WorldWideScience

Sample records for resistance causal agent

  1. [Antibibiotic resistance by nosocomial infections' causal agents].

    Science.gov (United States)

    Salazar-Holguín, Héctor Daniel; Cisneros-Robledo, María Elena

    2016-01-01

    The antibibiotic resistance by nosocomial infections (NI) causal agents constitutes a seriously global problematic that involves the Mexican Institute of Social Security's Regional General Hospital 1 in Chihuahua, Mexico; although with special features that required to be specified and evaluated, in order to concrete an effective therapy. Observational, descriptive and prospective study; by means of active vigilance all along 2014 in order to detect the nosocomial infections, for epidemiologic study, culture and antibiogram to identify its causal agents and antibiotics resistance and sensitivity. Among 13527 hospital discharges, 1079 displayed NI (8 %), standed out: the related on vascular lines, of surgical site, pneumonia and urinal track; they added up two thirds of the total. We carried out culture and antibiogram about 300 of them (27.8 %); identifying 31 bacterian species, mainly seven of those (77.9 %): Escherichia coli, Staphylococcus aureus and epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter cloacae; showing multiresistance to 34 tested antibiotics, except in seven with low or without resistance at all: vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin, piperacilin-tazobactam, amikacin and carbapenems. When we contrasted those results with the recommendations in the clinical practice guides, it aroused several contradictions; so they must be taken with reserves and has to be tested in each hospital, by means of cultures and antibiograms in practically every case of nosocomial infection.

  2. Resistência de variedades comerciais de cana-de-açúcar ao agente causal do raquitismo-da-soqueira Resistance of sugarcane commercials cultivars to causal agent of ratoon stunting disease

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Gagliardi

    2009-07-01

    Full Text Available O raquitismo-da-soqueira (RSD, causado pela bactéria Leifsonia xyli subsp. xyli, é uma das mais importantes doenças da cana-de-açúcar nas regiões produtoras do mundo. O presente trabalho teve como objetivo avaliar o grau de resistência de 10 variedades comerciais RB de cana-de-açúcar mais a variedade CB 49-260, a qual foi incluída como padrão suscetível. O trabalho visou avaliar os danos amostrados em campo pelo peso das parcelas em função da relação entre a produtividade de parcelas inoculadas e não inoculadas artificialmente com a bactéria. Os resultados mostraram que as variedades RB 72 454, RB 83 5486, RB 86 7515, RB 92 5211, RB 92 5268, RB 92 5345, RB 92 8064 e a variedade padrão CB 49-260 comportaram-se como variedades suscetíveis. A variedade RB 85 5156 comportou-se como de resistência intermediária e apenas as variedades RB 85 5453 e RB 85 5536 comportaram-se como tolerantes.Ratoon stunting disease (RSD caused by bacteria Leifsonia xyli subsp. xyli is one of the most economically important disease of sugarcane worldwide. The present survey had objective to evaluate the resistance of 10 RB commercial cultivars of sugarcane including CB 49-260 as a susceptible standard. The study evaluated the correlating the damages presented for overhauls productivity of inoculate and non inoculate parcels with the bacteria. The results showed that varieties RB 72 454, RB 83 5486, RB 86 7515, RB 92 8064, RB 92 5211, RB 92 5345 and RB 92 5268 were susceptible. RB 85 5156 had a intermediary resistance and varieties RB 85 5453 and RB 85 5536 both showed tolerant behavior.

  3. Fungicide resistance among Cladobotryum spp. – causal agents of cobweb disease of the edible mushroom Agaricus bisporus

    OpenAIRE

    Grogan, Helen M.; Gaze, R. H.

    2000-01-01

    A survey of fungicide resistance among isolates of the mushroom pathogens Cladobotryum mycophilum and C. dendroides Types I and II was undertaken, with respect to the active ingredients thiabendazole, carbendazim (benzimidazoles) and prochloraz manganese following an epidemic in Britain and Ireland in 1994/95. The majority of isolates (41/57) were strongly resistant to thiabendazole (ED50 > 200 ppm) and were exclusively C. dendroides Type II. All C. mycophilum and C. dendroides Type I isolate...

  4. Sources of resistance in chickpea (cicer arietinum l.) land races against ascochyta rabiei causal agent of ascochyta blight disease

    International Nuclear Information System (INIS)

    Duzdemir, O.; Selvi, B.; Yanar, Y.

    2014-01-01

    Ascochyta blight disease, caused by the fungus Ascochyta rabiei, is a major yield limiting factor of chickpea in Turkey and around the world. This study was conducted to identify sources of genetic resistance against chickpea blight caused by Ascochyta rabiei. For this purpose, 68 chickpea land races of different origins were evaluated in both field and growth chamber conditions during 2008-2009 growing seassons. Two standard cultivars were used as a reference, Inci (resistant) and Canitez (susceptible). Disease severity scoring was conducted on a 1-9 rating scale 21 days after inoculation in growth chamber test and at flowering and pot filling stages in field tests. Analysis of variance (ANOVA) test showed a significant difference among the chickpea landraces in ascochyta blight resistance at p<0.05. None of the chickpea land races was highly resistant to the pathogen in growth chamber and field conditions. Only two landraces (10A and 28B) were moderately resistant to the disease. Some of the landraces resulted in a particular plant to exhibit no disease symptoms, indicating that the variation within chickpea land races was high. Therefore, seeds of this plant were harvested separately and preserved for further evaluations. (author)

  5. Fitness and competition studies of QoI resistant and sensitive Cercospora sojina isolates, the causal agent of frogeye leaf spot

    Science.gov (United States)

    Frogeye leaf spot (FLS), caused by Cercospora sojina, is a yearly foliar disease of soybean in Tennessee and causes substantial economic losses if not properly managed. Quinone outside inhibitor (QoI) fungicides are often used to manage FLS, but C. sojina isolates have developed resistance to this c...

  6. Moniliophthora roreri, causal agent of cacao frosty pod rot.

    Science.gov (United States)

    Bailey, Bryan A; Evans, Harry C; Phillips-Mora, Wilbert; Ali, Shahin S; Meinhardt, Lyndel W

    2017-12-01

    Taxonomy: Moniliophthora roreri (Cif.) H.C. Evans et al. ; Phylum Basidiomycota; Class Agaricomycetes; Order Agaricales; Family Marasmiaceae; Genus Moniliophthora. Biology: Moniliophthora roreri attacks Theobroma and Herrania species causing frosty pod rot. Theobroma cacao (cacao) is the host of major economic concern. Moniliophthora roreri is a hemibiotroph with a long biotrophic phase (45-90 days). Spore masses, of apparent asexual origin, are produced on the pod surface after initiation of the necrotrophic phase. Spores are spread by wind, rain and human activity. Symptoms of the biotrophic phase can include necrotic flecks and, in some cases, pod malformation, but pods otherwise remain asymptomatic. Relationship to Moniliophthora perniciosa: Moniliophthora roreri and Moniliophthora perniciosa, causal agent of witches' broom disease of cacao, are closely related. Their genomes are similar, including many of the genes they carry which are considered to be important in the disease process. Moniliophthora perniciosa, also a hemibiotroph, has a typical basidiomycete lifestyle and morphology, forming clamp connections and producing mushrooms. Basidiospores infect meristematic tissues including flower cushions, stem tips and pods. Moniliophthora roreri does not form clamp connections or mushrooms and infects pods only. Both pathogens are limited to the Western Hemisphere and are a threat to cacao production around the world. Agronomic importance: Disease losses caused by frosty pod rot can reach 90% and result in field abandonment. Moniliophthora roreri remains in the invasive phase in the Western Hemisphere, not having reached Brazil, some islands within the Caribbean and a few specific regions within otherwise invaded countries. The disease can be managed by a combination of cultural (for example, maintenance of tree height and removal of infected pods) and chemical methods. These methods benefit from regional application, but can be cost prohibitive. Breeding for

  7. Perceived causality, force, and resistance in the absence of launching.

    Science.gov (United States)

    Hubbard, Timothy L; Ruppel, Susan E

    2017-04-01

    In the launching effect, a moving object (the launcher) contacts a stationary object (the target), and upon contact, the launcher stops and the target begins moving in the same direction and at the same or slower velocity as previous launcher motion (Michotte, 1946/1963). In the study reported here, participants viewed a modified launching effect display in which the launcher stopped before or at the moment of contact and the target remained stationary. Participants rated perceived causality, perceived force, and perceived resistance of the launcher on the target or the target on the launcher. For launchers and for targets, increases in the size of the spatial gap between the final location of the launcher and the location of the target decreased ratings of perceived causality and ratings of perceived force and increased ratings of perceived resistance. Perceived causality, perceived force, and perceived resistance exhibited gradients or fields extending from the launcher and from the target and were not dependent upon contact of the launcher and target. Causal asymmetries and force asymmetries reported in previous studies did not occur, and this suggests that such asymmetries might be limited to typical launching effect stimuli. Deviations from Newton's laws of motion are noted, and the existence of separate radii of action extending from the launcher and from the target is suggested.

  8. Causality and Information Dynamics in Networked Systems with Many Agents

    Science.gov (United States)

    2017-05-11

    algorithms. 6 Future Perspectives Causal graph reconstruction from noisy data is a problem of central importance. In our research we have shown how the idea ...thrust of the research was to develop methods for GCG sparsification using ideas from Tikhonov regularization and ADMM based proximal algorithms...not vary with time. The notion of Granger-causality is captured in the following definition . Definition 2.1 If ξ̂[xi(t) |Ht] < ξ̂[xi(t) |H−jt ] , (2.2

  9. Identification and Control of Cladobotryum spp., Causal Agents of Cobeweb Disease of Cultivated Mushroom

    Directory of Open Access Journals (Sweden)

    Ivana Potočnik

    2009-01-01

    Full Text Available Cladobotryum spp. are causal agents of cobweb disease, one of the most serious diseases of cultivated mushroom (Agaricus bisporus (Lange Imbach in Serbia and worldwide, which affects product quality and yield. The disease symptoms are: cottony fluffy white oryellowish to pink colonies on mushroom casing, rapid colonization of casing surface, covering of host basidiomata by mycelia, and their decay. Prochloraz-Mn has been officially recommended for mushroom cultivation in EU countries. However, inefficiency of prochloraz-Mn has been noted at a level of spotting symptoms of cobweb disease. With regard to cases of resistance evolution and a general threat to the environment and human health, special attention should be focused on good programmes of hygiene, and inventing and developing alternative methods of disease control.

  10. Causality

    Science.gov (United States)

    Pearl, Judea

    2000-03-01

    Written by one of the pre-eminent researchers in the field, this book provides a comprehensive exposition of modern analysis of causation. It shows how causality has grown from a nebulous concept into a mathematical theory with significant applications in the fields of statistics, artificial intelligence, philosophy, cognitive science, and the health and social sciences. Pearl presents a unified account of the probabilistic, manipulative, counterfactual and structural approaches to causation, and devises simple mathematical tools for analyzing the relationships between causal connections, statistical associations, actions and observations. The book will open the way for including causal analysis in the standard curriculum of statistics, artifical intelligence, business, epidemiology, social science and economics. Students in these areas will find natural models, simple identification procedures, and precise mathematical definitions of causal concepts that traditional texts have tended to evade or make unduly complicated. This book will be of interest to professionals and students in a wide variety of fields. Anyone who wishes to elucidate meaningful relationships from data, predict effects of actions and policies, assess explanations of reported events, or form theories of causal understanding and causal speech will find this book stimulating and invaluable.

  11. In vitro evidence for sexual reproduction in Venturia effusa, causal agent of pecan scab

    Science.gov (United States)

    Venturia effusa is the causal agent of pecan scab, the most prevalent disease of pecan in the southeastern US. Venturia effusa is currently only known to reproduce asexually, yet the genetic diversity among populations of pecan scab suggest it is a sexually reproducing pathogen. Analysis of the mati...

  12. Draft Genome Sequence of an Isolate of Colletotrichum fructicola, a Causal Agent of Mango Anthracnose.

    Science.gov (United States)

    Li, Qili; Bu, Junyan; Yu, Zhihe; Tang, Lihua; Huang, Suiping; Guo, Tangxun; Mo, Jianyou; Hsiang, Tom

    2018-02-22

    Here, we present a draft genome sequence of isolate 15060 of Colletotrichum fructicola , a causal agent of mango anthracnose. The final assembly consists of 1,048 scaffolds totaling 56,493,063 bp (G+C content, 53.38%) and 15,180 predicted genes. Copyright © 2018 Li et al.

  13. Mechanisms of bacterial resistance to antimicrobial agents.

    NARCIS (Netherlands)

    van Duijkeren, Engeline; Schink, Anne-Kathrin; Roberts, Marilyn C; Wang, Yang; Schwarz, Stefan

    During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either

  14. Mechanisms of resistance to alkylating agents

    OpenAIRE

    Damia, G.; D‘Incalci, M.

    1998-01-01

    Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of...

  15. Antagonistic activity Trichoderma harzianum Rifai on the causal agent of rice blast (Pyricularia grisea Sacc.

    Directory of Open Access Journals (Sweden)

    Ernesto Juniors Pérez Torres

    2017-10-01

    Full Text Available With the objective to evaluate the antagonistic activity of T. harzianum (strain A-34 on the causal agent of rice blast (P. grisea, were developed several in vitro experiments. It was evaluated the biocontrol mechanisms such as competition through mounted the percent inhibition of radial growth of hyphae of P. grisea from 24 to 240 hours and the antagonistic capacity. In addition, was evaluated micoparasitism to inclination the observation of events Microscopy winding, penetration, vacuolization, lysis, and antibiosis by observing 24 hours a confrontation between the hyphae of the phytopathogenic fungus and biological control agent. It was obtained at 120 hours 100 % inhibition of micelial growth of causal agent, what corresponded with the degree 1 of antagonistic capacity (scale and is recorded as a hyperparasitic action on P. grisea. It was evidenced an antibiotic effect of metabolites produced by T. harzianum (strain A-34 to 24 hours of confrontation, where there was time interaction between the hyphae of microorganisms with 14,3 % inhibition, also was evidence the micoparasitism events by penetration, vacuolization and lysis in the cells of phytopathogenic fungus. These results demonstrated the ability of T. harzianum (strain A-34 on causal agent of rice blast (P. grisea.

  16. Morphological and Molecular Identification of the Causal Agent of Anthracnose Disease of Avocado in Kenya.

    Science.gov (United States)

    Kimaru, S K; Monda, E; Cheruiyot, R C; Mbaka, J; Alakonya, A

    2018-01-01

    Anthracnose disease of avocado contributes to a huge loss of avocado fruits due to postharvest rot in Kenya. The causal agent of this disease has not been clear but presumed to be Colletotrichum gloeosporioides as reported in other regions where avocado is grown. The fungus mainly infects fruits causing symptoms such as small blackish spots, "pepper spots," and black spots with raised margin which coalesce as infection progresses. Due to economic losses associated with the disease and emerging information of other species of fungi as causal agents of the disease, this study was aimed at identifying causal agent(s) of the disease. A total of 80 fungal isolates were collected from diseased avocado fruits in Murang'a County, the main avocado growing region in Kenya. Forty-six isolates were morphologically identified as Colletotrichum spp. based on their cultural characteristics, mainly whitish, greyish, and creamish colour and cottony/velvety mycelia on the top side of the culture and greyish cream with concentric zonation on the reverse side. Their spores were straight with rounded end and nonseptate. Thirty-four isolates were identified as Pestalotiopsis spp. based on their cultural characteristics: whitish grey mycelium with black fruiting structure on the upper side and greyish black one on the lower side and septate spores with 3-4 septa and 2 or 3 appendages at one end. Further molecular studies using ITS indicated Colletotrichum gloeosporioides , Colletotrichum boninense , and Pestalotiopsis microspora as the causal agents of anthracnose disease in avocado. However, with this being the first report, there is a need to conduct further studies to establish whether there is coinfection or any interaction thereof.

  17. Morphological and Molecular Identification of the Causal Agent of Anthracnose Disease of Avocado in Kenya

    Directory of Open Access Journals (Sweden)

    S. K. Kimaru

    2018-01-01

    Full Text Available Anthracnose disease of avocado contributes to a huge loss of avocado fruits due to postharvest rot in Kenya. The causal agent of this disease has not been clear but presumed to be Colletotrichum gloeosporioides as reported in other regions where avocado is grown. The fungus mainly infects fruits causing symptoms such as small blackish spots, “pepper spots,” and black spots with raised margin which coalesce as infection progresses. Due to economic losses associated with the disease and emerging information of other species of fungi as causal agents of the disease, this study was aimed at identifying causal agent(s of the disease. A total of 80 fungal isolates were collected from diseased avocado fruits in Murang’a County, the main avocado growing region in Kenya. Forty-six isolates were morphologically identified as Colletotrichum spp. based on their cultural characteristics, mainly whitish, greyish, and creamish colour and cottony/velvety mycelia on the top side of the culture and greyish cream with concentric zonation on the reverse side. Their spores were straight with rounded end and nonseptate. Thirty-four isolates were identified as Pestalotiopsis spp. based on their cultural characteristics: whitish grey mycelium with black fruiting structure on the upper side and greyish black one on the lower side and septate spores with 3-4 septa and 2 or 3 appendages at one end. Further molecular studies using ITS indicated Colletotrichum gloeosporioides, Colletotrichum boninense, and Pestalotiopsis microspora as the causal agents of anthracnose disease in avocado. However, with this being the first report, there is a need to conduct further studies to establish whether there is coinfection or any interaction thereof.

  18. Identification and Control of Cladobotryum spp., Causal Agents of Cobeweb Disease of Cultivated Mushroom

    OpenAIRE

    Ivana Potočnik

    2009-01-01

    Cladobotryum spp. are causal agents of cobweb disease, one of the most serious diseases of cultivated mushroom (Agaricus bisporus (Lange) Imbach) in Serbia and worldwide, which affects product quality and yield. The disease symptoms are: cottony fluffy white or yellowish to pink colonies on mushroom casing, rapid colonization of casing surface, covering of host basidiomata by mycelia, and their decay. Prochloraz-Mn has been officially recommended for mushroom cultivation in EU countries. Howe...

  19. Susceptibility of Haemophilus equigenitalis, the causal agent of contagious equine metritis, to 31 antimicrobial agents.

    Science.gov (United States)

    Sugimoto, C; Isayama, Y; Kashiwazaki, M; Mitani, K

    1981-01-01

    The minimal inhibitory concentrations of 31 antimicrobial agents were determined for 99 isolates of Haemophilus equigenitalis by the agar dilution method. All the isolates showed good susceptibility to 26 antimicrobial agents tests, minimal inhibitory concentrations of which were less than 3.13 micrograms/ml for more than 90% of the isolates. Of these agents, 4 macrolides (erythromycin, oleandomycin, kitasamycin, tylosin), 3 tetracyclines (tetracycline, chlortetracycline, oxytetracycline), 1 peptide (colistin), 1 penicillin (ampicillin) and 1 pleuromutilin (tiamulin) were the most active agents, showing a minimal inhibitory concentration of less than 0.39 micrograms/ml for more than 90% of the isolates. The growth of more than 90% of the isolates was not inhibited by 800 micrograms/ml of streptomycin.

  20. Control of Ralstonia Solanacearum The Causal Agent of Brown Rot in Potato Using Essential Oils

    International Nuclear Information System (INIS)

    Salem, E.A.

    2011-01-01

    Five essential oils, namely peppermint (Mentha piperita L.), caraway (Carium carvum L.), fennel (Foeniculum vulgare Mill.), lemongrass (Cymbopogon citratus Staph.) and thyme (Thymus vulgaris), were used separately against Ralstonia solanacearum; the causal agent of brown rot in potato. The most two effective oils (peppermint and thyme) were used in vitro and in vivo after testing their effects on potato tubers buds germination. Peppermint inhibited buds germination but thyme have no effects on buds germination. In vivo, the control of brown rot using thyme oil in glass house experiment reduced the percentage of brown rot infection to 30.6% and reduced the severity of disease from 5 to 3.

  1. Survival of Fusarium graminearum, the causal agent of Fusarium head blight. A review

    OpenAIRE

    Leplat , Johann; Friberg , Hanna; Abid , Muhammad; Steinberg , Christian

    2012-01-01

    International audience; Wheat is one of the most cultivated crops worldwide. In 2010, 20 % of wheat and durum wheat were cultivated in Europe, 17 % in China and 9 % in Russia and in North America. Wheat yield can be highly decreased by several factors. In particular Fusarium graminearum Schwabe is a worldwide fungal pest impacting wheat production. F. graminearum is the causal agent of Fusarium head blight, root and stem-base rot of cereals. Losses caused by Fusarium head blight in Northern a...

  2. Molecular Detection of Monilinia fructigena as Causal Agent of Brown Rot on Quince

    Directory of Open Access Journals (Sweden)

    Jovana Hrustić

    2012-01-01

    Full Text Available Species of the genus Monilinia are important causal agents of fruit rot on pome and stone fruits in Serbia. The pathogen is very harmful, especially on small properties and cottage plantations where intensive control measures are not applied. Quince is importanthost for the pathogens of this genus. During spring 2010, intensive occurrence of mummified fruits overwintering on branches of the quince was observed. The pathogen was isolated using standard phytopathological methods. Pathogenicity of eight obtained isolates was tested by artificial inoculation of injured apple fruits. Identification was performed according to pathogenic, morphological and ecological properties, and was confirmed by Multiplex polimeraze chain reaction, PCR. All the isolates studied caused brown rot on inoculated apple fruits. The isolates form light yellow colonies with lobate margins,with single-celled, transparent, elliptical or oval conidia in chains, regardless temperature or light presence. Sclerotia are observed in 14 days old cultures. The highest growth rate of most of the isolates is at 27°C and in dark. Based on studied pathogenic, morphological and ecological characteristics, it was found that the Monilinia fructigena is causal agent of brown rot of quince. Using specific primers (MO368-5, MO368-8R, MO368-10R, Laxa-R2for detection of Monilinia species in Multiplex PCR reaction, the expected fragment 402 bp in size was amplified, which confirmed that the studied isolates belonged to the speciesM. fructigena.

  3. Integrated Management of Causal Agents of Postharvest Fruit Rot of Apple

    Directory of Open Access Journals (Sweden)

    Mila Grahovac

    2011-01-01

    Full Text Available One of the major causes of poor quality and fruit loss (during storage and transportare diseases caused by phytopathogenic fungi. Economic losses which are the consequenceof the phytopathogenic fungus activity after harvest exceed the losses in the field.Themost important postharvest fungal pathogens of apple fruits are: Botrytis cinerea Pers. exFr., Penicillium expansum (Lk. Thom., Cryptosporiopsis curvispora (Peck. Grem., Colletotrichumgloeosporioides (Penz. Sacc., Monilinia sp., Gloeosporium album Osterw, Alternaria alternata(Fr. Keissler, Cladosporium herbarium Link., Cylindrocarpon mali (Alles. Wollenw., Stemphyliumbotryosum Wallr. The use of available protection technologies can significantly reducelosses caused by pathogens in storage. The concept of integrated pest management (IPMin apple fruits i.e. sustainable approach in control of causal agents of postharvest fruit rot,using cultural, physical, biological and chemical measures, to minimize economic, healthand risks to consumers and environment, is presented in the paper.

  4. El consumo de basuco* como agente causal de alteraciones en la encía

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    Lorena Dávila

    2001-08-01

    Full Text Available El abuso en el consumo de drogas, entre ellas al BASUCO, es uno de los grandes problemas de salud pública que tiene que afrontar nuestra comunidad. En este estudio se utilizaron 40 ratas de la cepa Wistar, 20 con carácter experimental y 20 de control utilizando agua destilada durante 16 semanas. Se demostró que existe una relación directa entre el uso de BASUCO y las alteraciones clínicas e histológicas en la encía, de las cuales que el absceso gingival la patología más frecuente (63,2 % de los casos. Tomando en cuenta el incremento del consumo de drogas en nuestra sociedad y los resultados obtenidos, es importante que el odontólgo relacione el uso de las drogas como un agente causal de alteraciones en la encía.The abuse of drugs, and among them of BASUCO, is one of the great public health problems our communioty has to face. 40 Wistar strain rats were used in this study: 20 with an experimental character and 20 as controls. Distilled water was utilized during 16 weeks. It was demonstrated that there is a direct relationship between the use of BASUCO and the clinical and histological alterations of the gingiva, of which the gingival abscess is the most frequent pathology (63.2 % of the cases. Taking into account the increasing consumption of drugs in our society and the results obtained, it is important that the odontologist considers the use of drugs as a causal agent of gingival alterations.

  5. Periodontitis and Insulin Resistance: Casual or Causal Relationship?

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav

    2012-12-01

    Full Text Available Insulin resistance (IR is now considered as a chronic and low level inflammatory condition. It is closely related to altered glucose tolerance, hypertriglyceridemia, abdominal obesity, and coronary heart disease. IR is accompanied by the increase in the levels of inflammatory cytokines like interleukin-1 and 6, tumor necrosis factor-α. These inflammatory cytokines also play a crucial part in pathogenesis and progression of insulin resistance. Periodontitis is the commonest of oral diseases, affecting tooth investing tissues. Pro-inflammatory cytokines are released in the disease process of periodontitis. Periodontitis can be attributed with exacerbation of IR. Data in the literature supports a "two way relationship" between diabetes and periodontitis. Periodontitis is asymptomatic in the initial stages of disease process and it often escapes diagnosis. This review presents the blurred nexus between periodontitis and IR, underlining the pathophysiology of the insidious link. The knowledge of the association between periodontitis and IR can be valuable in planning effectual treatment modalities for subjects with altered glucose homeostasis and diabetics. Presently, the studies supporting this association are miniscule. Further studies are mandatory to substantiate the role of periodontitis in the deterioration of IR.

  6. White rot of garlic and onion (Causal agent, Sclerotium cepivorum): A status report from the Pacific Northwest

    Science.gov (United States)

    There is evidence from literature, state department of agriculture documents, and recent diagnoses that Sclerotium cepivorum, causal agent of white rot of garlic and onion, is spreading and/or becoming more established in the Pacific Northwest. Previously documented distributions are summarized, an...

  7. A simple culture method inducing sexual reproduction by Fusarium graminearum, the primary causal agent of Fusarium head blight

    Science.gov (United States)

    The homothallic ascomycete fungus Fusarium graminearum is the primary causal agent of Fusarium head blight (FHB), a devastating disease of wheat and barley worldwide. The fungus undergoes both asexual and sexual stages in its life cycle. The asexual stage produces conidiospores, whereas the sexual s...

  8. Analysis of genetic diversity of Fusarium tupiense, the main causal agent of mango malformation disease in southern Spain

    Science.gov (United States)

    Mango malformation disease (MMD) has become an important global disease affecting this crop. The aim of this study was to identify the main causal agents of MMD in the Axarquía region of southern Spain and determine their genetic diversity. Fusarium mangiferae was previously described in the Axarquí...

  9. Dieback of rose caused by Acremonium sclerotigenum as a new causal agent of rose dieback in Iran

    International Nuclear Information System (INIS)

    Mirtalebi, M.; Banihashemi, Z.; Sabahi, F.; Mafakheri, H.

    2016-01-01

    Severe dieback of rose has been recently observed in several rose greenhouses in Fars province of Iran. During 2014 and 2015, stems of rose plants showing yellow to brown discoloration and dieback were collected from rose greenhouses. Coniothyrium fuckelii, Botrytis cinerea and Acremonium were subsequently isolated from the margin between healthy and symptomatic tissue. B. cinerea and C. fuckelii isolates were similar to those previously reported for dieback of rose worldwide. Morphological and cultural characters along with molecular analysis based on partial sequences of the internal transcribed spacer (ITS) region of the ribosomal RNA genome allowed confirming the affiliation of the Acremonium isolates, corresponding to A. sclerotigenum as a new causal agent of rose dieback. To determine its pathogenicity on rose, Koch's postulates were fulfilled by stem inoculation of nine rose cultivars under greenhouse conditions. While A. sclerotigenum is considered as a soil-born pathogen, and produces sclerotia that are resistant to adverse conditions enables the fungus to survive extended period in soil, propagule trapping in our study revealed that conidia can become airborn, imply that an aerial phase, forms an important component of the disease cycle.

  10. Dieback of rose caused by Acremonium sclerotigenum as a new causal agent of rose dieback in Iran

    Energy Technology Data Exchange (ETDEWEB)

    Mirtalebi, M.; Banihashemi, Z.; Sabahi, F.; Mafakheri, H.

    2016-07-01

    Severe dieback of rose has been recently observed in several rose greenhouses in Fars province of Iran. During 2014 and 2015, stems of rose plants showing yellow to brown discoloration and dieback were collected from rose greenhouses. Coniothyrium fuckelii, Botrytis cinerea and Acremonium were subsequently isolated from the margin between healthy and symptomatic tissue. B. cinerea and C. fuckelii isolates were similar to those previously reported for dieback of rose worldwide. Morphological and cultural characters along with molecular analysis based on partial sequences of the internal transcribed spacer (ITS) region of the ribosomal RNA genome allowed confirming the affiliation of the Acremonium isolates, corresponding to A. sclerotigenum as a new causal agent of rose dieback. To determine its pathogenicity on rose, Koch's postulates were fulfilled by stem inoculation of nine rose cultivars under greenhouse conditions. While A. sclerotigenum is considered as a soil-born pathogen, and produces sclerotia that are resistant to adverse conditions enables the fungus to survive extended period in soil, propagule trapping in our study revealed that conidia can become airborn, imply that an aerial phase, forms an important component of the disease cycle.

  11. Resistencia bacteriana Bacterial resistance to antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Jesualdo Fuentes

    1993-01-01

    Full Text Available

    Se presenta un panorama de la resistencia bacteriana incluyendo su fisiopatogenia y formas de presentación y se establecen algunas consideraciones generales de tipo clínico como auxiliares para racionalizar el uso de los antimicrobianos y evitar o retardar el problema de la resistencia; éste plantea la necesidad de un reordenamiento definitivo en la prescripción de antimicrobianos. No será tanto la creación o descubrimiento de nuevos antibióticos sino la racionalización del manejo de los existentes lo que permitirá alcanzar victorias sobre estos microorganismos. Es Importante mantener educación continua sobre el uso adecuado de los antimicrobianos desde los puntos de vista epidemiológico, farmacocinético y fisiopatogénico.

    An overview on bacterial resistance to antimicrobial agents is presented. It includes the different genetic mechanisms for Its development and the biochemical phenomena that explain It. Some clinical considerations are proposed in order to rationalize the use of these drugs and to avoid or delay the appearance of resistance.

  12. Monitoring the infective process of the downy mildew causal agent within micropropagated rose plants

    Directory of Open Access Journals (Sweden)

    Sonia Yamile Gómez

    2012-08-01

    Full Text Available Downy mildew in the rose caused by a species of the Peronospora genus is a very restrictive disease for the Colombian greenhouse rose production. The damage observed in the susceptible varieties of commercial rose include symptoms affect young steams and tiny leaves causing reddish and brown spots and defoliation; leading to 10% production losses. The infective behavior of this pathogen was studied with the aim of increasing the knowledge about the biology of the rose downy mildew. The study of the infective process was performed on the Charlotte variety using micropropagated roses inoculated with suspensions of sporangia. A germinal tube was observed during the germination process, it came from a lateral papilla and reached up to 300 microns in length. During this study, the ability of the pathogen to use vascular sieves as communication systems within the plant was determined. Oogonia and antheridia were also observed inside the epidermal cells, and oospores inside the parenchymal tissue close to xylem vessels. To the best of our knowledge, these sexual structures have not been reported on in Colombia before. This study verifies the ability of the downy mildew causal agent to move through the xylem vessels and produce sexual structures, such as oogonia, antheridia and oospores within those tissues.

  13. Morphological and molecular characterization of the causal agent of downy mildew on Quinoa (Chenopodium quinoa).

    Science.gov (United States)

    Choi, Young-Joon; Danielsen, Solveig; Lübeck, Mette; Hong, Seung-Beom; Delhey, Rolf; Shin, Hyeon-Dong

    2010-05-01

    Downy mildew is an economically important and widespread disease in quinoa (Chenopodium quinoa) growing areas. Although in many studies Peronospora farinosa is most commonly regarded as the causal agent of the disease, identification and classification of the pathogen remain still uncertain due to its taxonomic confusion. Thirty-six Peronospora isolates from quinoa with different geographic origins including Argentina, Bolivia, Denmark, Ecuador, and Peru were morphologically and molecularly compared with Peronospora species from other Chenopodium species. The morphology of three herbarium specimens was similar to that of P. variabilis, which originated from C. album, characterized by flexuous to curved ultimate branchlets and pedicellated conidia. Phylogenetic analysis based on ITS rDNA sequences also placed the quinoa pathogen within the same clade as P. variabilis. Within the ITS rDNA sequences of the quinoa pathogens, two base substitutions were found, which separated the majority of the Danish isolates from isolates from South America, but no sequence difference was found among the isolates from different cultivars of quinoa. The present results indicate that the pathogen responsible for the quinoa downy mildew is identical to Peronospora variabilis and that it should not be lumped with P. farinosa as claimed previously by most studies.

  14. Potential of Pest and Host Phenological Data in the Attribution of Regional Forest Disturbance Detection Maps According to Causal Agent

    Science.gov (United States)

    Spruce, Joseph; Hargrove, William; Norman Steve; Christie, William

    2014-01-01

    Near real time forest disturbance detection maps from MODIS NDVI phenology data have been produced since 2010 for the conterminous U.S., as part of the on-line ForWarn national forest threat early warning system. The latter has been used by the forest health community to identify and track many regional forest disturbances caused by multiple biotic and abiotic damage agents. Attribution of causal agents for detected disturbances has been a goal since project initiation in 2006. Combined with detailed cover type maps, geospatial pest phenology data offer a potential means for narrowing the candidate causal agents responsible for a given biotic disturbance. U.S. Aerial Detection Surveys (ADS) employ such phenology data. Historic ADS products provide general locational data on recent insect-induced forest type specific disturbances that may help in determining candidate causal agents for MODIS-based disturbance maps, especially when combined with other historic geospatial disturbance data (e.g., wildfire burn scars and drought maps). Historic ADS disturbance detection polygons can show severe and extensive regional forest disturbances, though they also can show polygons with sparsely scattered or infrequent disturbances. Examples will be discussed that use various historic disturbance data to help determine potential causes of MODIS-detected regional forest disturbance anomalies.

  15. Effect of Acacia raddiana extracts on Fusarium oxysporum f. sp. albedinis, the causal agent of Bayoud

    Directory of Open Access Journals (Sweden)

    Noureddine BOULENOUAR

    2016-07-01

    Full Text Available In the present study, a medicinal plant from algerian Sahara (South-West of Algeria, Acacia raddiana has been used (leaves, bark to evaluate its extracts (reflux extraction with four solvents: methanol, ethyl acetate, dichloromethane, hexane on Fusarium oxysporum f. sp. albedinis (Foa. The Foa is the causal agent of the most dangerous disease of date palm (Phoenix dactylifera L.. The preliminary evaluation has been realized by agar diffusion technique and virulence test on potato tuber tissues. The extracts that present an inhibition or decrease the relative virulence (RV below 50% undergo phytochemical screening and direct bioautography. The bioautography has been used to localize the antifungal activity on the chromatogram and study the correlation with phytochemical screening data. Among eight extracts, five has been chosen for phytochemical screening and bioautography (2 leaves extracts and 3 bark extracts. Only six tests among 32 (22.58% present a detectable effect. The best effect is related to bark extract with ethyl acetate (inhibition diameter: 18mm, which is a moderate effect. Some extracts show an increase in RV. On the other hand, others decrease the RV. The best effect on RV is presented by hexanic extract of bark (RV=48%. The phytochemical screening highlighted the presence of flavonoids, tannins, coumarins and alkaloids in the studied plant. The direct bioautography has demonstrated no detectable effect. According to realized analyses, we can conclude that this species contains bioactive substances on Foa but need more precise analyses. The reason is simple, in addition to synergy principle in the crude extracts; the quantity of these metabolites is low compared to the detection level.

  16. Draft Genome Sequences of Two Isolates of Colletotrichum lindemuthianum, the Causal Agent of Anthracnose in Common Beans.

    Science.gov (United States)

    de Queiroz, Casley Borges; Correia, Hilberty L Nunes; Menicucci, Renato Pedrozo; Vidigal, Pedro M Pereira; de Queiroz, Marisa Vieira

    2017-05-04

    Colletotrichum lindemuthianum is the causal agent of anthracnose in common beans, one of the main limiting factors of their culture. Here, we report for the first time, to our knowledge, a draft of the complete genome sequences of two isolates belonging to 83.501 and 89 A 2 2-3 of C. lindemutuianum . Copyright © 2017 de Queiroz et al.

  17. Noise resistance of the violation of local causality for pure three-qutrit entangled states

    International Nuclear Information System (INIS)

    Laskowski, Wiesław; Ryu, Junghee; Żukowski, Marek

    2014-01-01

    Bell's theorem started with two qubits (spins 1/2). It is a ‘no-go’ statement on classical (local causal) models of quantum correlations. After 25 years, it turned out that for three qubits the situation is even more astonishing. General statements concerning higher dimensional systems, qutrits, etc, started to appear even later, once the picture with spin (higher than 1/2) was replaced by a broader one, allowing all possible observables. This work is a continuation of the Gdansk effort to take advantage of the fact that Bell's theorem can be put in the form of a linear programming problem, which in turn can be translated into a computer code. Our results are numerical and classify the strength of the violation of local causality by various families of three-qutrit states, as measured by the resistance to noise. This is previously uncharted territory. The results may be helpful in suggesting which three-qutrit states will be handy for applications in quantum information protocols. One of the surprises is that the W state turns out to reveal a stronger violation of local causality than the GHZ (Greenberger–Horne–Zeilinger) state. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘50 years of Bell's theorem’. (paper)

  18. Noise resistance of the violation of local causality for pure three-qutrit entangled states

    Science.gov (United States)

    Laskowski, Wiesław; Ryu, Junghee; Żukowski, Marek

    2014-10-01

    Bell's theorem started with two qubits (spins 1/2). It is a ‘no-go’ statement on classical (local causal) models of quantum correlations. After 25 years, it turned out that for three qubits the situation is even more astonishing. General statements concerning higher dimensional systems, qutrits, etc, started to appear even later, once the picture with spin (higher than 1/2) was replaced by a broader one, allowing all possible observables. This work is a continuation of the Gdansk effort to take advantage of the fact that Bell's theorem can be put in the form of a linear programming problem, which in turn can be translated into a computer code. Our results are numerical and classify the strength of the violation of local causality by various families of three-qutrit states, as measured by the resistance to noise. This is previously uncharted territory. The results may be helpful in suggesting which three-qutrit states will be handy for applications in quantum information protocols. One of the surprises is that the W state turns out to reveal a stronger violation of local causality than the GHZ (Greenberger-Horne-Zeilinger) state. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘50 years of Bell's theorem’.

