic, prophylactic and nutritional purposes both in humans and in animals. Interest into probiotics has been spurred on by the growing abundance of civilization disorders such as neoplasms, atherosclerosis, heart disease, hypertension and HIV infection. Probiotics are potentially capable of annihilating these disorders. Starter cultures are pure mixed bacterial, fungal or mold cultures which by transformation of their metabolism faciliate favourable changes in apperance, aroma, consistency, and durability of foodstuffs. Contemporary knowledge concerning probiotics and their action is derived from many years of tradition in consumption of fermented milk products and the documentation of much research into strains of lactic bacteria, their harmless action on health and overall beneficial effect.

  11. Recent advances in rhinovirus therapeutics.

    Science.gov (United States)

    Charles, Catherine H; Yelmene, Michele; Luo, Guang X

    2004-12-01

    Human rhinoviruses are the major causative agents of the common cold. Because there are greater than 100 viral serotypes, little immunological protection is afforded to humans by prior rhinovirus exposure, which accounts for the high incidence of infection. In most cases, rhinovirus leads to a short self-limiting illness. However, for asthmatics, the elderly and immunocompromised patients, rhinovirus infection can lead to life-threatening complications. This has spurred a consistent effort over recent decades to identify effective treatments and preventions for rhinovirus infection. While some work has focused on alleviating the symptoms induced as a result of inflammatory pathways stimulated by rhinoviruses, the majority of the research has been focused on limiting or preventing viral infection altogether. Various approaches have been taken to halt rhinovirus infection. Prevention of virus-cell interaction has been the aim of research on viral capsid binders and cell receptor blockers. Interference with correct viral protein processing is the goal of the design and testing of protease inhibitors. Current work is attempting to interfere with viral RNA replication by testing silencing RNA molecules. In this review, we will discuss recent advances in the development and testing of human rhinovirus therapeutics.

  12. Melasma. Etiologic and therapeutic considerations.

    Science.gov (United States)

    Grimes, P E

    1995-12-01

    Melasma is a common acquired symmetric hypermelanosis characterized by irregular light- to gray-brown macules and patches involving sun-exposed areas of skin. Etiologic factors in the pathogenesis of melasma include genetic influences, exposure to UV radiation, pregnancy, hormonal therapies, cosmetics, phototoxic drugs, and antiseizure medications. Melasma is often a therapeutically challenging disease, and current treatments include hypopigmenting agents, chemical peels, and lasers. Hypopigmenting agents include phenolic and nonphenolic derivatives. Phenolic agents include hydroquinone and hydroquinone combination preparations. Despite controversies regarding the issue of hydroquinone-induced ochronosis, hydroquinone remains the most effective topically applied bleaching agent approved by the Food and Drug Administration for the treatment of melasma. Nonphenolic bleaching agents include tretinoin and azelaic acid. Superficial, medium, and deep chemical peels are more often used in lighter-complexioned patients. Such peels should be used with caution in blacks. Although lasers have demonstrated significant efficacy in the treatment of a variety of hyperpigmentary disorders, their precise efficacy and place in the therapy of melasma have yet to be established. In the hierarchy of therapies for melasma, the treating physician must consider the devastating psychosocial impact of pigmentary imperfections within the realm of the benefits and risks associated with each treatment.

  13. Discovering approximate-associated sequence patterns for protein-DNA interactions

    KAUST Repository

    Chan, Tak Ming

    2010-12-30

    Motivation: The bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) are fundamental protein-DNA interactions in transcriptional regulation. Extensive efforts have been made to better understand the protein-DNA interactions. Recent mining on exact TF-TFBS-associated sequence patterns (rules) has shown great potentials and achieved very promising results. However, exact rules cannot handle variations in real data, resulting in limited informative rules. In this article, we generalize the exact rules to approximate ones for both TFs and TFBSs, which are essential for biological variations. Results: A progressive approach is proposed to address the approximation to alleviate the computational requirements. Firstly, similar TFBSs are grouped from the available TF-TFBS data (TRANSFAC database). Secondly, approximate and highly conserved binding cores are discovered from TF sequences corresponding to each TFBS group. A customized algorithm is developed for the specific objective. We discover the approximate TF-TFBS rules by associating the grouped TFBS consensuses and TF cores. The rules discovered are evaluated by matching (verifying with) the actual protein-DNA binding pairs from Protein Data Bank (PDB) 3D structures. The approximate results exhibit many more verified rules and up to 300% better verification ratios than the exact ones. The customized algorithm achieves over 73% better verification ratios than traditional methods. Approximate rules (64-79%) are shown statistically significant. Detailed variation analysis and conservation verification on NCBI records demonstrate that the approximate rules reveal both the flexible and specific protein-DNA interactions accurately. The approximate TF-TFBS rules discovered show great generalized capability of exploring more informative binding rules. © The Author 2010. Published by Oxford University Press. All rights reserved.

  14. Using Electronic Patient Records to Discover Disease Correlations and Stratify Patient Cohorts

    DEFF Research Database (Denmark)

    Roque, Francisco S.; Jensen, Peter B.; Schmock, Henriette

    2011-01-01

    Electronic patient records remain a rather unexplored, but potentially rich data source for discovering correlations between diseases. We describe a general approach for gathering phenotypic descriptions of patients from medical records in a systematic and non-cohort dependent manner. By extracti...... Classification of Disease ontology and is therefore in principle language independent. As a use case we show how records from a Danish psychiatric hospital lead to the identification of disease correlations, which subsequently can be mapped to systems biology frameworks....

  15. Quasiparticle excitations in newly discovered antiperovskite superconductor ZnNNi{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Ohishi, Kazuki, E-mail: kazuki.ohishi@riken.j [Advanced Meson Science Laboratory, Nishina Center for Accelerator-Based Science, RIKEN, Wako 351-0198 (Japan); Ito, Takashi U.; Higemoto, Wataru [Advanced Science Research Center, Japan Atomic Energy Agency, Ibaraki 319-1195 (Japan); Yamazaki, Takahiro; Uehara, Akira; Kozawa, Katsuya; Kimishima, Yoshihide; Uehara, Masatomo [Department of Physics, Faculty of Engineering, Yokohama National University, Yokohama 240-8501 (Japan)

    2010-12-15

    We report on transverse field muon spin rotation measurements of the superconducting penetration depth {lambda} in newly discovered antiperovskite superconductor ZnNNi{sub 3} in order to investigate the symmetry of order parameter. The penetration depth at T = 0 K is estimated to be {lambda}(0) 362(2) nm. Temperature dependence of muon spin relaxation rate {sigma}{sub v} shows {approx}T{sup 2} dependence, suggesting unconventional superconductor.

  16. A new hard X-ray transient discovered by INTEGRAL: IGR J17559-2612

    DEFF Research Database (Denmark)

    Esposito, V.; Ferrigno, C.; Bozzo, E.

    2012-01-01

    INTEGRAL discovered a new hard X-ray transient, IGR J17559-2612, during the Galactic center observations performed from 2012-08-14 00:02:14 to 2012-08-14 14:45:54 UTC. The source is detected in the IBIS/ISGRI mosaic at a significance level of 8 σ (observation good time: 50 ks) both in the 20-40 k...

  17. Development of a global land cover characteristics database and IGBP DISCover from 1 km AVHRR data

    Science.gov (United States)

    Loveland, T.R.; Reed, B.C.; Brown, J.F.; Ohlen, D.O.; Zhu, Z.; Yang, L.; Merchant, J.W.

    2000-01-01

    Researchers from the U.S. Geological Survey, University of Nebraska-Lincoln and the European Commission's Joint Research Centre, Ispra, Italy produced a 1 km resolution global land cover characteristics database for use in a wide range of continental-to global-scale environmental studies. This database provides a unique view of the broad patterns of the biogeographical and ecoclimatic diversity of the global land surface, and presents a detailed interpretation of the extent of human development. The project was carried out as an International Geosphere-Biosphere Programme, Data and Information Systems (IGBP-DIS) initiative. The IGBP DISCover global land cover product is an integral component of the global land cover database. DISCover includes 17 general land cover classes defined to meet the needs of IGBP core science projects. A formal accuracy assessment of the DISCover data layer will be completed in 1998. The 1 km global land cover database was developed through a continent-by-continent unsupervised classification of 1 km monthly Advanced Very High Resolution Radiometer (AVHRR) Normalized Difference Vegetation Index (NDVI) composites covering 1992-1993. Extensive post-classification stratification was necessary to resolve spectral/temporal confusion between disparate land cover types. The complete global database consists of 961 seasonal land cover regions that capture patterns of land cover, seasonality and relative primary productivity. The seasonal land cover regions were aggregated to produce seven separate land cover data sets used for global environmental modelling and assessment. The data sets include IGBP DISCover, U.S. Geological Survey Anderson System, Simple Biosphere Model, Simple Biosphere Model 2, Biosphere-Atmosphere Transfer Scheme, Olson Ecosystems and Running Global Remote Sensing Land Cover. The database also includes all digital sources that were used in the classification. The complete database can be sourced from the website: http://edcwww.cr.usgs.gov/landdaac/glcc/glcc.html.

  18. Tools to discover anionic and nonionic polyfluorinated alkyl surfactants by liquid chromatography electrospray ionisation mass spectrometry

    DEFF Research Database (Denmark)

    Trier, Xenia; Granby, Kit; Christensen, Jan H.

    2011-01-01

    such as [M−H+solvent]− and [(M−H)(M−H+Na)n]− were used to confirm the identity of the precursor ions. In relation to quantification of PFASs, we discuss how their surfactancy influence the ESI processes, challenge their handling in solution and choices of precursor-to-product ions for MSMS of e.......g., structural PFAS isomers. The method has been used to discover PFASs in industrial blends and in extracts from food contact materials....

  19. Mining Low-Variance Biclusters to Discover Coregulation Modules in Sequencing Datasets

    OpenAIRE

    Zhen Hu; Raj Bhatnagar

    2012-01-01

    High-throughput sequencing (CHIP-Seq) data exhibit binding events with possible binding locations and their strengths, followed by interpretation of the locations of peaks. Recent methods tend to summarize all CHIP-Seq peaks detected within a limited up and down region of each gene into one real-valued score in order to quantify the probability of regulation in a region. Applying subspace clustering techniques on these scores can help discover important knowledge such as the potential co-regu...

  20. GeoWeb Crawler: An Extensible and Scalable Web Crawling Framework for Discovering Geospatial Web Resources

    Directory of Open Access Journals (Sweden)

    Chih-Yuan Huang

    2016-08-01

    Full Text Available With the advance of the World-Wide Web (WWW technology, people can easily share content on the Web, including geospatial data and web services. Thus, the “big geospatial data management” issues start attracting attention. Among the big geospatial data issues, this research focuses on discovering distributed geospatial resources. As resources are scattered on the WWW, users cannot find resources of their interests efficiently. While the WWW has Web search engines addressing web resource discovery issues, we envision that the geospatial Web (i.e., GeoWeb also requires GeoWeb search engines. To realize a GeoWeb search engine, one of the first steps is to proactively discover GeoWeb resources on the WWW. Hence, in this study, we propose the GeoWeb Crawler, an extensible Web crawling framework that can find various types of GeoWeb resources, such as Open Geospatial Consortium (OGC web services, Keyhole Markup Language (KML and Environmental Systems Research Institute, Inc (ESRI Shapefiles. In addition, we apply the distributed computing concept to promote the performance of the GeoWeb Crawler. The result shows that for 10 targeted resources types, the GeoWeb Crawler discovered 7351 geospatial services and 194,003 datasets. As a result, the proposed GeoWeb Crawler framework is proven to be extensible and scalable to provide a comprehensive index of GeoWeb.

  1. Using semantic and structural properties of the Unified Medical Language System to discover potential terminological relationships.

    Science.gov (United States)

    Patel, Chintan O; Cimino, James J

    2009-01-01

    To use the semantic and structural properties in the Unified Medical Language System (UMLS) Metathesaurus to characterize and discover potential relationships. The UMLS integrates knowledge from several biomedical terminologies. This knowledge can be used to discover implicit semantic relationships between concepts. In this paper, the authors propose a problem-independent approach for discovering potential terminological relationships that employs semantic abstraction of indirect relationship paths to perform classification and analysis of network theoretical measures such as topological overlap, preferential attachment, graph partitioning, and number of indirect paths. Using different versions of the UMLS, the authors evaluate the proposed approach's ability to predict newly added relationships. Classification accuracy, precision-recall. Strong discriminative characteristics were observed with a semantic abstraction based classifier (classification accuracy of 91%), the average number of indirect paths, preferential attachment, and graph partitioning to identify potential relationships. The proposed relationship prediction algorithm resulted in 56% recall in top 10 results for new relationships added to subsequent versions of the UMLS between 2005 and 2007. The UMLS has sufficient knowledge to enable discovery of potential terminological relationships.

  2. Mutations, associated with early-onset Alzheimer's disease, discovered in Asian countries.

    Science.gov (United States)

    Bagyinszky, Eva; Youn, Young Chul; An, Seong Soo A; Kim, SangYun

    2016-01-01

    Alzheimer's disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People's Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People's Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.

  3. Using data mining techniques on discovering physician practice patterns regarding to medication prescription - an exploratory study.

    Science.gov (United States)

    Feng, Jianzhou; Shen, Weijia; Cao, Feng; Ni, Yuan; Cai, Peng; Sun, Wen; Li, Xiang

    2013-01-01

    In this paper, we propose a data mining method for exploring the decision-making processes of physicians from electronic patient records and test it on the medical records of patients with type-2 diabetes mellitus. This method runs in two modes: general and partitioned. In the general mode, it mines rules from the whole medical records. In the partitioned mode, with a given partition factor, medical records are assigned into categories and a corresponding set of rules will be discovered for each category. Medication prescription predictions can be provided based on these rules. By comparing mined rules and prescription prediction accuracy under different modes, we discover that: 1) both the averaged precision and recall rate of the general mode can reach around 80%; 2) physicians tend to conform to the guideline instead of having their own preferences; 3) the medication decision can be affected by some hidden factors. These findings suggest this method show promise in discovering physician practice patterns and obtaining insights from real medical records.

  4. Discovering Multimodal Behavior in Ms. Pac-Man through Evolution of Modular Neural Networks.

    Science.gov (United States)

    Schrum, Jacob; Miikkulainen, Risto

    2016-03-12

    Ms. Pac-Man is a challenging video game in which multiple modes of behavior are required: Ms. Pac-Man must escape ghosts when they are threats and catch them when they are edible, in addition to eating all pills in each level. Past approaches to learning behavior in Ms. Pac-Man have treated the game as a single task to be learned using monolithic policy representations. In contrast, this paper uses a framework called Modular Multi-objective NEAT (MM-NEAT) to evolve modular neural networks. Each module defines a separate behavior. The modules are used at different times according to a policy that can be human-designed (i.e. Multitask) or discovered automatically by evolution. The appropriate number of modules can be fixed or discovered using a genetic operator called Module Mutation. Several versions of Module Mutation are evaluated in this paper. Both fixed modular networks and Module Mutation networks outperform monolithic networks and Multitask networks. Interestingly, the best networks dedicate modules to critical behaviors (such as escaping when surrounded after luring ghosts near a power pill) that do not follow the customary division of the game into chasing edible and escaping threat ghosts. The results demonstrate that MM-NEAT can discover interesting and effective behavior for agents in challenging games.

  5. Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    2017-01-01

    Full Text Available Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model.

  6. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  7. Emerging therapeutic strategies for obesity.

    Science.gov (United States)

    Foster-Schubert, Karen E; Cummings, David E

    2006-12-01

    The rising tide of obesity is one of the most pressing health issues of our time, yet existing medicines to combat the problem are disappointingly limited in number and effectiveness. Fortunately, a recent burgeoning of mechanistic insights into the neuroendocrine regulation of body weight provides an expanding list of molecular targets for novel, rationally designed antiobesity pharmaceuticals. In this review, we articulate a set of conceptual principles that we feel could help prioritize among these molecules in the development of obesity therapeutics, based on an understanding of energy homeostasis. We focus primarily on central targets, highlighting selected strategies to stimulate endogenous catabolic signals or inhibit anabolic signals. Examples of the former approach include methods to enhance central leptin signaling through intranasal leptin delivery, use of superpotent leptin-receptor agonists, and mechanisms to increase leptin sensitivity by manipulating SOCS-3, PTP-1B, ciliary neurotrophic factor, or simply by first losing weight with traditional interventions. Techniques to augment signaling by neurochemical mediators of leptin action that lie downstream of at least some levels of obesity-associated leptin resistance include activation of melanocortin receptors or 5-HT2C and 5-HT1B receptors. We also describe strategies to inhibit anabolic molecules, such as neuropeptide Y, melanin-concentrating hormone, ghrelin, and endocannabinoids. Modulation of gastrointestinal satiation and hunger signals is discussed as well. As scientists continue to provide fundamental insights into the mechanisms governing body weight, the future looks bright for development of new and better antiobesity medications to be used with diet and exercise to facilitate substantial weight loss.

  8. Therapeutic strategies in pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Leonello eFuso

    2011-04-01

    Full Text Available Pulmonary hypertension (PH is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an ideal therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

  9. Therapeutic Work with Children: A Contextual Overview

    Science.gov (United States)

    Robson, Maggie

    2010-01-01

    This overview sets therapeutic work with children in context. It begins with a rationale for why this work is necessary and describes and explores the needs and rights of children and young people. Resilience as a factor in mitigating the effects of distress is discussed and an overview of the history of therapeutic work is offered. Different…

  10. [A therapeutic education tool in paediatric dentistry].

    Science.gov (United States)

    Marquillier, Thomas; Trentesaux, Thomas; Catteau, Céline; Delfosse, Caroline

    Therapeutic education for children is developing in the treatment of dental caries. The Elmy pathway, a pedagogical game aiming to improve children's oral health skills, has been designed. The qualitative assessment of this tool seems to confirm its benefit for use in therapeutic education sessions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Translational nanomedicine : Through the therapeutic window

    NARCIS (Netherlands)

    Pierce, Robin

    2015-01-01

    Translational nanomedicine occurs only through the successful integration of multiple inputs and iterative modifications. The therapeutic window plays a pivotal role in the trajectory of translational nanomedicine. Often defined in terms of the range of dosage for safe and effective therapeutic

  12. Poetry and Therapeutic Factors in Group Therapy.

    Science.gov (United States)

    Goldstein, Marion

    1989-01-01

    Describes the ways in which the use of poetry in group therapy facilitates therapeutic goals consistent with interpersonal theory. Discusses the relationship between poetic interventions and I. D. Yalom's therapeutic factors, and offers a case example of an in-patient therapy group. (SR)

  13. Woodland in Practical Skills Therapeutic Education

    Science.gov (United States)

    Mata, Paula; Gibons, Kenneth; Mata, Fernando

    2016-01-01

    Modern urban life provides less opportunities to contact with nature, which is a potential cause of developmental deviances in children. We investigated the potential therapeutic effect of woodlands, within the context of Practical Skills Therapeutic Education at the Ruskin Mill College, UK. Data on physical and emotional perceptions were…

  14. The effects of therapeutic touch on pain.

    Science.gov (United States)

    Monroe, Carolyn Magdalen

    2009-06-01

    To better understand how Therapeutic Touch can be used in today's health care arena, this integrative literature review will examine current research that will help answer the question, Does Therapeutic Touch reduce pain? An extensive search was conducted of the online databases MEDLINE, CINAHL, Cochrane Library, EMBASE, PsychLIT, and PubMed to retrieve research articles published from 1997 to 2007. Seven studies that were conducted between 1997 and 2004 were found and only five of the seven were included as pertinent evidence to answer the question. All of the research that was reviewed to answer whether Therapeutic Touch could significantly reduce pain revealed a majority of statistically significant positive results for implementing this intervention. Because there are no identified risks to Therapeutic Touch as a pain relief measure, it is safe to recommend despite the limitations of current research. Therapeutic Touch should be considered among the many possible nursing interventions for the treatment of pain.

  15. [Health security--GMOs in therapeutics].

    Science.gov (United States)

    Trouvin, J-H

    2003-03-01

    The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.

  16. Therapeutic orchids: traditional uses and recent advances--an overview.

    Science.gov (United States)

    Hossain, Mohammad Musharof

    2011-03-01

    Orchids have been used as a source of medicine for millennia to treat different diseases and ailments including tuberculosis, paralysis, stomach disorders, chest pain, arthritis, syphilis, jaundice, cholera, acidity, eczema, tumour, piles, boils, inflammations, menstrual disorder, spermatorrhea, leucoderma, diahorrhea, muscular pain, blood dysentery, hepatitis, dyspepsia, bone fractures, rheumatism, asthma, malaria, earache, sexually transmitted diseases, wounds and sores. Besides, many orchidaceous preparations are used as emetic, purgative, aphrodisiac, vermifuge, bronchodilator, sex stimulator, contraceptive, cooling agent and remedies in scorpion sting and snake bite. Some of the preparations are supposed to have miraculous curative properties but rare scientific demonstration available which is a primary requirement for clinical implementations. Incredible diversity, high alkaloids and glycosides content, research on orchids is full of potential. Meanwhile, some novel compounds and drugs, both in phytochemical and pharmacological point of view have been reported from orchids. Linking of the indigenous knowledge to the modern research activities will help to discover new drugs much more effective than contemporary synthetic medicines. The present study reviews the traditional therapeutic uses of orchids with its recent advances in pharmacological investigations that would be a useful reference for plant drug researches, especially in orchids. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Bioengineering natural product biosynthetic pathways for therapeutic applications.

    Science.gov (United States)

    Wu, Ming-Cheng; Law, Brian; Wilkinson, Barrie; Micklefield, Jason

    2012-12-01

    With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Glioblastoma: Molecular Pathways, Stem Cells and Therapeutic Targets

    Energy Technology Data Exchange (ETDEWEB)

    Jhanwar-Uniyal, Meena, E-mail: meena_jhanwar@nymc.edu; Labagnara, Michael; Friedman, Marissa; Kwasnicki, Amanda; Murali, Raj [Department of Neurosurgery, New York Medical College, Valhalla, NY 10595 (United States)

    2015-03-25

    Glioblastoma (GBM), a WHO-defined Grade IV astrocytoma, is the most common and aggressive CNS malignancy. Despite current treatment modalities, the survival time remains dismal. The main cause of mortality in patients with this disease is reoccurrence of the malignancy, which is attributed to treatment-resistant cancer stem cells within and surrounding the primary tumor. Inclusion of novel therapies, such as immuno- and DNA-based therapy, may provide better means of treating GBM. Furthermore, manipulation of recently discovered non-coding microRNAs, some of which regulate tumor growth through the development and maintenance of GBM stem cells, could provide new prospective therapies. Studies conducted by The Cancer Genome Atlas (TCGA) also demonstrate the role of molecular pathways, specifically the activated PI3K/AKT/mTOR pathway, in GBM tumorigenesis. Inhibition of the aforementioned pathway may provide a more direct and targeted method to GBM treatment. The combination of these treatment modalities may provide an innovative therapeutic approach for the management of GBM.

  19. An ensemble heterogeneous classification methodology for discovering health-related knowledge in social media messages.

    Science.gov (United States)

    Tuarob, Suppawong; Tucker, Conrad S; Salathe, Marcel; Ram, Nilam

    2014-06-01

    The role of social media as a source of timely and massive information has become more apparent since the era of Web 2.0.Multiple studies illustrated the use of information in social media to discover biomedical and health-related knowledge.Most methods proposed in the literature employ traditional document classification techniques that represent a document as a bag of words.These techniques work well when documents are rich in text and conform to standard English; however, they are not optimal for social media data where sparsity and noise are norms.This paper aims to address the limitations posed by the traditional bag-of-word based methods and propose to use heterogeneous features in combination with ensemble machine learning techniques to discover health-related information, which could prove to be useful to multiple biomedical applications, especially those needing to discover health-related knowledge in large scale social media data.Furthermore, the proposed methodology could be generalized to discover different types of information in various kinds of textual data. Social media data is characterized by an abundance of short social-oriented messages that do not conform to standard languages, both grammatically and syntactically.The problem of discovering health-related knowledge in social media data streams is then transformed into a text classification problem, where a text is identified as positive if it is health-related and negative otherwise.We first identify the limitations of the traditional methods which train machines with N-gram word features, then propose to overcome such limitations by utilizing the collaboration of machine learning based classifiers, each of which is trained to learn a semantically different aspect of the data.The parameter analysis for tuning each classifier is also reported. Three data sets are used in this research.The first data set comprises of approximately 5000 hand-labeled tweets, and is used for cross validation of the

  20. Screening Libraries of Semifluorinated Arylene Bisimides to Discover and Predict Thermodynamically Controlled Helical Crystallization.