  19. Molecular characterization and pathogenicity assays of Colletotrichum acutatum, causal agent for lime anthracnose in Texas

    Science.gov (United States)

    Several distorted Mexican lime [Citrus aurantiifolia (Christm). Swingle] fruit, leaf, and twig samples with lime anthracnose symptoms were collected from three trees in residential areas of Brownsville, Texas. The causal fungal organism, Colletotrichum acutatum J. H. Simmonds was isolated from leave...

  20. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

    Science.gov (United States)

    Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T; Allin, Kristine H; Witte, Daniel R; Jørgensen, Marit E; Grarup, Niels; Pedersen, Oluf; Kilpeläinen, Tuomas O; Hansen, Torben

    2017-05-01

    Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10 -7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10 -6 , β 0.96 [95% CI 0.45, 1.47] p = 3 × 10 -4 , and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION

  1. ANTAGONISTIC EFFECT OF FOUR FUNGAL ISOLATES TO GANODERMA BONINENSE, THE CAUSAL AGENT OF BASAL STEM ROT OF OIL PALM

    Directory of Open Access Journals (Sweden)

    OKKY SETYAWATI DHARMAPUTRA

    1990-01-01

    Full Text Available Four fungal isolates from soils obtained from three sites of the oil palm plantations in North Sumatra were found antagonistic to Ganoderma boninense, the causal agent of basal stem rot of oil palm. Penicillium citrinum inhibited the growth of the pathogen and formed a zone of inhibition on the agar media. Trichoderma harzianum BIO - 1 as well as BIO - 2 and T. viride not only repressed the growth of the pathogen but also caused lysis of the hyphae, and the colony was totally overgrown by the antagonists.

  2. The Born Rule and Free Will: why Libertarian Agent-Causal Free Will is not "antiscientific"

    Science.gov (United States)

    Kastner, Ruth E.

    In the libertarian "agent causation" view of free will, free choices are attributable only to the choosing agent, as opposed to a specific cause or causes outside the agent. An often-repeated claim in the philosophical literature on free will is that agent causation necessarily implies lawlessness, and is therefore "antiscientific." That claim is critiqued and it is argued, on the contrary, that the volitional powers of a free agent need not be viewed as anomic, specifically with regard to the quantum statistical law (the Born Rule). Assumptions about the role and nature of causation, taken as bearing on volitional agency, are examined and found inadequate to the task. Finally, it is suggested that quantum theory may constitute precisely the sort of theory required for a nomic grounding of libertarian free will.

  3. Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders?

    Science.gov (United States)

    Hasche, Daniel; Vinzón, Sabrina E; Rösl, Frank

    2018-01-01

    There is still controversy in the scientific field about whether certain types of cutaneous human papillomaviruses (HPVs) are causally involved in the development of non-melanoma skin cancer (NMSC). Deciphering the etiological role of cutaneous HPVs requires - besides tissue culture systems - appropriate preclinical models to match the obtained results with clinical data from affected patients. Clear scientific evidence about the etiology and underlying mechanisms involved in NMSC development is fundamental to provide reasonable arguments for public health institutions to classify at least certain cutaneous HPVs as group 1 carcinogens. This in turn would have implications on fundraising institutions and health care decision makers to force - similarly as for anogenital cancer - the implementation of a broad vaccination program against "high-risk" cutaneous HPVs to prevent NMSC as the most frequent cancer worldwide. Precise knowledge of the multi-step progression from normal cells to cancer is a prerequisite to understand the functional and clinical impact of cofactors that affect the individual outcome and the personalized treatment of a disease. This overview summarizes not only recent arguments that favor the acceptance of a viral etiology in NMSC development but also reflects aspects of causality in medicine, the use of empirically meaningful model systems and strategies for prevention.

  4. Cutaneous Papillomaviruses and Non-melanoma Skin Cancer: Causal Agents or Innocent Bystanders?

    Directory of Open Access Journals (Sweden)

    Daniel Hasche

    2018-05-01

    Full Text Available There is still controversy in the scientific field about whether certain types of cutaneous human papillomaviruses (HPVs are causally involved in the development of non-melanoma skin cancer (NMSC. Deciphering the etiological role of cutaneous HPVs requires – besides tissue culture systems – appropriate preclinical models to match the obtained results with clinical data from affected patients. Clear scientific evidence about the etiology and underlying mechanisms involved in NMSC development is fundamental to provide reasonable arguments for public health institutions to classify at least certain cutaneous HPVs as group 1 carcinogens. This in turn would have implications on fundraising institutions and health care decision makers to force – similarly as for anogenital cancer – the implementation of a broad vaccination program against “high-risk” cutaneous HPVs to prevent NMSC as the most frequent cancer worldwide. Precise knowledge of the multi-step progression from normal cells to cancer is a prerequisite to understand the functional and clinical impact of cofactors that affect the individual outcome and the personalized treatment of a disease. This overview summarizes not only recent arguments that favor the acceptance of a viral etiology in NMSC development but also reflects aspects of causality in medicine, the use of empirically meaningful model systems and strategies for prevention.

  5. A review of the Mycrocylus ulei Ascomycetes fungus, causative agent of South American rubber-leaf blight Revisión sobre el hongo Microcyclus ulei, agente causal del mal suramericano de la hoja del caucho

    Directory of Open Access Journals (Sweden)

    Ancízar Aristizábar Fabio

    2006-12-01

    Full Text Available The Microcyclus ulei Ascomycetes fungus is the causal agent of south-American leaf blight (SALB, this being one of the most important diseases affecting the natural rubber tree (Hevea brasiliensis in Latina-America and has been responsible for numerous economic losses. This fungus has presented high physiological variability, suggesting its great adaptability. HCN tolerance has been described as being one of the mechanisms associated with its virulence. Resistant Hevea clones have been obtained by genetic improvement; however, the mechanisms associated with this are still not well known. Greater knowledge of this pathogen will lead to developing new control strategies and better understanding of the mechanisms associated with host resistance. Key words: Microcyclus ulei, SALB, Hevea brasiliensis.El hongo ascomycete Microcyclus ulei es el agente causal del SALB que es una de las enfermedades más importan­tes del árbol de caucho natural (Hevea brasiliensis en América Latina y ha sido responsable de numerosas pérdidas económicas. Este hongo ha presentado alta variabilidad fisiológica y se sugiere su alta adaptabilidad, dentro de los mecanismos asociados a su virulencia se ha descrito la tolerancia al HCN. Se han obtenido clones de Hevea resistentes mediante mejoramiento genético, sin embargo, aun no son bien conocidos los mecanismos asociados a ésta. Un mayor conocimiento de este patógeno permitirá el desarrollo de nuevas estrategias de control así como el mayor entendimiento de los mecanismos asociados a resistencia del hospedero. Palabras clave: Microcyclus ulei, SALB, Hevea brasiliensis.

  6. Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes

    NARCIS (Netherlands)

    H. Yaghootkar (Hanieh); C. Lamina (Claudia); R.A. Scott (Robert); Z. Dastani (Zari); M.-F. Hivert (Marie-France); L.L. Warren (Liling); A. Stancáková (Alena); S.G. Buxbaum (Sarah); L.-P. Lyytikäinen (Leo-Pekka); P. Henneman (Peter); Y. Wu (Ying); C.Y.Y. Cheung (Chloe); J.S. Pankow (James); A.U. Jackson (Anne); S. Gustafsson (Stefan); J.H. Zhao (Jing Hua); C. Ballantyne (Christie); W. Xie (Weijia); R.N. Bergman (Richard); M. Boehnke (Michael); F. El Bouazzaoui (Fatiha); F.S. Collins (Francis); S.H. Dunn (Sandra); J. Dupuis (Josée); N.G. Forouhi (Nita); C.J. Gillson (Christopher); A.T. Hattersley (Andrew); J. Hong (Jaeyoung); M. Kähönen (Mika); J. Kuusisto (Johanna); L. Kedenko (Lyudmyla); F. Kronenberg (Florian); A. Doria (Andrea); T.L. Assimes (Themistocles); E. Ferrannini (Ele); T. Hansen (Torben); K. Hao (Ke); H. Häring (Hans); J.W. Knowles (Joshua); C.M. Lindgren (Cecilia); J.J. Nolan (John); J. Paananen (Jussi); O. Pedersen (Oluf); T. Quertermous (Thomas); U. Smith (Ulf); T. Lehtimäki (Terho); C.-T. Liu (Ching-Ti); R.J.F. Loos (Ruth); M.I. McCarthy (Mark); A.D. Morris (Andrew); R.S. Vasan (Ramachandran Srini); T.D. Spector (Timothy); T.M. Teslovich (Tanya); J. Tuomilehto (Jaakko); J.A.P. Willems van Dijk (Ko); J. Viikari (Jorma); N. Zhu (Na); C. Langenberg (Claudia); E. Ingelsson (Erik); R.K. Semple (Robert); A. Sinaiko (Alan); C.N.A. Palmer (Colin); M. Walker (Mark); K.S.L. Lam (Karen); B. Paulweber (Bernhard); K.L. Mohlke (Karen); C.M. van Duijn (Cornelia); O. Raitakari (Olli); A. Bidulescu (Aurelian); N.J. Wareham (Nick); M. Laakso (Markku); D. Waterworth (Dawn); D.A. Lawlor (Debbie); J.B. Meigs (James); J.B. Richards (Brent); T.M. Frayling (Timothy)

    2013-01-01

    textabstractAdiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used

  7. Mendelian Randomisation Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A

    2013-01-01

    Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes but its causal role remains controversial. We used a Mendelian randomisation approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic varian...

  8. First Isolation and Molecular Characterization of Bacteriophages Infecting Acidovorax citrulli, the Causal Agent of Bacterial Fruit Blotch

    Directory of Open Access Journals (Sweden)

    Aryan Rahimi-Midani

    2018-02-01

    Full Text Available Bacteriophages of Acidovorax citrulli, the causal agent of bacterial fruit blotch, were isolated from 39 watermelon, pumpkin, and cucumber leaf samples collected from various regions of Korea and tested against 18 A. citrulli strains. Among the six phages isolated, ACP17 forms the largest plaque, and exhibits the morphology of phages in the Myoviridae family with a head diameter of 100 ± 5 nm and tail length of 150 ± 5 nm. ACP17 has eclipse and latent periods of 25 ± 5 min and 50 ± 5 min, respectively, and a burst size of 120. The genome of ACP17 is 156,281 base pairs with a G + C content of 58.7%, 263 open reading frames, and 4 transfer RNA genes. Blast search and phylogenetic analysis of the major capsid protein showed that ACP17 has limited homology to two Stentrophomonas phages, suggesting that ACP17 is a new type of Myoviridae isolated from A. citrulli.

  9. Indole-3-acetic acid biosynthesis in Fusarium delphinoides strain GPK, a causal agent of Wilt in Chickpea.

    Science.gov (United States)

    Kulkarni, Guruprasad B; Sanjeevkumar, S; Kirankumar, B; Santoshkumar, M; Karegoudar, T B

    2013-02-01

    Fusarium delphinoides (Ascomycota; Nectriaceae) is an indole-3-acetic acid (IAA) producing plant pathogen and a causal agent of wilt in chickpea. The IAA biosynthetic pathway in F. delphinoides strain GPK (FDG) was examined by analyzing metabolic intermediates and by feeding experiments. Gas chromatograph (GC) analysis of FDG culture filtrates showed the presence of metabolic intermediates of indole-3-pyruvic acid (IPyA), indole-3-acetamide (IAM), and tryptamine (TRA) pathways. The different IAA biosynthetic pathways were further confirmed by identifying the presence of different enzymes of these pathways. Substrate specificity study of aromatic amino acid aminotransferase revealed that the enzyme is highly specific for tryptophan (Trp) and α-ketoglutarate (α-kg) as amino group donor and acceptor, respectively. Furthermore, the concentration-dependent effect of exogenous IAA on fungal growth was established. Low concentration of exogenous IAA increases the fungal growth and at high concentration it decreases the growth of FDG.

  10. Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels

    DEFF Research Database (Denmark)

    Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T

    2017-01-01

    variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. RESULTS: Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10(-7)). However......, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0......(-4), and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION-PRO indicated that HOMA-IR is causally related to higher circulating fasting BCAA levels (β 0.73 [95% CI 0.26, 1.19] p = 0.002). CONCLUSIONS/INTERPRETATION: Our...

  11. Improved Diagnoses and Quantification of Fusarium virguliforme, Causal Agent of Soybean Sudden Death Syndrome.

    Science.gov (United States)

    Wang, Jie; Jacobs, Janette L; Byrne, Jan M; Chilvers, Martin I

    2015-03-01

    Fusarium virguliforme (syn. F. solani f. sp. glycines) is the primary causal pathogen responsible for soybean sudden death syndrome (SDS) in North America. Diagnosis of SDS is difficult because symptoms can be inconsistent or similar to several soybean diseases and disorders. Additionally, quantification and identification of F. virguliforme by traditional dilution plating of soil or ground plant tissue is problematic due to the slow growth rate and plastic morphology of F. virguliforme. Although several real-time quantitative polymerase chain reaction (qPCR)-based assays have been developed for F. virguliforme, the performance of those assays does not allow for accurate quantification of F. virguliforme due to the reclassification of the F. solani species complex. In this study, we developed a TaqMan qPCR assay based on the ribosomal DNA (rDNA) intergenic spacer (IGS) region of F. virguliforme. Specificity of the assay was demonstrated by challenging it with genomic DNA of closely related Fusarium spp. and commonly encountered soilborne fungal pathogens. The detection limit of this assay was determined to be 100 fg of pure F. virguliforme genomic DNA or 100 macroconidia in 0.5 g of soil. An exogenous control was multiplexed with the assay to evaluate for PCR inhibition. Target locus copy number variation had minimal impact, with a range of rDNA copy number from 138 to 233 copies per haploid genome, resulting in a minor variation of up to 0.76 cycle threshold values between strains. The qPCR assay is transferable across platforms, as validated on the primary real-time PCR platform used in the Northcentral region of the National Plant Diagnostic Network. A conventional PCR assay for F. virguliforme detection was also developed and validated for use in situations where qPCR is not possible.

  12. Nutritional improvement of the rose handling Peronospora Sparsa Berkeley, causal agent of downy mildew

    International Nuclear Information System (INIS)

    Castillo Carlos Fernando; Alvarez Elizabeth; Gomez Eduardo; Llano, German A; Castano Zapata, Jairo

    2010-01-01

    Nutritional solutions, silica, resistance, downy mildew. The downy mildew (Peronospora sparsa), is one of the most important diseases of rose in Colombia, causing losses up to 8%. The objective of this research was to determine a preventive control of the disease, through the improvement of the nutritional balance of the plant. The first phase, involved the effect of different concentrations of N, K, Ca, B and Mn, on the incidence and severity of the disease, and in the second one, the evaluation of the best five treatments of the first phase. The treatments were applied to the varieties Charlotte, Classy and Malibu during 4 weeks, using a splitting plot design with six replications. After one month the plants were inoculated with the fungus at a concentration of 3x104 sporangia mL.The results of the area under the disease progress curve (AUDPC), showed that the plants of Charlotte with 200 ppm of Si had the lowest expression of the disease. In Classy, the best treatment was the standard solution, demonstrating that the effects of the treatments depend of the variety. Charlotte and Malibu showed susceptibility, while Classy, partial resistance to the disease.

  13. Isolation and characterization of the mating type locus of Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana

    NARCIS (Netherlands)

    Conde, L.; Waalwijk, C.; Canto-Canché, B.B.; Kema, G.H.J.; Crous, P.W.; James, A.C.; Abeln, E.C.A.

    2007-01-01

    Idiomorphs mat1-1 and mat1-2 from Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana, were isolated. Degenerate oligos were used to amplify the HMG box of the mat1-2 idiomorph from M. fijiensis, showing homology with the HMG box of Mycosphaerella graminicola. Using a

  14. Variable number of tandem repeat markers in the genome sequence of Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana (Musa spp)

    NARCIS (Netherlands)

    Garcia, S.A.L.; Lee, van der T.A.J.; Ferreira, C.F.; Lintel Hekkert, te B.; Zapater, M.F.; Goodwin, S.B.; Guzmán, M.; Kema, G.H.J.; Souza, M.T.

    2010-01-01

    ABSTRACT. We searched the genome of Mycosphaerella fijiensis for molecular markers that would allow population genetics analysis of this plant pathogen. M. fijiensis, the causal agent of banana leaf streak disease, also known as black Sigatoka, is the most devastating pathogen attacking bananas

  15. Development of VNTR Markers to Assess Genetic Diversity of Mycosphaerella Fijiensis, the Causal Agent of Black Leaf Streak Disease in Bananas (Musa spp.)

    Science.gov (United States)

    Mycosphaerella fijiensis is the causal agent of black leaf streak (BLS) disease in bananas. This pathogen threatens global banana production as the main export cultivars are highly susceptible. As a consequence, commercial banana plantations must be protected chemically with fungicides; up to 40 app...

  16. Variable Number of Tandem Repeat Markers in the Genome Sequence of Mycosphaerella Fijiensis, the Causal Agent of Black Leaf Streak Disease of Banana (Musa spp.)

    Science.gov (United States)

    Mycosphaerella fijiensis, the causal agent of banana leaf streak disease (commonly known as black Sigatoka), is the most devastating pathogen attacking bananas (Musa spp). Recently the whole genome sequence of M. fijiensis became available. This sequence was screened for the presence of Variable Num...

  17. The Prevalence of Trypanosoma cruzi, the Causal Agent of Chagas Disease, in Texas Rodent Populations.

    Science.gov (United States)

    Aleman, Adriana; Guerra, Trina; Maikis, Troy J; Milholland, Matthew T; Castro-Arellano, Ivan; Forstner, Michael R J; Hahn, Dittmar

    2017-03-01

    Rodent species were assessed as potential hosts of Trypanosoma cruzi, the etiologic agent of Chagas disease, from five sites throughout Texas in sylvan and disturbed habitats. A total of 592 rodents were captured, resulting in a wide taxonomic representation of 11 genera and 15 species. Heart samples of 543 individuals were successfully analyzed by SybrGreen-based quantitative PCR (qPCR) targeting a 166 bp fragment of satellite DNA of T. cruzi. Eight rodents representing six species from six genera and two families were infected with T. cruzi. This is the first report of T. cruzi in the pygmy mouse (Baiomys taylori) and the white-footed mouse (Peromyscus leucopus) for the USA. All infected rodents were from the southernmost site (Las Palomas Wildlife Management Area). No differences in pathogen prevalence existed between disturbed habitats (5 of 131 tested; 3.8%) and sylvan habitats (3 of 40 tested; 7.5%). Most positives (n = 6, 16% prevalence) were detected in late winter with single positives in both spring (3% prevalence) and fall (1% prevalence). Additionally, 30 Triatoma insects were collected opportunistically from sites in central Texas. Fifty percent of these insects, i.e., 13 T. gerstaeckeri (68%), and two T. lecticularia (100%) were positive for T. cruzi. Comparative sequence analyses of 18S rRNA of samples provided identical results with respect to detection of the presence or absence of T. cruzi and assigned T. cruzi from rodents collected in late winter to lineage TcI. T. cruzi from Triatoma sp. and rodents from subsequent collections in spring and fall were different, however, and could not be assigned to other lineages with certainty.

  18. Identification of Agrobacterium vitis as a causal agent of grapevine crown gall in Serbia

    Directory of Open Access Journals (Sweden)

    Kuzmanović N.

    2012-01-01

    Full Text Available In 2010, a serious outbreak of crown gall disease was observed on grapevines (Vitis vinifera L. cv. Cabernet Sauvignon in several commercial vineyards located in the Vojvodina province, Serbia. Bacteria were isolated from the young tumor tissue on nonselective YMA medium and five representative strains were selected for further identification. Tumorigenic (Ti plasmid was detected in all strains by PCR using primers designed to amplify the virC pathogenicity gene, producing a 414-bp PCR product. The strains were identified as Agrobacterium vitis using differential physiological and biochemical tests, and a multiplex PCR assay targeting 23S rRNA gene sequences. In the pathogenicity assay, all strains induced characteristic symptoms on inoculated tomato and grapevine plants. They were less virulent on tomato plants in comparison to the reference strains of A. tumefaciens and A. vitis. [Ministarstva nauke Republike Srbije, br. III46008: Development of integrated management of harmful organisms in plant production in order to overcome resistance and to improve food quality and safety

  19. Genetic Diversity and Population Differentiation of the Causal Agent of Citrus Black Spot in Brazil

    Directory of Open Access Journals (Sweden)

    Ester Wickert

    2012-01-01

    Full Text Available One of the most important diseases that affect sweet orange orchards in Brazil is the Citrus Black Spot that is caused by the fungus Guignardia citricarpa. This disease causes irreparable losses due to the premature falling of fruit, as well as its severe effects on the epidermis of ripe fruit that renders them unacceptable at the fresh fruit markets. Despite the fact that the fungus and the disease are well studied, little is known about the genetic diversity and the structure of the fungi populations in Brazilian orchards. The objective of this work was study the genetic diversity and population differentiation of G. citricarpa associated with four sweet orange varieties in two geographic locations using DNA sequence of ITS1-5.8S-ITS2 region from fungi isolates. We observed that different populations are closely related and present little genetic structure according to varieties and geographic places with the highest genetic diversity distributed among isolates of the same populations. The same haplotypes were sampled in different populations from the same and different orange varieties and from similar and different origins. If new and pathogenic fungi would become resistant to fungicides, the observed genetic structure could rapidly spread this new form from one population to others.

  20. Nutritional improvement of the rose handling Peronospora Sparsa Berkeley, causal agent of downy mildew

    International Nuclear Information System (INIS)

    Castillo, Carlos Fernando; Alvarez, Elizabeth; Gomez, Eduardo; Llano, German; Castano Zapata, Jairo

    2010-01-01

    The downy mildew (Peronospora sparsa), is one of the most important diseases of rose in Colombia, causing losses up to 8%. The objective of this research was to determine a preventive control of the disease, through the improvement of the nutritional balance of the plant. The first phase, involved the effect of different concentrations of N, K, Ca, B and Mn, on the incidence and severity of the disease, and in the second one, the evaluation of the best five treatments of the first phase. The treatments were applied to the varieties Charlotte, Classy and Malibu during 4 weeks, using a splitting plot design with six replications. After one month the plants were inoculated with the fungus at a concentration of 3x104 sporangia mL. The results of the area under the disease progress curve (AUDPC), showed that the plants of Charlotte with 200 ppm of Si had the lowest expression of the disease. In Classy, the best treatment was the standard solution, demonstrating that the effects of the treatments depend of the variety. Charlotte and Malibu showed susceptibility, while Classy, partial resistance to the disease.

  1. Radicinin from Cochliobolus sp. inhibits Xylella fastidiosa, the causal agent of Pierce's Disease of grapevine.

    Science.gov (United States)

    Aldrich, Thomas J; Rolshausen, Philippe E; Roper, M Caroline; Reader, Jordan M; Steinhaus, Matthew J; Rapicavoli, Jeannette; Vosburg, David A; Maloney, Katherine N

    2015-08-01

    The fastidious phytopathogenic bacterium, Xylella fastidiosa, poses a substantial threat to many economically important crops, causing devastating diseases including Pierce's Disease of grapevine. Grapevines (Vitis vinifera L.) planted in an area under Pierce's Disease pressure often display differences in disease severity and symptom expression, with apparently healthy vines growing alongside the dying ones, despite the fact that all the vines are genetic clones of one another. Under the hypothesis that endophytic microbes might be responsible for this non-genetic resistance to X. fastidiosa, endophytic fungi were isolated from vineyard cvs. 'Chardonnay' and 'Cabernet Sauvignon' grown under high Pierce's Disease pressure. A Cochliobolus sp. isolated from a Cabernet Sauvignon grapevine inhibited the growth of X. fastidiosa in vitro. Bioassay-guided isolation of an organic extract of Cochliobolus sp. yielded the natural product radicinin as the major active compound. Radicinin also inhibited proteases isolated from the culture supernatant of X. fastidiosa. In order to assess structure-activity relationships, three semi-synthetic derivatives of radicinin were prepared and tested for activity against X. fastidiosa in vitro. Assay results of these derivatives are consistent with enzyme inactivation by conjugate addition to carbon-10 of radicinin, as proposed previously. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. In vitro antibacterial effect of exotic plants essential oils on the honeybee pathogen Paenibacillus larvae, causal agent of American foul brood

    Energy Technology Data Exchange (ETDEWEB)

    Fuselli, S. R.; Garcia de la Rosa, S. B.; Eguaras, M. J.; Fritz, R.

    2010-07-01

    Chemical composition and antimicrobial activity of exotic plants essential oils to potentially control Paenibacillus larvae, the causal agent of American foul brood disease (AFB) were determined. AFB represents one of the main plagues that affect the colonies of honeybees Apis mellifera L. with high negative impact on beekeepers worldwide. Essential oils tested were niaouli (Melaleuca viridiflora) and tea tree (Melaleuca alternifolia) from Myrtaceae, and citronella grass (Cymbopogon nardus) and palmarosa (Cymbopogon martinii) from Gramineae. The components of the essential oils were identified by SPME-GC/MS analysis. The antimicrobial activity of the oils against P. larvae was determined by the broth micro dilution method. In vitro assays of M. viridiflora and C. nardus oils showed the inhibition of the bacterial strains at the lowest concentrations tested, with minimal inhibitory concentration (MIC) mean value about 320 mg L{sup -}1 for both oils, respectively. This property could be attributed to the kind and percentage of the components of the oils. Terpinen-4-ol (29.09%), {alpha}-pinene (21.63%) and limonene (17.4%) were predominant in M. viridiflora, while limonene (24.74%), citronelal (24.61%) and geraniol (15.79%) were the bulk of C. nardus. The use of these essential oils contributes to the screening of alternative natural compounds to control AFB in the apiaries; toxicological risks and other undesirable effects would be avoided as resistance factors, developed by the indiscriminate use of antibiotics. (Author) 40 refs.

  3. Variable number of tandem repeat markers in the genome sequence of Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana (Musa spp).

    Science.gov (United States)

    Garcia, S A L; Van der Lee, T A J; Ferreira, C F; Te Lintel Hekkert, B; Zapater, M-F; Goodwin, S B; Guzmán, M; Kema, G H J; Souza, M T

    2010-11-09

    We searched the genome of Mycosphaerella fijiensis for molecular markers that would allow population genetics analysis of this plant pathogen. M. fijiensis, the causal agent of banana leaf streak disease, also known as black Sigatoka, is the most devastating pathogen attacking bananas (Musa spp). Recently, the entire genome sequence of M. fijiensis became available. We screened this database for VNTR markers. Forty-two primer pairs were selected for validation, based on repeat type and length and the number of repeat units. Five VNTR markers showing multiple alleles were validated with a reference set of isolates from different parts of the world and a population from a banana plantation in Costa Rica. Polymorphism information content values varied from 0.6414 to 0.7544 for the reference set and from 0.0400 and 0.7373 for the population set. Eighty percent of the polymorphism information content values were above 0.60, indicating that the markers are highly informative. These markers allowed robust scoring of agarose gels and proved to be useful for variability and population genetics studies. In conclusion, the strategy we developed to identify and validate VNTR markers is an efficient means to incorporate markers that can be used for fungicide resistance management and to develop breeding strategies to control banana black leaf streak disease. This is the first report of VNTR-minisatellites from the M. fijiensis genome sequence.

  4. Assessment of diversity and genetic relationships of Neonectria ditissima: the causal agent of fruit tree canker.

    Science.gov (United States)

    Ghasemkhani, Marjan; Garkava-Gustavsson, Larisa; Liljeroth, Erland; Nybom, Hilde

    2016-01-01

    Neonectria ditissima is one of the most important fungal pathogens of apple trees, where it causes fruit tree canker. Information about the amount and partitioning of genetic variation of this fungus could be helpful for improving orchard management strategies and for breeding apple cultivars with high levels of genetically determined resistance. In this study single-spore Neonectria isolates originating from both the same and from different perithecia, apple cultivars and apple orchards in Sweden and Belgium, were evaluated for AFLP- and SSR-based genetic similarity and for mating system. Seven SSR loci produced a total of 31 alleles with an average of 4 alleles per locus, while 11 AFLP primer combinations produced an average of 35 fragments per primer combination and 71 % polymorphic fragments. An AFLP-based analysis of molecular variance (AMOVA) revealed that 89 % of the variation was found within orchards and 11 % between orchards. Genetic similarity among the studied isolates was illustrated with a principal coordinate analyseis (PCoA) and a dendrogram. AFLP-based Jaccard's similarity coefficients were the highest when single-ascospore isolates obtained from the same perithecium were compared, medium-high for isolates from different perithecia on the same tree, and lowest when isolates from different trees were compared. Based on the results of PCoA and AMOVA analysis, isolates from the same or geographically close orchards did not group together. Since AFLP profiles differed also when single-ascospore isolates from the same perithecium were compared, the mating system of N. ditissima is most likely heterothallic.

  5. Presencia de Blastocystis Hominis como agente causal de enfermedades gatrointestinales en la comuna 7 (Gaira del Distrito de Santa Marta

    Directory of Open Access Journals (Sweden)

    Sonja Liliana Lozano Socarras

    2013-10-01

    Full Text Available La Blastocystis hominis es un protozoo que causa cuadros diarreicos. Es altamente prevalente en poblaciones que no cuentan con servicios adecuados de higiene, alcantarillado y salud pública. La infección con Blastocystis hominis frecuentemente concomita con otros enteropatógenos de reconocida patogenicidad, además se ha reportado como parásito oportunista en pacientes con VIII SIDA. El objetivo del presente estudio es determinar la presencia de Blastocystis hominis en pacientes de consulta externa con síntomas asociados a enfermedades gastrointestinales, en la comuna 7 del distrito de Santa Marta, Colombia, durante el mes de Enero a Diciembre de 2004. El método de diagnóstico utilizado fue examen coproparasitológico seriado y el número de pacientes analiza-dos fue de 291. Los resultados muestran una alta presencia de Blastocystis hominken pacientes con enfermedad diarreica residentes en Gaira. Un alto porcentaje de la población parasitada (62,6% presento como único agente causal de la enfermedad diarreica al Blastocystis hominis lo que sugiere la presencia de otras enfermedades que pueden involucrar un compromiso inmunológico, el efecto será una respuesta inmune débil contra el parásito.

  6. Morphological and molecular identification of Fusarium tricinctum and Fusarium acuminatum as causal agents of garlic bulbs rot in Serbia

    Directory of Open Access Journals (Sweden)

    Ignjatov Maja V.

    2017-01-01

    Full Text Available Garlic (Allium sativum L. is considered to be one of the oldest crops in the world. During 2016, infected garlic bulbs occurred in storages on several localities of the Province of Vojvodina. Symptomatic cloves showed typical rot symptoms such as softened and spongy areas covered with white fungal growth with deep lesions formed on the cloves which became dry over time. A total of 36 isolates of Fusarium species were obtained from diseased cloves of garlic. Colony morphology and microscopic properties of isolated Fusarium species were recorded from the cultures grown on PDA and CLA, respectively. Identification of two chosen isolates was performed by sequencing the EF-1α gene. The TEF sequence of isolate JBL12 showed 100% similarity with several F. tricinctum sequences and sequence of JBL539 showed 99% identity with several F. acuminatum sequences and they were deposited in the NCBI GenBank. Based on the results of the morphological and molecular identification, isolates JBL12 and JBL539 were identified as F. tricinctum and F. acuminatum, respectively, as new causal agents of garlic bulbs rot in Serbia. Specific primers were designed for the PCR identification of the F. tricinctum. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. TR31030

  7. Development of Nested-PCR Assay to Detect Acidovorax citrulli, a Causal Agent of Bacterial Fruit Blotch at Cucurbitaceae

    Directory of Open Access Journals (Sweden)

    Young-Tak Kim

    2015-06-01

    Full Text Available The specific and sensitive nested-PCR method to detect Acidovorax citrulli, a causal agent of bacterial fruit blotch on cucurbitaceae, was developed. PCR primers were designed from the draft genome sequence which was obtained with the Next Generation Sequencing of A. citrulli KACC10651, and the nested-PCR primer set (Ac-ORF 21F/Ac-ORF 21R were selected by checking of specificity to A. citrulli with PCR assays. The selected nested-PCR primer amplified the 140 bp DNA only from A. citrulli strains, and detection sensitivity of the nested PCR increased 10,000 times of 1st PCR detection limit (10 ng genomic DNA/PCR. The nested PCR detected A. citrulli from the all samples of seed surface wash (external seed detection of the artificially inoculated watermelon seeds with 101 cfu/ml and above population of A. citrulli while the nested PCR could not detected A. citrulli from the mashed seed suspension (internal seed detection of the all artificially inoculated watermelon seeds. When the naturally infested watermelon seeds (10% seed infested rate with grow-out test used, the nested PCR detected A. citrulli from 2 seed samples out of 10 replication samples externally and 5 seed samples out of 10 replication samples internally. We believe that the nested-PCR developed in this study will be useful method to detect A. citrulli from the Cucurbitaceae seeds.

  8. Xanthomonas oryzae pv oryzae the Causal Agent of Bacterial Leaf Blight of rice: Isolation, Characterization, and Study of Transposon Mutagenesis

    Directory of Open Access Journals (Sweden)

    Abdjad Asih Nawangsih

    2011-04-01

    Full Text Available Xanthomonas oryzae pv oryzae the Causal Agent of Bacterial Leaf Blight of rice: Isolation, Characterization, and Study of Transposon Mutagenesis. X. oryzae pv. oryzae (Xoo causes bacterial leaf blight (BLB of rice (Oryza sativa L., a major disease that constrains production of the staple crop in many countries of the world. Identification of X. oryzae pv. oryzae (Xoo was conducted based on the disease symptoms, pathogenicity, morphological, physiological, and genetic characteristics of bacterial cultures isolated from the infected plants. Fifty bacterial isolates predicted as Xoo have been successfully isolated. They are aerobic, rod shaped, and Gram negative bacteria. The isolates were evaluated for their hypersensitivity in tobacco and pathogenicity in rice plant. Fifty isolates induced hypersensitive reaction in tobacco and showed pathogenicity symptom in rice in different length. Based on physiological test, hypersensitivity and pathogenicity reactions, three bacterial isolates strongly predicted as Xoo, i.e. STG21, STG42, and STG46, were non indole formation, non pigment fluorescent, hydrolyzed casein, catalase activity positive, but negative oxidase. Partial sequencing of 16S rRNA genes of STG21 and STG42 showed 80% and 82% homology with X. oryzae, respectively, while STG46 showed 84% homology with X. campestris. Mini-Tn5 transposon mutagenesis of STG21 generated one of the mutants (M5 lossed it’s ability to induce hypersensitive reaction in tobacco plant and deficient in pathogenicity on rice. The lesion length of rice leaf caused by the mutant M5 decreased up to 80%.

  9. [Susceptibility and resistence of Pseudomonas aeruginosa to antimicrobial agents].

    Science.gov (United States)

    Gamero Delgado, M C; García-Mayorgas, A D; Rodríguez, F; Ibarra, A; Casal, M

    2007-06-01

    Pseudomonas aeruginosa is an opportunistic microorganism that is frequently the cause of nosocomial infections. Multiple mechanisms are involved in its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. The objective of this study was to assess the susceptibility and resistance patterns of P. aeruginosa strains isolated in Hospital Reina Sofia between 2000 and 2005, as well as to analyze the differences between intrahospital and extrahospital isolates in 2005 and to compare the results with those obtained in other studies. A total of 3,019 strains of P. aeruginosa from different hospitals and nonhospital settings were evaluated, taking into consideration their degree of sensitivity to different antibiotics. The MICs were determined by means of the Wider I automated system (Soria Melguizo), taking into consideration the criteria of susceptibility and resistance recommended by MENSURA. Results of the analysis showed that P. aeruginosa maintained similar levels of antimicrobial susceptibility during the period 2000-2005, with increased susceptibility to amikacin, gentamicin and tobramycin. There were also important differences in the degree of susceptibility between intrahospital and extrahospital strains, except for imipenem and fosfomycin. The intrahospital difference in susceptibility was also evaluated, emphasizing the importance of periodically studying susceptibility and resistance patterns of P. aeruginosa in each setting in order to evaluate different therapeutic guidelines, as it is not always advisable to extrapolate data from different regions. These differences can be explained by the different use of antibiotics in each center and the geographic variations of the resistance mechanisms of P. aeruginosa.

  10. Podredumbres basales de Gypsophila paniculata (Caryophyllaceae: Agentes causales y su patogenicidad potencial sobre Dianthus caryophyllus (Caryophyllaceae Basal rots of Gypsophila paniculata (Caryophyllaceae: Causal agents and its potential pathogenicity on Dianthus caryophyllus (Caryophyllaceae

    Directory of Open Access Journals (Sweden)

    Silvia María Wolcan

    Full Text Available Los objetivos del trabajo fueron identificar a los agentes causales de las podredumbres basales de Gypsophila paniculata en la Argentina y probar su posible patogenicidad sobre Dianthus caryophyllus . A partir de plantas con síntomas de «podredumbre de la corona» (la más importante se aislaron en orden decreciente: Fusarium solani , F. oxysporum , Phytophthora nicotianae , Rhizoctonia solani , F. graminearum , F. verticillioides, F. equiseti y Pythium sp. y de plantas con «podredumbre basal del tallo» F. graminearum , F. oxysporum y F. solani . Con distintas cepas de cada hongo se hicieron pruebas de patogenicidad mediante la infestación del suelo y el depósito de inóculo en heridas producidas en los tallos. En la «podredumbre de la corona» fueron patógenos P. nicotianae causando decaimiento rápido de la parte aérea y podredumbre blanda de la corona y R. solani causando una pudrición más lenta y tejidos desintegrados. F. graminearum fue el patógeno de la «podredumbre basal del tallo» de gipsofila, que se describe por primera vez en este hospedante , comprobando que el hongo penetra sólo por heridas del tallo. En condiciones de inoculación se confirmó que algunas cepas de R. solani y de F. graminearum aisladas de gipsofila pueden ser patógenas de clavel mientras que sólo algunas de P. nicotianae resultaron patógenas débiles.The aims of the paper were to determine the causal agents of basal rots of Gypsophila paniculata in Argentina, and to evaluate its possible pathogenicity on Dianthus caryophyllus. Fusarium solani, F. oxysporum , Phytophthora nicotianae , Rhizoctonia solani , F. graminearum , F. verticilloides, F. equiseti and Pythium sp. were isolated in decreasing order from plants with symptoms of «crown rot» (the major basal rot. F. graminearum , F. oxysporum and F. solani were isolated from plants with «basal stem rot». Inoculations of gypsophila were performed by soil infestation and by placing inoculum on

  11. ITS-rDNA phylogeny of Colletotrichum spp. causal agent of apple Glomerella leaf spot Filogenia por ITS-rDNA de Colletotrichum spp., agente causal da mancha foliar da Gala em macieira

    Directory of Open Access Journals (Sweden)

    Diorvania Ribeiro Giaretta

    2010-04-01

    Full Text Available Several diseases have affected apple production, among them there is Glomerella leaf spot (GLS caused by Colletotrichum spp. The first report of this disease in apple was in plants nearby citrus orchards in São Paulo State, Brazil. The origin of this disease is still not clear, and studies based on the molecular phylogeny could relate the organisms evolutionarily and characterize possible mechanisms of divergent evolution. The amplification of 5.8S-ITS (Internal Transcribed Spacer of rDNA of 51 pathogenic Colletotrichum spp. isolates from apples, pineapple guava and citrus produced one fragment of approximately 600 bases pairs (bp for all the isolates analyzed. The amplified fragments were cleaved with restriction enzymes, and fragments from 90 to 500bp were obtained. The sequencing of this region allowed the generation of a phylogenetic tree, regardless of their hosts, and 5 isolated groups were obtained. From the "in silico" comparison, it was possible to verify a variation from 93 to 100% of similarity between the sequences studied and the Genbank data base. The causal agent of GLS is nearly related (clustered to isolates of pineapple guava and to the citrus isolates used as control.A produção de maçã vem sendo comprometida pela ocorrência de muitas doenças, entre as quais se destaca a Mancha Foliar de Glomerella (MFG, causada por Colletotrichum spp. O primeiro relato dessa doença em maçã foi registrado em plantas próximas a pomares de citrus no Estado de São Paulo, Brasil. A origem da MFG ainda não está bem clara, e estudos baseados na filogenia permitirão relacionar o organismo evolutivamente, possibilitando caracterizar possíveis mecanismos divergentes de evolução. A amplificação da região 5.8S-ITS (espaçador interno transcrito do rDNA de 51 isolados de Colletotrichum patogênicos em de maçã, goiabeira serrana e citrus produziu um fragmento de aproximadamente 600 pares de bases (pb para todos os isolados analisados

  12. Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences.