    Science.gov (United States)

    Ho, Ming-Shou; Partridge, Benjamin E; Sun, Hao-Jan; Sahoo, Dipankar; Leowanawat, Pawaret; Peterca, Mihai; Graf, Robert; Spiess, Hans W; Zeng, Xiangbing; Ungar, Goran; Heiney, Paul A; Hsu, Chain-Shu; Percec, Virgil

    2016-12-12

    Synthesis, structural, and retrostructural analysis of a library containing 16 self-assembling perylene (PBI), 1,6,7,12-tetrachloroperylene (Cl 4 PBI), naphthalene (NBI), and pyromellitic (PMBI) bisimides functionalized with environmentally friendly AB 3 chiral racemic semifluorinated minidendrons at their imide groups via m = 0, 1, 2, and 3 methylene units is reported. These semifluorinated compounds melt at lower temperatures than homologous hydrogenated compounds, permitting screening of all their thermotropic phases via structural analysis to discover thermodynamically controlled helical crystallization from propeller-like, cogwheel, and tilted molecules as well as lamellar-like structures. Thermodynamically controlled helical crystallization was discovered for propeller-like PBI, Cl 4 PBI and NBI with m = 0. Unexpectedly, assemblies of twisted Cl 4 PBIs exhibit higher order than those of planar PBIs. PBI with m = 1, 2, and 3 form a thermodynamically controlled columnar hexagonal 2D lattice of tilted helical columns with intracolumnar order. PBI and Cl 4 PBI with m = 1 crystallize via a recently discovered helical cogwheel mechanism, while NBI and PMBI with m = 1 form tilted helical columns. PBI, NBI and PMBI with m = 2 generate lamellar-like structures. 3D and 2D assemblies of PBI with m = 1, 2, and 3, NBI with m = 1 and PMBI with m = 2 exhibit 3.4 Å π-π stacking. The library approach applied here and in previous work enabled the discovery of six assemblies which self-organize via thermodynamic control into 3D and 2D periodic arrays, and provides molecular principles to predict the supramolecular structure of electronically active components.

  1. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

    Science.gov (United States)

    Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

    2013-01-01

    Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

  2. Fine-scale WRF-CMAQ Modeling for the 2013 DISCOVER-AQ Campaign in California

    Science.gov (United States)

    Gilliam, R. C.; Pleim, J. E.; Appel, W.

    2014-12-01

    Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ) is an ongoing four year NASA campaign to improve remote sensing in order to better resolve the distribution of pollutants in the lower atmosphere for public health reasons. These observational campaigns are a prime opportunity to evaluate and improve weather and air quality models, in particular the finer scales, since the collected observations are not only unique (boundary layer profiles, planetary boundary layer height and LIDAR), but of high spatial density. For the first campaign in the Washington DC-Baltimore region, a number of meteorological model improvements were crucial for quality results at the finer grid scales. The main techniques tested in the DISCOVER-AQ Washington DC-Baltimore experiment were iterative indirect soil nudging, a simple urban parameterization based on highly resolved impervious surface data, and the use of a high resolution 1 km sea surface temperature dataset. A fourth technique, first tested in a separate cold season application in the US Rocky Mountains, was the assimilation of high resolution 1 km SNOw Data Assimilation System (SNODAS) data for better snow cover representation in retrospective modeling. These methods will be leveraged using a nested 12-4-2 km WRF-CMAQ modeling platform for the 2013 DISCOVER-AQ California campaign where the 2 km domain covers the entire San Joaquin Valley (SJV), coastal areas and all of Los Angeles. The purpose is to demonstrate methods to derive high quality meteorology for retrospective air quality modeling over geographically complex areas of the Western US where current coarser resolution modeling may not be sufficient. Accurate air quality modeling is particularly important for California, which has some of the most polluted areas in the US, within the SJV. Furthermore, this work may inform modeling in other areas of the Intermountain West that are experiencing air

  3. New variable stars discovered in the fields of three Galactic open clusters using the VVV survey

    Science.gov (United States)

    Palma, T.; Minniti, D.; Dékány, I.; Clariá, J. J.; Alonso-García, J.; Gramajo, L. V.; Ramírez Alegría, S.; Bonatto, C.

    2016-11-01

    This project is a massive near-infrared (NIR) search for variable stars in highly reddened and obscured open cluster (OC) fields projected on regions of the Galactic bulge and disk. The search is performed using photometric NIR data in the J-, H- and Ks- bands obtained from the Vista Variables in the Vía Láctea (VVV) Survey. We performed in each cluster field a variability search using Stetson's variability statistics to select the variable candidates. Later, those candidates were subjected to a frequency analysis using the Generalized Lomb-Scargle and the Phase Dispersion Minimization algorithms. The number of independent observations range between 63 and 73. The newly discovered variables in this study, 157 in total in three different known OCs, are classified based on their light curve shapes, periods, amplitudes and their location in the corresponding color-magnitude (J -Ks ,Ks) and color-color (H -Ks , J - H) diagrams. We found 5 possible Cepheid stars which, based on the period-luminosity relation, are very likely type II Cepheids located behind the bulge. Among the newly discovered variables, there are eclipsing binaries, δ Scuti, as well as background RR Lyrae stars. Using the new version of the Wilson & Devinney code as well as the "Physics Of Eclipsing Binaries" (PHOEBE) code, we analyzed some of the best eclipsing binaries we discovered. Our results show that these studied systems turn out to be ranging from detached to double-contact binaries, with low eccentricities and high inclinations of approximately 80°. Their surface temperatures range between 3500 K and 8000 K.

  4. A Systematic Mid-Infrared Survey of A Sample of Tidal Disruption Events Discovered by ZTF

    Science.gov (United States)

    Yan, Lin; Van, Sjoert; Kulkarni, Shri; Kasliwal, Mansi; Gezari, Suvi; Cenko, Brad; Blagorodnova, Nadia; Hung, Tiara

    2017-12-01

    Zwicky Transient Facility (ZTF) saw its first light (press release on Nov 14, 2017) and is currently in the commissioning phase. The science operation is scheduled to start on Feb 1, 2018. Based on the data from Palomar Transient Factory (PTF), ZTF is expected to discover 30 new tidal disruption events (TDE) in the centers of galaxies containing supermassive blackholes. TDEs are rare transient events, and have only been discovered in recent years by large area transient surveys. Observations of optically discovered TDEs appear to show common characteristics, including blackbody temperatures of a few 10,000K, derived bolometric peak luminosities of several 10^43 - 10^44 erg/s, and photospheric radius of 10^15 - 10^16 cm. These properties are in conflict with the classic TDE model predictions, which suggest an order of magnitude higher temperature and peak luminosity. One proposed explanation is the possible existence of a reprocessing gas layer which absorbs X-ray, UV/optical photons and produces a cooler spectral energy distribution (SED). So far, there are only two published mid-IR light curves of TDEs, each with two epochal data. To solve this mystery, we require higher cadence Spitzer observations of a sample of uniformly selected TDEs. Next year is the only opportunity to obtain the critical observations because Spitzer is expected to operate only to March 2019. We request 24.1 hours of Spitzer time to observe 7 ZTF TDEs. This will produce a unique legacy dataset for many future studies of physics of TDEs.

  5. Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

    Science.gov (United States)

    Bagyinszky, Eva; Youn, Young Chul; An, Seong Soo A; Kim, SangYun

    2016-01-01

    Alzheimer’s disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention. PMID:27799753

  6. Identifying new therapeutic targets via modulation of protein corona formation by engineered nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rochelle R Arvizo

    Full Text Available We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development.Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF that is found exclusively on positively charged AuNPs ((+AuNPs after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells.We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer.

  7. Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

    Science.gov (United States)

    Arvizo, Rochelle R.; Giri, Karuna; Moyano, Daniel; Miranda, Oscar R.; Madden, Benjamin; McCormick, Daniel J.; Bhattacharya, Resham; Rotello, Vincent M.; Kocher, Jean-Pierre; Mukherjee, Priyabrata

    2012-01-01

    Background We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development. Methods/Principal Findings Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs (+AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to +AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells. Conclusion We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer. PMID:22442705

  8. Palomar Transient Factory Discovers Another Possible super- Chandrasekhar Type Ia Supernova

    Science.gov (United States)

    Nugent, P. E.; Howell, D. A.; Sullivan, M.; Suzuki, N.; Cucchiara, A.; Botyanszki, J.; Hsiao, E. Y.

    2010-10-01

    The Type Ia supernova science working group of the Palomar Transient Factory (ATEL#1964) reports the discovery of a possible super-Chandrasekhar mass supernova, PTF10xgx. The supernova is at RA = 00:12:23.15, Dec = +02:30:44.1 (J2000) in the galaxy identified as APMUKS(BJ) B000949.39+021401.7 (Maddox et al. 1990, MNRAS, 243, 692). The supernova was discovered and classified by Oarical, an autonomous software framework of the PTF collaboration, based on observations made with the Palomar 48-inch Oschin Schmidt telescope.

  9. Discovering novel causal patterns from biomedical natural-language texts using Bayesian nets.

    Science.gov (United States)

    Atkinson, John; Rivas, Alejandro

    2008-11-01

    Most of the biomedicine text mining approaches do not deal with specific cause--effect patterns that may explain the discoveries. In order to fill this gap, this paper proposes an effective new model for text mining from biomedicine literature that helps to discover cause--effect hypotheses related to diseases, drugs, etc. The supervised approach combines Bayesian inference methods with natural-language processing techniques in order to generate simple and interesting patterns. The results of applying the model to biomedicine text databases and its comparison with other state-of-the-art methods are also discussed.

  10. Building on the International Polar Year: Discovering Interdisciplinary Data Through Federated Search

    Directory of Open Access Journals (Sweden)

    L Yarmey

    2014-10-01

    Full Text Available The legacy of the International Polar Year 2007–2008 (IPY includes advances in open data and meaningful progress towards interoperability of data, systems, and standards. Enabled by metadata brokering technologies and by the growing adoption of international metadata standards, federated data search welcomes diversity in Arctic data and recognizes the value of expertise in community data repositories. Federated search enables specialized data holdings to be discovered by broader audiences and complements the role of metadata registries such as the Global Change Master Directory, providing interoperability across the Arctic web-of-repositories.

  11. A gymkhana to discover and generate curves in a cooperative work

    Directory of Open Access Journals (Sweden)

    Anna Vidal Meló

    2014-03-01

    Full Text Available The student who access the University understands a curve as a function represented by an equality involving the Cartesian variables x and y. But he does not know another great set of curves such as those described by parametric equations and polar coordinates. We show an experience developed in two consecutive courses in the first course of a bachelor's degree, which allows the students to discover and create many curves in parametric or polar representation, working in group. Also the experience facilitate the students to achieve several generic skills.

  12. Engineering reliability and maintainability review - A regimen for discovering production deficiencies

    Science.gov (United States)

    McKelvey, Michael H.; Babin, Robert S.

    An engineering reliability and maintainability review (ER&MR) is a methodical disassembly, visual inspection, and physical examination of a production unit of airborne equipment by a team of reviewers from reliability, maintainability, and other technical disciplines. Established at Douglas Aircraft for the DC-10 program and recently upgraded, ER&MR facilitates detection of unit design and assembly flaws and deficiencies that traditional design reviews and inspections may fail to discover. ER&MR also verifies required circuit separation and segregation in the unit and incorporation of unit design changes authorized by the critical design review team.

  13. Stem-Like Memory T Cells Are Discovered | Center for Cancer Research

    Science.gov (United States)

    T cells are the white blood cells that are the body’s first line of attack against foreign invaders.  When designing immunotherapies to treat cancer the goal is to prolong the immune response of T cells a bit beyond what the body normally does when a bacterium or a virus is encountered.   Nicholas P. Restifo, M.D., working with Luca Gattinoni, M.D., and other colleagues in CCR’s Surgery Branch recently discovered a subset within the human T cell population that may help clinicians to do just  this.

  14. Discover Earth: An earth system science program for libraries and their communities

    Science.gov (United States)

    Curtis, L.; Dusenbery, P.

    2010-12-01

    The view from space has deepened our understanding of Earth as a global, dynamic system. Instruments on satellites and spacecraft, coupled with advances in ground-based research, have provided us with astonishing new perspectives of our planet. Now more than ever, enhancing the public’s understanding of Earth’s physical and biological systems is vital to helping citizens make informed policy decisions especially when they are faced with the consequences of global climate change. In spite of this relevance, there are many obstacles to achieving broad public understanding of key earth system science (ESS) concepts. Strategies for addressing climate change can only succeed with the full engagement of the general public. As reported by U.S. News and World Report in 2010, small towns in rural America are emerging as the front line in the climate change debate in the country. The Space Science Institute’s National Center for Interactive Learning (NCIL) in partnership with the American Library Association (ALA), the Lunar and Planetary Institute (LPI), and the National Girls Collaborative Project (NGCP) have received funding from NSF to develop a national project called the STAR Library Education Network: a hands-on learning program for libraries and their communities (or STAR-Net for short). STAR stands for Science-Technology, Activities and Resources. There are two distinct components of STAR-Net: Discover Earth and Discover Tech. While the focus for education reform is on school improvement, there is considerable research that supports the role that out-of-school experiences can play in student achievement. Libraries provide an untapped resource for engaging underserved youth and their families in fostering an appreciation and deeper understanding of science and technology topics. The overarching goal of the project is to reach underserved youth and their families with informal STEM learning experiences. The Discover Earth part of STAR_Net will produce ESS

  15. Discovering genes-diseases associations from specialized literature using the grid.

    Science.gov (United States)

    Faro, Alberto; Giordano, Daniela; Maiorana, Francesco; Spampinato, Concetto

    2009-07-01

    This paper proposes a novel method for text mining on the Grid, aimed at pointing out hidden relationships for hypothesis generation and suitable for semi-interactive querying. The method is based on unsupervised clustering and the outputs are visualized with contextual information. Grid implementation is crucial for feasibility. We demonstrate it with a mining run for discovering genes-diseases associations from bibliographic sources and annotated databases. The proposed methodology is in view of a Grid architecture specialized in bioinformatics mining tasks. Some performance considerations are provided.