    NARCIS (Netherlands)

    Broxterman, H.J.; Lankelma, J.; Hoekman, K.

    2003-01-01

    Intrinsic resistance to anticancer drugs, or resistance developed during chemotherapy, remains a major obstacle to successful treatment. This is the case both for resistance to cytotoxic agents, directed at malignant cells, and for resistance to anti-angiogenic agents, directed at non-malignant

  13. Children as agents of change in combatting antibiotic resistance.

    Science.gov (United States)

    Molnar, Andreea

    2017-01-01

    Antibiotic resistance is a worldwide problem and changes are needed in the way antibiotics are used. The value of engaging children as key contributors in health care campaigns to increase the appropriate use of antibiotics has not been fully recognized. Little is known about how to design educational materials for children in order to enable them to be agents of change in their communities. Science education needs to improve the way it engages children so as to give them the tools needed to make responsible decisions on antibiotic use.

  14. Efecto biofungicida del gel de Aloe vera sobre Mycosphaerella fijiensis, agente causal de la Sigatoka negra en Musa (AAA

    Directory of Open Access Journals (Sweden)

    Edwin Jaramillo Aguilar

    2017-01-01

    Full Text Available El objetivo de este trabajo fue evaluar a nivel in vitro la actividad antifúngica del gel de Aloe vera sobre el crecimiento micelial de Mycosphaerella fijiensis. Se utilizó la técnica de envenenamiento en el medio de cultivo PDA para determinar la actividad antifúngica del gel. El diseño utilizado fue completamente al azar, con siete tratamientos y tres repeticiones. En los tratamientos se utilizó un fungicida químico comercial (propiconazol, a 250 ppm y 500 ppm; un biofungicida comercial (Trichoderma sp. a 500 ppm y 1000 ppm; ambos productos se usaron como testigo químico y biológico, respectivamente; el gel de Aloe vera a 500 ppm y 1000 ppm; y un testigo absoluto. Se determinó diferencias significativas entre los tratamientos (ANOVA, El test de Tukey demostró que todos los tratamientos registraron diferencia significativa (p ≤ 0,05 con respecto al testigo absoluto. El propiconazol presentó el mayor porcentaje de inhibición del micelio (73,10%; el test de Tukey y el porcentaje de inhibición del micelio presentaron valores similares en el control del crecimiento del hongo a los 30 días de inoculación, en los tratamientos gel de Aloe vera y el T6 de Trichoderma sp. Los resultados sugieren que el Aloe vera podría ser un adecuado biofungicida para el control de Mycosphaerella fijiensis, agente causal de la Sigatoka negra.

  15. Nutritional capability of and substrate suitability for Pseudogymnoascus destructans, the causal agent of bat white-nose syndrome.

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    Daniel B Raudabaugh

    Full Text Available Pseudogymnoascus destructans, the causal agent of bat white-nose syndrome, has caused nearly six million deaths in North American bats since its introduction into the United States in 2006. Current research has shown that caves can harbor P. destructans even after the infected bats are removed and bats no longer visit or inhabit previously infected caves. Our research focuses on elucidating reservoir requirements by investigating the nutritional capabilities of and substrate suitability requirements for six different P. destructans isolates from various localities including Illinois, Indiana, New York (Type specimen, and Pennsylvania. Enzyme assays implicate that both urease and b-glucosidase appear to be constitutive, lipase and esterase activity were more rapid than proteinase activity on 6% gelatin, gelatin degradation was accompanied by medium alkalinization, the reduction of thiosulfate generated hydrogen sulfide gas, chitinase and manganese dependent peroxidase activity were not visually demonstrated within eight weeks, and keratinase activity was not evident at pH 8 within eight weeks. We demonstrate that all P. destructans isolates are capable of growth and sporulation on dead fish, insect, and mushroom tissues. Sole nitrogen source assays demonstrated that all P. destructans isolates exhibit Class 2 nitrogen utilization and that growth-dependent interactions occur among different pH and nitrogen sources. Substrate suitability assays demonstrated that all isolates could grow and sporulate on media ranging from pH 5-11 and tolerated media supplemented with 2000 mg/L of calcium and 700 mg/L of three separated sulfur compounds: thiosulfate L-cysteine, and sulfite. All isolates were intolerant to PEG-induced matric potential with delayed germination and growth at -2.5 MPa with no visible germination at -5 MPa. Interestingly, decreasing the surface tension with Tween 80 permitted germination and growth of P. destructans in -5 MPa PEG medium

  16. Nutritional capability of and substrate suitability for Pseudogymnoascus destructans, the causal agent of bat white-nose syndrome.

    Science.gov (United States)

    Raudabaugh, Daniel B; Miller, Andrew N

    2013-01-01

    Pseudogymnoascus destructans, the causal agent of bat white-nose syndrome, has caused nearly six million deaths in North American bats since its introduction into the United States in 2006. Current research has shown that caves can harbor P. destructans even after the infected bats are removed and bats no longer visit or inhabit previously infected caves. Our research focuses on elucidating reservoir requirements by investigating the nutritional capabilities of and substrate suitability requirements for six different P. destructans isolates from various localities including Illinois, Indiana, New York (Type specimen), and Pennsylvania. Enzyme assays implicate that both urease and b-glucosidase appear to be constitutive, lipase and esterase activity were more rapid than proteinase activity on 6% gelatin, gelatin degradation was accompanied by medium alkalinization, the reduction of thiosulfate generated hydrogen sulfide gas, chitinase and manganese dependent peroxidase activity were not visually demonstrated within eight weeks, and keratinase activity was not evident at pH 8 within eight weeks. We demonstrate that all P. destructans isolates are capable of growth and sporulation on dead fish, insect, and mushroom tissues. Sole nitrogen source assays demonstrated that all P. destructans isolates exhibit Class 2 nitrogen utilization and that growth-dependent interactions occur among different pH and nitrogen sources. Substrate suitability assays demonstrated that all isolates could grow and sporulate on media ranging from pH 5-11 and tolerated media supplemented with 2000 mg/L of calcium and 700 mg/L of three separated sulfur compounds: thiosulfate L-cysteine, and sulfite. All isolates were intolerant to PEG-induced matric potential with delayed germination and growth at -2.5 MPa with no visible germination at -5 MPa. Interestingly, decreasing the surface tension with Tween 80 permitted germination and growth of P. destructans in -5 MPa PEG medium within 14 days

  17. Parasitosis intestinales en Argentina: principales agentes causales encontrados en la población y en el ambiente

    Directory of Open Access Journals (Sweden)

    María M Juárez

    Full Text Available Las parasitosis intestinales se encuentran ampliamente distribuidas en el mundo, con mayor prevalencia en los países en desarrollo. Principalmente afectan a los niños, en los que además provocan disminución del desarrollo físico y mental, situación que puede potenciarse enormemente cuando se suma a un estado nutricional deficiente. La Organización Mundial de la Salud las considera una de las principales causas de morbilidad, estrechamente ligada a la pobreza y relacionada con inadecuada higiene personal, incorrecta manipulación de los alimentos crudos, falta de servicios sanitarios, falta de provisión de agua potable y contaminación fecal del ambiente. Algunas enfermedades parasitarias se vinculan con condiciones de transmisión que existen universalmente, por lo que son cosmopolitas, mientras que otras tienen distribución geográfica variable. En los últimos años, debido a la globalización, el movimiento de personas de zonas endémicas a regiones no endémicas ha permitido la diseminación de ciertas parasitosis. Y aunque también influyen en la frecuencia de algunas de estas enfermedades las costumbres de los pueblos, las condiciones ambientales son un factor determinante para la supervivencia de los parásitos. En nuestro país, debido a la diversidad de suelos y condiciones climáticas que existen, es posible hallar variedad de agentes causales de estas parasitosis. El objetivo de este trabajo fue realizar una revisión bibliográfica de los agentes parasitarios causantes de enfermedades entéricas encontrados en la República Argentina, tanto en materia fecal de personas como en el ambiente, ya que la contaminación parasitaria de este último constituye un indicador directo del riesgo de infección por parásitos intestinales.

  18. Novel agents in the management of castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Shruti Chaturvedi

    2014-01-01

    Full Text Available Prostate cancer (PCa is a leading cause of cancer mortality in men and despite high cure rates with surgery and/or radiation, 30-40% of patients will eventually develop advanced disease. Androgen deprivation is the first line therapy for standard of care for men with advanced disease. Eventually however all men will progress to castration-resistant prostate cancer (CRPC. Insight into the molecular mechanisms of androgen resistance has led to the development of alternative novel hormonal agents. Newer hormonal agents such as abiraterone, enzalutamide and TOK-001; and the first cancer vaccine, Sipuleucel T have been approved for use in men with CRPC. The recognition of the importance of bone health and morbidity associated with skeletal related events has led to the introduction of the receptor activator of nuclear factor kappa-B-ligand inhibitor denosumab. Other molecularly targeted therapies have shown promise in pre-clinical studies, but this has not consistently translated into clinical efficacy. It is increasingly evident that CRPC is a heterogeneous disease and an individualized approach directed at identifying primary involvement of specific pathways could maximize the benefit from targeted therapies. This review focuses on targeted therapy for PCa with special emphasis on therapies that have been Food and Drug Administration approved for use in men with CRPC.

  19. Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance?

    NARCIS (Netherlands)

    Li, Naishi; Fu, Jingyuan; Koonen, Debby P.; Kuivenhoven, Jan Albert; Snieder, Harold; Hofker, Marten H.

    Insulin resistance often occurs with dyslipidemia as part of the metabolic syndrome and the current dominant paradigm is that insulin resistance leads to dyslipidemia. However, dyslipidemia may also cause insulin resistance; this was postulated 30 years ago, but has never been substantiated.

  20. Murcha do manjericão (Ocimum basilicum no Brasil: agente causal, círculo de plantas hospedeiras e transmissão via semente Sweet basil (Ocimum basilicum wilt in Brazil: causal agent, host range and seed transmission

    Directory of Open Access Journals (Sweden)

    Ailton Reis

    2007-06-01

    Full Text Available O manjericão (Ocimum basilicum L. é uma hortaliça da família Lamiaceae, utilizada na culinária ou como matéria prima para a indústria de fármacos e óleos essenciais. Amostras de plantas de manjericão apresentando sintomas de murcha, seca de hastes e podridão de colo foram coletadas na área rural de Brazlândia (DF durante a estação chuvosa de 2005. Outras duas amostras foram coletadas em plantas cultivadas em campo aberto e casas de vegetação na região de Ponte Alta (DF. Isolados de um fungo, identificado como Fusarium oxysporum, foram obtidos em todas as amostras. Testes de patogenicidade foram conduzidos com mudas das cultivares O. basilicum 'Dark Opal' e 'Italian Large Leaf', e de acessos das espécies O. americanum L. (manjericão de folha miúda, O. campechianum Mill. (alfavaca, Origanum manjorana L. (manjerona, Origanum vulgare L. (orégano, Mentha arvensis L. (menta, Coleus blumei Benth. (tapete, Leonorus sibiricus L. (rubim e Leonotis nepetaefolia (L. W.T. Aiton (cordão-de-frade. Todos os isolados fúngicos mostraram-se altamente virulentos sobre as duas cultivares de manjericão. Em O. campechianum e O. americanum os isolados causaram apenas suave escurecimento vascular e leve redução de crescimento, sendo avirulentos sobre acessos das espécies O. manjorana, O. vulgare, M. arvensis, C. blumei, L. sibiricus e L. nepetaefolia. Este conjunto de dados indicou que o agente causal da doença é o fungo F. oxysporum f. sp. basilici, constituindo-se no primeiro registro formal deste patógeno no Brasil. Os lotes de sementes utilizados nas áreas de ocorrência da doença foram submetidos a um teste de sanidade visando verificar a presença do patógeno. O fungo F. oxysporum f. sp. basilici foi detectado em quatro dos seis lotes e os isolados obtidos das sementes contaminadas mostraram similar sintomatologia e um idêntico perfil de virulência aos verificados em campo e casa de vegetação, sugerindo que as sementes

  1. Hepatitis C Virus Resistance to Carbohydrate-Binding Agents.

    Directory of Open Access Journals (Sweden)

    Laure Izquierdo

    Full Text Available Carbohydrate binding agents (CBAs, including natural lectins, are more and more considered as broad-spectrum antivirals. These molecules are able to directly inhibit many viruses such as Human Immunodeficiency Virus (HIV, Hepatitis C Virus (HCV, Dengue Virus, Ebola Virus or Severe Acute Respiratory Syndrome Coronavirus through binding to envelope protein N-glycans. In the case of HIV, it has been shown that CBAs select for mutant viruses with N-glycosylation site deletions which are more sensitive to neutralizing antibodies. In this study we aimed at evaluating the HCV resistance to CBAs in vitro. HCV was cultivated in the presence of increasing Galanthus nivalis agglutinin (GNA, Cyanovirin-N, Concanavalin-A or Griffithsin concentrations, during more than eight weeks. At the end of lectin exposure, the genome of the isolated strains was sequenced and several potential resistance mutations in the E1E2 envelope glycoproteins were identified. The effect of these mutations on viral fitness as well as on sensitivity to inhibition by lectins, soluble CD81 or the 3/11 neutralizing antibody was assessed. Surprisingly, none of these mutations, alone or in combination, conferred resistance to CBAs. In contrast, we observed that some mutants were more sensitive to 3/11 or CD81-LEL inhibition. Additionally, several mutations were identified in the Core and the non-structural proteins. Thus, our results suggest that in contrast to HIV, HCV resistance to CBAs is not directly conferred by mutations in the envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms.

  2. Specific PCR detection of Fusarium oxysporum f. sp. raphani: a causal agent of Fusarium wilt on radish plants.

    Science.gov (United States)

    Kim, H; Hwang, S-M; Lee, J H; Oh, M; Han, J W; Choi, G J

    2017-08-01

    Fusarium oxysporum, a causal agent of Fusarium wilt, is one of the most important fungal pathogens worldwide, and detection of F. oxysporum DNA at the forma specialis level is crucial for disease diagnosis and control. In this study, two novel F. oxysporum f. sp. raphani (For)-specific primer sets were designed, FOR1-F/FOR1-R and FOR2-F/FOR2-R, to target FOQG_17868 and FOQG_17869 ORFs, respectively, which were selected based on the genome comparison of other formae speciales of F. oxysporum including conglutinans, cubense, lycopersici, melonis, and pisi. The primer sets FOR1-F/FOR1-R and FOR2-F/FOR2-R that amplified a 610- and 425-bp DNA fragment, respectively, were specific to For isolates which was confirmed using a total of 40 F. oxysporum isolates. From infected plants, the FOR2-F/FOR2-R primer set directly detected the DNA fragment of For isolates even when the radish plants were collected in their early stage of disease development. Although the loci targeted by the For-specific primer sets were not likely involved in the pathogenesis, the primer set FOR2-F/FOR2-R is available for the determination of pathogenicity of radish-infecting F. oxysporum isolates. This study is the first report providing novel primer sets to detect F. oxysporum f. sp. raphani. Because plant pathogenic Fusarium oxysporum has been classified into special forms based on its host specificity, identification of F. oxysporum usually requires a pathogenicity assay as well as knowledge of the morphological characteristics. For rapid and reliable diagnosis, this study provides PCR primer sets that specifically detect Fusarium oxysporum f. sp. raphani (For) which is a devastating pathogen of radish plants. Because one of the primer sets directly detected the DNA fragment of For isolates from infected plants, the specific PCR method demonstrated in this study will provide a foundation for integrated disease management practices in commodity crops. © 2017 The Society for Applied Microbiology.

  3. Phenotypic Diversity of Causal agent Strains of Potato Common Scab (Streptomyces sp. in Chaharmahal va Bakhtiari Province

    Directory of Open Access Journals (Sweden)

    A. A. Fadaei Tehrani

    2016-06-01

    Full Text Available Introduction: Common scab is one of the most important diseases in the potato fields caused by several species of bacteria of the genus Streptomyces. Symptoms and severity of common scab of potato caused by different factors, is different. The control also will be different. Materials and Methods: About 500 samples of potato tubers with common scab symptoms were collected from different regions in Charmahal VA Bakhtiari province during 2009 and 2010. Isolation of causal agent was performed by standard methods, then the isolates were studied, using biochemical, physiological and nutritional standard test. Thus, the color of the colony and spore mass color YMEA medium after 10 to 14 days were examined. The Gram staining reaction was conducted by Suslow et al. (34. Aerobic and anaerobic growth test (O / F in the presence of glucose was done by Hugh and Leifson (14. The isolates ability to use sugars (L-arabinose, D-fructose, D-glucose, D-mannitol, raffinose, sucrose, cellulose, D-xylose, rhamnose and mesoinositol and amino acids were investigated by Faucher et al method (6. Toxic substances inhibiting bacterial growth were evaluated in culture medium malt and yeast extract containing potassium tellurite (10 and 100 micrograms per ml, thallium acetate (10 and 100 micrograms per ml, crystal violet (0.5 g ml and phenol (0.1% by Lambert and Loria method (23. Using lysosomes, total protein of 14 isolates representing of different phenotypes groups and two reference strains of S. acidiscabies and S. scabies, were extracted by Paradis et al. (29, and their diversity was investigated by acrylamide gel electrophoresis contain dodecyl sulfate (SDS according to Laemmeli (22 The pathogenicity of isolates was evaluated by inoculation of radish and potato tubers Schaad et al. (30 method. Isolates were amplified by spore inoculation in the flask containing 100 grams of vermiculite saturated with nutrient solutions (20 g of sucrose, 2.1 grams of L-asparagine, 0

  4. Heat-resistant agent used for control sand of steam huff and puff heavy oil well

    Science.gov (United States)

    Zhang, F. S.; Liu, G. L.; Lu, Y. J.; Xiong, X. C.; Ma, J. H.; Su, H. M.

    2018-01-01

    Heat-resistant agent containing hydroxymethyl group was synthesized from coal tar, which has similar structure with phenolic resin and could improve the heat resistance of phenolic resin sand control agent. The results showed that the heat resistance of the sand control agent was improved by adding 10% to 30% heat-resistant agent, after 280°C high temperature treatment for 7d, the compressive strength of consolidated core was increased to more than 5MPa. The compressive strength of consolidation core was not decreased after immersion in formation water, crude oil, acid or alkaline medium, which showed good resistance to medium immersion. The sand control agent had small core damage and the core permeability damage ratio of sand control agent consolidation was only 18.7%.

  5. Causality in Classical Electrodynamics

    Science.gov (United States)

    Savage, Craig

    2012-01-01

    Causality in electrodynamics is a subject of some confusion, especially regarding the application of Faraday's law and the Ampere-Maxwell law. This has led to the suggestion that we should not teach students that electric and magnetic fields can cause each other, but rather focus on charges and currents as the causal agents. In this paper I argue…

  6. MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

    Science.gov (United States)

    Brøns, Charlotte; Grunnet, Louise Groth

    2017-02-01

    Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver. © 2017 European Society of Endocrinology.

  7. Causality of small and large intestinal microbiota in weight regulation and insulin resistance

    Directory of Open Access Journals (Sweden)

    Torsten P.M. Scheithauer

    2016-09-01

    Conclusions: Interventions aimed to restoring gut microbial homeostasis, such as ingestion of specific fibers or therapeutic microbes, are promising strategies to reduce insulin resistance and the related metabolic abnormalities in obesity, metabolic syndrome, and type 2 diabetes. This article is part of a special issue on microbiota.

  8. Acción inhibitoria de una cepa de Zymomonas mobilis mobilis aislada de caña de azúcar sobre Xanthomonas citri subsp. citri, agente causal de la cancrosis de los cítricos Inhibition of Xanthomonas citri subsp. citri, causal agent of citrus canker, by a strain of Zymomonas mobilis mobilis isolated from sugarcane

    Directory of Open Access Journals (Sweden)

    María E. Romero

    2008-06-01

    a wide range of microorganisms pathogenic to man, animals, and plants. An important problem to solve with antimicrobial treatments is the development of resistance in these microorganisms, including phytopathogenic bacteria, to the currently used active ingredients. In this study, antagonism tests with cells (cross-streaking and cell-free culture supernatants (CCS (agar diffusion test from Zm cultures, isolated from sugarcane juice in Tucumán, were carried out, measuring activity against Xanthomonas citri subsp. citri (Xcc, the causal agent of citrus canker. Xcc isolates sensitive (Xc and resistant (Xcr to copper pesticides were included in these tests. Results showed that indicator bacteria were completely inhibited by cells of Zm, which had a bactericide effect. Both Xc and Xcr were sensitive to the CCS in the agar diffusion method. Previous studies had revealed the deleterious effects of metabolites from Zm on cell membranes of E. coli AB1133, inhibiting the respiration of the bacteria inmediately after CCS addition. On the basis of these results, the effects of CCS on Xcc respiration were studied, verifyng a similar response. This would indicate that the site of action of these antimicrobial compounds is also located at the cell membrane of the bacteria under study. Based on these results, additional studies are suggested to evaluate Zm-derived products on the control of diseases that affect economically important crops, such as citrus canker.

  9. Construction and characterization of a bacterial artificial chromosome library of the causal agent of Black Sigatoka fungal leaf spot disease of banana and plantain, Mycosphaerella fijiensis.

    Science.gov (United States)

    Canto-Canché, Blondy; Guillén-Maldonado, Diana Karina; Peraza-Echeverría, Leticia; Conde-Ferráez, Laura; James-Kay, Andrew

    2007-05-01

    A bacterial artificial chromosome library of the causal agent of the Black Sigatoka leaf spot disease of banana and plantain, Mycosphaerella fijiensis, has been constructed using a non-sphaeroplasting technique and characterized using both homologous and heterologous probes. After first and a second size selection of PFGE-fractionated DNA, a ligation was obtained using a 1:4 molar ratio (insert:vector). One hundred random clones were analyzed, and the mean insert size was estimated to be 90 kb. The range of the insert sizes was between 40 and 160 kb. The highest percentage of inserts belonged to the range between 80 and 100 kb; 32% of the inserts had 2 or 3 internal NotI sites. This library consists of 1920 clones, if the genomic size is at least 35 Mb, then this represents 4.9 x genome equivalents, which was supported by hybridization results with homologous and heterologous probes.

  10. Effect of bodily fluids from honey bee (Apis mellifera) larvae on growth and genome-wide transcriptional response of the causal agent of American Foulbrood disease (Paenibacillus larvae).

    Science.gov (United States)

    De Smet, Lina; De Koker, Dieter; Hawley, Alyse K; Foster, Leonard J; De Vos, Paul; de Graaf, Dirk C

    2014-01-01

    Paenibacillus larvae, the causal agent of American Foulbrood disease (AFB), affects honey bee health worldwide. The present study investigates the effect of bodily fluids from honey bee larvae on growth velocity and transcription for this Gram-positive, endospore-forming bacterium. It was observed that larval fluids accelerate the growth and lead to higher bacterial densities during stationary phase. The genome-wide transcriptional response of in vitro cultures of P. larvae to larval fluids was studied by microarray technology. Early responses of P. larvae to larval fluids are characterized by a general down-regulation of oligopeptide and sugar transporter genes, as well as by amino acid and carbohydrate metabolic genes, among others. Late responses are dominated by general down-regulation of sporulation genes and up-regulation of phage-related genes. A theoretical mechanism of carbon catabolite repression is discussed.

  11. Rickettsia typhi in rodents and R. felis in fleas in Yucatán as a possible causal agent of undefined febrile cases.

    Science.gov (United States)

    Peniche-Lara, Gaspar; Dzul-Rosado, Karla; Pérez-Osorio, Carlos; Zavala-Castro, Jorge

    2015-01-01

    Rickettsia typhi is the causal agent of murine typhus; a worldwide zoonotic and vector-borne infectious disease, commonly associated with the presence of domestic and wild rodents. Human cases of murine typhus in the state of Yucatán are frequent. However, there is no evidence of the presence of Rickettsia typhi in mammals or vectors in Yucatán. The presence of Rickettsia in rodents and their ectoparasites was evaluated in a small municipality of Yucatán using the conventional polymerase chain reaction technique and sequencing. The study only identified the presence of Rickettsia typhi in blood samples obtained from Rattus rattus and it reported, for the first time, the presence of R. felis in the flea Polygenis odiosus collected from Ototylomys phyllotis rodent. Additionally, Rickettsia felis was detected in the ectoparasite Ctenocephalides felis fleas parasitizing the wild rodent Peromyscus yucatanicus. This study's results contributed to a better knowledge of Rickettsia epidemiology in Yucatán.

  12. First isolation of Mycoplasma capricolum subsp. capricolum, one of the causal agents of caprine contagious agalactia, on the island of Lanzarote (Spain).

    Science.gov (United States)

    De la Fe, C; Gutiérrez, A; Poveda, J B; Assunção, P; Ramírez, A S; Fabelo, F

    2007-03-01

    During an unusually long period of bad weather, several outbreaks of caprine contagious agalactia (CCA) were reported in a number of flocks on the island of Lanzarote (Canary Islands, Spain). Clinical and subclinical mastitis in lactating goats and some cases of arthritis and pneumonia in kids were observed in the affected flocks. Mycoplasma capricolum subsp. capricolum was isolated as the main causal agent of the outbreaks, associated with M. mycoides subsp. mycoides "large colony type" (Mmm LC) in two flocks. This is the first report of an isolation of M. capricolum subsp. capricolum on the island of Lanzarote. The finding is of epidemiological importance and could complicate plans to control the disease. The significance of this mycoplasma species in association with CCA must now be studied in detail.

  13. Causality in Europeanization Research

    DEFF Research Database (Denmark)

    Lynggaard, Kennet

    2012-01-01

    to develop discursive institutional analytical frameworks and something that comes close to the formulation of hypothesis on the effects of European Union (EU) policies and institutions on domestic change. Even if these efforts so far do not necessarily amount to substantive theories or claims of causality......Discourse analysis as a methodology is perhaps not readily associated with substantive causality claims. At the same time the study of discourses is very much the study of conceptions of causal relations among a set, or sets, of agents. Within Europeanization research we have seen endeavours......, it suggests that discourse analysis and the study of causality are by no means opposites. The study of Europeanization discourses may even be seen as an essential step in the move towards claims of causality in Europeanization research. This chapter deals with the question of how we may move from the study...

  14. Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns.

    Science.gov (United States)

    Williamson, Deborah A; Carter, Glen P; Howden, Benjamin P

    2017-07-01

    Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future. Copyright © 2017 American Society for Microbiology.

  15. Contrasting amino acid profiles among permissive and non-permissive hosts of Candidatus Liberibacter asiaticus, putative causal agent of Huanglongbing.

    Directory of Open Access Journals (Sweden)

    Mamoudou Sétamou

    Full Text Available Huanglongbing is a devastating disease of citrus. In this study, a comprehensive profile of phloem sap amino acids (AA in four permissive host plants of Candidatus Liberibacter asiaticus (CLas and three non-permissive Rutaceae plants was conducted to gain a better understanding of host factors that may promote or suppress the bacterium. The AA profiles of Diaphorina citri nymphs and adults were similarly analyzed. A total of 38 unique AAs were detected in phloem sap of the various plants and D. citri samples, with phloem sap of young shoots containing more AAs and at higher concentrations than their mature counterparts. All AAs detected in phloem sap of non-permissive plants were also present in CLas -permissive hosts plus additional AAs in the latter class of plants. However, the relative composition of 18 commonly shared AAs varied between CLas -permissive hosts and non-permissive plants. Multivariate analysis with a partial least square discriminant methodology revealed a total of 12 AAs as major factors affecting CLas host status, of which seven were positively related to CLas tolerance/resistance and five positively associated with CLas susceptibility. Most of the AAs positively associated with CLas susceptibility were predominantly of the glutamate family, notably stressed-induced AAs such as arginine, GABA and proline. In contrast, AAs positively correlated with CLas tolerance/resistance were mainly of the serine family. Further analysis revealed that whereas the relative proportions of AAs positively associated with CLas susceptibility did not vary with host developmental stages, those associated with CLas tolerance/resistance increased with flush shoot maturity. Significantly, the proline-to-glycine ratio was determined to be an important discriminating factor for CLas permissivity with higher values characteristic of CLas -permissive hosts. This ratio could be exploited as a biomarker in HLB-resistance breeding programs.

  16. Mutants of Aspergillus nidulans with increased resistance to the alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine.

    Science.gov (United States)

    Hooley, P; Shawcross, S G; Strike, P

    1988-05-01

    The isolation and characterisation of mutants of Aspergillus nidulans showing resistance to MNNG is described. Such isolates were stable through prolonged subculture in the absence of the selective agent, and resistance segregated as an allele of a single gene in meiotic and mitotic analysis. MNNG-resistant strains showed an increase in resistance to EMS and UV irradiation but no cross-resistance to MMS was detected. Possible mechanisms of resistance to alkylating agents are discussed.

  17. Resistance of Streptococcus sanguis biofilms to antimicrobial agents

    DEFF Research Database (Denmark)

    Larsen, T; Fiehn, N E

    1996-01-01

    of Streptococcus sanguis 804 and ATCC 10556 to amoxicillin, doxycycline and chlorhexidine was determined by a broth dilution method. Subsequently, S. sanguis biofilms established in an in vitro flow model were perfused with the antimicrobial agents for 48 h at concentrations equal to and up to 500 times the MIC...

  18. Effect of Two Biological Formulations Based on Bacillus subtilis and Pseudomonas fluorescens on Control of Didymella applanata, the Causal Agent of Red Raspberry Cane Spur Blight

    Directory of Open Access Journals (Sweden)

    Margarita Shternshis

    2016-01-01

    Full Text Available In vitro and in vivo studies were conducted to estimate the efficacy of the two microbial formulations based on Bacillus subtilis Cohn. and Pseudomonas fluorescens Mig. on the fungus Didymella applanata (Niessl. Sacc., the causal agent of red raspberry (Rubus idaeus L. spur blight. In vitro, both bacteria reduced the growth of D. applanata. In inoculation experiments with raspberry canes in two cultivars with different susceptibility to D. applanata, these antagonistic bacteria suppressed fungal development by reducing the lesions area and the number of D. applanata fruiting bodies. Field trials of two biological formulations under natural conditions showed a significant suppression of the disease. B. subtilis and P. fluorescens included in the formulations revealed antagonistic activity towards D. applanata that depended on the red raspberry cultivar and weather conditions. In all cases, B. subtilis showed better results than P. fluorescens in biocontrol of the raspberry spur blight. This study demonstrated for the first time the ability of the biocontrol agents B. subtilis and P. fluorescens to suppress red raspberry cane spur blight, a serious worldwide disease.

  19. Cladosporium cladosporioides and Cladosporium pseudocladosporioides as potential new fungal antagonists of Puccinia horiana Henn., the causal agent of chrysanthemum white rust.

    Directory of Open Access Journals (Sweden)

    David Eduardo Torres

    Full Text Available Puccinia horiana Hennings, the causal agent of chrysanthemum white rust, is a worldwide quarantine organism and one of the most important fungal pathogens of Chrysanthemum × morifolium cultivars, which are used for cut flowers and as potted plants in commercial production regions of the world. It was previously reported to be controlled by Lecanicillium lecanii, Cladosporium sphaerospermum, C. uredinicola and Aphanocladium album, due to their antagonistic and hyperparasitic effects. We report novel antagonist species on Puccinia horiana. Fungi isolated from rust pustules in a commercial greenhouse from Villa Guerrero, México, were identified as Cladosporium cladosporioides and Cladosporium pseudocladosporioides based upon molecular analysis and morphological characters. The antagonism of C. cladosporioides and C. pseudocladosporioides on chrysanthemum white rust was studied using light and electron microscopy in vitro at the host/parasite interface. Cladosporium cladosporioides and C. pseudocladosporioides grew towards the white rust teliospores and colonized the sporogenous cells, but no direct penetration of teliospores was observed; however, the structure and cytoplasm of teliospores were altered. The two Cladosporium spp. were able to grow on media containing laminarin, but not when chitin was used as the sole carbon source; these results suggest that they are able to produce glucanases. Results from the study indicate that both Cladosporium species had potential as biological control agents of chrysanthemum white rust.

  20. Circumvention of inherent or acquired cytotoxic drug resistance in vitro using combinations of modulating agents.

    Science.gov (United States)

    Cadagan, David; Merry, Stephen

    2013-10-01

    Modulating agents are used to circumvent drug resistance in the clinical setting. However achievable serum concentrations are often lower than those which are optimal in vitro. Combination of modulating agents with non-overlapping toxicities may overcome this obstacle. We have investigated combinations of three modulating agents (quinine, verapamil, and cinnarizine) to circumvent inherent or acquired resistance to the cytotoxic drugs doxorubicin, vincristine and paclitaxel. Dose-response curves to cytotoxic drugs in the presence/absence of modulating agents were determined using colony formation and cell proliferation assays. Doxorubicin accumulation into cell monolayers was measured by fluorescence spectrophotometry. Greater (1.9-fold) sensitisation to particular cytotoxic drugs was observed for certain combinations of modulating agents compared to individual effects. The most effective combination was quinine-plus-verapamil with the cytotoxic drug doxorubicin. This increase in sensitivity was associated with increased doxorubicin accumulation. Such enhanced activity was, however, not observed for all combinations of modulating agents or for all studied cytotoxic drugs. The findings of the present study suggest certain combinations of modulating agents to have a clinical role in circumventing drug resistance. Particular combinations of modulating agents must be carefully chosen to suit particular cytotoxic drug treatments.

  1. Reação de cultivares de batata a Streptomyces scabies, agente causal da sarna comum profunda Reaction of potato cultivars to Streptomyces scabies, causal agent of deep common scab

    Directory of Open Access Journals (Sweden)

    Ivan Herman Fischer

    2009-09-01

    Full Text Available Este trabalho visou caracterizar quanto a critérios morfológicos e fisiológicos isolados de Streptomyces causadores de sarna comum profunda em batata; avaliar o comportamento de cultivares em relação à doença e a variação na agressividade entre os isolados da bactéria. Os isolados de Streptomyces apresentaram coloração cinza em meio extrato de levedura e malte e cadeias de esporos espiraladas, produzidas sobre um micélio aéreo. Ocorreu produção de melanina em meio de tirosina-ágar e a utilização de oito fontes de carbono recomendadas, propriedades estas que correspondem às descritas para S. scabies. Batatas-semente sadias de seis cultivares foram plantadas em substrato infestado com seis isolados de S. scabies separadamente e as plantas cultivadas em vasos e ambiente aberto. A severidade da doença foi estimada com auxílio de uma escala diagramática e avaliou-se o rendimento de tubérculos (g/planta. As cvs. Mondial e Jaete Bintje foram as mais resistentes à sarna comum com severidade média nos dois experimentos de 10,5% e 14,0%, respectivamente, seguidas por Asterix (17,4%, Ágata (21,8%, Monalisa (23,0% e Cupido (23,3%. A agressividade dos isolados variou quantitativamente, com severidade maior para o isolado M4 (34,7% e menor para o isolado M1 (6,2%. Redução da produção de tubérculos foi verificada na cv. Jaete Bintje, no primeiro experimento, e quando as cultivares foram infectadas pelos isolados A1, M2 e M3, no primeiro experimento, e pelo isolado M4, no segundo experimento.This work aimed to characterize the isolates of Streptomyces, responsible for deep common scab symptoms in potato, according to morphological and physiological criteria; to evaluate the resistance of potato cultivars to the disease and the aggressiveness of bacterium isolates. The Streptomyces isolates presented gray coloration on yeast extract and malt medium and spiral spore chains, produced on aerial hyphae. Production of melanina occurred

  2. Controle alternativo de Colletotrichum acutatum agente causal da queda prematura dos frutos cítricos Alternative control of Colletotrichum acutatum, causal agent of postbloom fruit drop of citrus

    Directory of Open Access Journals (Sweden)

    Katia Cristina Kupper

    2009-12-01

    Full Text Available A queda prematura dos frutos cítricos (QPFC, causada por Colletotrichum acutatum, dados os grandes prejuízos que têm causado aos produtores, constitui-se numa doença de grande importância econômica. O controle da doença é feito predominantemente mediante uso de fungicidas, que eleva o custo de produção e afeta negativamente o meio ambiente. Diante disso, este trabalho teve por objetivo buscar um método alternativo de controle da QPFC, mediante o uso de agentes de biocontrole ou de biofertilizantes. Diferentes concentrações de biofertilizantes (originários de duas fontes distintas e denominados de Bio1 e Bio 2; três isolados de Bacillus subtilis (ACB-69; 72 e 77 e três isolados de Trichoderma spp. (ACB-14; 37 e 39 foram testados, isoladamente ou em combinação, sob condições de laboratório, quanto à capacidade inibitória da germinação de conídios de C. acutatum. Estudaram-se, ainda, a produção de metabólitos termoestáveis por B. subtilis e o efeito sobre a germinação do patógeno. Quinze isolados de B. subtilis foram testados quanto à capacidade de prevenir a infecção por C. acutatum em flores destacadas de lima- ácida 'Tahiti' e, no campo, foram instalados dois experimentos, visando a testar ACBs e biofertilizantes no controle da doença. Verificou-se que o isolado ACB-72 (B. subtilis e ACB-37 (T. pseudokoningii foram os que mais inibiram a germinação do patógeno. Quanto à produção de metabólitos termoestáveis, ACB-69 e 77 foram os mais eficientes em produzir substâncias antifúngicas, e em quantidades suficientes para inibirem a germinação do patógeno. A mistura dos quatro isolados de Bacillus (ACBs: 69; 72; 77 e AP3 foi o que apresentou maior porcentagem de inibição (73%. Os biofertilizantes (Bio1 e Bio2, em concentrações acima de 10% e, quando em associação com isolados de Trichoderma spp., promoveram maiores inibições na germinação de C. acutatum. Em testes com flores destacadas

  3. Functional and biophysical studies on four ceratoplatanins from the fungus Moniliophthora perniciosa, causal agent of the Witche's broom disease

    International Nuclear Information System (INIS)

    Barsottini, M.; Zaparoli, G.; Garcia, O.; Pereira, G.A.G.; Oliveira, J.F.; Tiezzi, H.O.; Ambrosio, A.L.B.; Dias, S.M.G.