  16. Newly discovered sediment rock-hosted disseminated gold deposits in the People's Republic of China

    Science.gov (United States)

    Cunningham, Charles G.; Ashley, Roger P.; Chou, I. -Ming; Huang, Zushu; Chaoyuan, Wan; Li, Wenkang

    1988-01-01

    Five deposits discovered in Guizhou Province, Yata, Getang, Sanchahe, Ceyang, and Banqi are described for the first time in Western literature. The deposits have geologic features and geochemical signatures that are remarkably similar to those of sedimentary rock-hosted precious metal deposits in the United States. The sizes of the deposits are as yet undetermined, but they each contain significant reserves at average grades of 4 to 5 g of gold per metric ton. Exploration and drilling are in progress at all of the deposits, and other areas where the geologic setting and geochemical anomalies are similar are being tested.

  17. Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

    Science.gov (United States)

    Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

    2016-11-01

    In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially misfolded intermediates aggregate via the interaction with the complementary intermediates and consequently enhance oligomers formation that grows into fibrils and proto-fibrils. The amyloid fibrils for example, accumulate in the brain and central nervous system (CNS) as amyloid deposits in the Parkinson's disease (PD), Alzheimer's disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other neurodegenerative diseases. Treatment of such misfolding maladies is considered as one of the most important challenges of the 21st century. Currently, several treatments strategies have been and are being discovered. These therapeutic interventions partly reversed or prevented the pathological state. More recently, a new approach was discovered, which employs nanobodies that targets multisteps in fibril formation pathway that may possibly completely cure these misfolding diseases. Keeping the above views in mind in the current review, we have comprehensively discussed the different mechanisms underlying protein misfolding thereby leading to diseases conditions and their therapeutic interventions.

  18. Oncolytic Viruses: Therapeutics With an Identity Crisis.

    Science.gov (United States)

    Breitbach, Caroline J; Lichty, Brian D; Bell, John C

    2016-07-01

    Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a "one-size fits all" approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Oncolytic Viruses: Therapeutics With an Identity Crisis

    Directory of Open Access Journals (Sweden)

    Caroline J. Breitbach

    2016-07-01

    Full Text Available Oncolytic viruses (OV are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a “one-size fits all” approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.

  20. Group 9 organometallic compounds for therapeutic and bioanalytical applications.

    Science.gov (United States)

    Ma, Dik-Lung; Chan, Daniel Shiu-Hin; Leung, Chung-Hang

    2014-12-16

    CONSPECTUS: Compared with organic small molecules, metal complexes offer several distinct advantages as therapeutic agents or biomolecular probes. Carbon atoms are typically limited to linear, trigonal planar, or tetrahedral geometries, with a maximum of two enantiomers being formed if four different substituents are attached to a single carbon. In contrast, an octahedral metal center with six different substituents can display up to 30 different stereoisomers. While platinum- and ruthenium-based anticancer agents have attracted significant attention in the realm of inorganic medicinal chemistry over the past few decades, group 9 complexes (i.e., iridium and rhodium) have garnered increased attention in therapeutic and bioanalytical applications due to their adjustable reactivity (from kinetically liable to substitutionally inert), high water solubility, stability to air and moisture, and relative ease of synthesis. In this Account, we describe our efforts in the development of group 9 organometallic compounds of general form [M(C(∧)N)2(N(∧)N)] (where M = Ir, Rh) as therapeutic agents against distinct biomolecular targets and as luminescent probes for the construction of oligonucleotide-based assays for a diverse range of analytes. Earlier studies by researchers had focused on organometallic iridium(III) and rhodium(III) half-sandwich complexes that show promising anticancer activity, although their precise mechanisms of action still remain unknown. More recently, kinetically-inert group 9 complexes have arisen as fascinating alternatives to organic small molecules for the specific targeting of enzyme activity. Research in our laboratory has shown that cyclometalated octahedral rhodium(III) complexes were active against Janus kinase 2 (JAK2) or NEDD8-activating enzyme (NAE) activity, or against NO production leading to antivasculogenic activity in cellulo. At the same time, recent interest in the development of small molecules as modulators of protein

  1. A New Species of Frog (Anura: Dicroglossidae Discovered from the Mega City of Dhaka.

    Directory of Open Access Journals (Sweden)

    Mohammad Sajid Ali Howlader

    Full Text Available We describe a new species of frog of the genus Zakerana discovered from the urban core of Dhaka, Bangladesh, one of the most densely populated cities in the world. Although the new species is morphologically similar to the geographically proximate congeners in the Bangladeshi cricket frog group, we show that it can be distinguished from all congeners on the basis of morphological characters, advertisement calls and variation in two mitochondrial DNA genes (12S rRNA and 16S rRNA. Apart from several diagnostic differences in body proportions, the new species differs from other Zakerana species in having a flattened snout (from ventral view projecting over the lower jaw, and diagnostic trapezoid-shaped red markings on the vocal sac in males. Molecular genetic analyses show that the new species is highly divergent (3.1-20.1% sequence divergence from all congeneric species, and forms a well-supported clade with its sister species, Zakerana asmati. The discovery of a new amphibian species from the urban core of Dhaka together with several recent descriptions of new amphibian species from Bangladesh may indicate that more amphibian species remain to be discovered from this country.

  2. A New Species of Frog (Anura: Dicroglossidae) Discovered from the Mega City of Dhaka.

    Science.gov (United States)

    Howlader, Mohammad Sajid Ali; Nair, Abhilash; Merilä, Juha

    2016-01-01

    We describe a new species of frog of the genus Zakerana discovered from the urban core of Dhaka, Bangladesh, one of the most densely populated cities in the world. Although the new species is morphologically similar to the geographically proximate congeners in the Bangladeshi cricket frog group, we show that it can be distinguished from all congeners on the basis of morphological characters, advertisement calls and variation in two mitochondrial DNA genes (12S rRNA and 16S rRNA). Apart from several diagnostic differences in body proportions, the new species differs from other Zakerana species in having a flattened snout (from ventral view) projecting over the lower jaw, and diagnostic trapezoid-shaped red markings on the vocal sac in males. Molecular genetic analyses show that the new species is highly divergent (3.1-20.1% sequence divergence) from all congeneric species, and forms a well-supported clade with its sister species, Zakerana asmati. The discovery of a new amphibian species from the urban core of Dhaka together with several recent descriptions of new amphibian species from Bangladesh may indicate that more amphibian species remain to be discovered from this country.

  3. Discovering protein–DNA binding sequence patterns using association rule mining

    Science.gov (United States)

    Wong, Ka-Chun; Chan, Tak-Ming; Wong, Man-Hon; Lee, Kin-Hong; Lau, Chi-Kong; Tsui, Stephen K. W.

    2010-01-01

    Protein–DNA bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) play an essential role in transcriptional regulation. Over the past decades, significant efforts have been made to study the principles for protein–DNA bindings. However, it is considered that there are no simple one-to-one rules between amino acids and nucleotides. Many methods impose complicated features beyond sequence patterns. Protein-DNA bindings are formed from associated amino acid and nucleotide sequence pairs, which determine many functional characteristics. Therefore, it is desirable to investigate associated sequence patterns between TFs and TFBSs. With increasing computational power, availability of massive experimental databases on DNA and proteins, and mature data mining techniques, we propose a framework to discover associated TF–TFBS binding sequence patterns in the most explicit and interpretable form from TRANSFAC. The framework is based on association rule mining with Apriori algorithm. The patterns found are evaluated by quantitative measurements at several levels on TRANSFAC. With further independent verifications from literatures, Protein Data Bank and homology modeling, there are strong evidences that the patterns discovered reveal real TF–TFBS bindings across different TFs and TFBSs, which can drive for further knowledge to better understand TF–TFBS bindings. PMID:20529874

  4. Discovering governing equations from data by sparse identification of nonlinear dynamical systems.

    Science.gov (United States)

    Brunton, Steven L; Proctor, Joshua L; Kutz, J Nathan

    2016-04-12

    Extracting governing equations from data is a central challenge in many diverse areas of science and engineering. Data are abundant whereas models often remain elusive, as in climate science, neuroscience, ecology, finance, and epidemiology, to name only a few examples. In this work, we combine sparsity-promoting techniques and machine learning with nonlinear dynamical systems to discover governing equations from noisy measurement data. The only assumption about the structure of the model is that there are only a few important terms that govern the dynamics, so that the equations are sparse in the space of possible functions; this assumption holds for many physical systems in an appropriate basis. In particular, we use sparse regression to determine the fewest terms in the dynamic governing equations required to accurately represent the data. This results in parsimonious models that balance accuracy with model complexity to avoid overfitting. We demonstrate the algorithm on a wide range of problems, from simple canonical systems, including linear and nonlinear oscillators and the chaotic Lorenz system, to the fluid vortex shedding behind an obstacle. The fluid example illustrates the ability of this method to discover the underlying dynamics of a system that took experts in the community nearly 30 years to resolve. We also show that this method generalizes to parameterized systems and systems that are time-varying or have external forcing.

  5. Discovering governing equations from data by sparse identification of nonlinear dynamics

    Science.gov (United States)

    Brunton, Steven

    The ability to discover physical laws and governing equations from data is one of humankind's greatest intellectual achievements. A quantitative understanding of dynamic constraints and balances in nature has facilitated rapid development of knowledge and enabled advanced technology, including aircraft, combustion engines, satellites, and electrical power. There are many more critical data-driven problems, such as understanding cognition from neural recordings, inferring patterns in climate, determining stability of financial markets, predicting and suppressing the spread of disease, and controlling turbulence for greener transportation and energy. With abundant data and elusive laws, data-driven discovery of dynamics will continue to play an increasingly important role in these efforts. This work develops a general framework to discover the governing equations underlying a dynamical system simply from data measurements, leveraging advances in sparsity-promoting techniques and machine learning. The resulting models are parsimonious, balancing model complexity with descriptive ability while avoiding overfitting. The only assumption about the structure of the model is that there are only a few important terms that govern the dynamics, so that the equations are sparse in the space of possible functions. This perspective, combining dynamical systems with machine learning and sparse sensing, is explored with the overarching goal of real-time closed-loop feedback control of complex systems. This is joint work with Joshua L. Proctor and J. Nathan Kutz. Video Abstract: https://www.youtube.com/watch?v=gSCa78TIldg

  6. Discover Patterns and Mobility of Twitter Users—A Study of Four US College Cities

    Directory of Open Access Journals (Sweden)

    Yue Li

    2017-02-01

    Full Text Available Geo-tagged tweets provide useful implications for studies in human geography, urban science, location-based services, targeted advertising, and social network. This research aims to discover the patterns and mobility of Twitter users by analyzing the spatial and temporal dynamics in their tweets. Geo-tagged tweets are collected over a period of six months for four US Midwestern college cities: (1 West Lafayette, IN; (2 Bloomington, IN; (3 Ann Arbor, MI; (4 Columbus, OH. Various analytical and statistical methods are used to reveal the spatial and temporal patterns of tweets, and the tweeting behaviors of Twitter users. It is discovered that Twitter users are most active between 9:00 pm and 11:00 pm. In smaller cities, tweets aggregate at campuses and apartment complexes, while tweets in residential areas of bigger cities make up the majority of tweets. We also found that most Twitter users have two to four places of frequent visits. The mean mobility range of frequent Twitter users is linearly correlated to the size of the city, specifically, about 40% of the city radius. The research therefore confirms the feasibility and promising future for using geo-tagged microblogging services such as Twitter to understand human behavior patterns and carry out other geo-social related studies.

  7. Discover Gene Specific Local Co-Regulations from Time-Course Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Ji Zhang

    2008-01-01

    Full Text Available Discovering gene co-regulatory relationships is one of most important research in DNA microarray data analysis. The problem of gene specific co-regulation discovery is to, for a particular gene of interest (called target gene, identify the condition subsets where strong gene co-regulations of the target gene are observed and its co-regulated genes in these condition subsets. The co-regulations are local in the sense that they occur in some subsets of full experimental conditions. The study on this problem can contribute to better understanding and characterizing the target gene during the biological activity involved. In this paper, we propose an innovative method for finding gene specific co-regulations using genetic algorithm (GA. A sliding window is used to delimit the allowed length of conditions in which gene co-regulations occur and an ad hoc GA, called the progressive GA, is performed in each window position to find those condition subsets having high fitness. It is called progressive because the initial population for the GA in a window position inherits the top-ranked individuals obtained in its preceding window position, enabling the GA to achieve a better accuracy than the non-progressive algorithm. kNN Lookup Table is utilized to substantially speed up fitness evaluation in the GA. Experimental results with a real-life gene expression data demonstrate the efficiency and effectiveness of our technique in discovering gene specific co-regulations.