    2012-01-01

    Full text: Ceratoplatanin (CP) is a secreted protein of 12.4 kDa initially identified in culture filtrates of the disease ascomycete Ceratocystis fimbriata f. sp. platani, etiological agent of the canker stain disease. CP is also the founding member of the namesake protein family, which contains fungal-secreted proteins involved in various stages of the host-fungus interaction and may act as phytotoxins or elicitors of defense response. Besides the low molecular weight, CPs have a high percentage of hydrophobic residues and share two conserved intramolecular disulfide bonds. It has been suggested that CPs have important physiological functions, including interaction with cell wall or cell membrane and manipulation of the host's defense system. Furthermore, a recent work showed that the ceratoplatanin from C. fimbriata has some degree of affinity for the saccharide 4-N-acetylglucosamine. However, its precise molecular function remains elusive. Five putative CPs have been identified in Moniliophthora perniciosa a basidiomycete fungus responsible for great economic losses in cocoa industry in the form of Witches' broom disease (WBD) , four of which had their crystal structures resolved by our group. In this work we report biophysical and functional studies on these MpCPs aiming at understanding their role and importance during the WBD progression. (author)

  4. Study the Reaction of Some Barley Cultivars to Rhizoctonia solani AG-8, the Causal Agent of Root Rot Disease

    Directory of Open Access Journals (Sweden)

    M. Yazdani Kohanstani

    2016-03-01

    Full Text Available Introduction: Barley is one of the important agricultural products, mostly as livestock feed, and secondly for its important role in human nutrition as bread, soups, baby food and etc. It has the second-largest rank of cultivation area and yield of the national grain production and the Isfahan province, with production 5% of total barley yield, has been ranked eighth in 2010. Because its consumption exceed over the production, barley is one of the major imports to the country. In addition to, agronomy operations, plant diseases are important factors in yield loss. Rhizoctonia root rot (caused by soil-inhabiting fungus Rhizoctonia solani is one of the important diseases of cereals include barley over the worldwide cultivation area. Apropriate soil fertility, delaying planting dates, crop rotation with insensitive crops such as legumes, planting resistant varieties and fungicide seed dressing are recommended methods to reduce disease damage. Chemical control of this disease is difficult because of its soil-born the pathogen. Therefore, reducing disease level requires application of other methods especially resistance cultivars. Materials and Methods In this research, the reaction of 8 barley cultivars were examined against root rot disease in greenhouse conditions, in the winter of 2009. Fifteen isolates of the fungus were isolated from infected barley fields in the Isfahan province and their pathogenicity was examined on barley. One isolate with the highest pathogenicity potential was selected and special tests showed that the isolate was Rhizoctonia solani AG-8. The experiment was conducted in a completely randomized design with 4 replications. The test plants were harvested at two times of 4 & 8 weeks after planting. Following parameters were measured: 1- dry weight of plant root and aerial part, 2- disease severity as an index of subcrown internodes infection. Results and discussion Statistical analysis of recorded data showed that there were

  5. Leaf crinkle disease in urdbean (Vigna mungo L. Hepper): An overview on causal agent, vector and host.

    Science.gov (United States)

    Gautam, Narinder Kumar; Kumar, Krishna; Prasad, Manoj

    2016-05-01

    Urdbean leaf crinkle disease (ULCD) is an economically significant widespread and devastating disease resulting in extreme crinkling, puckering and rugosity of leaves inflicting heavy yield losses annually in major urdbean-producing countries of the world. This disease is caused by urdbean leaf crinkle virus (ULCV). Urdbean (Vigna mungo L. Hepper) is relatively more susceptible than other pulses to leaf crinkle disease. Urdbean is an important and useful crop cultivated in various parts of South-East Asia and well adapted for cultivation under semi-arid and subtropical conditions. Aphids, insects and whiteflies have been reported as vectors of the disease. The virus is also transmitted through sap inoculation, grafting and seed. The loss in seed yield in ULCD-affected urdbean crop ranges from 35 to 81%, which is dependent upon type of genotype location and infection time. The diseased material and favourable climatic conditions contribute for the widespread viral disease. Anatomical and biochemical changes take place in the affected diseased plants. Genetic variations have been reported in the germplasm screening which suggest continuous screening of available varieties and new germplasm to search for new traits (new genes) and identify new sources of disease resistance. There are very few reports on breeding programmes for the development and release of varieties tolerant to ULCD. Mostly random amplified polymorphic DNA (RAPD) as well as inter-simple sequence repeat (ISSR) molecular markers have been utilized for fingerprinting of blackgram, and a few reports are there on sequence-tagged micro-satellite site (STMS) markers. There are so many RNA viruses which have also developed strategies to counteract silencing process by encoding suppressor proteins that create hindrances in the process. But, in the case of ULCV, there is no report available indicating which defence pathway is operating for its resistance in the plants and whether same silencing suppression

  6. Preservação de urediniósporos de Puccinia melanocephala, agente causal de ferrugem em cana-de-açúcar Preservation of uredospores of Puccinia melanocephala, the causal agent of sugarcane rust

    Directory of Open Access Journals (Sweden)

    Ely Oliveira Garcia

    2007-06-01

    and the other part was not dehydrated. Then they were all stored at different temperatures (room temperature, 5ºC, -20ºC and -80ºC. Subsequently, uredospores viability was periodically evaluated using the water-agar method. After the fourth month, the infectivity was also evaluated through inoculations in leaves of the sugarcane susceptible variety SP70-1143 following disease evaluation. Regardless of the dehydration treatment used, uredospores stored at room temperature and at 5ºC were viable for the maximum periods of 1 and 2 months, respectively. The best results were obtained with the silica gel dehydration treatment followed by storage at -20ºC or -80ºC. Even after one year of storage, these uredospores were able to cause rust in inoculated plants at levels of severity which are adequate to start screening tests for sugarcane resistance to rust.

  7. Genetic Diversity of Alternaria alternata Causal Agent of Early Blight of Tomato in Khuzestan Province Using SSRs Marker

    Directory of Open Access Journals (Sweden)

    Khoshnood Nourollahi

    2017-03-01

    sampled regions and geographical closeness as well. Conclusion: This study have been carried out for the first time in Iran, and in comparison of international populations, a different level of diversity was detected within and between populations of worldwide A. alternata isolates. In this study, the high genetic diversity of A. alternata detected in five populations exposed a potential risk to tomato farms. Genetic diversity of A. alternata in Khuzestan province as an air born pathogen is a warning for a breeder to apply the successful use of resistance genes in local disease management. This gene diversity helps breeders for screening potential resistant cultivars according to gene diversity of A. alternata population in order to develop of durable resistant. Quarantine regulations will need to prevent the introduction of more diverse isolates into these populations and prevent transmission any isolates from this area to other regions of the country. Understanding the genetic structure of pathogen populations in the present study may provide insights into the epidemiology and evolutionary potential of pathogens and could lead to improved strategies for managing the disease. The obtained results indicating the high genetic diversity due to mutation, recombinant and a sexual mating ability of the pathogen in the Khuzestan province. Results in this study will be useful in breeding for tomato early blight resistant cultivars and developing necessary control measures.

  8. Endophytic bacteria from Piper tuberculatum Jacq.: isolation, molecular characterization, and in vitro screening for the control of Fusarium solani f. sp piperis, the causal agent of root rot disease in black pepper (Piper nigrum L.).

    Science.gov (United States)

    Nascimento, S B; Lima, A M; Borges, B N; de Souza, C R B

    2015-07-06

    Endophytic bacteria have been found to colonize internal tissues in many different plants, where they can have several beneficial effects, including defense against pathogens. In this study, we aimed to identify endophytic bacteria associated with roots of the tropical piperaceae Piper tuberculatum, which is known for its resistance to infection by Fusarium solani f. sp piperis, the causal agent of black pepper (Piper nigrum) root rot disease in the Amazon region. Based on 16S rRNA gene sequence analysis, we isolated endophytes belonging to 13 genera: Bacillus, Paenibacillus, Pseudomonas, Enterobacter, Rhizobium, Sinorhizobium, Agrobacterium, Ralstonia, Serratia, Cupriavidus, Mitsuaria, Pantoea, and Staphylococcus. The results showed that 56.52% of isolates were associated with the phylum Proteobacteria, which comprised α, β, and γ classes. Other bacteria were related to the phylum Firmicutes, including Bacillus, which was the most abundant genus among all isolates. Antagonistic assays revealed that Pt12 and Pt13 isolates, identified as Pseudomonas putida and Pseudomonas sp, respectively, were able to inhibit F. solani f. sp piperis growth in vitro. We describe, for the first time, the molecular identification of 23 endophytic bacteria from P. tuberculatum, among which two Pseudomonas species have the potential to control the pathogen responsible for root rot disease in black pepper in the Amazon region.

  9. Causal universe

    CERN Document Server

    Ellis, George FR; Pabjan, Tadeusz

    2013-01-01

    Written by philosophers, cosmologists, and physicists, this collection of essays deals with causality, which is a core issue for both science and philosophy. Readers will learn about different types of causality in complex systems and about new perspectives on this issue based on physical and cosmological considerations. In addition, the book includes essays pertaining to the problem of causality in ancient Greek philosophy, and to the problem of God's relation to the causal structures of nature viewed in the light of contemporary physics and cosmology.

  10. Association between the consumption of antimicrobial agents in animal husbandry and the occurrence of resistant bacteria among food animals

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller

    1999-01-01

    Antimicrobial agents are used in food animals for therapy and prophylaxis of bacterial infections and in feed to promote growth. The use of antimicrobial agents for food animals may cause problems in the therapy of infections by selecting for resistance among bacteria pathogenic for animals...... animals, the quantitative impact of the use of different antimicrobial agents on selection for resistance and the most appropriate treatment regimens to limit the development of resistance is incomplete. Surveillance programmes monitoring the occurrence and development of resistance and consumption...... or humans. The emergence of resistant bacteria and resistance genes following the use of antimicrobial agents is relatively well documented and it seems evident that all antimicrobial agents will select for resistance. However, current knowledge regarding the occurrence of antimicrobial resistance in food...

  11. Characteristics and overcome of the resistance to chemotherapeutic agents

    International Nuclear Information System (INIS)

    Hong, Weon Seon; Im, Young Hyuck; Kim, Young Sun

    1993-01-01

    Although the clinical use of colony-stimulating factor (CSF) improves the therapeutic results, there have been a lot of evidences that CSF may stimulate the growth of cancer cells. This study was conducted to investigate the effects of granulocytemacrophage(GM)-CSF and granulocyte(G)-CSF on the colony formations in eight human cancer cell lines. The stimulatory effects of GM-CSF and G-CSF on the colony formation were evaluated in human tumor colony assay against four human cancer cell lines, four sublines resistant to adriamycin or cisplatin : PC-9 and PC-14 (pulmonary adenoca), MKN-45 and KATO III (gastric adenoca), PC/ADM and PC/CDDP (sublines of PC-14 resistant to adriamycin and cisplatin, respectively), MKN/ADM and MKN/CDDP (sublines of MKN-45 resistant to adriamycin and cisplatin, respectively). Cancer cells were plated at concentrations of 1x10 3 and 1x10 5 cells/well in the upper layer. Two kinds of GM-CSF (LBD-005 and CSF 39-300) and two kinds of G-CSF (Grasin and Neutrogin) were tested by the addition of final concentrations of GM-CSF and G-CSF (0.01, 0.1 and 1.0 μg/ml) to the lower layer to allow continuous exposure for 14 days. The colony formations (%) of eight cell lines tested were 85-113% and 92-106% in wells plated at the concentrations (/well) of 1x10 3 and 1x10 5 plated, respectively, in all cell lines compared to those of control wells. These results suggest that GM-CSF and G-CSF dose not directly stimulate the growth of cancer cells in all cell lines tested. (Author)

  12. Causal and causally separable processes

    Science.gov (United States)

    Oreshkov, Ognyan; Giarmatzi, Christina

    2016-09-01

    The idea that events are equipped with a partial causal order is central to our understanding of physics in the tested regimes: given two pointlike events A and B, either A is in the causal past of B, B is in the causal past of A, or A and B are space-like separated. Operationally, the meaning of these order relations corresponds to constraints on the possible correlations between experiments performed in the vicinities of the respective events: if A is in the causal past of B, an experimenter at A could signal to an experimenter at B but not the other way around, while if A and B are space-like separated, no signaling is possible in either direction. In the context of a concrete physical theory, the correlations compatible with a given causal configuration may obey further constraints. For instance, space-like correlations in quantum mechanics arise from local measurements on joint quantum states, while time-like correlations are established via quantum channels. Similarly to other variables, however, the causal order of a set of events could be random, and little is understood about the constraints that causality implies in this case. A main difficulty concerns the fact that the order of events can now generally depend on the operations performed at the locations of these events, since, for instance, an operation at A could influence the order in which B and C occur in A’s future. So far, no formal theory of causality compatible with such dynamical causal order has been developed. Apart from being of fundamental interest in the context of inferring causal relations, such a theory is imperative for understanding recent suggestions that the causal order of events in quantum mechanics can be indefinite. Here, we develop such a theory in the general multipartite case. Starting from a background-independent definition of causality, we derive an iteratively formulated canonical decomposition of multipartite causal correlations. For a fixed number of settings and

  13. Causal and causally separable processes

    International Nuclear Information System (INIS)

    Oreshkov, Ognyan; Giarmatzi, Christina

    2016-01-01

    The idea that events are equipped with a partial causal order is central to our understanding of physics in the tested regimes: given two pointlike events A and B , either A is in the causal past of B , B is in the causal past of A , or A and B are space-like separated. Operationally, the meaning of these order relations corresponds to constraints on the possible correlations between experiments performed in the vicinities of the respective events: if A is in the causal past of B , an experimenter at A could signal to an experimenter at B but not the other way around, while if A and B are space-like separated, no signaling is possible in either direction. In the context of a concrete physical theory, the correlations compatible with a given causal configuration may obey further constraints. For instance, space-like correlations in quantum mechanics arise from local measurements on joint quantum states, while time-like correlations are established via quantum channels. Similarly to other variables, however, the causal order of a set of events could be random, and little is understood about the constraints that causality implies in this case. A main difficulty concerns the fact that the order of events can now generally depend on the operations performed at the locations of these events, since, for instance, an operation at A could influence the order in which B and C occur in A ’s future. So far, no formal theory of causality compatible with such dynamical causal order has been developed. Apart from being of fundamental interest in the context of inferring causal relations, such a theory is imperative for understanding recent suggestions that the causal order of events in quantum mechanics can be indefinite. Here, we develop such a theory in the general multipartite case. Starting from a background-independent definition of causality, we derive an iteratively formulated canonical decomposition of multipartite causal correlations. For a fixed number of settings and

  14. In vitro Antagonistic Mechanisms of Trichoderma spp. and Talaromyces flavus to Control Gaeumannomyces graminis var. tritici the Causal Agent of Wheat Take-all Disease

    Directory of Open Access Journals (Sweden)

    Seddighe Mohammadi

    2015-07-01

    Full Text Available Wheat take-all disease caused by Gaeumannomyces graminis var. tritici has recently been detected in different regions of Iran. With respect to biocontrol effect of Trichoderma spp. on many pathogenic fungi, seven isolates of Trichoderma and four isolates of Talaromyces were in vitro evaluated in terms of their biological control against the disease causal agent. In dual culture test the five isolates showed efficient competition for colonization against pathogenic fungus and the highest percentages of inhibition belonging to Talaromyces flavus 60 and Talaromyces flavus 136 were 59.52 and 57.61%, respectively. Microscopic investigations showed that in regions where antagonistic isolates and Gaeumannomyces graminis var. tritici coincide, hyphal contact, penetration and fragmentation of Gaeumannomyces graminis var. tritici were observed. Investigating the effect of volatile and non-volatile compounds at 10 ml concentration showed that the highest inhibition percentage on mycelium growth of the pathogen caused by T. harzianum (44.76% and T. longibrachiatum (52.38% respectively.

  15. Rickettsia typhi IN RODENTS AND R. felis IN FLEAS IN YUCATÁN AS A POSSIBLE CAUSAL AGENT OF UNDEFINED FEBRILE CASES

    Directory of Open Access Journals (Sweden)

    Gaspar PENICHE-LARA

    2015-04-01

    Full Text Available Rickettsia typhi is the causal agent of murine typhus; a worldwide zoonotic and vector-borne infectious disease, commonly associated with the presence of domestic and wild rodents. Human cases of murine typhus in the state of Yucatán are frequent. However, there is no evidence of the presence of Rickettsia typhi in mammals or vectors in Yucatán. The presence of Rickettsia in rodents and their ectoparasites was evaluated in a small municipality of Yucatán using the conventional polymerase chain reaction technique and sequencing. The study only identified the presence of Rickettsia typhi in blood samples obtained from Rattus rattus and it reported, for the first time, the presence of R. felis in the flea Polygenis odiosus collected from Ototylomys phyllotis rodent. Additionally, Rickettsia felis was detected in the ectoparasite Ctenocephalides felis fleas parasitizing the wild rodent Peromyscus yucatanicus. This study’s results contributed to a better knowledge of Rickettsia epidemiology in Yucatán.

  16. Radiation resistant polypropylene blended with mobilizer,. antioxidants and nucleating agent

    Science.gov (United States)

    Shamshad, A.; Basfar, A. A.

    2000-03-01

    Post-irradiation storage of medical disposables prepared from isotactic polypropylene renders them brittle due to degradation. To avoid this, isotactic polypropylene [(is)PP] was blended with a mobilizer, dioctyl pthallate (DOP), three antioxidants (hindered amines and a secondary antioxidant) and benzoic acid to obtain radiation-resistant, thermally-stable and transparent material. Different formulations prepared were subjected to gamma radiation to doses of 25 and 50 kGy. Tests of breakage on bending after ageing in an oven at 70°C up to 12 months have shown that the addition of DOP and the antioxidants imparts improved radiation and thermal stability as compared to (is)PP alone or its blend with DOP. All the formulations irradiated or otherwise demonstrated excellent colour stability even after accelerated ageing at 70°C for prolonged periods.

  17. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

    Science.gov (United States)

    Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

    2011-11-01

    The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

  18. Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine

    Directory of Open Access Journals (Sweden)

    Benitez-Bribiesca Luis

    2006-08-01

    Full Text Available Abstract Background The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance. Methods MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin. Results MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype. Conclusion We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype.

  19. Change agent's contribution to recipients' resistance to change: A two-sided story

    NARCIS (Netherlands)

    Vos, Janita F.J.; Rupert, Joyce

    2018-01-01

    In the change management literature, most studies on recipients’ resistance to change include only the views of agents or of recipients, thereby ignoring that these parties may have different perceptions. In this quantitative study, we include the perceptions of both parties in studying the

  20. Phytophthora palmivora, agente da podridão de raiz e frutos de mamoeiro no Estado de Alagoas Phytophthora palmivora, causal agent of root and fruit rots of papaya in the State of Alagoas, Brazil

    Directory of Open Access Journals (Sweden)

    Juliana Paiva Carnaúba

    2006-04-01

    Full Text Available O mamoeiro (Carica papaya é uma das mais importantes fruteiras tropicais, e seus frutos contribuem com uma produção de 1,65 milhão de toneladas por ano para o Brasil. Um isolado de Phytophthora sp. obtido de frutos de mamoeiro da cultivar Havaí, em Alagoas, foi caracterizado morfologicamente e sua patogenicidade foi confirmada em frutos e mudas deste hospedeiro. Em meio suco V-8, os esporangióforos apresentaram-se delgados, simples ou pouco ramificados, enquanto os esporângios se apresentaram ovóides a elipsóides, proeminentemente papilados e um pedicelo curto na porção basal, medindo em média 37,68 x 27,52 mm. Através das características apresentadas pelo isolado e os sintomas induzidos, o agente causal foi identificado como Phytophthora palmivora. Apesar de essa doença já ocorrer em outros estados, como Bahia, Espírito Santo, São Paulo, Pernambuco e Pará, este é o primeiro relato de Phytophthora palmivora em mamoeiro no Estado de Alagoas.The papaya (Carica papaya is one of the most important tropical fruit crops and its fruit contribute with a production of 1.65 millions tons/year in Brazil. An isolated of Phytophthora sp. gotten from papaya fruits cv. Hawaii, in the state of Alagoas, was characterized morphologically and its pathogenicity to this fruits and seedling was confirmed. In a V-8 medium, the sporangiophores presented to be slim, simple or little ramified, while the sporangia presented ovoid to ellipsoid, prominently papillae and one short pedicel in the basal portion, measuring in average 37,68 x 27,52 (m. Through the characteristics presented by the isolated and the induced symptoms, the causal agent was identified as Phytophthora palmivora. Despite of this disease already occurring in other states like in Bahia, Espirito Santo, São Paulo, Pernambuco and Pará, this is the first report of Phytophthora palmivora on papaya in the state of Alagoas, Brazil.

  1. ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

    Science.gov (United States)

    Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

    2014-10-01

    Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

  2. Resistance of bacterial biofilms formed on stainless steel surface to disinfecting agent.

    Science.gov (United States)

    Królasik, Joanna; Zakowska, Zofia; Krepska, Milena; Klimek, Leszek

    2010-01-01

    The natural ability of microorganisms for adhesion and biofilm formation on various surfaces is one of the factors causing the inefficiency of a disinfection agent, despite its proven activity in vitro. The aim of the study was to determine the effectiveness of disinfecting substances on bacterial biofilms formed on stainless steel surface. A universally applied disinfecting agent was used in the tests. Bacterial strains: Listeria innocua, Pseudomonas putida, Micrococcus luteus, Staphylococcus hominis strains, were isolated from food contact surfaces, after a cleaning and disinfection process. The disinfecting agent was a commercially available acid specimen based on hydrogen peroxide and peroxyacetic acid, the substance that was designed for food industry usage. Model tests were carried out on biofilm formed on stainless steel (type 304, no 4 finish). Biofilms were recorded by electron scanning microscope. The disinfecting agent in usable concentration, 0.5% and during 10 minutes was ineffective for biofilms. The reduction of cells in biofilms was only 1-2 logarithmic cycles. The use of the agent in higher concentration--1% for 30 minutes caused reduction of cell number by around 5 logarithmic cycles only in the case of one microorganism, M. luteus. For other types: L. innocua, P. putida, S. hominis, the requirements placed on disinfecting agents were not fulfilled. The results of experiments proved that bacterial biofilms are resistant to the disinfectant applied in its operational parameters. Disinfecting effectiveness was achieved after twofold increase of the agent's concentration.

  3. Epidemiological causality.

    Science.gov (United States)

    Morabia, Alfredo

    2005-01-01

    Epidemiological methods, which combine population thinking and group comparisons, can primarily identify causes of disease in populations. There is therefore a tension between our intuitive notion of a cause, which we want to be deterministic and invariant at the individual level, and the epidemiological notion of causes, which are invariant only at the population level. Epidemiologists have given heretofore a pragmatic solution to this tension. Causal inference in epidemiology consists in checking the logical coherence of a causality statement and determining whether what has been found grossly contradicts what we think we already know: how strong is the association? Is there a dose-response relationship? Does the cause precede the effect? Is the effect biologically plausible? Etc. This approach to causal inference can be traced back to the English philosophers David Hume and John Stuart Mill. On the other hand, the mode of establishing causality, devised by Jakob Henle and Robert Koch, which has been fruitful in bacteriology, requires that in every instance the effect invariably follows the cause (e.g., inoculation of Koch bacillus and tuberculosis). This is incompatible with epidemiological causality which has to deal with probabilistic effects (e.g., smoking and lung cancer), and is therefore invariant only for the population.

  4. Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

    Science.gov (United States)

    Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

    2017-12-02

    Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

  5. Quantitative relationships of the harmful effect of ionizing radiation on natural resistance of the organism to various infectious agents

    International Nuclear Information System (INIS)

    Mal'tsev, V.N.; Strel'nikov, V.A.

    1978-01-01

    An analysis of data from the literature and own experimental results shows that there is an inverse linear correlation between the dose of irradiation and natural resistance of the organism to infection with various infectious agents. With increasing doses of irradiation, the irradiated organism is exposed to the greatest risk from the agents of intestinal infections and representatives of normal microflora. These are followed by agents of various diseases of microbial nature. The minimum reduction can be observed in resistance to viruses. (author)

  6. The risk of some veterinary antimicrobial agents on public health associated with antimicrobial resistance and their molecular basis

    OpenAIRE

    Haihong Hao; Zahid Iqbal; Yulian Wang; Guyue Cheng; Zong-Hui Yuan

    2016-01-01

    The risk of antimicrobial agents used in food-producing animals on public health associated with antimicrobial resistance continues to be a current topic of discussion as related to animal and human public health. In the present review, resistance monitoring data and risk assessment result of some important antimicrobial agents were cited to elucidate the possible association of antimicrobial use in food animals and antimicrobial resistance in human. From the selected examples, it was obvious...

  7. Resistance of Staphylococcus aureus to antimicrobial agents in Ethiopia: a meta-analysis.

    Science.gov (United States)

    Deyno, Serawit; Fekadu, Sintayehu; Astatkie, Ayalew

    2017-01-01

    Emergence of antimicrobial resistance by Staphylococcus aureus has limited treatment options against its infections. The purpose of this study was to determine the pooled prevalence of resistance to different antimicrobial agents by S. aureus in Ethiopia. Web-based search was conducted in the databases of PubMed, Google Scholar, Hinari, Scopus and the Directory of Open Access Journals (DOAJ) to identify potentially eligible published studies. Required data were extracted and entered into Excel spread sheet. Statistical analyses were performed using Stata version 13.0. The metaprop Stata command was used to pool prevalence values. Twenty-one separate meta-analysis were done to estimate the pooled prevalence of the resistance of S. aureus to twenty-one different antimicrobial agents. Heterogeneity among the studies was assessed using the I 2 statistic and chi-square test. Publication bias was assessed using Egger's test. Because of significant heterogeneity amongst the studies, the random effects model was used to pool prevalence values. The electronic database search yielded 1317 studies among which 45 studies met our inclusion criteria. Our analyses demonstrated very high level of resistance to amoxicillin (77% [95% confidence interval (CI): 68%, 0.85%]), penicillin (76% [95% CI: 67%, 84%]), ampicillin (75% [95% CI: 65%, 85%]), tetracycline (62% [95% CI: 55%, 68%]), methicillin (47% [95% CI: 33%, 61%]), cotrimoxaziole (47% [95% CI: 40%, 55%]), doxycycline (43% [95% CI: 26%, 60%]), and erythromycin (41% [95% CI: 29%, 54%]). Relatively low prevalence of resistance was observed with kanamycin (14% [95% CI: 5%, 25%]) and ciprofloxacin (19% [95% CI: 13%, 26%]). The resistance level to vancomycin is 11% 995% CI: (4%, 20%). High heterogeneity was observed for each of the meta-analysis performed (I 2 ranging from 79.36% to 95.93%; all p -values ≤0.01). Eggers' test did not show a significant publication bias for all antimicrobial agents except for erythromycin and

  8. Resistance of Staphylococcus aureus to antimicrobial agents in Ethiopia: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Serawit Deyno

    2017-08-01

    Full Text Available Abstract Background Emergence of antimicrobial resistance by Staphylococcus aureus has limited treatment options against its infections. The purpose of this study was to determine the pooled prevalence of resistance to different antimicrobial agents by S. aureus in Ethiopia. Methods Web-based search was conducted in the databases of PubMed, Google Scholar, Hinari, Scopus and the Directory of Open Access Journals (DOAJ to identify potentially eligible published studies. Required data were extracted and entered into Excel spread sheet. Statistical analyses were performed using Stata version 13.0. The metaprop Stata command was used to pool prevalence values. Twenty-one separate meta-analysis were done to estimate the pooled prevalence of the resistance of S. aureus to twenty-one different antimicrobial agents. Heterogeneity among the studies was assessed using the I2 statistic and chi-square test. Publication bias was assessed using Egger’s test. Because of significant heterogeneity amongst the studies, the random effects model was used to pool prevalence values. Results The electronic database search yielded 1317 studies among which 45 studies met our inclusion criteria. Our analyses demonstrated very high level of resistance to amoxicillin (77% [95% confidence interval (CI: 68%, 0.85%], penicillin (76% [95% CI: 67%, 84%], ampicillin (75% [95% CI: 65%, 85%], tetracycline (62% [95% CI: 55%, 68%], methicillin (47% [95% CI: 33%, 61%], cotrimoxaziole (47% [95% CI: 40%, 55%], doxycycline (43% [95% CI: 26%, 60%], and erythromycin (41% [95% CI: 29%, 54%]. Relatively low prevalence of resistance was observed with kanamycin (14% [95% CI: 5%, 25%] and ciprofloxacin (19% [95% CI: 13%, 26%]. The resistance level to vancomycin is 11% 995% CI: (4%, 20%. High heterogeneity was observed for each of the meta-analysis performed (I2 ranging from 79.36% to 95.93%; all p-values ≤0.01. Eggers’ test did not show a significant publication bias for all

  9. Diversidade fenotípica e patogênica de Colletotrichum, agente causal da antracnose em mangueira, e identificação de espécie

    Directory of Open Access Journals (Sweden)

    I.M.R.S. Serra

    2011-03-01

    Full Text Available O presente trabalho teve como objetivo estudar a diversidade fenotípica e patogênica de 40 isolados de Colletotrichum obtidos de mangueira no Nordeste do Brasil e identificar diferentes espécies desse fitopatógeno, agente causal de antracnose, através da análise da seqüência da região ITS do rDNA. Quanto à caracterização morfológica e cultural, as colônias dos isolados apresentaram diversidade em relação à cor e aspecto, sendo mais comum à cor branco-cinza, característica de Colletotrichum gloeosporioides. Não foram observadas variações expressivas na morfologia dos 40 isolados. Os conídios apresentaram-se, predominantemente, hialinos e unicelulares, com formato variando de bastonete para cilíndrico. Todos os isolados produziram apressórios variados em formato e quantidade e apenas 10 isolados apresentaram setas. Para efeito do crescimento micelial e taxa de crescimento foi possível classificar os isolados em sete grupos. Vinte e dois isolados exibiram taxa de crescimento >10mm/dia, considerada típica da espécie C. gloeosporioides. Os isolados foram patogênicos em folhas destacadas de mangueira, induzindo sintomas de antracnose, na forma de manchas escuras levemente deprimidas, e apresentando variações quanto à agressividade. Na identificação específica, baseada na análise da seqüência ITS do DNA ribossomal, 36 isolados amplificaram com o oligonucleotídeos CgInt, específico para C. gloeosporioides e o ITS4, Os isolados CM1, CM4, CM5 e CM10, não amplificaram produtos para nenhum dos oligonucleotídeos específicos, sendo identificados como Colletotrichum spp. Os resultados desse trabalho demonstraram que isolados de Colletotrichum, obtidos de mangueira, apresentam ampla variabilidade morfofisiológica e patogênica. E que, possivelmente, existe mais de uma espécie de Colletotrichum que causa antracnose em mangueira no Nordeste do Brasil.

  10. Trends and Sources of Zoonoses, Zoonotic Agents and Antimicrobial resistance in the European Union in 2004

    DEFF Research Database (Denmark)

    Helwigh, Birgitte

    EFSA's Community Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Antimicrobial resistance in the European Union in 2004 was published in December 2005. The zoonoses, meaning infectious diseases transmissible from animals to humans, affected over 380,000 EU citizens in 2004....... Often the human form of the disease is acquired through contaminated food. According to the report, the two most frequently reported zoonotic diseases in humans were Salmonella and Campylobacter infections. These bacteria were also commonly found in food and animals. The report includes information...... of 11 zoonoses, antimicrobial resistance in zoonotic agents as well as foodborne outbreaks. The national zoonoses country reports which have been used as a basis for this Summary report are below. The utmost effort was made to keep the information in the Summary Report and the national reports identical...

  11. Sea urchin coelomocytes are resistant to a variety of DNA damaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Loram, Jeannette; Raudonis, Renee; Chapman, Jecar; Lortie, Mae [Bermuda Institute of Ocean Sciences, St. George' s, Bermuda, GE 01 (Bermuda); Bodnar, Andrea, E-mail: andrea.bodnar@bios.edu [Bermuda Institute of Ocean Sciences, St. George' s, Bermuda, GE 01 (Bermuda)

    2012-11-15

    Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H{sub 2}O{sub 2}), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD{sub 50} values determined for coelomocytes after 24 h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H{sub 2}O{sub 2}, MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.

  12. Sea urchin coelomocytes are resistant to a variety of DNA damaging agents

    International Nuclear Information System (INIS)

    Loram, Jeannette; Raudonis, Renee; Chapman, Jecar; Lortie, Mae; Bodnar, Andrea

    2012-01-01

    Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H 2 O 2 ), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD 50 values determined for coelomocytes after 24 h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H 2 O 2 , MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.

  13. Change Agent – A Force Generating Resistance To Change Within An Organization?

    Directory of Open Access Journals (Sweden)

    Mariana Prediscan

    2012-12-01

    Full Text Available The purpose of this research is to identify if the change agent represents or not a force generating resistance to change within an organization. The employees affected by a change process are usually the ones who oppose to new implementations. Their opposition is bigger or smaller, depending on the extent that they are affected and also by the direction, either positive or negative. However, employee’s opposition can be potentiated or reduced, depending on the manifestation of the following forces within an organization: communications, the type of organizational structure, management style and organizational culture, forces which refer to the organizational climate. To answer our question, we have researched the current literature and discovered that the change agent can represent a force generating resistance to change within an organization in those situations when he or she identifies with a middle or top manager from the organizational pyramid. This information is valuable to researchers and practitioners, as for a long time, employees were considered the only ones manifesting resistance, the possibility that the change agent can oppose new changes being ignored.

  14. Development of bacterial resistance to biocides and antimicrobial agents as a consequence of biocide usage

    DEFF Research Database (Denmark)

    Seier-Petersen, Maria Amalie

    to antimicrobial agents. So far, only few studies have investigated the susceptibility of livestock-associated isolates to biocides used in their environment. Pigs are increasingly recognised as a potential reservoir of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA), especially clones...... be of potential risk for human health, since these disinfectants are widely used at hospitals and in the food industry. Mobile genetic elements such as conjugative transposons are important vectors in the dissemination of antibiotic resistance determinants. Tn916 including the tetracycline resistance gene tet......Biocides are chemical compounds with antimicrobial properties and they are widely used for disinfection, antiseptic and preservation purposes. Biocides have been applied for centuries due to early empirical approaches, such as cleansing of wounds with wine, vinegar and honey and salting of fish...

  15. Macromolecular agents with antimicrobial potentialities: A drive to combat antimicrobial resistance.

    Science.gov (United States)

    Bilal, Muhammad; Rasheed, Tahir; Iqbal, Hafiz M N; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

    2017-10-01

    In recent years, the antimicrobial resistance (AMR) or multidrug resistance (MDR) has become a serious health concern and major challenging issue, worldwide. After decades of negligence, the AMR has now captured global attention. The increasing number of antibiotic-resistant strains has threatened the achievements of science and medicine since it inactivates conventional antimicrobial therapeutics. Scientists are trying to respond to AMR/MDR threat by exploring innovative platforms and new therapeutic strategies to tackle infections from these resistant strains and bypass treatment limitations related to these pathologies. The present review focuses on the utilization of bio-inspired novel constructs and their potential applications as novel antimicrobial agents. The first part of the review describes plant-based biological macromolecules containing an immense variety of secondary metabolites, which could be potentially used as alternative strategies to combat antimicrobial resistance. The second part discusses the potential of metal-based macromolecules as effective antimicrobial platforms for preventing infections from resistant strains. The third part comprehensively elucidates how nanoparticles, in particular, metal-integrated nanoparticles can overcome this AMR or MDR issue. Towards the end, information is given with critical concluding remarks, gaps, and finally envisioned with future considerations. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Hymenoscyphus fraxineus vs. Hymenoscyphus albidus – A comparative light microscopic study on the causal agent of European ash dieback and related foliicolous, stroma-forming species

    Science.gov (United States)

    Baral, Hans-Otto; Bemmann, Martin

    2014-01-01

    Five species of Hymenoscyphus that fruit on black stromatized parts of dead leaves of deciduous trees are presented, giving details on their morphological and ecological characteristics. Several of these species have previously been misplaced in rutstroemiaceous genera because of the presence of a substratal stroma. However, the heteropolar, scutuloid ascospores with an often hook-like lateral protrusion at the rounded apex and the ascus apical ring of the Hymenoscyphus-type represent two reliable morphological characteristics that, together with molecular data, provide clear evidence for their placement in the genus Hymenoscyphus (Helotiaceae). Among the species treated is Hymenoscyphus fraxineus (=Hymenoscyphus pseudoalbidus), the causal agent of the European ash dieback disease. Since 1992 this species started within Europe to replace the rather uncommon Hymenoscyphus albidus, which is likewise confined to leaves of Fraxinus. Hy. fraxineus has been recorded already since 1990 in Eastern Asia (Japan, Korea, northeast of China), where it had been initially misidentified as Lambertella albida (≡Hy. albidus). In these regions, it occurs as a harmless saprotroph on Fraxinus mandshurica and Fraxinus rhynchophylla, suggesting that those populations are native while the European ash dieback disease has a recent Eastern Asiatic origin. The distinctly higher genetic diversity found in Japanese Hy. fraxineus in contrast to European Hy. fraxineus supports this view. Genetic similarities between Japanese Hy. fraxineus and European Hy. albidus suggest that also Hy. albidus might be a descendant of Asian Hy. fraxineus, though having invaded Europe much earlier. However, consistent genetic deviation between European and Asian Hy. fraxineus at two nucleotide positions of the ITS region indicates that the European ash disease originates from a region different from the presently known areas in Eastern Asia. Our results underline the importance of detailed morphological studies

  17. Identification and characterization of SSE15206, a microtubule depolymerizing agent that overcomes multidrug resistance

    KAUST Repository

    Manzoor, Safia

    2018-02-13

    Microtubules are highly dynamic structures that form spindle fibres during mitosis and are one of the most validated cancer targets. The success of drugs targeting microtubules, however, is often limited by the development of multidrug resistance. Here we describe the discovery and characterization of SSE15206, a pyrazolinethioamide derivative [3-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide] that has potent antiproliferative activities in cancer cell lines of different origins and overcomes resistance to microtubule-targeting agents. Treatment of cells with SSE15206 causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation, a phenotype often associated with drugs that interfere with microtubule dynamics. SSE15206 inhibits microtubule polymerization both in biochemical and cellular assays by binding to colchicine site in tubulin as shown by docking and competition studies. Prolonged treatment of cells with the compound results in apoptotic cell death [increased Poly (ADP-ribose) polymerase cleavage and Annexin V/PI staining] accompanied by p53 induction. More importantly, we demonstrate that SSE15206 is able to overcome resistance to chemotherapeutic drugs in different cancer cell lines including multidrug-resistant KB-V1 and A2780-Pac-Res cell lines overexpressing MDR-1, making it a promising hit for the lead optimization studies to target multidrug resistance.

  18. Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases

    Science.gov (United States)

    Speziale, Pietro; Rindi, Simonetta

    2018-01-01

    Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of antibiotic usage. This has generated renewed interest within the scientific community in alternative therapeutic agents, such as anti-S. aureus antibodies. Although the role of antibodies in the management of S. aureus diseases is controversial, the success of this pathogen in neutralizing humoral immunity clearly indicates that antibodies offer the host extensive protection. In this review, we report an update on efforts to develop antibody-based agents, particularly monoclonal antibodies, and their therapeutic potential in the passive immunization approach to the treatment and prevention of S. aureus infections. PMID:29533985

  19. Patterns of infections, aetiological agents and antimicrobial resistance at a tertiary care hospital in northern Tanzania.

    Science.gov (United States)

    Kumburu, Happiness Houka; Sonda, Tolbert; Mmbaga, Blandina Theophil; Alifrangis, Michael; Lund, Ole; Kibiki, Gibson; Aarestrup, Frank M

    2017-04-01

    To determine the causative agents of infections and their antimicrobial susceptibility at a tertiary care hospital in Moshi, Tanzania, to guide optimal treatment. A total of 590 specimens (stool (56), sputum (122), blood (126) and wound swabs (286)) were collected from 575 patients admitted in the medical and surgical departments. The bacterial species were determined by conventional methods, and disc diffusion was used to determine the antimicrobial susceptibility pattern of the bacterial isolates. A total of 249 (42.2%) specimens were culture-positive yielding a total of 377 isolates. A wide range of bacteria was isolated, the most predominant being Gram-negative bacteria: Proteus spp. (n = 48, 12.7%), Escherichia coli (n = 44, 11.7%), Pseudomonas spp. (n = 40, 10.6%) and Klebsiella spp (n = 38, 10.1%). Wound infections were characterised by multiple isolates (n = 293, 77.7%), with the most frequent being Proteus spp. (n = 44, 15%), Pseudomonas (n = 37, 12.6%), Staphylococcus (n = 29, 9.9%) and Klebsiella spp. (n = 28, 9.6%). All Staphylococcus aureus tested were resistant to penicillin (n = 22, 100%) and susceptible to vancomycin. Significant resistance to cephalosporins such as cefazolin (n = 62, 72.9%), ceftriaxone (n = 44, 51.8%) and ceftazidime (n = 40, 37.4%) was observed in Gram-negative bacteria, as well as resistance to cefoxitin (n = 6, 27.3%) in S. aureus. The study has revealed a wide range of causative agents, with an alarming rate of resistance to the commonly used antimicrobial agents. Furthermore, the bacterial spectrum differs from those often observed in high-income countries. This highlights the imperative of regular generation of data on aetiological agents and their antimicrobial susceptibility patterns especially in infectious disease endemic settings. The key steps would be to ensure the diagnostic capacity at a sufficient number of sites and implement structures to routinely exchange, compare, analyse and report data. Sentinel sites

  20. A screen to identify drug resistant variants to target-directed anti-cancer agents

    Directory of Open Access Journals (Sweden)

    Azam Mohammad

    2003-01-01

    Full Text Available The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia (CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.

  1. Fracture resistance improvement of polypropylene by joint action of core-shell particles and nucleating agent

    International Nuclear Information System (INIS)

    Yang Gang; Han Liang; Ding Haifeng; Wu Haiyan; Huang Ting; Li Xiaoxi; Wang Yong

    2011-01-01

    Research highlights: →The core-shell particles, which were prepared from melt blending of POE and nano-CaCO 3 , and different nucleating agents (α-form NA or β-form NA) were first introduced into PP to prepare the super toughened PP materials. →NAs control the crystalline structures of PP matrix including the spherulites diameter and the crystal form. →NAs and core-shell particles exhibit apparent joint effect in improving the fracture resistance of PP. - Abstract: As a serial work about the fracture resistance improvement of polypropylene (PP), this work reports the joint effect of core-shell particles and nucleating agent (NA) on the microstructure and fracture resistance of PP. Core-shell particles were prepared through melt blending of ethylene-octene copolymer (POE) and calcium carbonate (CaCO 3 ). Different NA, i.e. α-form NA (P-tert-butylbenzoic acid-Al, MD-NA-28) and β-form NA (aryl amides compound, TMB-5) were introduced into PP matrix to control the crystalline structure. The phase morphology of POE and the distribution of CaCO 3 were characterized by using scanning electron microscope (SEM), and the crystallization behavior of PP matrix were investigated by using differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarization optical microscope (POM). The mechanical properties were obtained through universal tensile measurement and notched Izod impact measurement. Surprisingly, the results show that through addition of so-called core-shell particles and NA simultaneously, the fracture resistance of PP can be dramatically improved.

  2. Positive selection and intragenic recombination contribute to high allelic diversity in effector genes of Mycosphaerella fijiensis, causal agent of the black leaf streak disease of banana

    NARCIS (Netherlands)

    Stergiopoulos, I.; Cordovez da Cunha, V.; Okmen, B.; Beenen, H.G.; Kema, G.H.J.; Wit, de P.J.G.M.

    2014-01-01

    Previously, we have determined the nonhost-mediated recognition of the MfAvr4 and MfEcp2 effector proteins from the banana pathogen Mycosphaerella fijiensis in tomato, by the cognate Cf-4 and Cf-Ecp2 resistance proteins, respectively. These two resistance proteins could thus mediate resistance

  3. Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria.

    Science.gov (United States)

    Chung, Pooi Yin; Khanum, Ramona

    2017-08-01

    Bacterial resistance to commonly used drugs has become a global health problem, causing increased infection cases and mortality rate. One of the main virulence determinants in many bacterial infections is biofilm formation, which significantly increases bacterial resistance to antibiotics and innate host defence. In the search to address the chronic infections caused by biofilms, antimicrobial peptides (AMP) have been considered as potential alternative agents to conventional antibiotics. Although AMPs are commonly considered as the primitive mechanism of immunity and has been extensively studied in insects and non-vertebrate organisms, there is now increasing evidence that AMPs also play a crucial role in human immunity. AMPs have exhibited broad-spectrum activity against many strains of Gram-positive and Gram-negative bacteria, including drug-resistant strains, and fungi. In addition, AMPs also showed synergy with classical antibiotics, neutralize toxins and are active in animal models. In this review, the important mechanisms of action and potential of AMPs in the eradication of biofilm formation in multidrug-resistant pathogen, with the goal of designing novel antimicrobial therapeutics, are discussed. Copyright © 2017. Published by Elsevier B.V.

  4. Insights on antimicrobial resistance, biofilms and the use of phytochemicals as new antimicrobial agents.

    Science.gov (United States)

    Borges, Anabela; Saavedra, Maria J; Simões, Manuel

    2015-01-01

    Antimicrobial resistance is one of the most serious public health problems. This is of particular concern when bacteria become resistant to various antimicrobial agents simultaneously and when they form biofilms. Consequently, therapeutic options for the treatment of infections have become limited, leading frequently to recurrent infections, treatment failure and increase of morbidity and mortality. Both, persistence and spread of antibiotic resistance, in combination with decreased effectiveness and increased toxicity of current antibiotics have emphasized the urgent need to search alternative sources of antimicrobial substances. Plants are recognized as a source of unexplored chemical structures with high therapeutic potential, including antimicrobial activity against clinically important microorganisms. Additionally, phytochemicals (plant secondary metabolites) present several advantages over synthetic molecules, including green status and different mechanisms of action from antibiotics which could help to overcome the resistance problem. In this study, an overview of the main classes of phytochemicals with antimicrobial properties and their mode of action is presented. A revision about the application of phytochemicals for biofilm prevention and control is also done. Moreover, the use of phytochemicals as scaffolds of new functional molecules to expand the antibiotics pipeline is reviewed.

  5. Streptococcus sanguinis isolate displaying a phenotype with cross-resistance to several rRNA-targeting agents.

    Science.gov (United States)

    Mendes, Rodrigo E; Deshpande, Lalitagauri M; Kim, Jihye; Myers, Debra S; Ross, James E; Jones, Ronald N

    2013-08-01

    This study describes a clinical case of a 71-year-old male with a history of ischemic cardiomyopathy after left ventricular assist device (LVAD) endocarditis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and a rare linezolid-resistant Streptococcus sanguinis strain (MIC, 32 μg/ml). The patient received courses of several antimicrobial agents, including linezolid for 79 days. The S. sanguinis strain had mutations in the 23S rRNA (T2211C, T2406C, G2576T, C2610T) and an amino acid substitution (N56D) in L22 and exhibited cross-resistance to ribosome-targeting agents.

  6. Resistance profiles to antimicrobial agents in bacteria isolated from acute endodontic infections: systematic review and meta-analysis.

    Science.gov (United States)

    Lang, Pauline M; Jacinto, Rogério C; Dal Pizzol, Tatiane S; Ferreira, Maria Beatriz C; Montagner, Francisco

    2016-11-01

    Infected root canal or acute apical abscess exudates can harbour several species, including Fusobacterium, Porphyromonas, Prevotella, Parvimonas, Streptococcus, Treponema, Olsenella and not-yet cultivable species. A systematic review and meta-analysis was performed to assess resistance rates to antimicrobial agents in clinical studies that isolated bacteria from acute endodontic infections. Electronic databases and the grey literature were searched up to May 2015. Clinical studies in humans evaluating the antimicrobial resistance of primary acute endodontic infection isolates were included. PRISMA guidelines were followed. A random-effect meta-analysis was employed. The outcome was described as the pooled resistance rates for each antimicrobial agent. Heterogeneity and sensitivity analyses were performed. Subgroup analyses were conducted based upon report or not of the use of antibiotics prior to sampling as an exclusion factor (subgroups A and B, respectively). Data from seven studies were extracted. Resistance rates for 15 different antimicrobial agents were evaluated (range, 3.5-40.0%). Lower resistance rates were observed for amoxicillin/clavulanic acid and amoxicillin; higher resistance rates were detected for tetracycline. Resistance rates varied according to previous use of an antimicrobial agent as demonstrated by the subgroup analyses. Heterogeneity was observed for the resistance profiles of penicillin G in subgroup A and for amoxicillin, clindamycin, metronidazole and tetracycline in subgroup B. Sensitivity analyses demonstrated that resistance rates changed for metronidazole, clindamycin, tetracycline and amoxicillin. These findings suggest that clinical isolates had low resistance to β-lactams. Further well-designed studies are needed to clarify whether the differences in susceptibility among the antimicrobial agents may influence clinical responses to treatment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights

  7. Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

    International Nuclear Information System (INIS)

    Tanaka, Mamoru; Kamiya, Takeshi; Joh, Takashi; Kataoka, Hiromi; Yano, Shigenobu; Ohi, Hiromi; Kawamoto, Keisuke; Shibahara, Takashi; Mizoshita, Tsutomu; Mori, Yoshinori; Tanida, Satoshi

    2013-01-01

    Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients. We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl 2 (L)] and [PdCl 2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl 2 (L)] and [PdCl 2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo. CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl 2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl 2 (L)] induced DNA double-strand breaks. These results indicate that [PdCl 2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications

  8. Multidrug resistant Salmonella enterica isolated from conventional pig farms using antimicrobial agents in preventative medicine programmes.

    Science.gov (United States)

    Cameron-Veas, Karla; Fraile, Lorenzo; Napp, Sebastian; Garrido, Victoria; Grilló, María Jesús; Migura-Garcia, Lourdes

    2018-04-01

    A longitudinal study was conducted to investigate the presence of multidrug antimicrobial resistance (multi-AR) in Salmonella enterica in pigs reared under conventional preventative medicine programmes in Spain and the possible association of multi-AR with ceftiofur or tulathromycin treatment during the pre-weaning period. Groups of 7-day-old piglets were treated by intramuscular injection with ceftiofur on four farms (n=40 piglets per farm) and with tulathromycin on another four farms (n=40 piglets per farm). A control group of untreated piglets (n=30 per farm) was present on each farm. Faecal swabs were collected for S. enterica culture prior to treatment, at 2, 7 and 180days post-treatment, and at slaughter. Minimal inhibitory concentrations of 14 antimicrobial agents, pulsed-field gel electrophoresis and detection of resistance genes representing five families of antimicrobial agents were performed. Plasmids carrying cephalosporin resistant (CR) genes were characterised. Sixty-six S. enterica isolates were recovered from five of eight farms. Forty-seven isolates were multi-AR and four contained bla CTX-M genes harboured in conjugative plasmids of the IncI1 family; three of these isolates were recovered before treatment with ceftiofur. The most frequent AR genes detected were tet(A) (51/66, 77%), sul1 (17/66, 26%); tet(B) (15/66, 23%) and qnrB (10/66, 15%). A direct relation between the use of ceftiofur in these conditions and the occurrence of CR S. enterica was not established. However, multi-AR was common, especially for ampicillin, streptomycin, sulphonamides and tetracycline. These antibiotics are used frequently in veterinary medicine in Spain and, therefore, should be used sparingly to minimise the spread of multi-AR. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Resistance to antimicrobial agents among Salmonella isolates recovered from layer farms and eggs in the Caribbean region.

    Science.gov (United States)

    Adesiyun, Abiodun; Webb, Lloyd; Musai, Lisa; Louison, Bowen; Joseph, George; Stewart-Johnson, Alva; Samlal, Sannandan; Rodrigo, Shelly

    2014-12-01

    This investigation determined the frequency of resistance of 84 isolates of Salmonella comprising 14 serotypes recovered from layer farms in three Caribbean countries (Trinidad and Tobago, Grenada, and St. Lucia) to eight antimicrobial agents, using the disc diffusion method. Resistance among isolates of Salmonella was related to the country of recovery, type of sample, size of layer farms, and isolate serotype. Overall, all (100.0%) of the isolates exhibited resistance to one or more of seven antimicrobial agents tested, and all were susceptible to chloramphenicol. The resistance detected ranged from 11.9% to sulphamethoxazole-trimethoprim (SXT) to 100.0% to erythromycin. The difference was, however, not statistically significant (P = 0.23). Across countries, for types of samples that yielded Salmonella, significant differences in frequency of resistance were detected only to SXT (P = 0.002) in Trinidad and Tobago and to gentamycin (P = 0.027) in St. Lucia. For the three countries, the frequency of resistance to antimicrobial agents was significantly different for ampicillin (P = 0.001) and SXT (P = 0.032). A total of 83 (98.8%) of the 84 isolates exhibited 39 multidrug resistance patterns. Farm size significantly (P = 0.032) affected the frequency of resistance to kanamycin across the countries. Overall, among the 14 serotypes of Salmonella tested, significant (P resistance were detected to kanamycin, ampicillin, and SXT. Results suggest that the relatively high frequency of resistance to six of the antimicrobial agents (erythromycin, streptomycin, gentamycin, kanamycin, ampicillin, and tetracycline) tested and the multidrug resistance detected may pose prophylactic and therapeutic concerns for chicken layer farms in the three countries studied.

  10. Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours

    International Nuclear Information System (INIS)

    Horsman, M.

    1996-01-01

    Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitize murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms. However, recent studies in mouse tumours have shown that these drugs prevent transient cessations in blood flow, thus inhibiting the development of acute hypoxia. This novel discovery led to the suggestion that the potential role of these agents as radiosensitizers would be when combined with treatments that overcame chronic hypoxia. The combined nicotinamide with hyperthermia proved that the enhancement of radiation damage by both agents together was greater than that seen with each agent alone. Similar results were later seen for nicotinamide combined with a perfluorochemical emulsion, carbogen breathing, and pentoxifylline, and in all these studies the effects in tumours were always greater than those seen in appropriate normal tissues. Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically, with daily doses of up to 6 g, associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to

  11. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (II

    Directory of Open Access Journals (Sweden)

    Rongshi Li

    2013-08-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA continues to be a major problem, causing severe and intractable infections worldwide. MRSA is resistant to all beta-lactam antibiotics, and alternative treatments are limited. A very limited number of new antibiotics have been discovered over the last half-century, novel agents for the treatment of MRSA infections are urgently needed. Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008. After we reported the first total synthesis of (±-marinopyrrole A, we designed and synthesized a series of marinopyrrole derivatives. Our structure activity relationship (SAR studies of these novel derivatives against a panel of Gram-positive pathogens in antibacterial assays have revealed that a para-trifluoromethyl analog (33 of marinopyrrole A is ≥63-, 8-, and 4-fold more potent than vancomycin against methicillin-resistant Staphylococcus epidermidis (MRSE, methicillin-susceptible Staphylococcus aureus (MSSA and MRSA, respectively. The results provide valuable information in the search for new-generation antibiotics.

  12. Graphene oxide-silver nanocomposite as a promising biocidal agent against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    de Moraes, Ana Carolina Mazarin; Lima, Bruna Araujo; de Faria, Andreia Fonseca; Brocchi, Marcelo; Alves, Oswaldo Luiz

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has been responsible for serious hospital infections worldwide. Nanomaterials are an alternative to conventional antibiotic compounds, because bacteria are unlikely to develop microbial resistance against nanomaterials. In the past decade, graphene oxide (GO) has emerged as a material that is often used to support and stabilize silver nanoparticles (AgNPs) for the preparation of novel antibacterial nanocomposites. In this work, we report the synthesis of the graphene-oxide silver nanocomposite (GO-Ag) and its antibacterial activity against relevant microorganisms in medicine. GO-Ag nanocomposite was synthesized through the reduction of silver ions (Ag(+)) by sodium citrate in an aqueous GO dispersion, and was extensively characterized using ultraviolet-visible absorption spectroscopy, X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, and transmission electron microscopy. The antibacterial activity was evaluated by microdilution assays and time-kill experiments. The morphology of bacterial cells treated with GO-Ag was investigated via transmission electron microscopy. AgNPs were well distributed throughout GO sheets, with an average size of 9.4±2.8 nm. The GO-Ag nanocomposite exhibited an excellent antibacterial activity against methicillin-resistant S. aureus, Acinetobacter baumannii, Enterococcus faecalis, and Escherichia coli. All (100%) MRSA cells were inactivated after 4 hours of exposure to GO-Ag sheets. In addition, no toxicity was found for either pristine GO or bare AgNPs within the tested concentration range. Transmission electronic microscopy images offered insights into how GO-Ag nanosheets interacted with bacterial cells. Our results indicate that the GO-Ag nanocomposite is a promising antibacterial agent against common nosocomial bacteria, particularly antibiotic-resistant MRSA. Morphological injuries on MRSA cells revealed a likely loss of viability as a result of the

  13. Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

    Directory of Open Access Journals (Sweden)

    Richard C Wang

    Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

  14. Graphene oxide-silver nanocomposite as a promising biocidal agent against methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    de Moraes ACM

    2015-11-01

    NPs within the tested concentration range. Transmission electronic microscopy images offered insights into how GO-Ag nanosheets interacted with bacterial cells. Conclusion: Our results indicate that the GO-Ag nanocomposite is a promising antibacterial agent against common nosocomial bacteria, particularly antibiotic-resistant MRSA. Morphological injuries on MRSA cells revealed a likely loss of viability as a result of the direct contact between bacteria and the GO-Ag sheets. Keywords: graphene oxide, silver nanoparticles, graphene oxide-silver nanocomposite, antibacterial agent, MRSA, Escherichia coli

  15. Management of vascular wilt of lentil through host plant resistance, biological control agents and chemicals

    International Nuclear Information System (INIS)

    Rafique, K.; Rauf, C.A.; Naz, F.

    2016-01-01

    The management of devastating lentil (Lens culinaris Medik.) wilt disease was investigated through evaluation of host plant resistance, biological control agents and seed treatment with different fungicides against a known most aggressive isolate i.e. FWL12 (KP297995) of Fusarium oxysporum f. sp. lentis. The In vitro screening of germplasm (23 advanced lines and cultivars) for host resistance by root dip method revealed five cultivars viz. Markaz-09, Masoor-86, Masoor-2006, Punjab Masoor-00518 and Punjab Masoor-09 resistant with 20 to 46.67% incidence, 4.44 to 12.95% severity index and 9.60 to 24.94% yield reduction compared with highly susceptible (100% incidence) local lentil line (NARC-08-1). The later line was treated with Trichoderma species as antagonists in pot experiment by drenching. The bio-control treatment revealed maximum positive effect of T. harzianum (26.7% incidence, 8.9% severity index and 16.27% yield reduction), followed by T. viride (66.7% incidence, 17.8% severity index and 31.13% yield reduction). On inoculated untreated control, the fungus produced the characteristic wilt symptoms and significantly caused increased severity index, incidence and decreased 100% yield. In vitro evaluation of four fungicides at five concentrations (10, 20, 30, 50 and 100 ppm) revealed maximum inhibition of the test fungus with benomyl (85.9%), followed by thiophanate methyl (81.2%). Determination of the efficacy of two best fungicides viz. benomyl and thiophanate methyl in reducing wilt infection through In vivo seed treatment of NARC-08-1 in previously inoculated potting mixture revealed 100% seed germination and suppressed wilt disease, the most effective being benomyl with 6.7% incidence, 1.5% wilt severity and 17.16% yield reduction compared to the control. The study concluded that the genetic diversity already present in lentil cultivars is an important source, which could be exploited for breeding wilt resistant lentil genotypes. Moreover, being seed and

  16. Clinical Features and Antimicrobial Resistance of Bacterial Agents of Ventilator-Associated Tracheobronchitis in Hamedan, Iran

    Directory of Open Access Journals (Sweden)

    Seyyed Hamid Hashemi

    2017-09-01

    Full Text Available Objectives: Ventilator-associated tracheobronchitis (VAT is a common cause of mortality and morbidity in patients admitted to intensive care units (ICUs. This study was conducted to evaluate the clinical course, etiology, and antimicrobial resistance of bacterial agents of VAT in ICUs in Hamedan, Iran. Methods: During a 12-month period, all patients with VAT in a medical and a surgical ICU were included. The criteria for the diagnosis of VAT were fever, mucus production, a positive culture of tracheal secretions, and the absence of lung infiltration. Clinical course, including changes in temperature and tracheal secretions, and outcomes were followed. The endotracheal aspirates were cultured on blood agar and chocolate agar, and antimicrobial susceptibility testing of isolates were performed using the disk diffusion method. Results: Of the 1 070 ICU patients, 69 (6.4% were diagnosed with VAT. The mean interval between the patient’s intubation and the onset of symptoms was 4.7±8.5 days. The mean duration of response to treatment was 4.9±4.7 days. A total of 23 patients (33.3% progressed to ventilator-associated pneumonia (VAP, and 38 patients (55.0% died. The most prevalent bacterial isolates included Acinetobacter baumannii (24.6%, Pseudomonas aeruginosa (20.2%, and Enterobacter(13.0%. P. aeruginosa and Enterobacter were the most prevalent bacteria in surgical ICU, and A. baumannii and K. pneumoniae were the most common in the medical ICU. All A. baumannii and Citrobacter species were multidrug-resistant (MDR. MDR pathogens were more prevalent in medical ICU compared to surgical ICU (p < 0.001. Conclusions: VAT increases the rates of progression to VAP, the need for tracheostomy, and the incidence of mortality in ICUs. Most bacterial agents of VAT are MDR. Preventive policies for VAP, including the use of ventilator care bundle, and appropriate empirical antibiotic therapy for VAT may reduce the incidence of VAP.

  17. Biocontrol agent Bacillus amyloliquefaciens LJ02 induces systemic resistance against cucurbits powdery mildew.

    Science.gov (United States)

    Li, Yunlong; Gu, Yilin; Li, Juan; Xu, Mingzhu; Wei, Qing; Wang, Yuanhong

    2015-01-01

    Powdery mildew is a fungal disease found in a wide range of plants and can significantly reduce crop yields. Bacterial strain LJ02 is a biocontrol agent (BCA) isolated from a greenhouse in Tianjin, China. In combination of morphological, physiological, biochemical and phylogenetic analyses, strain LJ02 was classified as a new member of Bacillus amyloliquefaciens. Greenhouse trials showed that LJ02 fermentation broth (LJ02FB) can effectively diminish the occurrence of cucurbits powdery mildew. When treated with LJ02FB, cucumber seedlings produced significantly elevated production of superoxide dismutase, peroxidase, polyphenol oxidase and phenylalanine ammonia lyase as compared to that of the control. We further confirmed that the production of free salicylic acid (SA) and expression of one pathogenesis-related (PR) gene PR-1 in cucumber leaves were markedly elevated after treating with LJ02FB, suggesting that SA-mediated defense response was stimulated. Moreover, LJ02FB-treated cucumber leaves could secrete resistance-related substances into rhizosphere that inhibit the germination of fungi spores and the growth of pathogens. Finally, we separated bacterium and its fermented substances to test their respective effects and found that both components have SA-inducing activity and bacterium plays major roles. Altogether, we identified a BCA against powdery mildew and its mode of action by inducing systemic resistance such as SA signaling pathway.

  18. Reversing resistance to vascular-disrupting agents by blocking late mobilization of circulating endothelial progenitor cells.

    Science.gov (United States)

    Taylor, Melissa; Billiot, Fanny; Marty, Virginie; Rouffiac, Valérie; Cohen, Patrick; Tournay, Elodie; Opolon, Paule; Louache, Fawzia; Vassal, Gilles; Laplace-Builhé, Corinne; Vielh, Philippe; Soria, Jean-Charles; Farace, Françoise

    2012-05-01

    The prevailing concept is that immediate mobilization of bone marrow-derived circulating endothelial progenitor cells (CEP) is a key mechanism mediating tumor resistance to vascular-disrupting agents (VDA). Here, we show that administration of VDA to tumor-bearing mice induces 2 distinct peaks in CEPs: an early, unspecific CEP efflux followed by a late yet more dramatic tumor-specific CEP burst that infiltrates tumors and is recruited to vessels. Combination with antiangiogenic drugs could not disrupt the early peak but completely abrogated the late VDA-induced CEP burst, blunted bone marrow-derived cell recruitment to tumors, and resulted in striking antitumor efficacy, indicating that the late CEP burst might be crucial to tumor recovery after VDA therapy. CEP and circulating endothelial cell kinetics in VDA-treated patients with cancer were remarkably consistent with our preclinical data. These findings expand the current understanding of vasculogenic "rebounds" that may be targeted to improve VDA-based strategies. Our findings suggest that resistance to VDA therapy may be strongly mediated by late, rather than early, tumor-specific recruitment of CEPs, the suppression of which resulted in increased VDA-mediated antitumor efficacy. VDA-based therapy might thus be significantly enhanced by combination strategies targeting late CEP mobilization. © 2012 AACR

  19. Acquisition of resistance to antitumor alkylating agent ACNU: a possible target of positron emission tomography monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Hideya [Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193 (Japan); Research Institute of Brain and Blood Vessels, Akita 010-0874 (Japan); Toyohara, Jun [Radiopharmaceutical Chemistry Section, Department of Medical Imaging, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Kado, Hirotsugu [Research Institute of Brain and Blood Vessels, Akita 010-0874 (Japan); Nakagawa, Takao [Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193 (Japan); Takamatsu, Shinji [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Furukawa, Takako [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Yonekura, Yoshiharu [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Kubota, Toshihiko [Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)]. E-mail: yfuji@fmsrsa.fukui-med.ac.jp

    2006-01-15

    Early detection of tumor response to chemotherapy is of great importance for appropriate treatment of tumors. In this study, characteristics of two positron emission tomography (PET) tracers, [{sup 18}F]2-fluoro-2-deoxy-D-glucose (FDG) and[{sup 18}F]3'-fluoro-3'-deoxy-thymidine (FLT), in the early detection of tumor cell response as well as tolerance development to chemotherapy was compared using rat C6 glioma cells and 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl) -3-nitrosoureahydrochloride (ACNU). ACNU is an alkylating agent known to induce drug resistance through expression of O {sup 6}-methylguanine-deoxyribonucleic acid methyl transferase (O {sup 6}-MGMT). We established an ACNU-resistant C6 glioma cell line (C6/ACNU) and investigated the effect of ACNU on the uptake of FLT and FDG. In C6 cells, DNA synthesis presented as [{sup 3}H]thymidine ([{sup 3}H]Thd) incorporation into DNA was quickly suppressed by ACNU. In C6/ACNU cells, the suppression was recovered promptly, indicating that DNA alkylation occurs initially but highly expressed O {sup 6}-MGMT repairs DNA, leading to the recovery of DNA synthesis. The patterns of FLT uptake in C6 and C6/ACNU were difficult to distinguish in the very early stage of the treatment, though it was reported that FLT uptake well correlated with proliferation in certain conditions. FDG uptake showed different patterns between the resistant and control cells, with significantly decreased uptake in C6 cells and unchanged uptake in C6/ACNU cells at 18-24 h after the treatment. Though difficult to be directly translated into clinical situation, the present study will provide a base to develop an appropriate protocol to assess tumor response to treatment by PET and to design effective treatment plans.

  20. Causally nonseparable processes admitting a causal model

    International Nuclear Information System (INIS)

    Feix, Adrien; Araújo, Mateus; Brukner, Caslav

    2016-01-01

    A recent framework of quantum theory with no global causal order predicts the existence of ‘causally nonseparable’ processes. Some of these processes produce correlations incompatible with any causal order (they violate so-called ‘causal inequalities’ analogous to Bell inequalities ) while others do not (they admit a ‘causal model’ analogous to a local model ). Here we show for the first time that bipartite causally nonseparable processes with a causal model exist, and give evidence that they have no clear physical interpretation. We also provide an algorithm to generate processes of this kind and show that they have nonzero measure in the set of all processes. We demonstrate the existence of processes which stop violating causal inequalities but are still causally nonseparable when mixed with a certain amount of ‘white noise’. This is reminiscent of the behavior of Werner states in the context of entanglement and nonlocality. Finally, we provide numerical evidence for the existence of causally nonseparable processes which have a causal model even when extended with an entangled state shared among the parties. (paper)

  1. Bleeding Sap and Old Wood Are the Two Main Sources of Contamination of Merging Organs of Vine Plants by Xylophilus ampelinus, the Causal Agent of Bacterial Necrosis

    OpenAIRE

    Grall, S.; Roulland, C.; Guillaumès, J.; Manceau, C.

    2005-01-01

    The spatial distribution of vine plants contaminated by Xylophilus ampelinus, the agent responsible for bacterial necrosis, was studied over a 5-year period within two vineyards in the Cognac area. Both vineyards were planted with Vitis vinifera cv. Ugni blanc but were different in age and agronomic location. The emission of X. ampelinus in contaminated bleeding sap was observed during vine sprouting. Contaminated bleeding sap is an important source of inoculum for external contamination due ...

  2. Glucanases and Chitinases as Causal Agents in the Protection of Acacia Extrafloral Nectar from Infestation by Phytopathogens1[W][OA

    Science.gov (United States)

    González-Teuber, Marcia; Pozo, María J.; Muck, Alexander; Svatos, Ales; Adame-Álvarez, Rosa M.; Heil, Martin

    2010-01-01

    Nectars are rich in primary metabolites and attract mutualistic animals, which serve as pollinators or as an indirect defense against herbivores. Their chemical composition makes nectars prone to microbial infestation. As protective strategy, floral nectar of ornamental tobacco (Nicotiana langsdorffii × Nicotiana sanderae) contains “nectarins,” proteins producing reactive oxygen species such as hydrogen peroxide. By contrast, pathogenesis-related (PR) proteins were detected in Acacia extrafloral nectar (EFN), which is secreted in the context of defensive ant-plant mutualisms. We investigated whether these PR proteins protect EFN from phytopathogens. Five sympatric species (Acacia cornigera, A. hindsii, A. collinsii, A. farnesiana, and Prosopis juliflora) were compared that differ in their ant-plant mutualism. EFN of myrmecophytes, which are obligate ant-plants that secrete EFN constitutively to nourish specialized ant inhabitants, significantly inhibited the growth of four out of six tested phytopathogenic microorganisms. By contrast, EFN of nonmyrmecophytes, which is secreted only transiently in response to herbivory, did not exhibit a detectable inhibitory activity. Combining two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with nanoflow liquid chromatography-tandem mass spectrometry analysis confirmed that PR proteins represented over 90% of all proteins in myrmecophyte EFN. The inhibition of microbial growth was exerted by the protein fraction, but not the small metabolites of this EFN, and disappeared when nectar was heated. In-gel assays demonstrated the activity of acidic and basic chitinases in all EFNs, whereas glucanases were detected only in EFN of myrmecophytes. Our results demonstrate that PR proteins causally underlie the protection of Acacia EFN from microorganisms and that acidic and basic glucanases likely represent the most important prerequisite in this defensive function. PMID:20023149

  3. The impact of aerosolized mucolytic agents on the airflow resistance of bacterial filters used in mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Han-Chung Hu

    2015-08-01

    Conclusion: This study demonstrated the aerosolized mucolytic agents could increase the pressure drop of the bacterial filters during mechanical ventilation. The pressure drop of the bacterial filters was higher with 10% acetylcysteine. It is critical to continuously monitor the expiration resistance, auto-positive end-expiratory pressure, and ventilator output waveform when aerosolized 10% acetylcysteine was used in mechanical ventilation patients.

  4. Café Icatu como fonte de resistência a colletotrichum coffeanum Icatu coffee cultivar as source of resistance to the agent of coffe berry disease

    Directory of Open Access Journals (Sweden)

    A. Carvalho

    1976-07-01

    Full Text Available Linhagens e progênies do cultivar icatu, selecionadas em Campinas, foram testadas na Coffee Research Station, Ruiru, Quênia, a fim de avaliar o grau de resistência ao ataque de Colletotrichum coffeanum, agente responsável pela moléstia mais conhecida por CBD. Os dados de infecção obtidos para 11 linhagens e sete progênies foram comparados com os dos cultivares testemunhas Rume Sudan, resistente, e SL 28, suscetível. Considerando apenas a freqüência de resistentes, com grau 1 de infecção, destacaram-se a progênie H 4782-10 M e a linhagem LCH 3851-4 T. As populações com graus de 1 a 4 de resistência ocorreram em menor escala do que no Rume Sudan, porém salientou-se a progênie H 4782-10 M, com elevada resistência. As maiores porcentagens de plantas suscetíveis foram verificadas nas linhagens LCH 3849-7 M e LCH 4782-13 T, as quais se aproximam da linhagem suscetível SL 28. Os dados preliminares indicam que o germoplasma icatu, como o híbrido de timor, oferece perspectivas de constituir razoável fonte de resistência genética ao agente da CBD.Several samples of the coffee cultivar Icatu were evaluated for resistance to the agent of the CBD (Colletotrichum coffeanum. All tests were performed at the Ruiru Coffee Experiment Station, Kenya. Resistant cultivars Rume Sudan and the susceptible SL 28 were used for comparison. Tests were performed using young seedlings innoculation. It was found that seedlings with grade 1 of the resistance scale occurred in several Icatu progenies. Seedlings of the grades 1 to 4, were noticed more frequently in the progenies H 4782-10 M and LCH 3851-4 M. Susceptible plants, in the class with 10-12 grades, occurred in higher proportion in the progenies LCH 3849-7 M and LCH 4782-10 T. All resistant seedlings were transplanted to the field for further tests of resistance. These preliminary data indicated that the Icatu coffee can be considered as a good source of genetic resistance to the agent of the

  5. Inhibitory effect of gut bacteria from the Japanese honey bee, Apis cerana japonica, against Melissococcus plutonius, the causal agent of European foulbrood disease

    Science.gov (United States)

    Wu, Meihua; Sugimura, Yuya; Iwata, Kyoko; Takaya, Noriko; Takamatsu, Daisuke; Kobayashi, Masaru; Taylor, DeMar; Kimura, Kiyoshi; Yoshiyama, Mikio

    2014-01-01

    Abstract European foulbrood is a contagious bacterial disease of honey bee larvae. Studies have shown that the intestinal bacteria of insects, including honey bees, act as probiotic organisms. Microbial flora from the gut of the Japanese honey bee, Apis cerana japonica F. (Hymenoptera: Apidae) , were characterized and evaluated for their potential to inhibit the growth of Melissococcus plutonius corrig. (ex White) Bailey and Collins (Lactobacillales: Enterococcaceae) , the causative agent of European foulbrood. Analysis of 16S rRNA gene sequences from 17 bacterial strains isolated by using a culture-dependent method revealed that most isolates belonged to Bacillus, Staphylococcus, and Pantoea. The isolates were screened against the pathogenic bacterium M. plutonius by using an in vitro growth inhibition assay, and one isolate (Acja3) belonging to the genus Bacillus exhibited inhibitory activity against M. plutonius. In addition, in vivo feeding assays revealed that isolate Acja3 decreased the mortality of honey bee larvae infected with M plutonius, suggesting that this bacterial strain could potentially be used as a probiotic agent against European foulbrood. PMID:25368073

  6. Phenotypic and molecular characterization of the causal agent of chafer beetle mortality in the wheat fields of the Kurdistan province, Iran

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    Karimi Keivan

    2015-07-01

    Full Text Available We report the first case of chafer beetle [Anisoplia austriaca (Herbst 1783] mortality caused by Actinomucor elegans var. elegans in wheat fields of the Kurdistan province, Iran. For three years, dead larvae of Anisoplia austriaca were collected from wheat fields of the Kurdistan province. Similar isolates of a fast-growing fungus were recovered from all samples. The fungal isolates were identified as A. elegans var. elegans based on morphological and cultural characteristics. The identity of the species was further confirmed using sequence data of the ITS (Internal Transcribed Spacer region of ribosomal DNA. Koch’s postulates were fulfilled by the inoculation of the larvae of A. austriaca and Galleria mellonella (Linnaeus, 1758 (as the model insect using the spore suspension of A. elegans var. elegans. The viability of sporangiospores was evaluated using a spore dilution technique on germination medium. The results on the pathogenicity (100% mortality in A. austriaca larvae and viability tests (germination: 95.45% demonstrated that A. elegans var. elegans can be considered as a potential biocontrol agent against the chafer beetle. Field experiments are still required to evaluate the capacity of A. elegans as a biological control agent.

  7. Genome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ~4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNA-damage-response pathways as well as genes whose role in the DNA-damage response had not been previously established. High-throughput individual growth analysis was used to independently confirm microarray results. Each compound produced a unique genome-wide profile. Analysis of these data allowed us to determine the relative importance of DNA-repair modules for resistance to each of the 12 profiled compounds. Clustering the data for 12 distinct compounds uncovered both known and novel functional interactions that comprise the DNA-damage response and allowed us to define the genetic determinants required for repair of interstrand cross-links. Further genetic analysis allowed determination of epistasis for one of these functional groups.

  8. Hybridization of an invasive shrub affects tolerance and resistance to defoliation by a biological control agent

    Science.gov (United States)

    Williams, Wyatt I.; Friedman, Jonathan M.; Gaskin, John F.; Norton, Andrew P.