  8. A density-based algorithm for discovering clusters in large spatial databases with noise

    Energy Technology Data Exchange (ETDEWEB)

    Ester, M.; Kriegel, H.P.; Sander, J.; Xu Xiaowei [Univ. of Munich (Germany)

    1996-12-31

    Clustering algorithms are attractive for the task of class identification in spatial databases. However, the application to large spatial databases rises the following requirements for clustering algorithms: minimal requirements of domain knowledge to determine the input parameters, discovery of clusters with arbitrary shape and good efficiency on large databases. The well-known clustering algorithms offer no solution to the combination of these requirements. In this paper, we present the new clustering algorithm DBSCAN relying on a density-based notion of clusters which is designed to discover clusters of arbitrary shape. DB SCAN requires only one input parameter and supports the user in determining an appropriate value for it. We performed an experimental evaluation of the effectiveness and efficiency of DBSCAN using synthetic data and real data of the SEQUOIA 2000 benchmark. The results of our experiments demonstrate that (1) DBSCAN is significantly more effective in discovering clusters of arbitrary shape than the well-known algorithm CLARANS, and that (2) DBSCAN outperforms CLARANS by a factor of more than 100 in terms of efficiency.

  9. Letting students discover the power, and the limits, of simple models: Coulomb's law

    Science.gov (United States)

    Bohacek, Peter; Vonk, Matthew; Dill, Joseph; Boehm, Emma

    2017-09-01

    The inverse-square law pops up all over. It's a simplified model of reality that describes light, sound, gravity, and static electricity. But when it's brought up in class, students are often just handed the equations. They rarely have an opportunity to discover Coulomb's law or Newton's law of gravitation for themselves. It's not hard to understand why. A quantitative demonstration of Coulomb's law can be difficult. The forces are smaller than many force sensors can measure and static electricity tends to be finicky. In addition, off-the-shelf units are expensive or difficult to use. As a result, many instructors skip this lab in favor of qualitative demonstrations or simulations. Adolf Cortel sought to remedy this by designing a straightforward experiment for measuring Coulomb's law using charged metalized-glass spheres (Christmas ornaments) and an electronic balance. Building on Cortel's design, we've made a series of video-based experiments that students can use to discover the relationships that underlie electric force.

  10. BIRI: a new approach for automatically discovering and indexing available public bioinformatics resources from the literature.

    Science.gov (United States)

    de la Calle, Guillermo; García-Remesal, Miguel; Chiesa, Stefano; de la Iglesia, Diana; Maojo, Victor

    2009-10-07

    The rapid evolution of Internet technologies and the collaborative approaches that dominate the field have stimulated the development of numerous bioinformatics resources. To address this new framework, several initiatives have tried to organize these services and resources. In this paper, we present the BioInformatics Resource Inventory (BIRI), a new approach for automatically discovering and indexing available public bioinformatics resources using information extracted from the scientific literature. The index generated can be automatically updated by adding additional manuscripts describing new resources. We have developed web services and applications to test and validate our approach. It has not been designed to replace current indexes but to extend their capabilities with richer functionalities. We developed a web service to provide a set of high-level query primitives to access the index. The web service can be used by third-party web services or web-based applications. To test the web service, we created a pilot web application to access a preliminary knowledge base of resources. We tested our tool using an initial set of 400 abstracts. Almost 90% of the resources described in the abstracts were correctly classified. More than 500 descriptions of functionalities were extracted. These experiments suggest the feasibility of our approach for automatically discovering and indexing current and future bioinformatics resources. Given the domain-independent characteristics of this tool, it is currently being applied by the authors in other areas, such as medical nanoinformatics. BIRI is available at http://edelman.dia.fi.upm.es/biri/.

  11. A New Species of Frog (Anura: Dicroglossidae) Discovered from the Mega City of Dhaka

    Science.gov (United States)

    Howlader, Mohammad Sajid Ali; Nair, Abhilash; Merilä, Juha

    2016-01-01

    We describe a new species of frog of the genus Zakerana discovered from the urban core of Dhaka, Bangladesh, one of the most densely populated cities in the world. Although the new species is morphologically similar to the geographically proximate congeners in the Bangladeshi cricket frog group, we show that it can be distinguished from all congeners on the basis of morphological characters, advertisement calls and variation in two mitochondrial DNA genes (12S rRNA and 16S rRNA). Apart from several diagnostic differences in body proportions, the new species differs from other Zakerana species in having a flattened snout (from ventral view) projecting over the lower jaw, and diagnostic trapezoid-shaped red markings on the vocal sac in males. Molecular genetic analyses show that the new species is highly divergent (3.1–20.1% sequence divergence) from all congeneric species, and forms a well-supported clade with its sister species, Zakerana asmati. The discovery of a new amphibian species from the urban core of Dhaka together with several recent descriptions of new amphibian species from Bangladesh may indicate that more amphibian species remain to be discovered from this country. PMID:26934699

  12. Semantic interestingness measures for discovering association rules in the skeletal dysplasia domain.

    Science.gov (United States)

    Paul, Razan; Groza, Tudor; Hunter, Jane; Zankl, Andreas

    2014-02-05

    Lately, ontologies have become a fundamental building block in the process of formalising and storing complex biomedical information. With the currently existing wealth of formalised knowledge, the ability to discover implicit relationships between different ontological concepts becomes particularly important. One of the most widely used methods to achieve this is association rule mining. However, while previous research exists on applying traditional association rule mining on ontologies, no approach has, to date, exploited the advantages brought by using the structure of these ontologies in computing rule interestingness measures. We introduce a method that combines concept similarity metrics, formulated using the intrinsic structure of a given ontology, with traditional interestingness measures to compute semantic interestingness measures in the process of association rule mining. We apply the method in our domain of interest - bone dysplasias - using the core ontologies characterising it and an annotated dataset of patient clinical summaries, with the goal of discovering implicit relationships between clinical features and disorders. Experimental results show that, using the above mentioned dataset and a voting strategy classification evaluation, the best scoring traditional interestingness measure achieves an accuracy of 57.33%, while the best scoring semantic interestingness measure achieves an accuracy of 64.38%, both at the recall cut-off point 5. Semantic interestingness measures outperform the traditional ones, and hence show that they are able to exploit the semantic similarities inherently present between ontological concepts. Nevertheless, this is dependent on the domain, and implicitly, on the semantic similarity metric chosen to model it.

  13. THE ROLE OF LAPAROSCOPY IN DISCOVERING THE CAUSES OF CHRONIC PELVIC PAIN

    Directory of Open Access Journals (Sweden)

    Jadranka Domazet Fink

    2003-12-01

    Full Text Available Background. The aim of this study was to assess the share of organic changes in patients with chronic pelvic pain (CPP as well as evaluate the need for invasive CPP diagnostics – laparoscopy.Methods. The data for the analysis were gathered retrospectively from the descriptions of 287 CPP patients who were treated at the Clinic of Gynaecology in Ljubljana from 1993 to 1999. In this analysis the share of laparoscopically established organic causes of CPP was assessed and the findings of invasive (laparoscopy and non-invasive diagnostics (clinical status and ultrasound were compared.Results. Out of 287 patients, 272 underwent laparoscopy, 7 underwent laparotomy while 8 were only observed. As regards organic CPP causes, an organic cause was established in 70.7% patients through laparoscopy. The most frequently observed phenomena were adhesions, namely in 97 (35.7% patients, endometriosis in 68 (25.0% and pelvic varices in 29 (10% patients.By comparing the results of invasive and non-invasive diagnostics it was established that up to three times more organic changes – a possible cause of CPP – can be discovered through laparoscopy than through the use of non-invasive diagnostics methods.Conclusions. Laparoscopy is considered to be the most reliable method of diagnostics and detection of organic causes of CPP. An adequate psychological treatment within a multidisciplinary approach is necessary in patients in whom an organic cause of CPP can not be discovered in their genital tract.

  14. Using machine learning to predict gene expression and discover sequence motifs

    Science.gov (United States)

    Li, Xuejing

    Recently, large amounts of experimental data for complex biological systems have become available. We use tools and algorithms from machine learning to build data-driven predictive models. We first present a novel algorithm to discover gene sequence motifs associated with temporal expression patterns of genes. Our algorithm, which is based on partial least squares (PLS) regression, is able to directly model the flow of information, from gene sequence to gene expression, to learn cis regulatory motifs and characterize associated gene expression patterns. Our algorithm outperforms traditional computational methods e.g. clustering in motif discovery. We then present a study of extending a machine learning model for transcriptional regulation predictive of genetic regulatory response to Caenorhabditis elegans. We show meaningful results both in terms of prediction accuracy on the test experiments and biological information extracted from the regulatory program. The model discovers DNA binding sites ab initio. We also present a case study where we detect a signal of lineage-specific regulation. Finally we present a comparative study on learning predictive models for motif discovery, based on different boosting algorithms: Adaptive Boosting (AdaBoost), Linear Programming Boosting (LPBoost) and Totally Corrective Boosting (TotalBoost). We evaluate and compare the performance of the three boosting algorithms via both statistical and biological validation, for hypoxia response in Saccharomyces cerevisiae.

  15. A Review of Patents on Therapeutic Potential and Delivery of Hydroge n Sulfide.

    Science.gov (United States)

    Verma, Richa; Akhtar, Yumna; Singh, Somnath

    2017-01-01

    Hydrogen sulfide (H2S) is a colorless gas with a characteristic smell of rotten eggs. Once only thought of as a toxic gas, evidence now shows that H2S plays major roles in pathological and physiological activities. These roles are being utilized to treat diseases and disorders ranging from hypertension, inflammation, edema, cardiovascular issues, chronic pain, cancer, and many more. Challenges facing the use of H2S currently involve achieving the optimum therapeutic concentrations, synthesizing chemically and physiologically stable donors, and developing clinically appropriate delivery systems. We did an extensive literature search on therapeutic potentials and related issues of H2S which were presented in a systematic flow pattern in introduction. Patents accepted/filed on various aspects of hydrogen sulfide were searched using the United States Patent and Trademark Office database at http://patft.uspto.gov/ and google patents at https://patents.google.com/. The important search terms combined with H2S were therapeutic effect, pharmacological action, biochemistry, measurement, and delivery. We also incorporated our own experiences and publications while discussing the delivery approaches and associated challenges. In the process, researchers have discovered novel techniques in preparing the noxious gas by discovering and synthesizing H2S donors and developing controlled and predictable delivery systems. Donors utilized thus far include derivatives of anti-inflammatory drugs like H2S -aspirin, Allium sativum extracts, inorganic salts, phosphorodithioate derivatives, and thioaminoacid derivatives. Use of controlled delivery systems for H2S is critical to maintain its physiological stability, optimum therapeutic window, increase patient compliance, and make it easier to manufacture and administer. Numerous patents overcoming the challenges of using H2S therapeutically with various donors and delivery mechanisms have been reviewed. The scientific knowledge gained from

  16. Therapeutic drug monitoring of aminoglycosides in neonates

    NARCIS (Netherlands)

    Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

    2009-01-01

    The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to

  17. FAQ about Recreational Therapy/Therapeutic Recreation

    Science.gov (United States)

    ... biological, and behavioral sciences and recreation and leisure theory. How can I get RT/TR services? Many ... facilities, as was daycare programs for individuals with disabilities." About the American Therapeutic Recreation Association: The American ...

  18. MicroRNA therapeutics in cardiovascular medicine

    National Research Council Canada - National Science Library

    Thum, Thomas

    2012-01-01

    Cardiovascular diseases are the most common causes of human morbidity and mortality despite significant therapeutic improvements by surgical, interventional and pharmacological approaches in the last decade. MicroRNAs (miRNAs...

  19. The Diagnostic/Therapeutic Preabortion Interview.

    Science.gov (United States)

    Boekelheide, Priscilla Day

    1978-01-01

    The therapeutic and diagnostic aspect of the preabortion interview are discussed with attention to specifics that will identify students with the greatest likelihood for psychological problems and/or repeat abortions. (JD)

  20. Towards new therapeutic strategies in chondrosarcoma

    NARCIS (Netherlands)

    Schrage, Yvonne Maria

    2009-01-01

    This thesis presents the identification of new targets for therapeutic treatment of chondrosarcoma, tumours that are highly insensitive to conventional chemo- and radiation thearapy. A relatively new array technique to identify active kinases in chondrosarcoma cell cultures was used, which

  1. Therapeutic radionuclides: Making the right choice

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1996-08-01

    Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article.

  2. Therapeutic potential of fecal microbiota transplantation

    NARCIS (Netherlands)

    Smits, Loek P.; Bouter, Kristien E. C.; de Vos, Willem M.; Borody, Thomas J.; Nieuwdorp, Max

    2013-01-01

    There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal

  3. [Therapeutic baths and relaxation in neurosurgery].