    2014-01-01

    Evolution has contributed to the successful invasion of exotic plant species in their introduced ranges, but how evolution affects particular control strategies is still under evaluation. For instance, classical biological control, a common strategy involving the utilization of highly specific natural enemies to control exotic pests, may be negatively affected by host hybridization because of shifts in plant traits, such as root allocation or chemical constituents. We investigated introgression between two parent species of the invasive shrub tamarisk (Tamarix spp.) in the western United States, and how differences in plant traits affect interactions with a biological control agent. Introgression varied strongly with latitude of origin and was highly correlated with plant performance. Increased levels of T. ramosissima introgression resulted in both higher investment in roots and tolerance to defoliation and less resistance to insect attack. Because tamarisk hybridization occurs predictably on the western U.S. landscape, managers may be able to exploit this information to maximize control efforts. Genetic differentiation in plant traits in this system underpins the importance of plant hybridization and may explain why some biological control releases are more successful than others.

  9. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

    Directory of Open Access Journals (Sweden)

    Maia Hightower

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

  10. Exceptionalist naturalism: Human agency and the causal order.

    Science.gov (United States)

    Turri, John

    2018-02-01

    This paper addresses a fundamental question in folk metaphysics: How do we ordinarily view human agency? According to the transcendence account, we view human agency as standing outside of the causal order and imbued with exceptional powers. According to a naturalistic account, we view human agency as subject to the same physical laws as other objects and completely open to scientific investigation. According to exceptionalist naturalism, the truth lies somewhere in between: We view human agency as fitting broadly within the causal order while still being exceptional in important respects. In this paper, I report seven experiments designed to decide between these three competing theories. Across a variety of contexts and types of action, participants agreed that human agents can resist outcomes described as inevitable, guaranteed, and causally determined. Participants viewed non-human animal agents similarly, whereas they viewed computers, robots, and simple inanimate objects differently. At the same time, participants judged that human actions are caused by many things, including psychological, neurological, and social events. Overall, in folk metaphysics, human and non-human animals are viewed as exceptional parts of the natural world.

  11. Enterobacter and Klebsiella species isolated from fresh vegetables marketed in Valencia (Spain) and their clinically relevant resistances to chemotherapeutic agents.

    Science.gov (United States)

    Falomir, María Pilar; Rico, Hortensia; Gozalbo, Daniel

    2013-12-01

    Occurrence of antibiotic-resistant pathogenic or commensal enterobacteria in marketed agricultural foodstuffs may contribute to their incorporation into the food chain and constitutes an additional food safety concern. In this work, we have determined the clinically relevant resistances to 11 common chemotherapeutic agents in Enterobacter and Klebsiella isolates from fresh vegetables from various sources (supermarkets and greengrocers' shops in Valencia, Spain). A total of 96 isolates were obtained from 160 vegetables analyzed (50% positive samples): 68 Enterobacter isolates (59 E. cloacae, two E. aerogenes, two E. cancerogenus, one E. gergoviae, and four E. sakazakii, currently Cronobacter spp.), and 28 Klebsiella isolates (19 K. oxytoca and 9 K. pneumoniae). Only seven isolates were susceptible to all agents tested, and no resistances to ceftazidime, ciprofloxacin, gentamicin, and chloramphenicol were detected. Most isolates were resistant to amoxicillin/clavulanic acid (74 [58 Enterobacter and 16 Klebsiella]) or to ampicillin (80 [55/25]). Other resistances were less frequent: nitrofurantoin (13 isolates [12/1]), tetracycline (6 [5/1]), co-trimoxazole (3 [3/0]), cefotaxime (1 [1/0]), and streptomycin (2 [1/1]). Multiresistant isolates to two (56 [41/15]), three (10 E. cloacae isolates), four (one E. cloacae and one K. pneumoniae isolate), and five (two E. cloacae isolates) chemotherapeutic agents were also detected. The presence of potential pathogens points to marketed fresh produce, which often is eaten raw, as a risk factor for consumer health. In addition, these results support the usefulness of these bacterial species as indicators of the spreading of antibiotic resistances into the environment, particularly in the food chain, and suggest their role as carriers of resistance determinants from farms to consumers, which may constitute an additional "silent" food safety concern. Therefore, there is a need to improve the hygienic quality of marketed fresh

  12. Evaluación a nivel de laboratorio del efecto de 7 extractos vegetales para el control de Colletotrichum sp agente causal de la antracnosis en el cultivo de tomate de árbol - Evaluación a nivel de laboratorio del efecto de 7 extractos vegetales para el control de Colletotrichum sp agente causal de la antracnosis en el cultivo de tomate de árbol

    Directory of Open Access Journals (Sweden)

    Christian Andrei Chacin Zambrano

    2013-08-01

    Full Text Available Was evaluated in the laboratory the effect of seven plant extracts of Neem leaves and fruit (Azadirachta indica leaves of lemon grass (Swinglea glutinosa, leaves of papaya (Carica papaya, Pringamosa leaves (Urtica dioica, eucalyptus leaves (Eucalyptus camaldulensis Dehn fruits of garlic (Allium sativum L. and fruits of pepper (Capsicum annuum in the control of the fungus Colletotrichum sp causal agent of anthracnose in tomato crop tree (Cyphomandra betacea. The pathogen was isolated on PDA medium from tomato fruit tree, the extracts were obtained taking into account the process by (Marin, et. Al 2007, which consists of chopping and blending plant material deposited in plastic bucket, add water ratio 2.5:1 (water: sample processed, vol.: w, subjecting to fermentation for 24 hours. The produto was filtered using sterile gauze and package them for further evaluation. The concentrations of the treatments that worked were 25, 50, 75 and 100% of the infectious agent, determining the degree of inhibition of the pathogen in Petri dishes. The best results were obtained with the application of eucalyptus leaves, since its effect was 100% at all concentrations, without neglecting the fruits of the Neem and garlic with inhibition percentages of 75 and 60% respectively, had a behavior directly proportional to the concentrations used, since the greater the amount of extract the inhibitory effect was better in this case 75% and 100%.

  13. Avaliação de genótipos tetraploides de bananeira cultivados em área infestada pelo agente causal do mal-do-Panamá

    Directory of Open Access Journals (Sweden)

    Sebastião de Oliveira e Silva

    2011-03-01

    Full Text Available O mal-do-Panamá é uma doença que causa grandes prejuízos à bananicultura no Brasil, uma vez que as principais cultivares em uso são suscetíveis ao Fusarium. Este trabalho teve como objetivos avaliar características agronômicas e resistência ao mal-do-Panamá de híbridos tetraploides de bananeira. O experimento foi conduzido no campo experimental da Embrapa Mandioca e Fruticultura Tropical, em delineamento casualizado, com 14 tratamentos e 10 repetições, nos anos de 2000 e 2001. Foram avaliados 14 tetraploides (FHIA-03, PV03-44, PC42-01, PV42-53, PV42-68, PV42-81, PV42-85, PV42-129, PV42-142, PV42-143, SH3640, ST12-31, ST42-08 e YB42-21 e a cultivar Maçã, usada como testemunha. Avaliaram-se as características altura da planta (m e diâmetro do pseudocaule (cm a 30 cm do solo, peso da massa do cacho (kg, penca (kg e fruto (g, número de pencas por cacho, de frutos por penca e de dias do florescimento à colheita, e a incidência do mal-do-Panamá. As médias dos genótipos foram agrupadas pelo teste de Scott e Knott, a 5% de probabilidade. Observa-se uma ampla variação genética nos caracteres avaliados. Os genótipos FHIA 03, ST12-31, SH3640, PV42-142, PV42-53 e PV42-68apresentam boas características agronômicas e resistência ao mal-do-Panamá.

  14. Causal reasoning in physics

    CERN Document Server

    Frisch, Mathias

    2014-01-01

    Much has been written on the role of causal notions and causal reasoning in the so-called 'special sciences' and in common sense. But does causal reasoning also play a role in physics? Mathias Frisch argues that, contrary to what influential philosophical arguments purport to show, the answer is yes. Time-asymmetric causal structures are as integral a part of the representational toolkit of physics as a theory's dynamical equations. Frisch develops his argument partly through a critique of anti-causal arguments and partly through a detailed examination of actual examples of causal notions in physics, including causal principles invoked in linear response theory and in representations of radiation phenomena. Offering a new perspective on the nature of scientific theories and causal reasoning, this book will be of interest to professional philosophers, graduate students, and anyone interested in the role of causal thinking in science.

  15. Theories of Causality

    Science.gov (United States)

    Jones, Robert

    2010-03-01

    There are a wide range of views on causality. To some (e.g. Karl Popper) causality is superfluous. Bertrand Russell said ``In advanced science the word cause never occurs. Causality is a relic of a bygone age.'' At the other extreme Rafael Sorkin and L. Bombelli suggest that space and time do not exist but are only an approximation to a reality that is simply a discrete ordered set, a ``causal set.'' For them causality IS reality. Others, like Judea Pearl and Nancy Cartwright are seaking to build a complex fundamental theory of causality (Causality, Cambridge Univ. Press, 2000) Or perhaps a theory of causality is simply the theory of functions. This is more or less my take on causality.

  16. Functional and biophysical studies on four ceratoplatanins from the fungus Moniliophthora perniciosa, causal agent of the Witche's broom disease

    Energy Technology Data Exchange (ETDEWEB)

    Barsottini, M.; Zaparoli, G.; Garcia, O.; Pereira, G.A.G. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Oliveira, J.F.; Tiezzi, H.O.; Ambrosio, A.L.B.; Dias, S.M.G. [Laboratorio Nacional de Biociencias - LNBIO, Campinas, SP (Brazil)

    2012-07-01

    Full text: Ceratoplatanin (CP) is a secreted protein of 12.4 kDa initially identified in culture filtrates of the disease ascomycete Ceratocystis fimbriata f. sp. platani, etiological agent of the canker stain disease. CP is also the founding member of the namesake protein family, which contains fungal-secreted proteins involved in various stages of the host-fungus interaction and may act as phytotoxins or elicitors of defense response. Besides the low molecular weight, CPs have a high percentage of hydrophobic residues and share two conserved intramolecular disulfide bonds. It has been suggested that CPs have important physiological functions, including interaction with cell wall or cell membrane and manipulation of the host's defense system. Furthermore, a recent work showed that the ceratoplatanin from C. fimbriata has some degree of affinity for the saccharide 4-N-acetylglucosamine. However, its precise molecular function remains elusive. Five putative CPs have been identified in Moniliophthora perniciosa a basidiomycete fungus responsible for great economic losses in cocoa industry in the form of Witches' broom disease (WBD) , four of which had their crystal structures resolved by our group. In this work we report biophysical and functional studies on these MpCPs aiming at understanding their role and importance during the WBD progression. (author)

  17. Bleeding sap and old wood are the two main sources of contamination of merging organs of vine plants by Xylophilus ampelinus, the causal agent of bacterial necrosis.

    Science.gov (United States)

    Grall, S; Roulland, C; Guillaumès, J; Manceau, C

    2005-12-01

    The spatial distribution of vine plants contaminated by Xylophilus ampelinus, the agent responsible for bacterial necrosis, was studied over a 5-year period within two vineyards in the Cognac area. Both vineyards were planted with Vitis vinifera cv. Ugni blanc but were different in age and agronomic location. The emission of X. ampelinus in contaminated bleeding sap was observed during vine sprouting. Contaminated bleeding sap is an important source of inoculum for external contamination due to the high susceptibility of young merging shoots to the pathogen. X. ampelinus emission by bleeding sap was not affected by the age of the plants or the location of the vineyards. However, its emission was irregular with time, and it varied between two fruit canes from individual plants and between plants as well as between years. Moreover, the two vineyards appeared to be entirely contaminated. Consequently, the behavior of the pathogen is not predictable. The distribution of the pathogen inside vine plant organs was analyzed through the four growing seasons. The old wood was contaminated throughout the year and constituted a stock inoculum for endophytic contamination of crude sap during the winter and the spring. Despite the fact that most of the young green shoots were contaminated in May, X.ampelinus was not found in green shoots in June and September, refuting the hypothesis of an epiphytic life of the pathogen under natural conditions. Although all plants were entirely contaminated in both vineyards, symptoms were rare and were observed on different plants each year.

  18. Identification of a New Antimicrobial Resistance Gene Provides Fresh Insights Into Pleuromutilin Resistance in Brachyspira hyodysenteriae, Aetiological Agent of Swine Dysentery

    Directory of Open Access Journals (Sweden)

    Roderick M. Card

    2018-06-01

    Full Text Available Brachyspira hyodysenteriae is the aetiological agent of swine dysentery, a globally distributed disease that causes profound economic loss, impedes the free trade and movement of animals, and has significant impact on pig health. Infection is generally treated with antibiotics of which pleuromutilins, such as tiamulin, are widely used for this purpose, but reports of resistance worldwide threaten continued effective control. In Brachyspira hyodysenteriae pleuromutilin resistance has been associated with mutations in chromosomal genes encoding ribosome-associated functions, however the dynamics of resistance acquisition are poorly understood, compromising stewardship efforts to preserve pleuromutilin effectiveness. In this study we undertook whole genome sequencing (WGS and phenotypic susceptibility testing of 34 UK field isolates and 3 control strains to investigate pleuromutilin resistance in Brachyspira hyodysenteriae. Genome-wide association studies identified a new pleuromutilin resistance gene, tva(A (tiamulin valnemulin antibiotic resistance, encoding a predicted ABC-F transporter. In vitro culture of isolates in the presence of inhibitory or sub-inhibitory concentrations of tiamulin showed that tva(A confers reduced pleuromutilin susceptibility that does not lead to clinical resistance but facilitates the development of higher-level resistance via mutations in genes encoding ribosome-associated functions. Genome sequencing of antibiotic-exposed isolates identified both new and previously described mutations in chromosomal genes associated with reduced pleuromutilin susceptibility, including the 23S rRNA gene and rplC, which encodes the L3 ribosomal protein. Interesting three antibiotic-exposed isolates harboured mutations in fusA, encoding Elongation Factor G, a gene not previously associated with pleuromutilin resistance. A longitudinal molecular epidemiological examination of two episodes of swine dysentery at the same farm indicated

  19. Causality in Science

    Directory of Open Access Journals (Sweden)

    Cristina Puente Águeda

    2011-10-01

    Full Text Available Causality is a fundamental notion in every field of science. Since the times of Aristotle, causal relationships have been a matter of study as a way to generate knowledge and provide for explanations. In this paper I review the notion of causality through different scientific areas such as physics, biology, engineering, etc. In the scientific area, causality is usually seen as a precise relation: the same cause provokes always the same effect. But in the everyday world, the links between cause and effect are frequently imprecise or imperfect in nature. Fuzzy logic offers an adequate framework for dealing with imperfect causality, so a few notions of fuzzy causality are introduced.

  20. Comparison of metals and tetracycline as selective agents for development of tetracycline resistant bacterial communities in agricultural soil

    DEFF Research Database (Denmark)

    Song, Jianxiao; Rensing, Christopher; Holm, Peter Engelund

    2017-01-01

    Environmental selection of antibiotic resistance may be caused by either antibiotic residues or coselecting agents. Using a strictly controlled experimental design, we compared the ability of metals (Cu or Zn) and tetracycline to (co)select for tetracycline resistance in bacterial communities. Soil...... microcosms were established by amending agricultural soil with known levels of Cu, Zn, or tetracycline known to represent commonly used metals and antibiotics for pig farming. Soil bacterial growth dynamics and bacterial community-level tetracycline resistance were determined using the [(3)H......]leucine incorporation technique, whereas soil Cu, Zn, and tetracycline exposure were quantified by a panel of whole-cell bacterial bioreporters. Tetracycline resistance increased significantly in soils containing environmentally relevant levels of Cu (≥365 mg kg(-1)) and Zn (≥264 mg kg(-1)) but not in soil spiked...

  1. [Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

    Science.gov (United States)

    Li, Z; Chen, Z W; Ren, H; Hu, P

    2017-03-20

    Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

  2. Efeito inibitório de extratos vegetais sobre Colletotrichum gloeosporioides - agente causal da podridão de frutos de mamoeiro

    Directory of Open Access Journals (Sweden)

    Ribeiro Luiz Fernando

    1999-01-01

    Full Text Available Extratos aquosos foram obtidos a partir de bulbilhos de alho, folhas de hortelã e mamona e frutos de pimenta. Após a incorporação destes extratos em BDA, obtendo-se concentrações de 100, 200, 500, 1000, 5000 e 10000 ppm, foi avaliado o crescimento e a produção de conídios de um isolado de Colletotrichum gloeosporioides, agente de podridão em frutos de mamoeiro. Os resultados demonstraram o efeito inibitório dos diferentes extratos a partir da concentração de 200 ppm. O extrato de alho inibiu o crescimento micelial, em porcentagens variáveis de 5,3 a 67,6%, porém não atuou de modo expressivo sobre a produção de conídios. Em contraposição, os extratos de hortelã, mamona e pimenta promoveram inibição menos acentuada do crescimento de micélio, porém reduziram drasticamente a produção de conídios em níveis variáveis de 41 a 84%, de acordo com as concentrações crescentes dos mesmos. As propriedades fungitóxicas detectadas nos extratos utilizados no ensaio evidenciaram o uso potencial dos mesmos como alternativa aos métodos físicos e químicos convencionalmente usados para o controle da doença.

  3. De Novo Assembly and Phasing of Dikaryotic Genomes from Two Isolates of Puccinia coronata f. sp. avenae, the Causal Agent of Oat Crown Rust.

    Science.gov (United States)

    Miller, Marisa E; Zhang, Ying; Omidvar, Vahid; Sperschneider, Jana; Schwessinger, Benjamin; Raley, Castle; Palmer, Jonathan M; Garnica, Diana; Upadhyaya, Narayana; Rathjen, John; Taylor, Jennifer M; Park, Robert F; Dodds, Peter N; Hirsch, Cory D; Kianian, Shahryar F; Figueroa, Melania

    2018-02-20

    Oat crown rust, caused by the fungus Pucinnia coronata f. sp. avenae , is a devastating disease that impacts worldwide oat production. For much of its life cycle, P. coronata f. sp. avenae is dikaryotic, with two separate haploid nuclei that may vary in virulence genotype, highlighting the importance of understanding haplotype diversity in this species. We generated highly contiguous de novo genome assemblies of two P. coronata f. sp. avenae isolates, 12SD80 and 12NC29, from long-read sequences. In total, we assembled 603 primary contigs for 12SD80, for a total assembly length of 99.16 Mbp, and 777 primary contigs for 12NC29, for a total length of 105.25 Mbp; approximately 52% of each genome was assembled into alternate haplotypes. This revealed structural variation between haplotypes in each isolate equivalent to more than 2% of the genome size, in addition to about 260,000 and 380,000 heterozygous single-nucleotide polymorphisms in 12SD80 and 12NC29, respectively. Transcript-based annotation identified 26,796 and 28,801 coding sequences for isolates 12SD80 and 12NC29, respectively, including about 7,000 allele pairs in haplotype-phased regions. Furthermore, expression profiling revealed clusters of coexpressed secreted effector candidates, and the majority of orthologous effectors between isolates showed conservation of expression patterns. However, a small subset of orthologs showed divergence in expression, which may contribute to differences in virulence between 12SD80 and 12NC29. This study provides the first haplotype-phased reference genome for a dikaryotic rust fungus as a foundation for future studies into virulence mechanisms in P. coronata f. sp. avenae IMPORTANCE Disease management strategies for oat crown rust are challenged by the rapid evolution of Puccinia coronata f. sp. avenae , which renders resistance genes in oat varieties ineffective. Despite the economic importance of understanding P. coronata f. sp. avenae , resources to study the

  4. Reduced Susceptibility to Rifampicin and Resistance to Multiple Antimicrobial Agents among Brucella abortus Isolates from Cattle in Brazil.

    Science.gov (United States)

    Barbosa Pauletti, Rebeca; Reinato Stynen, Ana Paula; Pinto da Silva Mol, Juliana; Seles Dorneles, Elaine Maria; Alves, Telma Maria; de Sousa Moura Souto, Monalisa; Minharro, Silvia; Heinemann, Marcos Bryan; Lage, Andrey Pereira

    2015-01-01

    This study aimed to determine the susceptibility profile of Brazilian Brucella abortus isolates from cattle to eight antimicrobial agents that are recommended for the treatment of human brucellosis and to correlate the susceptibility patterns with origin, biotype and MLVA16-genotype of the strains. Screening of 147 B. abortus strains showed 100% sensitivity to doxycycline and ofloxacin, one (0.68%) strain resistant to ciprofloxacin, two strains (1.36%) resistant to streptomycin, two strains (1.36%) resistant to trimethoprim-sulfamethoxazole and five strains (3.40%) resistant to gentamicin. For rifampicin, three strains (2.04%) were resistant and 54 strains (36.73%) showed reduced sensitivity. Two strains were considered multidrug resistant. In conclusion, the majority of B. abortus strains isolated from cattle in Brazil were sensitive to the antimicrobials commonly used for the treatment of human brucellosis; however, a considerable proportion of strains showed reduced susceptibility to rifampicin and two strains were considered multidrug resistant. Moreover, there was no correlation among the drug susceptibility pattern, origin, biotype and MLVA16-genotypes of these strains.

  5. Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent)

    International Nuclear Information System (INIS)

    Zhu Aizhi; Wang Xiangyun; Guo Zhenquan

    2001-01-01

    The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of 99m Tc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of 99m Tc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of 99m Tc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 μg/ml of tea polyphenol respectively. The uptake of 99m Tc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 μM of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment

  6. Combination of Bifunctional Alkylating Agent and Arsenic Trioxide Synergistically Suppresses the Growth of Drug-Resistant Tumor Cells

    Directory of Open Access Journals (Sweden)

    Pei-Chih Lee

    2010-05-01

    Full Text Available Drug resistance is a crucial factor in the failure of cancer chemotherapy. In this study, we explored the effect of combining alkylating agents and arsenic trioxide (ATO on the suppression of tumor cells with inherited or acquired resistance to therapeutic agents. Our results showed that combining ATO and a synthetic derivative of 3a-aza-cyclopenta[a]indenes (BO-1012, a bifunctional alkylating agent causing DNA interstrand cross-links, was more effective in killing human cancer cell lines (H460, H1299, and PC3 than combining ATO and melphalan or thiotepa. We further demonstrated that the combination treatment of H460 cells with BO-1012 and ATO resulted in severe G2/M arrest and apoptosis. In a xenograft mouse model, the combination treatment with BO-1012 and ATO synergistically reduced tumor volumes in nude mice inoculated with H460 cells. Similarly, the combination of BO-1012 and ATO effectively reduced the growth of cisplatin-resistant NTUB1/P human bladder carcinoma cells. Furthermore, the repair of BO-1012-induced DNA interstrand cross-links was significantly inhibited by ATO, and consequently, γH2AX was remarkably increased and formed nuclear foci in H460 cells treated with this drug combination. In addition, Rad51 was activated by translocating and forming foci in nuclei on treatment with BO-1012, whereas its activation was significantly suppressed by ATO. We further revealed that ATO might mediate through the suppression of AKT activity to inactivate Rad51. Taken together, the present study reveals that a combination of bifunctional alkylating agents and ATO may be a rational strategy for treating cancers with inherited or acquired drug resistance.

  7. In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Songzhe eHE

    2015-05-01

    Full Text Available Objective To investigate the in vitro and in vivo antibacterial activities of tigecycline and other 13 common antimicrobial agents, alone or in combination, against multi-drug resistant Acinetobacter baumannii.MethodsAn in vitro susceptibility test of 101 Acinetobacter baumannii was used to detect minimal inhibitory concentrations (MICs. A mouse lung infection model of multi-drug resistant Acinetobacter baumannii,established by the ultrasonic atomization method, was used to define in vivo antimicrobial activities.Results Multi-drug resistant Acinetobacter baumannii showed high sensitivity to tigecycline (98% inhibition, polymyxin B (78.2% inhibition, and minocycline (74.2% inhibition. However, the use of these antimicrobial agents in combination with other antimicrobial agents produced synergistic or additive effects. In vivo data showed that white blood cell (WBC counts in drug combination groups C (minocycline + amikacin and D (minocycline + rifampicin were significantly higher than in groups A (tigecycline and B (polymyxin B (P < 0.05, after administration of the drugs 24h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48h post infection. After three days of anti-infective therapy in groups A, B, C and D, lung tissue inflammation in each group gradually recovered with clear structures. The mortality rates in drug combination groups (groups C and D were much lower than in groups A and B.ConclusionThe combination of minocycline with either rifampicin or amikacin is more effective against multidrug-resistant Acinetobacter baumannii than single-agent tigecycline or polymyxin B. In addition, the mouse lung infection by ultrasonic atomization is a suitable model for drug screening and analysis of infection mechanism.

  8. Reasoning with Causal Cycles

    Science.gov (United States)

    Rehder, Bob

    2017-01-01

    This article assesses how people reason with categories whose features are related in causal cycles. Whereas models based on causal graphical models (CGMs) have enjoyed success modeling category-based judgments as well as a number of other cognitive phenomena, CGMs are only able to represent causal structures that are acyclic. A number of new…

  9. Onicomicosis: epidemiología, agentes causales y evaluación de los métodos diagnósticos de laboratorio Onychomycoses: epidemiology, causative agents and assessment of diagnostic laboratory methods

    OpenAIRE

    Javier R Nazar; Paula E Gerosa; Osvaldo A Díaz

    2012-01-01

    Desde marzo de 2007 hasta marzo de 2011 se estudiaron prospectivamente 414 pacientes con onicodistrofias en un laboratorio privado de Esquel. La prevalencia de onicomicosis de pie fue del 78 %; la de mano, del 58 %. Los principales agentes etiológicos fueron Trichophyton rubrum, Candida spp. y Trichophyton mentagrophytes. El desarrollo de dermatofitos prevaleció en las onicopatías de pie y el de Candida spp. en las de uñas de mano (ambos, p < 0,05). En las onicomicosis candidiásicas predomina...

  10. Frequency of resistance in obligate anaerobic bacteria isolated from dogs, cats, and horses to antimicrobial agents.

    Science.gov (United States)

    Lawhon, S D; Taylor, A; Fajt, V R

    2013-11-01

    Clinical specimens from dogs, cats, and horses were examined for the presence of obligate anaerobic bacteria. Of 4,018 specimens cultured, 368 yielded 606 isolates of obligate anaerobic bacteria (248 from dogs, 50 from cats, and 308 from horses). There were 100 specimens from 94 animals from which only anaerobes were isolated (25 dogs, 8 cats, and 61 horses). The most common sites tested were abdominal fluid (dogs and cats) and intestinal contents (horses). The most common microorganism isolated from dogs, cats, and horses was Clostridium perfringens (75, 13, and101 isolates, respectively). The MICs of amoxicillin with clavulanate, ampicillin, chloramphenicol, metronidazole, and penicillin were determined using a gradient endpoint method for anaerobes. Isolates collected at necropsy were not tested for antimicrobial susceptibility unless so requested by the clinician. There were 1/145 isolates tested that were resistant to amoxicillin-clavulanate (resistance breakpoint ≥ 16/8 μg/ml), 7/77 isolates tested were resistant to ampicillin (resistance breakpoint ≥ 2 μg/ml), 4/242 isolates tested were resistant to chloramphenicol (resistance breakpoint ≥ 32 μg/ml), 12/158 isolates tested were resistant to clindamycin (resistance breakpoint ≥ 8 μg/ml), 10/247 isolates tested were resistant to metronidazole (resistance breakpoint ≥ 32 μg/ml), and 54/243 isolates tested were resistant to penicillin (resistance breakpoint ≥ 2 μg/ml). These data suggest that anaerobes are generally susceptible to antimicrobial drugs in vitro.

  11. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    NARCIS (Netherlands)

    van Bree, Chris; Castro Kreder, Natasja; Loves, Willem J. P.; Franken, Nicolaas A. P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel,

  12. Research on DNA methylation of human osteosarcoma cell MGMT and its relationship with cell resistance to alkylating agents.

    Science.gov (United States)

    Guo, Jun; Cui, Qiu; Jiang, WeiHao; Liu, Cheng; Li, DingFeng; Zeng, Yanjun

    2013-08-01

    The objective of this study was to explore the O(6)-methylguanine-DNA methyltransferase (MGMT) gene methylation status and its protein expression, as well as the effects of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on MGMT gene expression and its resistance to alkylating agents, and to elucidate MGMT expression mechanism and significance in osteosarcoma. The human osteosarcoma cell lines Saos-2 and MG-63 were collected and treated with 5-Aza-CdR for 6 days. The cells not treated with 5-Aza-CdR were set as a negative control. The genomic DNA was extracted from the Saos-2 and MG-63 cells using methylation-specific PCR to detect the promoter CpG island methylation status of the MGMT gene. Cell sensitivity to alkylating agents before and after drug administration was detected by the MTT method. The variation in MGMT gene mRNA and protein was detected by reverse transcription PCR (RT-PCR) and Western blotting. The MGMT promoter gene of normal Saos-2 cells was methylated, with reduced MGMT mRNA and protein expression; the MGMT mRNA and protein expression of Saos-2 cells treated with 5-Aza-CdR was obviously enhanced, and its sensitivity to alkylating agents was reversed. Meanwhile, with promoter CpG island unmethylation of the MGMT gene, MGMT protein was expressed in the normal MG-63 cells and the MG-63 cells treated with 5-Aza-CdR, and both showed resistance to alkylating agents. The methylation status of the MGMT gene promoter in human osteosarcoma cells reflected the cells' ability to induce MGMT protein expression and can be used as a molecular marker to project the sensitivity of cancer tissues to alkylating agent drugs.

  13. Onicomicosis: epidemiología, agentes causales y evaluación de los métodos diagnósticos de laboratorio Onychomycoses: epidemiology, causative agents and assessment of diagnostic laboratory methods

    Directory of Open Access Journals (Sweden)

    Javier R Nazar

    2012-03-01

    Full Text Available Desde marzo de 2007 hasta marzo de 2011 se estudiaron prospectivamente 414 pacientes con onicodistrofias en un laboratorio privado de Esquel. La prevalencia de onicomicosis de pie fue del 78 %; la de mano, del 58 %. Los principales agentes etiológicos fueron Trichophyton rubrum, Candida spp. y Trichophyton mentagrophytes. El desarrollo de dermatofitos prevaleció en las onicopatías de pie y el de Candida spp. en las de uñas de mano (ambos, p Since March 2007 to March 2011, 414 patients with onychopathies were prospectively analyzed. Prevalence of the toenail and fingernail mycoses was 78 % and 58 %, respectively. The major etiological agents were Trichophyton rubrum, Candida spp. and Trichophyton mentagrophytes. Dermatophytes were more frequently cultured from toenails, whereas Candida spp. from fingernails (both, p < 0.05. In candidal onychomycosis, species different from C. albicans were prevalent. A higher prevalence of toenail and fingernail mycoses, a predominance of T. rubrum in toenails (p < 0.05, and greater positivity in the direct examination (DE and in culture (both, p < 0.05 were more frequently observed in men than in women. The correlation between DE and culture was 68 %. DE and culture yields were associated with a greater size lesion. DE was more effective in onycodystrophies with duration of more than 5 years. Culture positivity was independent of nail affection chronicity.

  14. Mutation of Rv2887, a marR-like gene, confers Mycobacterium tuberculosis resistance to an imidazopyridine-based agent.

    Science.gov (United States)

    Winglee, Kathryn; Lun, Shichun; Pieroni, Marco; Kozikowski, Alan; Bishai, William

    2015-11-01

    Drug resistance is a major problem in Mycobacterium tuberculosis control, and it is critical to identify novel drug targets and new antimycobacterial compounds. We have previously identified an imidazo[1,2-a]pyridine-4-carbonitrile-based agent, MP-III-71, with strong activity against M. tuberculosis. In this study, we evaluated mechanisms of resistance to MP-III-71. We derived three independent M. tuberculosis mutants resistant to MP-III-71 and conducted whole-genome sequencing of these mutants. Loss-of-function mutations in Rv2887 were common to all three MP-III-71-resistant mutants, and we confirmed the role of Rv2887 as a gene required for MP-III-71 susceptibility using complementation. The Rv2887 protein was previously unannotated, but domain and homology analyses suggested it to be a transcriptional regulator in the MarR (multiple antibiotic resistance repressor) family, a group of proteins first identified in Escherichia coli to negatively regulate efflux pumps and other mechanisms of multidrug resistance. We found that two efflux pump inhibitors, verapamil and chlorpromazine, potentiate the action of MP-III-71 and that mutation of Rv2887 abrogates their activity. We also used transcriptome sequencing (RNA-seq) to identify genes which are differentially expressed in the presence and absence of a functional Rv2887 protein. We found that genes involved in benzoquinone and menaquinone biosynthesis were repressed by functional Rv2887. Thus, inactivating mutations of Rv2887, encoding a putative MarR-like transcriptional regulator, confer resistance to MP-III-71, an effective antimycobacterial compound that shows no cross-resistance to existing antituberculosis drugs. The mechanism of resistance of M. tuberculosis Rv2887 mutants may involve efflux pump upregulation and also drug methylation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Obesity and infection: reciprocal causality.

    Science.gov (United States)

    Hainer, V; Zamrazilová, H; Kunešová, M; Bendlová, B; Aldhoon-Hainerová, I

    2015-01-01

    Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

  16. Causal imprinting in causal structure learning.

    Science.gov (United States)

    Taylor, Eric G; Ahn, Woo-Kyoung

    2012-11-01

    Suppose one observes a correlation between two events, B and C, and infers that B causes C. Later one discovers that event A explains away the correlation between B and C. Normatively, one should now dismiss or weaken the belief that B causes C. Nonetheless, participants in the current study who observed a positive contingency between B and C followed by evidence that B and C were independent given A, persisted in believing that B causes C. The authors term this difficulty in revising initially learned causal structures "causal imprinting." Throughout four experiments, causal imprinting was obtained using multiple dependent measures and control conditions. A Bayesian analysis showed that causal imprinting may be normative under some conditions, but causal imprinting also occurred in the current study when it was clearly non-normative. It is suggested that causal imprinting occurs due to the influence of prior knowledge on how reasoners interpret later evidence. Consistent with this view, when participants first viewed the evidence showing that B and C are independent given A, later evidence with only B and C did not lead to the belief that B causes C. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis.

    Science.gov (United States)

    Sinnott, Sarah-Jo; Tomlinson, Laurie A; Root, Adrian A; Mathur, Rohini; Mansfield, Kathryn E; Smeeth, Liam; Douglas, Ian J

    2017-02-01

    Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I 2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined.

  18. Activity of Topical Antimicrobial Agents Against Multidrug-Resistant Bacteria Recovered from Burn Patients

    Science.gov (United States)

    2010-01-01

    Spectrum of activity Pros Cons Resistance/ other Prior studies Bacitracin Polypeptide produced by Bacillus subtilis that inhibits cell wall synthesis and...concentrations (MICs) and zones of inhibition (ZI). Isolates had systemic antibiotic resistance and clonality determined. MDR included resistance to... antibiotics in three or more classes. Results: We assessed 22 ESBL-producing K. pneumoniae, 20 ABC (75% MDR), 20 P. aeruginosa (45% MDR), and 20 MRSA

  19. DEVELOPMENT OF RESISTANCE IN BACTERIA AGAINST ANTI - MICROBIAL AGENTS: REASONS, THREATS AND ONGOING ENCOUNTER

    Directory of Open Access Journals (Sweden)

    Shibabrata Pattanayak

    2011-07-01

    Full Text Available Development of Multi Druug Resistant bacteria is creating a very severe problem in anti-microbial chemotherapy. Many recently developed antibiotics are found incapable to control resistant organisms.The reasons of development of resistance gene in the bacterial plasmid and their quick spread among various related and unrelated bacteria are analysed in this article along with discussion of world wide ongoing research to combat the problem.

  20. DEVELOPMENT OF RESISTANCE IN BACTERIA AGAINST ANTI - MICROBIAL AGENTS: REASONS, THREATS AND ONGOING ENCOUNTER

    OpenAIRE

    Shibabrata Pattanayak

    2011-01-01

    Development of Multi Druug Resistant bacteria is creating a very severe problem in anti-microbial chemotherapy. Many recently developed antibiotics are found incapable to control resistant organisms.The reasons of development of resistance gene in the bacterial plasmid and their quick spread among various related and unrelated bacteria are analysed in this article along with discussion of world wide ongoing research to combat the problem.

  1. Improvement of the fungal biocontrol agent Trichoderma atroviride to enhance both antagonism and induction of plant systemic disease resistance.

    Science.gov (United States)

    Brunner, Kurt; Zeilinger, Susanne; Ciliento, Rosalia; Woo, Sheridian L; Lorito, Matteo; Kubicek, Christian P; Mach, Robert L

    2005-07-01

    Biocontrol agents generally do not perform well enough under field conditions to compete with chemical fungicides. We determined whether transgenic strain SJ3-4 of Trichoderma atroviride, which expresses the Aspergillus niger glucose oxidase-encoding gene, goxA, under a homologous chitinase (nag1) promoter had increased capabilities as a fungal biocontrol agent. The transgenic strain differed only slightly from the wild-type in sporulation or the growth rate. goxA expression occurred immediately after contact with the plant pathogen, and the glucose oxidase formed was secreted. SJ3-4 had significantly less N-acetylglucosaminidase and endochitinase activities than its nontransformed parent. Glucose oxidase-containing culture filtrates exhibited threefold-greater inhibition of germination of spores of Botrytis cinerea. The transgenic strain also more quickly overgrew and lysed the plant pathogens Rhizoctonia solani and Pythium ultimum. In planta, SJ3-4 had no detectable improved effect against low inoculum levels of these pathogens. Beans planted in heavily infested soil and treated with conidia of the transgenic Trichoderma strain germinated, but beans treated with wild-type spores did not germinate. SJ3-4 also was more effective in inducing systemic resistance in plants. Beans with SJ3-4 root protection were highly resistant to leaf lesions caused by the foliar pathogen B. cinerea. This work demonstrates that heterologous genes driven by pathogen-inducible promoters can increase the biocontrol and systemic resistance-inducing properties of fungal biocontrol agents, such as Trichoderma spp., and that these microbes can be used as vectors to provide plants with useful molecules (e.g., glucose oxidase) that can increase their resistance to pathogens.

  2. Repeated causal decision making.

    Science.gov (United States)

    Hagmayer, York; Meder, Björn

    2013-01-01

    Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in such situations and how they use their knowledge to adapt to changes in the decision context. Our studies show that decision makers' behavior is strongly contingent on their causal beliefs and that people exploit their causal knowledge to assess the consequences of changes in the decision problem. A high consistency between hypotheses about causal structure, causally expected values, and actual choices was observed. The experiments show that (a) existing causal hypotheses guide the interpretation of decision feedback, (b) consequences of decisions are used to revise existing causal beliefs, and (c) decision makers use the experienced feedback to induce a causal model of the choice situation even when they have no initial causal hypotheses, which (d) enables them to adapt their choices to changes of the decision problem. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  3. Antimicrobial Agent of Susceptibilities and Antiseptic Resistance Gene Distribution among Methicillin-Resistant Staphylococcus aureus Isolates from Patients with Impetigo and Staphylococcal Scalded Skin Syndrome

    Science.gov (United States)

    Noguchi, Norihisa; Nakaminami, Hidemasa; Nishijima, Setsuko; Kurokawa, Ichiro; So, Hiromu; Sasatsu, Masanori

    2006-01-01

    The susceptibilities to antimicrobial agents of and distributions of antiseptic resistance genes in methicillin-resistant Staphylococcus aureus (MRSA) strains isolated between 1999 and 2004 in Japan were examined. The data of MRSA strains that are causative agents of impetigo and staphylococcal scalded skin syndrome (SSSS) were compared with those of MRSA strains isolated from patients with other diseases. The susceptibilities to antiseptic agents in MRSA isolates from patients with impetigo and SSSS were higher than those in MRSA isolates from patients with other diseases. The distribution of the qacA/B genes in MRSA strains isolated from patients with impetigo and SSSS (1.3%, 1/76) was remarkably lower than that in MRSA strains isolated from patients with other diseases (45.9%, 95/207). Epidemiologic typings of staphylococcal cassette chromosome mec (SCCmec) and pulsed-field gel electrophoresis (PFGE) showed that MRSA strains isolated from patients with impetigo and SSSS had type IV SCCmec (75/76), except for one strain, and 64.5% (49/76) of the strains had different PFGE types. In addition, the patterns of restriction digestion of all tested qacA/B plasmid in MRSA isolates having different PFGE types were identical. The results showed that a specific MRSA clone carrying qacA/B was not prevalent, but qacA/B was spread among health care-associated MRSA strains. Therefore, it was concluded that the lower distribution rate of qacA/B resulted in higher susceptibilities to cationic antiseptic agents in MRSA isolated from patients with impetigo and SSSS. PMID:16757607

  4. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    International Nuclear Information System (INIS)

    Díaz-Montero, C Marcela; McIntyre, Bradley W

    2005-01-01

    Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy. Osteosarcoma cell lines (SAOS-2 and TE-85) obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI) staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). Moreover, suspended anoikis resistant TE-85 cells (TE-85ar) retained their sensitivity to chemotherapy as well. Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators

  5. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    Directory of Open Access Journals (Sweden)

    McIntyre Bradley W

    2005-04-01

    Full Text Available Abstract Background Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis in human osteosarcoma would result in resistance to chemotherapy. Methods Osteosarcoma cell lines (SAOS-2 and TE-85 obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Results Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended. Moreover, suspended anoikis resistant TE-85 cells (TE-85ar retained their sensitivity to chemotherapy as well. Conclusion Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.

  6. Distribution of phylogroups and co-resistance to antimicrobial agents in ampicillin resistant Escherichia coli isolated from healthy humans and from patients with bacteraemia

    DEFF Research Database (Denmark)

    Haugaard, A.; Hammerum, A. M.; Porsbo, Lone Jannok

    inhibitory concentration to antimicrobial agents and examined by PCR to determine their phylogroups. The phylotyping grouped the faecal samples into A (13%), B1 (10%), B2 (42%), D (19%), NT (16%) while the blood isolates grouped into A (16%), B1 (0%), B2 (48%), D (32%) and NT (3%). The frequency...... of resistance in faecal and blood isolates (F/B) was: tetracycline (48%/48%), gentamicin (0%/10%), ciprofloxacin (3%,13%), sulfonamide (68%/77%) and trimethoprim (39%/39%). Conclusion: B2 was the most prevalent phylogroup found both in faecal isolates collected from healthy humans and in blood isolates from...

  7. Shear Resistance Properties of Modified Nano-SiO2/AA/AM Copolymer Oil Displacement Agent

    Directory of Open Access Journals (Sweden)

    Nanjun Lai

    2016-12-01

    Full Text Available To address the problem regarding poor shear resistance of commonly employed polymers for oil displacement, modified nano-SiO2/AA/AM copolymer (HPMNS oil displacement agents were synthesized using acrylic acid (AA, acrylamide (AM, and modified nano-SiO2 of different modification degrees as raw materials. HPMNS was characterized by means of infrared spectroscopy (IR, nuclear magnetic resonance (1H-NMR, 13C-NMR, dynamic/static light scattering, and scanning electron microscope. A comparative study of the shear resistance properties for partially hydrolyzed polyacrylamide (HPAM and HPMNS was conducted. Compared to HPAM, the introduced hyperbranched structure endowed HPMNS with good shear resistance, which was quantified from the viscosity retention ratio of the polymer solutions. From the perspective of rheological property, HPMNS also showed great shear stability after shearing by a Mixing Speed Governor and porous media shear model. Furthermore, with a higher degree of modification, HPMNS-2 had better shear stability in terms of viscosity and rheological property than HPMNS-1. The phenomena were due to its lower hydrodynamic radius, weight-average molecular weight, and better flexibility of its molecular chains. In addition, upon the indoor displacement test, the resistance factor and residual resistance factor values of HPMNS-2 were higher than those of HPAM. This behavior is beneficial for increasing oil recovery.

  8. Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents.

    Directory of Open Access Journals (Sweden)

    Ryan J Mailloux

    2010-10-01

    Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.

  9. Multi-agent chemotherapy overcomes glucocorticoid resistance conferred by a BIM deletion polymorphism in pediatric acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Sheila Xinxuan Soh

    Full Text Available A broad range of anti-cancer agents, including glucocorticoids (GCs and tyrosine kinase inhibitors (TKIs, kill cells by upregulating the pro-apoptotic BCL2 family member, BIM. A common germline deletion in the BIM gene was recently shown to favor the production of non-apoptotic BIM isoforms, and to predict inferior responses in TKI-treated chronic myeloid leukemia (CML and EGFR-driven lung cancer patients. Given that both in vitro and in vivo GC resistance are predictive of adverse outcomes in acute lymphoblastic leukemia (ALL, we hypothesized that this polymorphism would mediate GC resistance, and serve as a biomarker of poor response in ALL. Accordingly, we used zinc finger nucleases to generate ALL cell lines with the BIM deletion, and confirmed the ability of the deletion to mediate GC resistance in vitro. In contrast to CML and lung cancer, the BIM deletion did not predict for poorer clinical outcome in a retrospective analysis of 411 pediatric ALL patients who were uniformly treated with GCs and chemotherapy. Underlying the lack of prognostic significance, we found that the chemotherapy agents used in our cohort (vincristine, L-asparaginase, and methotrexate were each able to induce ALL cell death in a BIM-independent fashion, and resensitize BIM deletion-containing cells to GCs. Together, our work demonstrates how effective therapy can overcome intrinsic resistance in ALL patients, and suggests the potential of using combinations of drugs that work via divergent mechanisms of cell killing to surmount BIM deletion-mediated drug resistance in other cancers.

  10. Potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or Coxsackievirus A16.

    Science.gov (United States)

    Kelly, James T; De Colibus, Luigi; Elliott, Lauren; Fry, Elizabeth E; Stuart, David I; Rowlands, David J; Stonehouse, Nicola J

    2015-12-01

    Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the two major causative agents of hand, foot and mouth disease (HFMD), for which there are currently no licenced treatments. Here, the acquisition of resistance towards two novel capsid-binding compounds, NLD and ALD, was studied and compared to the analogous compound GPP3. During serial passage, EV71 rapidly became resistant to each compound and mutations at residues I113 and V123 in VP1 were identified. A mutation at residue 113 was also identified in CVA16 after passage with GPP3. The mutations were associated with reduced thermostability and were rapidly lost in the absence of inhibitors. In silico modelling suggested that the mutations prevented the compounds from binding the VP1 pocket in the capsid. Although both viruses developed resistance to these potent pocket-binding compounds, the acquired mutations were associated with large fitness costs and reverted to WT phenotype and sequence rapidly in the absence of inhibitors. The most effective inhibitor, NLD, had a very large selectivity index, showing interesting pharmacological properties as a novel anti-EV71 agent. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Caracterización taxonómica y análisis de la variabilidad del agente causal del cancro del tallo de la soja en Buenos Aires (2005/2007

    Directory of Open Access Journals (Sweden)

    GRIJALBA, P.E

    2011-12-01

    Full Text Available ResumenEl complejo Diaporthe/Phomopsis es un importante grupo de hongos patógenos de la soja. Dentro del mismo, Diaporthe phaseolorum var. caulivora es uno de los agentes causales del cancro del tallo. Veintitrés aislamientos de este hongo, provenientes de diferentes zonas geográficas de la provincia de Buenos Aires, fueron caracterizados morfológica y genéticamente. Los criterios morfológicos fueron tipo y color de micelio; formación del teleomorfo y/o del anamorfo. La identificación molecular fue llevada a cabo utilizando una técnica de restricción de fragmentos de amplificación (PCR-RFLP de la región ITS de ADN ribosomal. Adicionalmente, los productos de amplificación fueron secuenciados y comparados con la información de bancos de datos. Los aislamientos presentaron características morfológicas y patogénicas propias de la variedad, y los patrones de restricción con la enzima Alu I fueron concordantes con la identificación morfológica y con la información de secuencias disponibles. Las reconstrucciones filogenéticas apoyan la idea de que D. meridionalis y D. caulivora son entidades biológicamente aisladas. Los resultados obtenidos confirmaron la utilidad del uso del método de PCR-RFLP para la identificación precisa y rápida de D. caulivora. Por sus características, este método puede ser implementado para análisis de rutina en laboratorios de pequeña y mediana escala.AbstractDiaporthe/Phomopsis is an important group of soybean pathogens. Diaporthe phaseolorum var. caulivora is one of the causal agents of stem canker. Twenty three isolates from different regions from the Province of Buenos Aires were morphologically and genetically characterized and assigned to different taxa within the Diaporthe/Phomopsis complex; diagnostic morphological traits were: mycelium type and color, teleomorph/anamorph occurrence. Molecular characterization was carried out using RFLP analyses of PCR-amplified DNA (PCRRFLP for the

  12. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    International Nuclear Information System (INIS)

    Bree, Chris van; Kreder, Natasja Castro; Loves, Willem J.P.; Franken, Nicolaas A.P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5-fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000 were determined by clonogenic assay. Bivariate flowcytometry was performed to study cell cycle changes. Results: In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level. This was accompanied by a 10-fold decrease in dCK activity which resulted in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50-100 μM dFdC) induced radioenhancement in the dFdC-resistant cell lines similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in the parental lines. An early S-phase arrest was found in all cell lines after dFdC treatment where radioenhancement was achieved. Conclusions: In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. No cross-resistance was observed to other anti-tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing radiation was not altered in two different dFdC-resistant cell lines. Resistance to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation

  13. Plasticity of the MFS1 promoter leads to multidrug resistance in the wheat pathogen Zymoseptoria tritici

    NARCIS (Netherlands)

    Omrane, Selim; Audéon, Colette; Ignace, Amandine; Duplaix, Clémentine; Aouini, Lamia; Kema, Gert; Walker, Anne Sophie; Fillinger, Sabine

    2017-01-01

    The ascomycete Zymoseptoria tritici is the causal agent of Septoria leaf blotch on wheat. Disease control relies mainly on resistant wheat cultivars and on fungicide applications. The fungus displays a high potential to circumvent both methods. Resistance against all unisite fungicides has been

  14. QTL identification for early blight resistance (Alternaria solani) in a Solanum lycopersicum x S. arcanum cross.

    NARCIS (Netherlands)

    Chaerani, R.; Smulders, M.J.M.; Linden, van der C.G.; Vosman, B.; Stam, P.; Voorrips, R.E.

    2007-01-01

    Alternaria solani (Ellis and Martin) Sorauer, the causal agent of early blight (EB) disease, infects aerial parts of tomato at both seedling and adult plant stages. Resistant cultivars would facilitate a sustainable EB management. EB resistance is a quantitatively expressed character, a fact that

  15. Engineered reversal of drug resistance in cancer cells--metastases suppressor factors as change agents.

    Science.gov (United States)

    Yadav, Vinod Kumar; Kumar, Akinchan; Mann, Anita; Aggarwal, Suruchi; Kumar, Maneesh; Roy, Sumitabho Deb; Pore, Subrata Kumar; Banerjee, Rajkumar; Mahesh Kumar, Jerald; Thakur, Ram Krishna; Chowdhury, Shantanu

    2014-01-01

    Building molecular correlates of drug resistance in cancer and exploiting them for therapeutic intervention remains a pressing clinical need. To identify factors that impact drug resistance herein we built a model that couples inherent cell-based response toward drugs with transcriptomes of resistant/sensitive cells. To test this model, we focused on a group of genes called metastasis suppressor genes (MSGs) that influence aggressiveness and metastatic potential of cancers. Interestingly, modeling of 84 000 drug response transcriptome combinations predicted multiple MSGs to be associated with resistance of different cell types and drugs. As a case study, on inducing MSG levels in a drug resistant breast cancer line resistance to anticancer drugs caerulomycin, camptothecin and topotecan decreased by more than 50-60%, in both culture conditions and also in tumors generated in mice, in contrast to control un-induced cells. To our knowledge, this is the first demonstration of engineered reversal of drug resistance in cancer cells based on a model that exploits inherent cellular response profiles.

  16. Hybrid joining of polyamide and hydrogenated acrylonitrile butadiene rubber through heat-resistant functional layer of silane coupling agent

    Energy Technology Data Exchange (ETDEWEB)

    Sang, Jing; Sato, Riku [Department of Frontier Materials and Function Engineering, Graduate School of Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551 (Japan); Aisawa, Sumio, E-mail: aisawa@iwate-u.ac.jp [Department of Frontier Materials and Function Engineering, Graduate School of Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551 (Japan); Hirahara, Hidetoshi [Department of Frontier Materials and Function Engineering, Graduate School of Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551 (Japan); Mori, Kunio [Department of Frontier Materials and Function Engineering, Graduate School of Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551 (Japan); Sulfur Chemical Institute, 210, Collabo MIU, 4-3-5, Ueda, Morioka 020-0066 (Japan)

    2017-08-01

    Highlights: • We modify PA6 surface using silane coupling agent layer of APTMS to link HNBR. • APTMS greatly improved heat resistance of PA6 from 153 °C up to 325 °C. • A PA6/HNBR joined body was obtained, and it exhibits high adhesion strength with cohesive failure. • Chemical structures of the adhesion interfaces of PA6/HNBR were confirmed by Nano-IR. - Abstract: A simple, direct adhesion method was developed to join polyamide (PA6) to hydrogenated acrylonitrile butadiene rubber (HNBR) by grafting a functional layer of a silane coupling agent on plasma functionalized PA6 surfaces. The functional layer of the silane coupling agent was prepared using a self-assembly method, which greatly improved the heat resistance of PA6 from 153 °C up to 325 °C and the resulting PA6/HNBR joints showed excellent adhesion properties with cohesive failure between PA6 and HNBR. X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and nanoscale infrared microscopy and chemical imaging (Nano-IR, AFM-IR) were employed to characterize the surfaces and interfaces. The Nano-IR analysis method was employed for the first time to analyze the chemical structures of the adhesion interfaces between different materials and to establish the interface formation mechanism. This study is of significant value for interface research and the study of adhesion between resins and rubbers. There is a promising future for heat-resistant functional layers on resin surfaces, with potential application in fuel hose composite materials for the automotive and aeronautical industries.

  17. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

    DEFF Research Database (Denmark)

    Xiao, Fei; Fofana, Isabel; Heydmann, Laura

    2014-01-01

    Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies....... In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV...... genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host...

  18. Bacterial resistance to antimicrobial agents in Latin America. The giant is awakening.

    Science.gov (United States)

    Guzmán-Blanco, M; Casellas, J M; Sader, H S

    2000-03-01

    Resistant bacteria are emerging in Latin America as a real threat to the favorable outcome of infections in community- and hospital-acquired infections. Despite present extensive surveillance, healthcare workers who most need the information may be unaware of this growing problem. Outbreaks of meningococci with diminished susceptibility to penicillin have been reported in the region; a constant increase of resistance to penicillin in pneumococci and poor activity of commonly used oral antibiotics for the treatment of community-acquired urinary tract infections have made the treatment of these infections more difficult. Reports from tertiary hospitals are similar to many other areas of the world, with increasing frequency of Klebsiella pneumoniae-carrying extended-spectrum beta-lactamase, multiresistant strains of Pseudomonas aeruginosa and Acinetobacter baumanni in ICU settings, and reports of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. A surveillance network readily accessible to those who prescribe antibiotics in Latin America is highly desirable.

  19. The resistance of Micrococcus radiodurans to killing and mutation by agents which damage DNA

    International Nuclear Information System (INIS)

    Sweet, D.M.; Moseley, B.E.B.

    1976-01-01

    The resistance of Micrococcus radiodurans to the lethal and mutagenic action of ultraviolet (UV) light, ionising (γ) radiation, mitomycin C (MTC), nitrous acid (NA), hydroxylamine (HA), N-methyl-N'-nitro-N-nitrosoguanidine (NG), ethylmethanesulphonate (EMS) and β-propiolactone (βPL) has been compared with that of Escherichia coli B/r. M. radiodurans was much more resistant than E. coli B/r to the lethal effects of UV light (by a factor of 33), γ-radiation (55), NG (15) and NA (62), showed intermediate resistance to MTC (4) and HA (7), but was sensitive to EMS (1) and βPL (2). M. radiodurans was very resistant to mutagens producing damage which can be repaired by a recombination system, indicating that it possesses an extremely efficient recombination repair mechanism. Both species were equally sensitive to mutation to trimethoprim resistance by NG, but M. radiodurans was more resistant than E. coli B/r to the other mutagens tested, being non-mutable by UV light, γ-radiation, MTC and HA, and only slightly sensitive to mutation by NA, EMS, and βPL. The resistance of M. radiodurans to mutation by UV light, γ-radiation and MTC is consistent with an hypothesis that recombination repair in M. radiodurans is accurate since these mutagens may depend on an 'error-prone' recombination system for their mutagenic effect in E. coli B/r. However, because M. radiodurans is also resistant to mutagens such as HA and EMS, which are mutagenic in E. coli in the absence of an 'error-prone' system, we propose that all the mutagens tested may have a common mode of action in E. coli B/r, but that this mutagenic pathway is missing in M. radiodurans

  20. Resistance of Micrococcus radiodurans to killing and mutation by agents which damage DNA

    Energy Technology Data Exchange (ETDEWEB)

    Sweet, D M; Moseley, B E.B. [Edinburgh Univ. (UK). School of Agriculture

    1976-02-01

    The resistance of Micrococcus radiodurans to the lethal and mutagenic action of ultraviolet (UV) light, ionising (..gamma..) radiation, mitomycin C (MTC), nitrous acid (NA), hydroxylamine (HA), N-methyl-N'-nitro-N-nitrosoguanidine (NG), ethylmethanesulphonate (EMS) and ..beta..-propiolactone (..beta..PL) has been compared with that of Escherichia coli B/r. M. radiodurans was much more resistant than E. coli B/r to the lethal effects of UV light (by a factor of 33), ..gamma..-radiation (55), NG (15) and NA (62), showed intermediate resistance to MTC (4) and HA (7), but was sensitive to EMS (1) and ..beta..PL (2). M. radiodurans was very resistant to mutagens producing damage which can be repaired by a recombination system, indicating that it possesses an extremely efficient recombination repair mechanism. Both species were equally sensitive to mutation to trimethoprim resistance by NG, but M. radiodurans was more resistant than E. coli B/r to the other mutagens tested, being non-mutable by UV light, ..gamma..-radiation, MTC and HA, and only slightly sensitive to mutation by NA, EMS, and ..beta..PL. The resistance of M. radiodurans to mutation by UV light, ..gamma.. radiation and MTC is consistent with an hypothesis that recombination repair in M. radiodurans is accurate since these mutagens may depend on an 'error-prone' recombination system for their mutagenic effect in E. coli B/r. However, because M. radiodurans is also resistant to mutagens such as HA and EMS, which are mutagenic in E. coli in the absence of an 'error-prone' system, we propose that all the mutagens tested may have a common mode of action in E. coli B/r, but that this mutagenic pathway is missing in M. radiodurans.

  1. Proteomics of cancer cell lines resistant to microtubule-stabilizing agents

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Angeletti, Ruth H; Horwitz, Susan Band

    2014-01-01

    Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellula...

  2. Repeated Causal Decision Making

    Science.gov (United States)

    Hagmayer, York; Meder, Bjorn

    2013-01-01

    Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in…

  3. Viscous causal cosmologies

    International Nuclear Information System (INIS)

    Novello, M.; Salim, J.M.; Torres, J.; Oliveira, H.P. de

    1989-01-01

    A set of spatially homogeneous and isotropic cosmological geometries generated by a class of non-perfect is investigated fluids. The irreversibility if this system is studied in the context of causal thermodynamics which provides a useful mechanism to conform to the non-violation of the causal principle. (author) [pt

  4. Causal Analysis After Haavelmo

    Science.gov (United States)

    Heckman, James; Pinto, Rodrigo

    2014-01-01

    Haavelmo's seminal 1943 and 1944 papers are the first rigorous treatment of causality. In them, he distinguished the definition of causal parameters from their identification. He showed that causal parameters are defined using hypothetical models that assign variation to some of the inputs determining outcomes while holding all other inputs fixed. He thus formalized and made operational Marshall's (1890) ceteris paribus analysis. We embed Haavelmo's framework into the recursive framework of Directed Acyclic Graphs (DAGs) used in one influential recent approach to causality (Pearl, 2000) and in the related literature on Bayesian nets (Lauritzen, 1996). We compare the simplicity of an analysis of causality based on Haavelmo's methodology with the complex and nonintuitive approach used in the causal literature of DAGs—the “do-calculus” of Pearl (2009). We discuss the severe limitations of DAGs and in particular of the do-calculus of Pearl in securing identification of economic models. We extend our framework to consider models for simultaneous causality, a central contribution of Haavelmo. In general cases, DAGs cannot be used to analyze models for simultaneous causality, but Haavelmo's approach naturally generalizes to cover them. PMID:25729123

  5. Molecular Basis of Resistance to Selected Antimicrobial Agents in the Emerging Zoonotic Pathogen Streptococcus suis.

    Science.gov (United States)

    Gurung, Mamata; Tamang, Migma Dorji; Moon, Dong Chan; Kim, Su-Ran; Jeong, Jin-Ha; Jang, Geum-Chan; Jung, Suk-Chan; Park, Yong-Ho; Lim, Suk-Kyung

    2015-07-01

    Characterization of 227 Streptococcus suis strains isolated from pigs during 2010 to 2013 showed high levels of resistance to clindamycin (95.6%), tilmicosin (94.7%), tylosin (93.8%), oxytetracycline (89.4%), chlortetracycline (86.8%), tiamulin (72.7%), neomycin (70.0%), enrofloxacin (56.4%), penicillin (56.4%), ceftiofur (55.9%), and gentamicin (55.1%). Resistance to tetracyclines, macrolides, aminoglycosides, and fluoroquinolone was attributed to the tet gene, erm(B), erm(C), mph(C), and mef(A) and/or mef(E) genes, aph(3')-IIIa and aac(6')-Ie-aph(2″)-Ia genes, and single point mutations in the quinolone resistance-determining region of ParC and GyrA, respectively. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Agency, time and causality

    Directory of Open Access Journals (Sweden)

    Thomas eWidlok

    2014-11-01

    Full Text Available Cognitive Scientists interested in causal cognition increasingly search for evidence from non-WEIRD people but find only very few cross-cultural studies that specifically target causal cognition. This article suggests how information about causality can be retrieved from ethnographic monographs, specifically from ethnographies that discuss agency and concepts of time. Many apparent cultural differences with regard to causal cognition dissolve when cultural extensions of agency and personhood to non-humans are taken into account. At the same time considerable variability remains when we include notions of time, linearity and sequence. The article focuses on ethnographic case studies from Africa but provides a more general perspective on the role of ethnography in research on the diversity and universality of causal cognition.

  7. Non-Causal Computation

    Directory of Open Access Journals (Sweden)

    Ämin Baumeler

    2017-07-01

    Full Text Available Computation models such as circuits describe sequences of computation steps that are carried out one after the other. In other words, algorithm design is traditionally subject to the restriction imposed by a fixed causal order. We address a novel computing paradigm beyond quantum computing, replacing this assumption by mere logical consistency: We study non-causal circuits, where a fixed time structure within a gate is locally assumed whilst the global causal structure between the gates is dropped. We present examples of logically consistent non-causal circuits outperforming all causal ones; they imply that suppressing loops entirely is more restrictive than just avoiding the contradictions they can give rise to. That fact is already known for correlations as well as for communication, and we here extend it to computation.

  8. New antibiotic agents in the pipeline and how they can help overcome microbial resistance.

    Science.gov (United States)

    Gould, Ian M; Bal, Abhijit M

    2013-02-15

    Bacterial resistance is a growing threat and yet few new antibiotics active against multi-resistant bacteria are being explored. A combination of falling profits, regulatory mechanisms and irrational and injudicious use of antibiotics has led to an alarming situation where some infections have no cure. In this article, we summarize the new developments that have been suggested to incentivize the pharmaceutical industries toward the field of infections. We also briefly mention the new compounds on the horizon and some newly approved compounds that might help us tide over this crisis.

  9. Patterns of infections, aetiological agents, and antimicrobial resistance at a tertiary care hospital in northern Tanzania

    DEFF Research Database (Denmark)

    Kumburu, Happiness Houka; Sonda, Tolbert; Mmbaga, Blandina Theophil

    2017-01-01

    a total of 377 isolates. A wide range of bacteria was isolated, the most predominant being Gram-negative bacteria: Proteus spp. (n=48, 12.7%), Escherichia coli (n=44, 11.7%), Pseudomonas spp. (n=40, 10.6%), and Klebsiella spp (n=38, 10.1%). Wound infections were characterised by multiple isolates (n=293......, 77.7%), with the most frequent being Proteus spp. (n=44, 15%), Pseudomonas (n=37, 12.6%), Staphylococcus (n=29, 9.9%), and Klebsiella spp. (n=28, 9.6%). All S. aureus tested were resistant to penicillin (n=22, 100%) and susceptible to vancomycin. Significant resistance to cephalosporins...

  10. Hybrid joining of polyamide and hydrogenated acrylonitrile butadiene rubber through heat-resistant functional layer of silane coupling agent

    Science.gov (United States)

    Sang, Jing; Sato, Riku; Aisawa, Sumio; Hirahara, Hidetoshi; Mori, Kunio

    2017-08-01

    A simple, direct adhesion method was developed to join polyamide (PA6) to hydrogenated acrylonitrile butadiene rubber (HNBR) by grafting a functional layer of a silane coupling agent on plasma functionalized PA6 surfaces. The functional layer of the silane coupling agent was prepared using a self-assembly method, which greatly improved the heat resistance of PA6 from 153 °C up to 325 °C and the resulting PA6/HNBR joints showed excellent adhesion properties with cohesive failure between PA6 and HNBR. X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and nanoscale infrared microscopy and chemical imaging (Nano-IR, AFM-IR) were employed to characterize the surfaces and interfaces. The Nano-IR analysis method was employed for the first time to analyze the chemical structures of the adhesion interfaces between different materials and to establish the interface formation mechanism. This study is of significant value for interface research and the study of adhesion between resins and rubbers. There is a promising future for heat-resistant functional layers on resin surfaces, with potential application in fuel hose composite materials for the automotive and aeronautical industries.

  11. Potentiation activity of multiple antibacterial agents by Salvianolate from the Chinese medicine Danshen against methicillin-resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Qing-Qing Liu

    2016-05-01

    Full Text Available Salvianolate (SAL is a prescribed medicine from the Chinese herb Danshen (Salvia miltiorrhiza Bunge. It has been widely used in treatment of coronary and other diseases with significant effects. The in vitro antimicrobial activities of SAL against infectious pathogens were assayed and its combined effects on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA with ten antibiotics were evaluated. Susceptibility to each agent alone was tested using a broth microdilution method, and the chequerboard and time-kill experiments were used for the combined activities. The results showed MIC was 128–256 mg/L for SAL used alone against MRSA. Significant synergies were observed for SAL/Ampicillin (Fosfomycin, Erythromycin, Piperacillin-tazobactam or Clindamycin combination against over half of the isolates, with their MICs reduced by times of dilution (TOD to 4–32 (FICIs 0.375–0.5, respectively. SAL/AMP combination showed the best combined effect of synergy on bacteriostatic and bactericidal activities, while SAL/AMK combination reversed the resistance of MRSA to AMK. The results demonstrated that SAL enhanced widely the in vitro anti-MRSA efficacy of the ten antibacterial agents, which had potential for combinatory therapy of patients infected with MRSA and warrants further investigations.

  12. Potentiation activity of multiple antibacterial agents by Salvianolate from the Chinese medicine Danshen against methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Liu, Qing-Qing; Han, Jun; Zuo, Guo-Ying; Wang, Gen-Chun; Tang, Hua-Shu

    2016-05-01

    Salvianolate (SAL) is a prescribed medicine from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It has been widely used in treatment of coronary and other diseases with significant effects. The in vitro antimicrobial activities of SAL against infectious pathogens were assayed and its combined effects on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA) with ten antibiotics were evaluated. Susceptibility to each agent alone was tested using a broth microdilution method, and the chequerboard and time-kill experiments were used for the combined activities. The results showed MIC was 128-256 mg/L for SAL used alone against MRSA. Significant synergies were observed for SAL/Ampicillin (Fosfomycin, Erythromycin, Piperacillin-tazobactam or Clindamycin) combination against over half of the isolates, with their MICs reduced by times of dilution (TOD) to 4-32 (FICIs 0.375-0.5), respectively. SAL/AMP combination showed the best combined effect of synergy on bacteriostatic and bactericidal activities, while SAL/AMK combination reversed the resistance of MRSA to AMK. The results demonstrated that SAL enhanced widely the in vitro anti-MRSA efficacy of the ten antibacterial agents, which had potential for combinatory therapy of patients infected with MRSA and warrants further investigations. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. The Herb Medicine Formula “Chong Lou Fu Fang” Increases the Cytotoxicity of Chemotherapeutic Agents and Down-Regulates the Expression of Chemotherapeutic Agent Resistance-Related Genes in Human Gastric Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Yongping Liu

    2011-01-01

    Full Text Available The herb medicine formula “Chong Lou Fu Fang” (CLFF has efficacy in inhibiting the proliferation of human gastric cancer in vitro and in vivo. To explore the potentially useful combination of CLFF with chemotherapeutic agents commonly used in gastric cancer therapy, we assess the interaction between CLFF and these chemotherapeutic agents in both SGC-7901 cell lines and BGC-823 cell lines using a median effect analysis and apoptosis analysis, and we also investigate the influence of CLFF on chemotherapeutic agent-associated gene expression. The synergistic analysis indicated that CLFF had a synergistic effect on the cytotoxicity of 5-fluorouracil (5-FU in a relative broad dose inhibition range (20–95% fraction affected in SGC-7901cell lines and 5–65% fraction affected in BGC-823 cell lines, while the synergistic interaction between CLFF and oxaliplatin or docetaxel only existed in a low dose inhibition range (≤50% fraction affected in both cell lines. Combination of CLFF and chemotherapeutic agents could also induce apoptosis in a synergistic manner. After 24 h, CLFF alone or CLFF combination with chemotherapeutic agents could significantly suppress the levels of expression of chemotherapeutic agent resistance related genes in gastric cancer cells. Our findings indicate that there are useful synergistic interactions between CLFF and chemotherapeutic agents in gastric cancer cells, and the possible mechanisms might be partially due to the down-regulation of chemotherapeutic agent resistance related genes and the synergistic apoptotic effect.

  14. Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Lund, Søren S; Wetterslev, Jørn

    2009-01-01

    This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk, and this......This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk......, and this beneficial effect may be conserved with the combination of metformin and insulin treatment. However, the effect of glitazones on CVD is uncertain. There is conflicting evidence from large randomized trials to support a protective effect against CVD of lowering blood glucose per se but a systematic review...

  15. Protective roles of bacterioruberin and intracellular KCl in the resistance of Halobacterium salinarium against DNA-damaging agents

    International Nuclear Information System (INIS)

    Shahmohammadi, H.R.; Asgarani, E.; Terato, Hiroaki; Saito, Takeshi; Ohyama, Yoshihiko; Gekko, Kunihiko; Yamamoto, Osamu; Ide, Hiroshi

    1998-01-01

    Halobacterium salinarium, a member of the extremely halophilic archaebacteria, contains a C 50 -carotenoid namely bacterioruberin. We have previously reported the high resistance of this organism against the lethal actions of DNA-damaging agents including ionizing radiation and ultraviolet light (UV). In this study, we have examined whether bacterioruberin and the highly concentrated salts in this bacterium play protective roles against the lethal actions of ionizing radiation, UV, hydrogen peroxide, and mitomycin-C (MMC). The colourless mutant of H. salinarium deficient in bacterioruberin was more sensitive than the red-pigmented wild-type to all tested DNA-damaging agents except MMC. Circular dichroism (CD) spectra of H. salinarium chromosomal DNA at various concentrations of KCl (0-3.5 M) were similar to that of B-DNA, indicating that no conformational changes occurred as a result of high salt concentrations. However, DNA strand-breaks induced by ionizing radiation were significantly reduced by the presence of either bacterioruberin or concentrated KCl, presumably due to scavenging of free radicals. These results suggest that bacterioruberin and intracellular KCl of H. salinarium protect this organism against the lethal effects of oxidative DNA-damaging agents. (author)

  16. Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis

    NARCIS (Netherlands)

    Alsaad, Noor; Wilffert, Bob; van Altena, Richard; de Lange, Wiel C. M.; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2014-01-01

    Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of

  17. Sartre's Contingency of Being and Asouzu's Principle of Causality ...

    African Journals Online (AJOL)

    The position of this work is that all contingent beings have a causal agent. This position is taken as a result of trying to delve into the issue of contingency and causality of being which has been discussed by many philosophers of diverse epochs of philosophy. This work tries to participate in the debate of whether contingent ...

  18. Causality and headache triggers

    Science.gov (United States)

    Turner, Dana P.; Smitherman, Todd A.; Martin, Vincent T.; Penzien, Donald B.; Houle, Timothy T.

    2013-01-01

    Objective The objective of this study was to explore the conditions necessary to assign causal status to headache triggers. Background The term “headache trigger” is commonly used to label any stimulus that is assumed to cause headaches. However, the assumptions required for determining if a given stimulus in fact has a causal-type relationship in eliciting headaches have not been explicated. Methods A synthesis and application of Rubin’s Causal Model is applied to the context of headache causes. From this application the conditions necessary to infer that one event (trigger) causes another (headache) are outlined using basic assumptions and examples from relevant literature. Results Although many conditions must be satisfied for a causal attribution, three basic assumptions are identified for determining causality in headache triggers: 1) constancy of the sufferer; 2) constancy of the trigger effect; and 3) constancy of the trigger presentation. A valid evaluation of a potential trigger’s effect can only be undertaken once these three basic assumptions are satisfied during formal or informal studies of headache triggers. Conclusions Evaluating these assumptions is extremely difficult or infeasible in clinical practice, and satisfying them during natural experimentation is unlikely. Researchers, practitioners, and headache sufferers are encouraged to avoid natural experimentation to determine the causal effects of headache triggers. Instead, formal experimental designs or retrospective diary studies using advanced statistical modeling techniques provide the best approaches to satisfy the required assumptions and inform causal statements about headache triggers. PMID:23534872

  19. Causality re-established.

    Science.gov (United States)

    D'Ariano, Giacomo Mauro

    2018-07-13

    Causality has never gained the status of a 'law' or 'principle' in physics. Some recent literature has even popularized the false idea that causality is a notion that should be banned from theory. Such misconception relies on an alleged universality of the reversibility of the laws of physics, based either on the determinism of classical theory, or on the multiverse interpretation of quantum theory, in both cases motivated by mere interpretational requirements for realism of the theory. Here, I will show that a properly defined unambiguous notion of causality is a theorem of quantum theory, which is also a falsifiable proposition of the theory. Such a notion of causality appeared in the literature within the framework of operational probabilistic theories. It is a genuinely theoretical notion, corresponding to establishing a definite partial order among events, in the same way as we do by using the future causal cone on Minkowski space. The notion of causality is logically completely independent of the misidentified concept of 'determinism', and, being a consequence of quantum theory, is ubiquitous in physics. In addition, as classical theory can be regarded as a restriction of quantum theory, causality holds also in the classical case, although the determinism of the theory trivializes it. I then conclude by arguing that causality naturally establishes an arrow of time. This implies that the scenario of the 'block Universe' and the connected 'past hypothesis' are incompatible with causality, and thus with quantum theory: they are both doomed to remain mere interpretations and, as such, are not falsifiable, similar to the hypothesis of 'super-determinism'.This article is part of a discussion meeting issue 'Foundations of quantum mechanics and their impact on contemporary society'. © 2018 The Author(s).

  20. Signaling requirements for Erwinia amylovora-induced disease resistance, callose deposition, and cell growth in the nonhost Arabidopsis thaliana

    Science.gov (United States)

    Erwinia amylovora is the causal agent of the fire blight disease in some plants of the Rosaceae family. The nonhost plant Arabidopsis serves as a powerful system to dissect mechanisms of resistance to E. amylovora. Although not yet known to mount gene-for-gene resistance to E. amylovora, we found ...

  1. Genetic stability in potato germplasm for resistance to root galling caused by the powdery scab pathogen spongospora subterranea

    Science.gov (United States)

    Spongospora subteranea, the causal agent of potato powdery scab is becoming increasingly important worldwide. Little is known about the genetic basis of resistance to this disease. The present study tested the hypothesis that potato genotypes with stable genetic resistance to "Spongospora root galli...

  2. Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.

    Directory of Open Access Journals (Sweden)

    Hyock Joo Kwon

    Full Text Available Ledipasvir, a direct acting antiviral agent (DAA targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.

  3. Udder pathogens and their resistance to antimicrobial agents in dairy cows in Estonia

    Directory of Open Access Journals (Sweden)

    Orro Toomas

    2011-02-01

    Full Text Available Abstract Background The goal of this study was to estimate the distribution of udder pathogens and their antibiotic resistance in Estonia during the years 2007-2009. Methods The bacteriological findings reported in this study originate from quarter milk samples collected from cows on Estonian dairy farms that had clinical or subclinical mastitis. The samples were submitted by local veterinarians to the Estonian Veterinary and Food Laboratory during 2007-2009. Milk samples were examined by conventional bacteriology. In vitro antimicrobial susceptibility testing was performed with the disc diffusion test. Logistic regression with a random herd effect to control for clustering was used for statistical analysis. Results During the study period, 3058 clinical mastitis samples from 190 farms and 5146 subclinical mastitis samples from 274 farms were investigated. Positive results were found in 57% of the samples (4680 out of 8204, and the proportion did not differ according to year (p > 0.05. The proportion of bacteriologically negative samples was 22.3% and that of mixed growth was 20.6%. Streptococcus uberis (Str. uberis was the bacterium isolated most frequently (18.4% from cases of clinical mastitis, followed by Escherichia coli (E. coli (15.9% and Streptococcus agalactiae (Str. agalactiae (11.9%. The bacteria that caused subclinical mastitis were mainly Staphylococcus aureus (S. aureus (20% and coagulase-negative staphylococci (CNS (15.4%. The probability of isolating S. aureus from milk samples was significantly higher on farms that had fewer than 30 cows, when compared with farms that had more than 100 cows (p Str. agalactiae infection was found on farms with more than 600 cows (p = 0.034 compared with smaller farms. The proportion of S. aureus and CNS isolates that were resistant to penicillin was 61.4% and 38.5%, respectively. Among the E. coli isolates, ampicillin, streptomycin and tetracycline resistance were observed in 24.3%, 15.6% and 13

  4. Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam - epidemiology, laboratory detection and treatment implications.