    Science.gov (United States)

    Leseigneur, Matthieu

    2017-03-01

    A neurosurgical nursing and nursing auxiliaries team has started using therapeutic baths. The wellbeing procured favours a re-appropriation of body awareness and a reduction in anxiety. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. [Relationship between defense mechanism and therapeutic alliance].

    Science.gov (United States)

    Laconi, S; Cailhol, L; Pourcel, L; Thalamas, C; Lapeyre-Mestre, M; Chabrol, H

    2015-10-01

    The therapeutic alliance can be defined as a collaborative relationship between the patient and the practitioner. It represents an essential component of the psychotherapeutic process (Ambresin et al., 2007; Cungi, 2006; Martin et al., 2000). Some authors suggest that a good alliance can have a favorable impact on the therapeutic success (Barber et al., 2000; Hubble, Duncan, & Miller 1999; Horvath & Luborsky, 1993; Horvath & Symonds, 1991). This alliance can be influenced by psychological and behavioral factors (Cungi, 2006) Thus, some defense mechanisms could prevent change or, on the contrary could facilitate adaptation (Ambresin et al., 2007) and have an impact on the therapeutic success (Muris & Merckelbach, 1996). However, the relationship between therapeutic alliance and defense mechanisms represents an insufficiently explored field (Ambresin et al., 2007; Cungi, 2006). The aim of the present study was to examine the relationship between therapeutic alliance and twenty defense mechanisms in a sample of French psychiatric patients, by differentiating results in men and women. We also examined the positive and the negative therapeutic alliance. Sixty patients aged from 18 to 58 (M=41.50; SD=11.03) completed the French versions of the Defense Style Questionnaire-40 (DSQ-40) and the Helping Alliance questionnaire-II (HAq-II). Therapeutic alliance was significantly associated with each defense style: mature (0.62), neurotic (0.45) Ptherapeutic alliance (R(2) adj=36, F=12.39, β=0.65, Ptherapeutic alliance (R(2) adj=36, F=12.34, β=0.62, Ptherapeutic alliance was significantly associated with all mature defenses, three neurotic defenses (reaction formation, pseudo-altruism, idealization) and four immature defenses (splitting, denial, somatization, passive aggression). Among men, three mature defenses were associated (anticipation, humor, sublimation), four neurotic (reaction formation, pseudo-altruism, idealization and undoing) and two immature (somatization and

  5. [Therapeutic approaches in court-ordered therapy].

    Science.gov (United States)

    Floris, Emmanuelle; De Jésus, Arnaud; Cano, Jean-Philippe; Raymondaud, Séverine; Rouveyrol, Éric; Bouchard, Jean-Pierre

    As is the case with other contexts of mental health treatments, the therapeutic approaches to court-ordered therapy are varied. They are based on the principle of their clinical indication and must be delivered by therapists trained in the specific area. The classic therapeutic approaches are used: medication, psychoanalysis and psychoanalytically inspired therapies, cognitive behavioural therapies, group therapies and body-oriented approach. Copyright © 2017. Published by Elsevier Masson SAS.

  6. Viral Oncolytic Therapeutics for Neoplastic Meningitis

    Science.gov (United States)

    2014-09-01

    Award Number: W81XWH-11-1-0387 TITLE: Viral Oncolytic Therapeutics for Neoplastic Meningitis PRINCIPAL INVESTIGATOR: Mikhail Papisov, PhD...SUBTITLE Viral Oncolytic Therapeutics for Neoplastic Meningitis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0387 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...for neoplastic meningitis ( meningeal metastasis of breast cancer). The proposed therapy will be based on direct (intrathecal) administration of

  7. Therapeutic Strategy for Chronic Headache in Children

    Directory of Open Access Journals (Sweden)

    H.O. Lezhenko

    2016-05-01

    Full Text Available The therapeutic efficacy of a combined homeopathic preparation Cefavora, which consists of alcoholic extracts of Ginkgo biloba, hawthorn (Crataegus and white mistletoe (Viscum album, has been studied in the treatment of chronic tension-type headache in children. It has been shown that alongside with elimination of headache manifestations, the use of homeopathic medicine has contributed to the normalization of adaptive mechanisms of autonomic regulation in children indicating its high therapeutic efficacy.

  8. [Therapeutic education for recurrent depressive disorder].

    Science.gov (United States)

    Carde, Soufiane; Hatif, Séverine; Samama, Diane; Charbonnel, Patricia; Jouvent, Roland

    2016-01-01

    Depression is a serious and recurrent condition which can become chronic. As a complement to other therapeutic approaches, therapeutic patient education (TPE) or psychoeducation is effective. TPE groups led by a multidisciplinary hospitalisation team in a psychiatric department are thereby integrated into the global care in order to reduce relapses and improve patients' quality of life. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Preconception care in therapeutic abortion applicants.

    Science.gov (United States)

    Shirmohammadi, Farzaneh; Nekuei, Nafisehsadat; Bahadoran, Parvin; Montazery, Gita

    2017-01-01

    Some risk factors that would lead to therapeutic abortion do even exist before pregnancy and could be resolved or corrected through appropriate interventions. The present study was conducted to evaluate the condition of preconception care among therapeutic abortion applicants. This research was a descriptive, cross-sectional study that was conducted on 200 applicants for therapeutic abortion at the Forensics Medicine Center of Isfahan (Iran) who were selected convenience sampling from October 2014 to March 2015. Data were gathered using a researcher made checklist. Data were analyzed using SPSS version 16 through descriptive statistics and Chi-square and independent t-test. Eighty-five percent of the participants were applicants for therapeutic abortion due to fetal problems, and the other 15% were due to maternal issues. About 41.7% of participants with fetal problems and all of the participants with maternal issues had not received preconception care. In 93.3% of the applicants with maternal issues, the disease existed before the pregnancy. About 48.2% of participants needed genetic counseling, but 28.6% had not received any. Results showed that in most of the participants, the risk factor for therapeutic abortion existed before the pregnancy. Providing preconception care along with the elimination of risk factors before the pregnancy could prevent some of the pregnancies with the indication of therapeutic abortion.

  10. Therapeutic angiogenesis: a fantastic new adventure.

    Science.gov (United States)

    Harjai, Kishore J; Chowdhury, Pertha; Grines, Cindy L

    2002-06-01

    A significant proportion of patients with coronary artery disease have symptoms refractory to medical treatment, yet are unsuitable for conventional revascularization techniques, like percutaneous coronary intervention and coronary artery bypass surgery. Such patients are potential candidates for alternative forms of coronary revascularization, like therapeutic angiogenesis. This strategy is designed to promote the development of supplemental collateral blood vessels that will act as endogenous bypass conduits. Two major avenues for achieving therapeutic angiogenesis are currently under intense investigation: gene therapy (the introduction of new genetic material into somatic cells to synthesize proteins that are missing, defective, or desired for specific therapeutic purposes) and protein-based therapy (administration of the growth factors, instead of the genes encoding for the growth factors responsible for angiogenesis). This article provides a concise review of the "components" of gene and protein-based therapy, namely, the growth factors, the vector (for gene therapy), the route of delivery, the therapeutic target, the desired therapeutic effect, and quantifiable clinical end points for trials of angiogenesis. Based on preliminary studies, the authors believe that therapeutic angiogenesis represents a promising novel therapy for treatment of the ischemic heart. In the future, angiogenesis will likely be offered as an adjunct to conventional revascularization strategies in subsets of patients who are only "suboptimally" revascularized with conventional techniques, and might evolve into a stand-alone treatment for some patients with nonrevascularizable disease.

  11. Therapeutically Active Biomolecules from Marine Actinomycetes

    OpenAIRE

    Mani Jayaprakashvel

    2012-01-01

    For the past few centuries, the biological sources of terrestrial origin have been explored and exploited for bioactive metabolites. This has resulted in the stagnancy of discovering either novel compounds or compounds with novel bioactivities. Thus, researchers across the globe have started exploring our big Oceans, for the search of bioactive metabolites. During the past few decades, the research on bioactive metabolites from marine biological resources has geared up and among the sources m...

  12. Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

    Directory of Open Access Journals (Sweden)

    Bagyinszky E

    2016-10-01

    Full Text Available Eva Bagyinszky,1,* Young Chul Youn,2 Seong Soo A An,1 SangYun Kim3,* 1Department of BioNano Technology, Gachon University, Gyeonggi-do, 2Department of Neurology, College of Medicine, Chung-Ang University, Seoul, 3Department of Neurology, Seoul National University Budang Hospital, Gyeonggi-do, South Korea *These authors contributed equally to this work Abstract: Alzheimer’s disease (AD, the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD causative genes (APP, PSEN1, and PSEN2 that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention. Keywords: mutation, Asia

  13. A Transport Analysis of In Situ Airborne Ozone Measurements from the 2011 DISCOVER-AQ Campaign

    Science.gov (United States)

    Arkinson, H. L.; Brent, L. C.; He, H.; Loughner, C.; Stehr, J. W.; Weinheimer, A. J.; Dickerson, R. R.

    2013-12-01

    Baltimore and Washington are currently designated as nonattainment areas with respect to the 2008 EPA National Ambient Air Quality Standard (NAAQS) for 8-hour Ozone (O3). Tropospheric O3 is the dominant component of summertime photochemical smog, and at high levels, has deleterious effects on human health, ecosystems, and materials. The University of Maryland (UMD) Regional Atmospheric Measurement Modeling and Prediction Program (RAMMPP) strives to improve understanding of air quality in the Mid-Atlantic States and to elucidate contributions of pollutants such as O3 from regional transport versus local sources through a combination of modeling and in situ measurements. The NASA Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ) project investigates the connection between column measurements and surface conditions to explore the potential of remote sensing observations in diagnosing air quality at ground level where pollutants can affect human health. During the 2011 DISCOVER-AQ field campaign, in situ airborne measurements of trace gases and aerosols were performed along the Interstate 95 corridor between Baltimore and Washington from the NASA P3B aircraft. To augment this data and provide regional context, measurements of trace gases and aerosols were also performed by the RAMMPP Cessna 402B aircraft over nearby airports in Maryland and Virginia. This work presents an analysis of O3 measurements made by the Ultraviolet (UV) Photometric Ambient O3 Analyzer on the RAMMPP Cessna 402B and by the NCAR 4-Channel Chemiluminescence instrument on the NASA P3B. In this analysis, spatial and temporal patterns of O3 data are examined within the context of forward and backward trajectories calculated from 12-km North American Mesoscale (NAM) meteorological data using the NOAA Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) Model and from a high resolution Weather Research and

  14. Discovering structural motifs using a structural alphabet: Application to magnesium-binding sites

    Directory of Open Access Journals (Sweden)

    Lim Carmay

    2007-03-01

    Full Text Available Abstract Background For many metalloproteins, sequence motifs characteristic of metal-binding sites have not been found or are so short that they would not be expected to be metal-specific. Striking examples of such metalloproteins are those containing Mg2+, one of the most versatile metal cofactors in cellular biochemistry. Even when Mg2+-proteins share insufficient sequence homology to identify Mg2+-specific sequence motifs, they may still share similarity in the Mg2+-binding site structure. However, no structural motifs characteristic of Mg2+-binding sites have been reported. Thus, our aims are (i to develop a general method for discovering structural patterns/motifs characteristic of ligand-binding sites, given the 3D protein structures, and (ii to apply it to Mg2+-proteins sharing 2+-structural motifs are identified as recurring structural patterns. Results The structural alphabet-based motif discovery method has revealed the structural preference of Mg2+-binding sites for certain local/secondary structures: compared to all residues in the Mg2+-proteins, both first and second-shell Mg2+-ligands prefer loops to helices. Even when the Mg2+-proteins share no significant sequence homology, some of them share a similar Mg2+-binding site structure: 4 Mg2+-structural motifs, comprising 21% of the binding sites, were found. In particular, one of the Mg2+-structural motifs found maps to a specific functional group, namely, hydrolases. Furthermore, 2 of the motifs were not found in non metalloproteins or in Ca2+-binding proteins. The structural motifs discovered thus capture some essential biochemical and/or evolutionary properties, and hence may be useful for discovering proteins where Mg2+ plays an important biological role. Conclusion The structural motif discovery method presented herein is general and can be applied to any set of proteins with known 3D structures. This new method is timely considering the increasing number of structures for

  15. Discover Our Earth: Web-Based Geophysical Data in the Classroom

    Science.gov (United States)

    Moore, A.; Seber, D.; Danowski, D.; Brindisi, C.

    2002-12-01

    Discover Our Earth is a web-based system designed for classroom use, allowing access and display of geospatial data sets . It is an education and outreach module built as part of Cornell University's Geoscience Information System, originally constructed as a tool for geophysical research (http://atlas.geo.cornell.edu). Discover Our Earth has been used in university, high school and middle school classrooms. Working with real data is a powerful tool for helping students learn scientific principles, content, and the processes of scientific inquiry. In order to give students access to data that is otherwise difficult to work with, Discover Our Earth is comprised of several elements. The central component is a Java applet called QUEST (Quick Use Earth Study Tool). QUEST allows students to query and display data from three data sets selected from the 100+ housed within the Information System. Any attribute of earthquake, volcano, or topographic data can be selected and displayed, and multiple data sets can be overlain on each other, or on assorted background images (such as a geographic base map, age of the sea floor etc). Each image is saved in the QUEST history window, allowing students to compare multiple selections, or to animate a series of images as a "filmstrip." In order to help students better understand their results, the QUEST applet is supported by several other components. There are guides for both teacher and student. The student guide gives step-by-step instructions for a series of problems, and suggests others that will help students answer questions of local and global interest. The teacher guide provides background material, context, and answers to the student exercises. There are animations and 3-D visualizations that allow students to better interpret their maps. Additionally, there are interactive experiments on topics such as continental drift, isostasy, viscosity, that allow students to explore the physics that underlie the processes they are

  16. A human systems biology approach to discover new drug targets in epilepsy.

    Science.gov (United States)

    Loeb, Jeffery A

    2010-07-01

    One of the major challenges in developing novel therapeutics for human epileptic disorders comes from the wide range of brain abnormalities capable of producing epilepsy. In children and adults that undergo epilepsy surgery for treatment of refractory seizures, these abnormalities range from developmental defects to injuries, infections, tumors, and ischemia. Given the many molecular mechanisms likely involved in each of these, finding common therapeutic targets seems a futile task. However, patients undergoing surgery for neocortical seizures have surprisingly similar electrophysiologic abnormalities, which consist of the synchronous firing of large neuronal populations. Surgical removal of these regions is the only means at present time to permanently reduce or eliminate seizures. The precise locations of these hypersynchronous firing regions that produce seizures can be revealed using long-term subdural electrical high-density recordings. This therapeutic strategy not only can dramatically reduce seizures, but also offers the potential to generate molecular and cellular information that can be used to ask why certain regions of the cortex become and remain epileptic. We have taken advantage of these detailed clinical and electrophysiologic human studies by taking a "systems biology" approach to identify novel biomarkers and drug targets in neocortical human epilepsy. In this article, we describe our multidisciplinary systems approach that utilizes a relational database to interrelate clinical, quantitative electrophysiologic, pathologic, and gene expression profiling data together as a means to identify and validate new biomarkers and potential drug targets for human epilepsy.

  17. Tuppiap Qeqertaa (Tobias Island): a newly discovered island off northeast Greenland

    DEFF Research Database (Denmark)

    Bennike, O.; Mikkelsen, N.; Forsberg, René

    2006-01-01

    The small island of Tuppiap Qeqertaa, formerly known as Tobias circle divide or Tobias Island, is situated 80 km off the northeast Greenland coast. The island was discovered in 1993 and is approximately 2 km long and 1.5 km wide. Most of the island is covered by an ice cap that rises to 35 in above...... sea level, as determined by airborne laser scanning. High-quality geodetic GPS measurements determine the position of a small cairn erected on the island to 79 degrees 20'34.48" N, 15 degrees 46'31.23" W. Minor parts of the island are ice free, with small hills of gravel. Late Holocene shells...... of marine bivalves have been found and were presumably brought up by ice floe push. Shell fragments of southern extralimital marine invertebrates point to the presence of pre-Holocene deposits. Three species of moss are the only land plants that have been found on the island....

  18. Combined Intrathoracic and Subcutaneous Splenosis Discovered 51 Years after Abdominal Trauma

    Science.gov (United States)

    Gleason, James Benjamin; Diacovo, Maria Julia; Schroeder, Jonathan Ryan

    2015-01-01

    Splenosis is a rare condition that results from the autotransplantation of splenic parenchyma into unexpected locations such as the abdomen or subcutaneous tissue. In the presence of coexisting injury to the diaphragm intrathoracic transplantation can occur emerging as single or multiple pleural-based masses. This occurs after traumatic rupture of the spleen and is usually asymptomatic, only to be discovered incidentally on routine thoracic or abdominal imaging. To our knowledge this is the third documented case of combined intrathoracic and subcutaneous splenosis found in English literature. This occurred in a 71-year-old male involved in a motor vehicle accident at age 19 requiring urgent splenectomy. He has a significant cigarette smoking history and was referred to our hospital for further evaluation of an abnormality seen on shoulder X-ray. PMID:26236530

  19. Combined Intrathoracic and Subcutaneous Splenosis Discovered 51 Years after Abdominal Trauma

    Directory of Open Access Journals (Sweden)

    James Benjamin Gleason

    2015-01-01

    Full Text Available Splenosis is a rare condition that results from the autotransplantation of splenic parenchyma into unexpected locations such as the abdomen or subcutaneous tissue. In the presence of coexisting injury to the diaphragm intrathoracic transplantation can occur emerging as single or multiple pleural-based masses. This occurs after traumatic rupture of the spleen and is usually asymptomatic, only to be discovered incidentally on routine thoracic or abdominal imaging. To our knowledge this is the third documented case of combined intrathoracic and subcutaneous splenosis found in English literature. This occurred in a 71-year-old male involved in a motor vehicle accident at age 19 requiring urgent splenectomy. He has a significant cigarette smoking history and was referred to our hospital for further evaluation of an abnormality seen on shoulder X-ray.

  20. A Higgs or Not a Higgs? What to Do if You Discover a New Scalar Particle

    CERN Document Server

    Burgess, C.P.; Pospelov, M.

    2002-01-01

    We show how to systematically analyze what may be inferred should a new scalar particle be discovered in collider experiments. Our approach is systematic in the sense that we perform the analysis in a manner which minimizes apriori theoretical assumptions as to the nature of the scalar particle. For instance, we do not immediately make the common assumption that a new scalar particle is a Higgs boson, and so must interact with a strength proportional to the mass of the particles with which it couples. We show how to compare different observables, and so to develop a decision tree from which the nature of the new particle may be discerned. We define several categories of models, which summarize the kinds of distinctions which the first experiments can make.

  1. TIMING AND INTERSTELLAR SCATTERING OF 35 DISTANT PULSARS DISCOVERED IN THE PALFA SURVEY

    Energy Technology Data Exchange (ETDEWEB)

    Nice, D. J. [Department of Physics, Lafayette College, Easton, PA 18042 (United States); Altiere, E.; Farrington, D.; Popa, L.; Wang, Y. [Department of Physics, Bryn Mawr College, Bryn Mawr, PA 19010 (United States); Bogdanov, S.; Camilo, F. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Cordes, J. M.; Brazier, A.; Chatterjee, S. [Astronomy Department, Cornell University, Ithaca, NY 14853 (United States); Hessels, J. W. T. [ASTRON, The Netherlands Institute for Radio Astronomy, Postbus 2, 7990-AA Dwingeloo (Netherlands); Kaspi, V. M. [Department of Physics, McGill University, Montreal, QC H3A 2T8 (Canada); Lyne, A. G.; Stappers, B. W. [Jodrell Bank Centre for Astrophysics, School of Physics and Astronomy, University of Manchester, Manchester M13 9PL (United Kingdom); Ransom, S. M. [NRAO, Charlottesville, VA 22903 (United States); Sanpa-arsa, S. [Department of Astronomy, University of Virginia, Charlottesville, VA 22903 (United States); Allen, B. [Max-Planck-Institut fuer Gravitationsphysik, D-30167 Hannover (Germany); Bhat, N. D. R. [Center for Astrophysics and Supercomputing, Swinburne University, Hawthorn, Victoria 3122 (Australia); Champion, D. J. [Max-Planck-Institut fuer Radioastronomie, D-53121 Bonn (Germany); Crawford, F. [Department of Physics and Astronomy, Franklin and Marshall College, Lancaster, PA 17604-3003 (United States); and others

    2013-07-20

    We have made extensive observations of 35 distant slow (non-recycled) pulsars discovered in the ongoing Arecibo PALFA pulsar survey. Timing observations of these pulsars over several years at Arecibo Observatory and Jodrell Bank Observatory have yielded high-precision positions and measurements of rotation properties. Despite being a relatively distant population, these pulsars have properties that mirror those of the previously known pulsar population. Many of the sources exhibit timing noise, and one underwent a small glitch. We have used multifrequency data to measure the interstellar scattering properties of these pulsars. We find scattering to be higher than predicted along some lines of sight, particularly in the Cygnus region. Finally, we present XMM-Newton and Chandra observations of the youngest and most energetic of the pulsars, J1856+0245, which has previously been associated with the GeV-TeV pulsar wind nebula HESS J1857+026.

  2. Discover the Universe with NASA during the International Year of Astronomy: A Workshop for Astronomy Educators

    Science.gov (United States)

    Dussault, M.; Smith, D.; Allen, J.; Backman, D.; Bartolone, L.; Bobrowsky, M.; Gould, A.; Mendez, B.; Lochner, J.; Mayo, L.; McLin, K.; Reinfeld, E.; Shupla, C.; Summers, F.; Thiemann, J.; Devore, E.

    2008-11-01

    NASA's space science missions are working together to provide educators with the knowledge and materials they need to discover and share the universe with their audiences during the International Year of Astronomy (IYA2009) and beyond. In this daylong intensive workshop, participants experienced a prototype version of NASA's IYA workshop series for educators. They explored Earth's place in the universe; light, energy, and optics; and the nature of astronomical models and evidence while investigating how NASA's spaced-based missions extend Galileo's legacy. Discussions included how to find and use NASA content and resources in the classroom, after-school programs, libraries, science centers, and museums, as well as how to connect to the international IYA2009 Galileo Teacher Training Program and U.S. Families and Classrooms efforts. All references, resources, and handouts from the workshop are available online at http://www.universeforum.org/iyaworkshop/.

  3. Discovering medical conditions associated with periodontitis using linked electronic health records

    Science.gov (United States)

    Boland, Mary Regina; Hripcsak, George; Albers, David J.; Wei, Ying; Wilcox, Adam B.; Wei, Jin; Li, Jianhua; Lin, Steven; Breene, Michael; Myers, Ronnie; Zimmerman, John; Papapanou, Panos N.; Weng, Chunhua

    2013-01-01

    Aim To use linked electronic medical and dental records to discover associations between periodontitis and medical conditions independent of a priori hypotheses. Materials and Methods This case-control study included 2475 patients who underwent dental treatment at the College of Dental Medicine at Columbia University and medical treatment at NewYork-Presbyterian Hospital. Our cases are patients who received periodontal treatment and our controls are patients who received dental maintenance but no periodontal treatment. Chi-square analysis was performed for medical treatment codes and logistic regression was used to adjust for confounders. Results Our method replicated several important periodontitis associations in a largely Hispanic population, including diabetes mellitus type I (OR = 1.6, 95% CI 1.30–1.99, p diabetes, obesity, lipid and circulatory system conditions, alcohol and tobacco abuse. Conclusions This study contributes a high-throughput method for associating periodontitis with systemic diseases using linked electronic records. PMID:23495669

  4. Discovering Performance Measurement System to Evaluate the Efficiency of E-Business Solutions

    Directory of Open Access Journals (Sweden)

    Laura Uturytė  -Vrubliauskienė

    2012-07-01

    Full Text Available Despite the significant growth of information technologies investments, evidence of their influence on organization performance remains inconclusive. Nowadays it is very important to realize whether expected economic benefits of information technologies investments are being recognized in organizations. Currently organizations can no longer afford basically to lose their money in e-business initiatives without developing and using suitable metrics to measure the effectiveness of such investments and to find out the relationship between e-business and organization performance. The study describes research aimed at determining the exact nature of such e-business performance measurement systems. The basic objective of this study is to discover performance measurement system for evaluating the efficiency of e-business solutions.Article in Lithuanian

  5. Function and application of a non-ester-hydrolyzing carboxylesterase discovered in tulip.

    Science.gov (United States)

    Nomura, Taiji

    2017-01-01

    Plants have evolved secondary metabolite biosynthetic pathways of immense rich diversity. The genes encoding enzymes for secondary metabolite biosynthesis have evolved through gene duplication followed by neofunctionalization, thereby generating functional diversity. Emerging evidence demonstrates that some of those enzymes catalyze reactions entirely different from those usually catalyzed by other members of the same family; e.g. transacylation catalyzed by an enzyme similar to a hydrolytic enzyme. Tuliposide-converting enzyme (TCE), which we recently discovered from tulip, catalyzes the conversion of major defensive secondary metabolites, tuliposides, to antimicrobial tulipalins. The TCEs belong to the carboxylesterase family in the α/β-hydrolase fold superfamily, and specifically catalyze intramolecular transesterification, but not hydrolysis. This non-ester-hydrolyzing carboxylesterase is an example of an enzyme showing catalytic properties that are unpredictable from its primary structure. This review describes the biochemical and physiological aspects of tulipalin biogenesis, and the diverse functions of plant carboxylesterases in the α/β-hydrolase fold superfamily.

  6. Local NASA Scientists Discover New Species of Organism in Mars-Like Environment

    Science.gov (United States)

    2003-01-01

    Microbiologist Dr. Elena V. Pikuta, and Astrobiologist Richard Hoover culture extremophiles, microorganisms that can live in extreme environments, in the astrobiology laboratory at the National Space Science and Technology Center (NSSTC) in Huntsville, Alabama. The scientists recently discovered a new species of extremophiles, Spirochaeta Americana. The species was found in Northern California's Mono Lake, an alkaline, briny oxygen-limited lake in a closed volcanic crater that Hoover believes may offer new clues to help identify sites to research for potential life on Mars. Hoover is an astrobiologist at NASA's Marshall Space Flight Center (MSFC), and Pikuta is a microbiologist with the Center for Space Plasma and Aeronomy Research Laboratory at the University of Alabama in Huntsville. The NSSTC is a partnership with MSFC, Alabama universities, industry, research institutes, and federal agencies.

  7. Dealing with Wormhole Attacks in Wireless Sensor Networks Through Discovering Separate Routes Between Nodes

    Directory of Open Access Journals (Sweden)

    F. Rezaei

    2017-08-01

    Full Text Available One of the most common attacks against Wireless Sensor Networks is the wormhole attack. In this attack, the enemy deploys two malicious nodes in two different areas of the network and establishes a high-speed dedicated channel between these two. This will cause the normal nodes in two different areas wrongly think that they are two-hop neighbors. Therefore, this attack will greatly affect the routing algorithms. In this paper, a new distributed algorithm is provided to deal with the wormhole attack. The main idea of the proposed algorithm is to discover separate routes between pairs of two-hop neighboring nodes. The proposed algorithm was implemented and evaluated in terms of true and false detection rate by performing a series of experiments and the results were compared with the base algorithm. The test results showed that the proposed algorithm has desirable efficacy.

  8. Monitoring and Discovering X-Ray Pulsars in the Small Magellanic Cloud (core Program)

    Science.gov (United States)

    A long-term program of repeated observations of the SMC has been highly successful. A huge number of new pulsars have been discovered, optical counterparts identified, and orbital periods found. We propose here to continue this campaign with the aims of both finding new X-ray pulsars and monitoring the pulsed flux of known pulsars. We will use the results to investigate and confirm several new relationships found between astrophysical parameters of these systems. Although we are requesting a relatively large amount of time we believe this program offers good ``value for money'' because of the large number of sources that will be studied and the scope for new astrophysical insight. For this round we propose to study three overlapping regions that will cover most of the SMC.

  9. Monitoring and Discovering X-Ray Pulsars in the Small Magellanic Cloud

    Science.gov (United States)

    Corbet, Robin

    A long-term program of repeated observations of the SMC has been highly successful. A huge number of new pulsars have been discovered, optical counterparts identified, and orbital periods found. We propose here to continue this campaign with the aims of both finding new X-ray pulsars and monitoring the pulsed flux of known pulsars. We will use the results to investigate and confirm several new relationships found between astrophysical parameters of these systems. Although we are requesting a relatively large amount of time we believe this program offers good ``value for money'' because of the large number of sources that will be studied and the scope for new astrophysical insight. For this round we propose to study three overlapping regions that will cover most of the SMC.

  10. Enterobius vermicularis eggs discovered in coprolites from a medieval Korean mummy.

    Science.gov (United States)

    Shin, Dong Hoon; Oh, Chang Seok; Chai, Jong-Yil; Lee, Hye-Jung; Seo, Min

    2011-09-01

    While the presence of pinworm eggs in archaeological samples has been reported by many researchers in the New World, those have been detected very scarcely in the Old World, especially in East Asian countries. In fact, many parasite species were recovered from the archeological remains in Korea, eggs of Enterobius vermicularis had not been found. Recently, a female mummy buried in the 17th century was discovered in the Joseon tomb from Dangjin-gun, Chungcheongnam-do, Korea. After rehydration process for 12 days, investigations were carried on the luminal surface of the colon. From them, 3 eggs of E. vermicularis were recovered. They were elliptical, transparent with a thin egg shell, 50.3±5.2 µm (length) and 28.2±3.9 µm (width) in size. This is the first discovery of E. vermicularis eggs in East Asia.

  11. Discovering, Indexing and Interlinking Information Resources [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Fabrizio Celli

    2015-11-01

    Full Text Available The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS.

  12. Restoration and Preservation of Engraved Limestone Blocks Discovered in Abu Mousa Excavation, Suez - Egypt

    Directory of Open Access Journals (Sweden)

    Nabil A. Abd El-Tawab BADER

    2013-03-01

    Full Text Available A lot of engraved limestone blocks were discovered at Awlad Abu Musa (east of Suez, Egypt in 1995/2007 by Supreme Council of Antiquities. The stone blocks were seriously affected by archaeological environments during burial environment in agriculture land. They were covered with thick clay layer with soil particles that disfigured them and hid their inscriptions. Prior to the conservation intervention, the materials were characterized by X-ray diffraction, optical microscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, Chemical analyses of ground water and microbiological study. After the material characterization, the conservation and restoration of the stone blocks were carried out including cleaning, consolidation, reduction of salts, Re-jointing, restoration and completion of lost parts. After that the blocks were exhibited in Suez museum.

  13. sp3-hybridized framework structure of group-14 elements discovered by genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Manh Cuong [Ames Laboratory; Zhao, Xin [Ames Laboratory; Wang, Cai-Zhuang [Ames Laboratory; Ho, Kai-Ming [Ames Laboratory

    2014-05-01

    Group-14 elements, including C, Si, Ge, and Sn, can form various stable and metastable structures. Finding new metastable structures of group-14 elements with desirable physical properties for new technological applications has attracted a lot of interest. Using a genetic algorithm, we discovered a new low-energy metastable distorted sp3-hybridized framework structure of the group-14 elements. It has P42/mnm symmetry with 12 atoms per unit cell. The void volume of this structure is as large as 139.7Å3 for Si P42/mnm, and it can be used for gas or metal-atom encapsulation. Band-structure calculations show that P42/mnm structures of Si and Ge are semiconducting with energy band gaps close to the optimal values for optoelectronic or photovoltaic applications. With metal-atom encapsulation, the P42/mnm structure would also be a candidate for rattling-mediated superconducting or used as thermoelectric materials.

  14. The Scientific Work of John A. McClelland: A Recently Discovered Manuscript

    Science.gov (United States)

    O'Connor, Thomas

    2010-09-01

    John Alexander McClelland (1870-1920) was educated at Queen’s College Galway and the Cavendish Laboratory in Cambridge. He was Professor of Experimental Physics at University College Dublin from 1900 to 1920. He was best known for his pioneering work on the scattering of β rays and on the conductivity of gases and the mobility of ions. He established a research school on atmospheric aerosols that was continued by his successor, John James Nolan (1887-1952), which strongly influenced physics research in Ireland up to the present. A recently discovered manuscript of a commemorative address by Nolan in 1920, which is reproduced in Appendix I, is a unique contemporary summary of McClelland’s research and character, and is an important contribution to the history of experimental physics in Ireland.

  15. Strategy to discover diverse optimal molecules in the small molecule universe.

    Science.gov (United States)

    Rupakheti, Chetan; Virshup, Aaron; Yang, Weitao; Beratan, David N

    2015-03-23

    The small molecule universe (SMU) is defined as a set of over 10(60) synthetically feasible organic molecules with molecular weight less than ∼500 Da. Exhaustive enumerations and evaluation of all SMU molecules for the purpose of discovering favorable structures is impossible. We take a stochastic approach and extend the ACSESS framework ( Virshup et al. J. Am. Chem. Soc. 2013 , 135 , 7296 - 7303 ) to develop diversity oriented molecular libraries that can generate a set of compounds that is representative of the small molecule universe and that also biases the library toward favorable physical property values. We show that the approach is efficient compared to exhaustive enumeration and to existing evolutionary algorithms for generating such libraries by testing in the NKp fitness landscape model and in the fully enumerated GDB-9 chemical universe containing 3 × 10(5) molecules.

  16. Supercomputing in the Age of Discovering Superearths, Earths and Exoplanet Systems

    Science.gov (United States)

    Jenkins, Jon M.

    2015-01-01

    NASA's Kepler Mission was launched in March 2009 as NASA's first mission capable of finding Earth-size planets orbiting in the habitable zone of Sun-like stars, that range of distances for which liquid water would pool on the surface of a rocky planet. Kepler has discovered over 1000 planets and over 4600 candidates, many of them as small as the Earth. Today, Kepler's amazing success seems to be a fait accompli to those unfamiliar with her history. But twenty years ago, there were no planets known outside our solar system, and few people believed it was possible to detect tiny Earth-size planets orbiting other stars. Motivating NASA to select Kepler for launch required a confluence of the right detector technology, advances in signal processing and algorithms, and the power of supercomputing.

  17. Origin of orbits of secondaries in the discovered trans-Neptunian binaries

    Science.gov (United States)

    Ipatov, S. I.

    2017-09-01

    The dependences of inclinations of orbits of secondaries in the discovered trans-Neptunian binaries on the distance between the primary and the secondary, on the eccentricity of orbits of the secondary around the primary, on the ratio of diameters of the secondary and the primary, and on the elements of heliocentric orbits of these binaries are studied. These dependences are interpreted using the model of formation of a satellite system in a collision of two rarefied condensations composed of dust and/or objects less than 1 m in diameter. It is assumed in this model that a satellite system forms in the process of compression of a condensation produced in such a collision. The model of formation of a satellite system in a collision of two condensations agrees with the results of observations: according to observational data, approximately 40% of trans-Neptunian binaries have a negative angular momentum relative to their centers of mass.

  18. Discovering relations between mind, brain, and mental disorders using topic mapping.

    Directory of Open Access Journals (Sweden)

    Russell A Poldrack

    Full Text Available Neuroimaging research has largely focused on the identification of associations between brain activation and specific mental functions. Here we show that data mining techniques applied to a large database of neuroimaging results can be used to identify the conceptual structure of mental functions and their mapping to brain systems. This analysis confirms many current ideas regarding the neural organization of cognition, but also provides some new insights into the roles of particular brain systems in mental function. We further show that the same methods can be used to identify the relations between mental disorders. Finally, we show that these two approaches can be combined to empirically identify novel relations between mental disorders and mental functions via their common involvement of particular brain networks. This approach has the potential to discover novel endophenotypes for neuropsychiatric disorders and to better characterize the structure of these disorders and the relations between them.

  19. How Korotkoff, the surgeon, discovered the auscultatory method of measuring arterial pressure.

    Science.gov (United States)

    Segall, H N

    1975-10-01

    The Korotkoff sounds that measure systolic and diastolic arterial pressure levels were described in a brief communication by N.C. Korotkoff in 1905. He did not state how it happened that he discovered this auscultatory method of measuring "blood" pressure. The search for information on this matter led to studying the thesis for his doctorate published in 1910 on Experiments for Determining the Efficiency of Arterial Collaterals. It seems that when he wanted to be sure that pressureonan artery (digital, or with an Esmarch ligature or a Riva-Rocci cuff) had completely obliterated its lumen, he listened over the artery below the area of pressure. The absence of any sounds meant complete obliteration; a sound appeared with each beat when some flow did occur during partial obliteration of the lumen and when no pulsation could be detected because of the small volume of flow.

  20. Potential therapeutic roles for antibody mixtures.

    Science.gov (United States)

    Raju, T Shantha; Strohl, William R

    2013-10-01

    With the enormous success of recombinant monoclonal antibodies (rMAbs) as human therapeutics, there are increasing efforts underway to explore new molecular entities that mimic rMAbs to replicate this huge success. In addition to naked intact rMAbs, antibody drug conjugates (ADCs), FAb and F(ab')2 fragments and also Fc fusion proteins have been developed and/or marketed as human therapeutics to treat different human diseases, including life-threatening diseases such as cancer. Several hundreds more intact rMAbs, ADCs, FAb, F(ab')2 fragments and Fc fusion proteins are currently undergoing human clinical trials. In addition to these molecules, new type of antibody fragments such as single-chain Fvs (scFvs), VH, scFv-Fc, scFv-CH, scFAb, scFv-zipper, diabodies, bispecific antibodies and similar types of constructs are also being investigated to be developed as human monotherapeutics. Further, there are quite a few current examples of combinations of biologics being developed. For example, currently, several biopharmaceutical companies are developing combinations of antibody mixtures as human therapeutics. Accordingly, the question posed here is whether it is time to consider the possibility of developing a broader range of combinations of therapeutic biologics. Combinations of small organic molecules have been successfully used as therapeutics for many years to treat many diseases, so the context of using polypharmacology to treat human diseases is not novel. For the past several decades, intravenous immunoglobulins have successfully been used in treating various autoimmune diseases. In this context, several biotechnology companies are exploring the use of combinations of antibody mixtures as human therapeutics. This editorial discusses these current efforts and the potential future role of antibody mixtures as human therapeutics.