    Science.gov (United States)

    Sherry, Norelle; Howden, Benjamin

    2018-04-01

    Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're-discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non-reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.

  5. Antibacterial and synergy of berberines with antibacterial agents against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Zuo, Guo-Ying; Li, Yang; Han, Jun; Wang, Gen-Chun; Zhang, Yun-Ling; Bian, Zhong-Qi

    2012-08-29

    Antibacterial activity of berberine (Ber) and 8-acetonyl-dihydroberberine (A-Ber) alone and combined uses with antibacterial agents ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (μg/mL) ranges were 32-128/64-256 (Ber) and 32-128/128-512 (A-Ber). Significant synergies were observed for the Ber (A-Ber)/AZM and Ber (A-Ber)/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs) values ranged from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

  6. Antibacterial and Synergy of Berberines with Antibacterial Agents against Clinical Multi-Drug Resistant Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Zhong-Qi Bian

    2012-08-01

    Full Text Available Antibacterial activity of berberine (Ber and 8-acetonyl-dihydroberberine (A-Ber alone and combined uses with antibacterial agents ampicillin (AMP, azithromycin (AZM, cefazolin (CFZ and levofloxacin (LEV was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA. Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (mg/mL ranges were 32–128/64–256 (Ber and 32-128/128-512 (A-Ber. Significant synergies were observed for the Ber (A-Ber/AZM and Ber (A-Ber/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs values ranged  from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

  7. Comparison of solutol HS 15, Cremophor EL and novel ethoxylated fatty acid surfactants as multidrug resistance modification agents.

    Science.gov (United States)

    Buckingham, L E; Balasubramanian, M; Emanuele, R M; Clodfelter, K E; Coon, J S

    1995-08-09

    Some well-known fatty acid ester surfactants, e.g., Cremophor EL and Solutol HS 15, are modulators of multidrug resistance in vitro and in vivo. Because they are polydisperse, and their active component(s) have not been identified, the therapeutic potential of such surfactants is unclear. To better define the active components of Solutol HS 15 and to make more potent surfactant multidrug resistance modulators, highly purified C-18 fatty acids were esterified with ethylene oxide at 5-200 molar ratios. Unexpectedly, ethylene oxide esters of pure 12-hydroxy stearic acid, the major components of Solutol HS 15, displayed negligible resistance modification activity compared with Solutol HS 15 itself or to stearic and oleic acid esters synthesized under identical conditions. Since oleic acid esters appeared to have good activity, a series of these compounds was prepared to determine the optimal ethylene oxide/fatty acid ratio. The optimal ratio was found to be 20 mole ethylene oxide: I mole fatty acid, with a steep decline in activity for products made with ratios above and below the optimum. The most active oleic acid ester, designated CRL 1337, was 8.4-fold as potent as Solutol HS 15 and over 19-fold as potent as Cremophor EL in promoting rhodamine 123 accumulation in multidrug-resistant KB 8-5-11 cells in vitro. Our results show that the structure of the hydrophobic domain (fatty acid) of surfactants as well as its hydrophile-lipophile balance are critical in determining the potency of surfactants as reversing agents.

  8. Tachyons and causal paradoxes

    International Nuclear Information System (INIS)

    Maund, J.B.

    1979-01-01

    Although the existence of tachyons is not ruled out by special relativity, it appears that causal paradoxes will arise if there are tachyons. The usual solutions to these paradoxes employ some form of the reinterpretation principle. In this paper it is argued first that, the principle is incoherent, second, that even if it is not, some causal paradoxes remain, and third, the most plausible ''solution,'' which appeals to boundary conditions of the universe, will conflict with special relativity

  9. Dynamics and causality constraints

    International Nuclear Information System (INIS)

    Sousa, Manoelito M. de

    2001-04-01

    The physical meaning and the geometrical interpretation of causality implementation in classical field theories are discussed. Causality in field theory are kinematical constraints dynamically implemented via solutions of the field equation, but in a limit of zero-distance from the field sources part of these constraints carries a dynamical content that explains old problems of classical electrodynamics away with deep implications to the nature of physicals interactions. (author)

  10. Resistance of an enamel-bonding agent to saliva and acid exposure in vitro assessed by liquid scintillation.

    Science.gov (United States)

    Schmidlin, P R; Göhring, T N; Sener, B; Lutz, F

    2002-06-01

    To determine the leakage and resistance of a bonding agent and a light-curing fine hybrid composite when exposed to saliva or lactic acid (pH 4) in vitro. Twenty discs in each of four groups of selected irradiated bovine lower central incisors were treated with one of three sealing options: an enamel bond (Heliobond, Vivadent, Schaan, Liechenstein) in a single-step application; Heliobond in a two-step application; and Tetric Flow (Vivadent) as the negative control. One group served as the positive control and remained unsealed. Loss of apatite was determined using the radiochemical method of liquid scintillation. The Cherenkov radiation was assessed in order to evaluate the acid resistance and leakage of smooth surface enamel bonding after exposure to saliva and lactic acid. In addition, replicas were made for SEM analysis of micromorphologic surface changes. A mean loss of 416.5 g (s.d. 57.0) apatite was observed over the unsealed sites following 14 days of exposure to lactic acid. The application of Heliobond in a one- and two-step application still revealed a remarkable degree of leakage, and substance losses of 196.5 g (s.d. 38.9) and 161.8 g (s.d. 39.7), but a protective potential was evident. In saliva, untreated, as well as sealed teeth, showed a modest leakage that was less than 20 g. When Tetric Flow was used (negative control) leakage was reduced to a minimum of 2.4 g (s.d. 1.0) in saliva and 12.8 g (s.d. 19.6) in lactic acid. These results were confirmed by SEM analysis. The method of liquid scintillation was revealed to be of considerable value in evaluating leakage and acid resistance of potential smooth enamel sealing options. Sealing with an unfilled resin still demonstrated remarkable levels of acid dissolution, although a protection tendency could be observed. This leads to the conclusion that there is a need for further investigation to establish more acid-resistant enamel sealing agents.

  11. Induction of systemic resistance in plants by biochar, a soil-applied carbon sequestering agent.

    Science.gov (United States)

    Elad, Yigal; David, Dalia Rav; Harel, Yael Meller; Borenshtein, Menahem; Kalifa, Hananel Ben; Silber, Avner; Graber, Ellen R

    2010-09-01

    Biochar is the solid coproduct of biomass pyrolysis, a technique used for carbon-negative production of second-generation biofuels. The biochar can be applied as a soil amendment, where it permanently sequesters carbon from the atmosphere as well as improves soil tilth, nutrient retention, and crop productivity. In addition to its other benefits in soil, we found that soil-applied biochar induces systemic resistance to the foliar fungal pathogens Botrytis cinerea (gray mold) and Leveillula taurica (powdery mildew) on pepper and tomato and to the broad mite pest (Polyphagotarsonemus latus Banks) on pepper. Levels of 1 to 5% biochar in a soil and a coconut fiber-tuff potting medium were found to be significantly effective at suppressing both diseases in leaves of different ages. In long-term tests (105 days), pepper powdery mildew was significantly less severe in the biochar-treated plants than in the plants from the unamended controls although, during the final 25 days, the rate of disease development in the treatments and controls was similar. Possible biochar-related elicitors of systemic induced resistance are discussed.

  12. Effects of cleaning agents on bond strength to dentin Efeitos de agentes de limpeza na resistência adesiva à dentina

    Directory of Open Access Journals (Sweden)

    Celso Rosin

    2005-06-01

    Full Text Available The cleaning of cavity walls aims to improve adhesive restorative procedures and longevity of restorations. This study has compared the effect of three cleaning agents - sodium bicarbonate jet (Profi II, Dabi Atlante, São Paulo, Brazil; pumice paste plus a biologic detergent (Tergestesim, Probem, São Paulo, Brazil; air water spray - on the bond strength between dentin and two different adhesive systems: Clearfil SE Bond (Kuraray, Kioto, Japan and Scotchbond Multi-Purpose Plus (3M-ESPE, São Paulo, Brazil. Six groups (n:10 of dental fragments obtained from young adult extracted teeth were prepared, and each one received one of the listed surface cleaning techniques. After the adhesive application, a cone-shaped test body was built with AP-X (Kuraray, Kioto, Japan or Z100 (3M-ESPE, São Paulo, Brazil composite resins, using a Teflon matrix. The specimens were tested for tensile bond strength after one-week storage in distilled water at 37°C. Two pairs of fractured specimens of each group were randomly chosen and processed for scanning electron microscopy (SEM analysis. ANOVA test of the bond strength values showed no statistical differences among the cleaning agents and neither between their interactions with the bonding systems. Upon SEM analysis, most surfaces showed mixed fractures of adhesive and cohesive failures in bonding resin to dentin. Based on statistical and SEM analysis, it was concluded that the cleaning agents studied did not interfere with the bond strength of the adhesive systems used to dentin.A limpeza das paredes cavitárias é um passo importante na clínica odontológica e visa otimizar os procedimentos adesivos e a longevidade das restaurações. O presente estudo comparou o efeito de três agentes de limpeza cavitária - jato abrasivo de bicarbonato de sódio/ar/água (Profi II, Dabi Atlante, São Paulo, Brasil; pasta de pedra-pomes e água, somada a um detergente biológico (Tergestesim, Probem, São Paulo, Brasil; e

  13. Kant on causal laws and powers.

    Science.gov (United States)

    Henschen, Tobias

    2014-12-01

    The aim of the paper is threefold. Its first aim is to defend Eric Watkins's claim that for Kant, a cause is not an event but a causal power: a power that is borne by a substance, and that, when active, brings about its effect, i.e. a change of the states of another substance, by generating a continuous flow of intermediate states of that substance. The second aim of the paper is to argue against Watkins that the Kantian concept of causal power is not the pre-critical concept of real ground but the category of causality, and that Kant holds with Hume that causal laws cannot be inferred non-inductively (that he accordingly has no intention to show in the Second analogy or elsewhere that events fall under causal laws). The third aim of the paper is to compare the Kantian position on causality with central tenets of contemporary powers ontology: it argues that unlike the variants endorsed by contemporary powers theorists, the Kantian variants of these tenets are resistant to objections that neo-Humeans raise to these tenets.

  14. Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram-Negative Bacteria.

    Science.gov (United States)

    Borselli, Diane; Blanchet, Marine; Bolla, Jean-Michel; Muth, Aaron; Skruber, Kristen; Phanstiel, Otto; Brunel, Jean Michel

    2017-02-01

    Dihydromotuporamine C and its derivatives were evaluated for their in vitro antimicrobial activities and antibiotic enhancement properties against Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives, MOTU-N44, was investigated against Enterobacter aerogenes by using fluorescent dyes to evaluate outer-membrane depolarization and permeabilization. Its efficiency correlated with inhibition of dye transport, thus suggesting that these molecules inhibit drug transporters by de-energization of the efflux pump rather than by direct interaction of the molecule with the pump. This suggests that depowering the efflux pump provides another strategy to address antibiotic resistance. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  15. Resistance evaluation expanded perlite the leaching acid: variation of parameters concentration, time and leaching agent

    International Nuclear Information System (INIS)

    Almeida, J.M.F. de; Damasceno Junior, E.; Oliveira, E.S.; Fernandes, N.S.

    2016-01-01

    The expanded perlite is an amorphous aluminosilicate which presents in its composition about 75.0% silicon oxide (SiO2), also having other species in the composition as oxides of some metals. Silicas and silicates have been used in the environmental field, in relevant anti-corrosive activity. In this context, materials that exposes too many highly acidic media, require preservation against this type of wear, as this type of damage causes a great financial loss, thereby requiring low-cost, abundant materials, non-toxic and easy to purchase as some silica coating. The study evaluated the perlite expanded resistance against an acid leaching process. With undeniability the use of strong acids and different working conditions were not able to remove the oxides present on the expanded perlite sample, thus demonstrating the high strength of the expanded perlite against acid attacks. (author)

  16. Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

    Directory of Open Access Journals (Sweden)

    Juliana Alves Parente-Rocha

    2017-01-01

    Full Text Available Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.

  17. Preparation of protein based surfactants from leather waste fleshings and their reutilization in leather as a water resisting agent

    International Nuclear Information System (INIS)

    Nawaz, H.; Nadeem, U.; Solangi, B.; Hany, O.E.

    2012-01-01

    Summary: Tanneries generate a huge amount of highly polluting solid and liquid wastes during leather processing at different stages such as fleshings, shavings, tanning, finishing etc. approximately, 250 kg of finished leather product is obtained from 1 ton of raw salted hide while other protein goes into wastes. leather fleshings are about 50-60% of the total solid waste generated in leather processing. three different surfactants have been prepared from soft wax, long chain fatty acid chlorides and leather waste protein isolated from alkaline hydrolysis of fleshings. products are milky in color and have been applied in goat leathers as a replacement of fat liquor and water resisting agent .the resulted crust leathers have been characterized for various physical parameters such as tensile strength, thickness, softness, tear strength, bursting load, water absorption etc, as per their standard test methods. leathers have also been evaluated for grain smoothness, fullness and feeling. leathers have shown satisfactory results as per international requirement specially for water resisting. thus a leather waste protein is converted into a useful product and reutilized in leather making. (author)

  18. Coral-Associated Bacteria as a Promising Antibiofilm Agent against Methicillin-Resistant and -Susceptible Staphylococcus aureus Biofilms

    Directory of Open Access Journals (Sweden)

    Shanmugaraj Gowrishankar

    2012-01-01

    Full Text Available The current study deals with the evaluation of two coral-associated bacterial (CAB extracts to inhibit the biofilm synthesis in vitro as well as the virulence production like hemolysin and exopolysaccharide (EPS, and also to assess their ability to modify the adhesion properties, that is cell surface hydrophobicity (CSH of methicillin-resistant (MRSA and -susceptible Staphylococcus aureus (MSSA. Out of nine CAB screened, the ethyl acetate extract of CAB-E2 (Bacillus firmus and CAB-E4 (Vibrio parahemolyticus have shown excellent antibiofilm activity against S. aureus. CAB-E2 reduced the production of EPS (57–79% and hemolysin (43–70%, which ultimately resulted in the significant inhibition of biofilms (80–87% formed by both MRSA and MSSA. Similarly, CAB-E4 was also found to decrease the production of EPS (43–57%, hemolysin (43–57% and biofilms (80–85% of test pathogens. CLSM analysis also proved the antibiofilm efficacy of CAB extracts. Furthermore, the CAB extracts strongly decreased the CSH of S. aureus. Additionally, FT-IR analysis of S. aureus treated with CAB extracts evidenced the reduction in cellular components compared to their respective controls. Thus, the present study reports for the first time, B. firmus—a coral-associated bacterium, as a promising source of antibiofilm agent against the recalcitrant biofilms formed by multidrug resistant S. aureus.

  19. PROBLEMATIC ISSUES OF CAUSAL TREATMENT FOR URINARY TRACT INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V. I. Kirillov

    2016-01-01

    Full Text Available The review gives data on shortcomings in the antimicrobial measures that are associated with the defects in the effective treatment of urinary system infections, such as the high risk of disease relapses and the stable proportion of secondary pyelonephritis among the causes of chronic renal failure. The vulnerability of this approach is to accelerate the rate of acquiring the resistance of uropathogens to the currently available antibiotics that may also have a number of side effects, including those involved in the pathogenesis of urinary tract infections. Difficulties in conducting adequate causal therapy are also associated with some subjective factors that largely hamper the personalized diagnosis of diseases of causative agents.

  20. Haplotype Analysis of the Pre-harvest Sprouting Resistance Locus Phs-A1 Reveals a Causal Role of TaMKK3-A in Global Germplasm.

    Science.gov (United States)

    Shorinola, Oluwaseyi; Balcárková, Barbara; Hyles, Jessica; Tibbits, Josquin F G; Hayden, Matthew J; Holušova, Katarina; Valárik, Miroslav; Distelfeld, Assaf; Torada, Atsushi; Barrero, Jose M; Uauy, Cristobal

    2017-01-01

    Pre-harvest sprouting (PHS) is an important cause of quality loss in many cereal crops and is particularly prevalent and damaging in wheat. Resistance to PHS is therefore a valuable target trait in many breeding programs. The Phs-A1 locus on wheat chromosome arm 4AL has been consistently shown to account for a significant proportion of natural variation to PHS in diverse mapping populations. However, the deployment of sprouting resistance is confounded by the fact that different candidate genes, including the tandem duplicated Plasma Membrane 19 ( PM19 ) genes and the mitogen-activated protein kinase kinase 3 ( TaMKK3-A) gene, have been proposed to underlie Phs-A1 . To further define the Phs-A1 locus, we constructed a physical map across this interval in hexaploid and tetraploid wheat. We established close proximity of the proposed candidate genes which are located within a 1.2 Mb interval. Genetic characterization of diverse germplasm used in previous genetic mapping studies suggests that TaMKK3-A , and not PM19 , is the major gene underlying the Phs-A1 effect in European, North American, Australian and Asian germplasm. We identified the non-dormant TaMKK3-A allele at low frequencies within the A-genome diploid progenitor Triticum urartu genepool, and show an increase in the allele frequency in modern varieties. In United Kingdom varieties, the frequency of the dormant TaMKK3-A allele was significantly higher in bread-making quality varieties compared to feed and biscuit-making cultivars. Analysis of exome capture data from 58 diverse hexaploid wheat accessions identified fourteen haplotypes across the extended Phs-A1 locus and four haplotypes for TaMKK3-A . Analysis of these haplotypes in a collection of United Kingdom and Australian cultivars revealed distinct major dormant and non-dormant Phs-A1 haplotypes in each country, which were either rare or absent in the opposing germplasm set. The diagnostic markers and haplotype information reported in the study will

  1. Haplotype Analysis of the Pre-harvest Sprouting Resistance Locus Phs-A1 Reveals a Causal Role of TaMKK3-A in Global Germplasm

    Directory of Open Access Journals (Sweden)

    Oluwaseyi Shorinola

    2017-09-01

    Full Text Available Pre-harvest sprouting (PHS is an important cause of quality loss in many cereal crops and is particularly prevalent and damaging in wheat. Resistance to PHS is therefore a valuable target trait in many breeding programs. The Phs-A1 locus on wheat chromosome arm 4AL has been consistently shown to account for a significant proportion of natural variation to PHS in diverse mapping populations. However, the deployment of sprouting resistance is confounded by the fact that different candidate genes, including the tandem duplicated Plasma Membrane 19 (PM19 genes and the mitogen-activated protein kinase kinase 3 (TaMKK3-A gene, have been proposed to underlie Phs-A1. To further define the Phs-A1 locus, we constructed a physical map across this interval in hexaploid and tetraploid wheat. We established close proximity of the proposed candidate genes which are located within a 1.2 Mb interval. Genetic characterization of diverse germplasm used in previous genetic mapping studies suggests that TaMKK3-A, and not PM19, is the major gene underlying the Phs-A1 effect in European, North American, Australian and Asian germplasm. We identified the non-dormant TaMKK3-A allele at low frequencies within the A-genome diploid progenitor Triticum urartu genepool, and show an increase in the allele frequency in modern varieties. In United Kingdom varieties, the frequency of the dormant TaMKK3-A allele was significantly higher in bread-making quality varieties compared to feed and biscuit-making cultivars. Analysis of exome capture data from 58 diverse hexaploid wheat accessions identified fourteen haplotypes across the extended Phs-A1 locus and four haplotypes for TaMKK3-A. Analysis of these haplotypes in a collection of United Kingdom and Australian cultivars revealed distinct major dormant and non-dormant Phs-A1 haplotypes in each country, which were either rare or absent in the opposing germplasm set. The diagnostic markers and haplotype information reported in the

  2. Isolation and Characterization of phiLLS, a Novel Phage with Potential Biocontrol Agent against Multidrug-Resistant Escherichia coli

    Directory of Open Access Journals (Sweden)

    Luis Amarillas

    2017-07-01

    Full Text Available Foodborne diseases are a serious and growing problem, and the incidence and prevalence of antimicrobial resistance among foodborne pathogens is reported to have increased. The emergence of antibiotic-resistant bacterial strains demands novel strategies to counteract this epidemic. In this regard, lytic bacteriophages have reemerged as an alternative for the control of pathogenic bacteria. However, the effective use of phages relies on appropriate biological and genomic characterization. In this study, we present the isolation and characterization of a novel bacteriophage named phiLLS, which has shown strong lytic activity against generic and multidrug-resistant Escherichia coli strains. Transmission electron microscopy of phiLLS morphology revealed that it belongs to the Siphoviridae family. Furthermore, this phage exhibited a relatively large burst size of 176 plaque-forming units per infected cell. Phage phiLLS significantly reduced the growth of E. coli under laboratory conditions. Analyses of restriction profiles showed the presence of submolar fragments, confirming that phiLLS is a pac-type phage. Phylogenetic analysis based on the amino acid sequence of large terminase subunits confirmed that this phage uses a headful packaging strategy to package their genome. Genomic sequencing and bioinformatic analysis showed that phiLLS is a novel bacteriophage that is most closely related to T5-like phages. In silico analysis indicated that the phiLLS genome consists of 107,263 bp (39.0 % GC content encoding 160 putative ORFs, 16 tRNAs, several potential promoters and transcriptional terminators. Genome analysis suggests that the phage phiLLS is strictly lytic without carrying genes associated with virulence factors and/or potential immunoreactive allergen proteins. The bacteriophage isolated in this study has shown promising results in the biocontrol of bacterial growth under in vitro conditions, suggesting that it may prove useful as an alternative

  3. Causality discovery technology

    Science.gov (United States)

    Chen, M.; Ertl, T.; Jirotka, M.; Trefethen, A.; Schmidt, A.; Coecke, B.; Bañares-Alcántara, R.

    2012-11-01

    Causality is the fabric of our dynamic world. We all make frequent attempts to reason causation relationships of everyday events (e.g., what was the cause of my headache, or what has upset Alice?). We attempt to manage causality all the time through planning and scheduling. The greatest scientific discoveries are usually about causality (e.g., Newton found the cause for an apple to fall, and Darwin discovered natural selection). Meanwhile, we continue to seek a comprehensive understanding about the causes of numerous complex phenomena, such as social divisions, economic crisis, global warming, home-grown terrorism, etc. Humans analyse and reason causality based on observation, experimentation and acquired a priori knowledge. Today's technologies enable us to make observations and carry out experiments in an unprecedented scale that has created data mountains everywhere. Whereas there are exciting opportunities to discover new causation relationships, there are also unparalleled challenges to benefit from such data mountains. In this article, we present a case for developing a new piece of ICT, called Causality Discovery Technology. We reason about the necessity, feasibility and potential impact of such a technology.

  4. Triaryl Benzimidazoles as a New Class of Antibacterial Agents against Resistant Pathogenic Microorganisms.

    Science.gov (United States)

    Picconi, Pietro; Hind, Charlotte; Jamshidi, Shirin; Nahar, Kazi; Clifford, Melanie; Wand, Matthew E; Sutton, J Mark; Rahman, Khondaker Miraz

    2017-07-27

    A new class of nontoxic triaryl benzimidazole compounds, derived from existing classes of DNA minor groove binders, were designed, synthesized, and evaluated for their antibacterial activity against multidrug resistant (MDR) Gram-positive and Gram-negative species. Molecular modeling experiments suggest that the newly synthesized class cannot be accommodated within the minor groove of DNA due to a change in the shape of the molecules. Compounds 8, 13, and 14 were found to be the most active of the series, with MICs in the range of 0.5-4 μg/mL against the MDR Staphylococci and Enterococci species. Compound 13 showed moderate activity against the MDR Gram-negative strains, with MICs in the range of 16-32 μg/mL. Active compounds showed a bactericidal mode of action, and a mechanistic study suggested the inhibition of bacterial gyrase as the mechanism of action (MOA) of this chemical class. The MOA was further supported by the molecular modeling study.

  5. A quantum causal discovery algorithm

    Science.gov (United States)

    Giarmatzi, Christina; Costa, Fabio

    2018-03-01

    Finding a causal model for a set of classical variables is now a well-established task—but what about the quantum equivalent? Even the notion of a quantum causal model is controversial. Here, we present a causal discovery algorithm for quantum systems. The input to the algorithm is a process matrix describing correlations between quantum events. Its output consists of different levels of information about the underlying causal model. Our algorithm determines whether the process is causally ordered by grouping the events into causally ordered non-signaling sets. It detects if all relevant common causes are included in the process, which we label Markovian, or alternatively if some causal relations are mediated through some external memory. For a Markovian process, it outputs a causal model, namely the causal relations and the corresponding mechanisms, represented as quantum states and channels. Our algorithm opens the route to more general quantum causal discovery methods.

  6. Associations between the use of antimicrobial agents for growth promotion and the occurrence of resistance among Enterococcus faecium from broilers and pigs in Denmark, Finland, and Norway

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Kruse, H.; Tast, E.

    2000-01-01

    This study compares the susceptibility of Enterococcus faecium isolated from pigs and poultry in Denmark, Finland, and Norway to antimicrobial agents used for growth promotion. E. faecium was isolated from 211 broilers and 55 pigs in Denmark in 1997, from Norwegian 55 poultry farms (turkey and br......%) of the virginiamycin-resistant isolates from pigs in Denmark. This study indicates that the use of antimicrobial agents for growth promotion in Denmark, Finland, and Norway have selected for resistance to most of these drugs among E. faecium in food animals....... as resistant to monensin or salinomycin. In general, an association between the usage of antimicrobial agents in the respective countries and the occurrence of associated resistance was observed. Resistance to avilamycin was frequently observed among isolates from broilers in Denmark, where avilamycin has been...... used, whereas all isolates from Finland and Norway, where these drugs have not been used, were susceptible. The same phenomenon could be observed for avoparcin, bacitracin, tylosin, and virginiamycin; resistance was frequently observed among isolates from where these antimicrobials have been widely...

  7. Down-regulation of DNA mismatch repair proteins in human and murine tumor spheroids: implications for multicellular resistance to alkylating agents.

    Science.gov (United States)

    Francia, Giulio; Green, Shane K; Bocci, Guido; Man, Shan; Emmenegger, Urban; Ebos, John M L; Weinerman, Adina; Shaked, Yuval; Kerbel, Robert S

    2005-10-01

    Similar to other anticancer agents, intrinsic or acquired resistance to DNA-damaging chemotherapeutics is a major obstacle for cancer therapy. Current strategies aimed at overcoming this problem are mostly based on the premise that tumor cells acquire heritable genetic mutations that contribute to drug resistance. Here, we present evidence for an epigenetic, tumor cell adhesion-mediated, and reversible form of drug resistance that is associated with a reduction of DNA mismatch repair proteins PMS2 and/or MLH1 as well as other members of this DNA repair process. Growth of human breast cancer, human melanoma, and murine EMT-6 breast cancer cell lines as multicellular spheroids in vitro, which is associated with increased resistance to many chemotherapeutic drugs, including alkylating agents, is shown to lead to a reproducible down-regulation of PMS2, MLH1, or, in some cases, both as well as MHS6, MSH3, and MSH2. The observed down-regulation is in part reversible by treatment of tumor spheroids with the DNA-demethylating agent, 5-azacytidine. Thus, treatment of EMT-6 mouse mammary carcinoma spheroids with 5-azacytidine resulted in reduced and/or disrupted cell-cell adhesion, which in turn sensitized tumor spheroids to cisplatin-mediated killing in vitro. Our results suggest that antiadhesive agents might sensitize tumor spheroids to alkylating agents in part by reversing or preventing reduced DNA mismatch repair activity and that the chemosensitization properties of 5-azacytidine may conceivably reflect its role as a potential antiadhesive agent as well as reversal agent for MLH1 gene silencing in human tumors.

  8. Causal symmetric spaces

    CERN Document Server

    Olafsson, Gestur; Helgason, Sigurdur

    1996-01-01

    This book is intended to introduce researchers and graduate students to the concepts of causal symmetric spaces. To date, results of recent studies considered standard by specialists have not been widely published. This book seeks to bring this information to students and researchers in geometry and analysis on causal symmetric spaces.Includes the newest results in harmonic analysis including Spherical functions on ordered symmetric space and the holmorphic discrete series and Hardy spaces on compactly casual symmetric spacesDeals with the infinitesimal situation, coverings of symmetric spaces, classification of causal symmetric pairs and invariant cone fieldsPresents basic geometric properties of semi-simple symmetric spacesIncludes appendices on Lie algebras and Lie groups, Bounded symmetric domains (Cayley transforms), Antiholomorphic Involutions on Bounded Domains and Para-Hermitian Symmetric Spaces

  9. Causal inference in econometrics

    CERN Document Server

    Kreinovich, Vladik; Sriboonchitta, Songsak

    2016-01-01

    This book is devoted to the analysis of causal inference which is one of the most difficult tasks in data analysis: when two phenomena are observed to be related, it is often difficult to decide whether one of them causally influences the other one, or whether these two phenomena have a common cause. This analysis is the main focus of this volume. To get a good understanding of the causal inference, it is important to have models of economic phenomena which are as accurate as possible. Because of this need, this volume also contains papers that use non-traditional economic models, such as fuzzy models and models obtained by using neural networks and data mining techniques. It also contains papers that apply different econometric models to analyze real-life economic dependencies.

  10. The causal structure of utility conditionals.

    Science.gov (United States)

    Bonnefon, Jean-François; Sloman, Steven A

    2013-01-01

    The psychology of reasoning is increasingly considering agents' values and preferences, achieving greater integration with judgment and decision making, social cognition, and moral reasoning. Some of this research investigates utility conditionals, ''if p then q'' statements where the realization of p or q or both is valued by some agents. Various approaches to utility conditionals share the assumption that reasoners make inferences from utility conditionals based on the comparison between the utility of p and the expected utility of q. This article introduces a new parameter in this analysis, the underlying causal structure of the conditional. Four experiments showed that causal structure moderated utility-informed conditional reasoning. These inferences were strongly invited when the underlying structure of the conditional was causal, and significantly less so when the underlying structure of the conditional was diagnostic. This asymmetry was only observed for conditionals in which the utility of q was clear, and disappeared when the utility of q was unclear. Thus, an adequate account of utility-informed inferences conditional reasoning requires three components: utility, probability, and causal structure. Copyright © 2012 Cognitive Science Society, Inc.

  11. Superhydrophobic powder additives to enhance chemical agent resistant coating systems for military equipment for the U.S. Marine Corps (USMC) Corrosion Prevention and Control (CPAC) Program

    Energy Technology Data Exchange (ETDEWEB)

    Pawel, Steven J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Armstrong, Beth L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Haynes, James A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-07-01

    The primary goal of the CPAC program at ORNL was to explore the feasibility of introducing various silica-based superhydrophobic (SH) powder additives as a way to improve the corrosion resistance of US Department of Defense (DOD) military-grade chemical agent resistant coating (CARC) systems. ORNL had previously developed and patented several SH technologies of interest to the USMC, and one of the objectives of this program was to identify methods to incorporate these technologies into the USMC’s corrosion-resistance strategy. This report discusses findings of the CPAC and their application.

  12. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: Results from a randomized controlled trial (CONTRAST)

    NARCIS (Netherlands)

    N.C. van der Weerd (Neelke); C.H. den Hoedt (Claire); P.J. Blankestijn (Peter); M.L. Bots (Michiel); M.A. van den Dorpel (Marinus); R. Lévesque (Renée); A.H.A. Mazairac (Albert); M.J. Nubé (Menso); E. Lars Penne; P.M. ter Wee (Piet); M.P.C. Grooteman (Muriel)

    2014-01-01

    textabstractResistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this

  13. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST)

    NARCIS (Netherlands)

    Weerd, N.C. van der; Hoedt, C.H. den; Blankestijn, P.J.; Bots, M.L.; Dorpel, M.A. van den; Levesque, R.; Mazairac, A.H.; Nube, M.J.; Penne, E.L.; Wee, P.M. ter; Grooteman, M.P.; Hamersvelt, H.W. van; et al.,

    2014-01-01

    Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the

  14. Resistance to antimicrobial agents used for animal therapy in pathogenic , zoonotic and indicator bacteria isolated from different food animals in Denmark: A baseline study for the Danish Integrated Antimicrobial Resistance Monitoring Programme (DANMAP)

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Bager, Flemming; Jensen, N. E.

    1998-01-01

    was found. The occurrence of resistance varied by animal origin and bacterial species. In general, resistance was observed more frequently among isolates from pigs than from cattle and broilers. The association between the occurrence of resistance and the consumption of the antimicrobial is discussed......, as is the occurrence of resistance in other countries. The results of this study show the present level of resistance to antimicrobial agents among a number of bacterial species isolated from food animals in Denmark. Thus, the baseline for comparison with future prospective studies has been established, enabling......This study describes the establishment and first results of a continuous surveillance system of antimicrobial resistance among bacteria isolated from pigs, cattle and broilers in Denmark. The three categories of bacteria tested were: 1) indicator bacteria (Escherichia coli, Enterococcus faecalis...

  15. A translational study of resistance emergence using sequential direct-acting antiviral agents for hepatitis C using ultra-deep sequencing.

    Science.gov (United States)

    Abe, Hiromi; Hayes, C Nelson; Hiraga, Nobuhiko; Imamura, Michio; Tsuge, Masataka; Miki, Daiki; Takahashi, Shoichi; Ochi, Hidenori; Chayama, Kazuaki

    2013-09-01

    Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) have recently been developed and are ultimately hoped to replace interferon-based therapy. However, DAA monotherapy results in rapid emergence of resistant strains and DAAs must be used in combinations that present a high genetic barrier to resistance, although viral kinetics of multidrug-resistant strains remain poorly characterized. The aim of this study is to track the emergence and fitness of resistance using combinations of telaprevir and NS5A or NS5B inhibitors with genotype 1b clones. HCV-infected chimeric mice were treated with DAAs, and resistance was monitored using direct and ultra-deep sequencing. Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy. Infection with dual NS5AL31V/NS5AY93H mutations resulted in poor response to combination therapy and development of telaprevir resistance. Although HCV RNA became undetectable soon after the beginning of combination therapy with BMS-788329 and BMS-821095 (NS5B inhibitor), rebound with emergence of resistance against all three drugs occurred. Triple resistance also occurred following infection with the NS3V36A/NS5AL31V/NS5AY93H triple mutation. Resistant strains easily develop from cloned virus strains. Sequential use of DAAs should be avoided to prevent emergence of multidrug-resistant strains.

  16. Comparison of 6-thioguanine-resistant mutation and sister chromatid exchanges in Chinese hamster V79 cells with forty chemical and physical agents

    International Nuclear Information System (INIS)

    Nishi, Y.; Hasegawa, M.M.; Taketomi, M.; Ohkawa, Y.; Inui, N.

    1984-01-01

    The induction of sister chromatid exchanges (SCE) and mutation at the hypoxanthine-guanine phosphoribosyl transferase locus and toxicities of 40 different chemical and physical agents were examined on Chinese hamster V79 cells. These agents included mono-, di-, tri-, and polyfunctional alkylating agents, intercalators, gamma-rays, and UV light irradiation. Mutation was measured as resistance to 6-thioguanine and toxicity as loss of cell-plating efficiency. SCE were examined 29 hr after treatment. With the agents examined, a highly positive correlation existed between SCE-inducing and mutagenic potencies, when expressed as increase in the number per a unit dose over the control values. But the great difference of the ratios of mutagenic potencies versus SCE-inducing potencies among agents was observed, the maximal difference in the ratios being about 200-fold. The agents that showed the higher values of the ratio (agents producing more mutations than SCE) were bleomycin, cobalt-60 gamma-rays, all ethylating agents (N-ethyl-N-nitrosourea, N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and diethylsulfate), N-propyl-N-nitrosourea, N-butyl-N-nitrosourea, isopropyl methanesulfonate, intercalating acridine compounds (2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]-acridine X 2HCl and 2-methoxy-6-chloro-9-[3-(chloroethyl)-aminopropylamino]acridine 2HCl) and UV light at 254 nm

  17. Maximally causal quantum mechanics

    International Nuclear Information System (INIS)

    Roy, S.M.

    1998-01-01

    We present a new causal quantum mechanics in one and two dimensions developed recently at TIFR by this author and V. Singh. In this theory both position and momentum for a system point have Hamiltonian evolution in such a way that the ensemble of system points leads to position and momentum probability densities agreeing exactly with ordinary quantum mechanics. (author)

  18. Causality in demand

    DEFF Research Database (Denmark)

    Nielsen, Max; Jensen, Frank; Setälä, Jari

    2011-01-01

    to fish demand. On the German market for farmed trout and substitutes, it is found that supply sources, i.e. aquaculture and fishery, are not the only determinant of causality. Storing, tightness of management and aggregation level of integrated markets might also be important. The methodological...

  19. Causality and Free Will

    Czech Academy of Sciences Publication Activity Database

    Hvorecký, Juraj

    2012-01-01

    Roč. 19, Supp.2 (2012), s. 64-69 ISSN 1335-0668 R&D Projects: GA ČR(CZ) GAP401/12/0833 Institutional support: RVO:67985955 Keywords : conciousness * free will * determinism * causality Subject RIV: AA - Philosophy ; Religion

  20. Explaining through causal mechanisms

    NARCIS (Netherlands)

    Biesbroek, Robbert; Dupuis, Johann; Wellstead, Adam

    2017-01-01

    This paper synthesizes and builds on recent critiques of the resilience literature; namely that the field has largely been unsuccessful in capturing the complexity of governance processes, in particular cause–effects relationships. We demonstrate that absence of a causal model is reflected in the

  1. Antibacterial activity of crude extracts of some South African medicinal plants against multidrug resistant etiological agents of diarrhoea.

    Science.gov (United States)

    Bisi-Johnson, Mary A; Obi, Chikwelu L; Samuel, Babatunde B; Eloff, Jacobus N; Okoh, Anthony I

    2017-06-19

    This study evaluated the antibacterial activity of some plants used in folklore medicine to treat diarrhoea in the Eastern Cape Province, South Africa. The acetone extracts of Acacia mearnsii De Wild., Aloe arborescens Mill., A. striata Haw., Cyathula uncinulata (Schrad.) Schinz, Eucomis autumnalis (Mill.) Chitt., E. comosa (Houtt.) Wehrh., Hermbstaedtia odorata (Burch. ex Moq.) T.Cooke, Hydnora africana Thunb, Hypoxis latifolia Wight, Pelargonium sidoides DC, Psidium guajava L and Schizocarphus nervosus (Burch.) van der Merwe were screened against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, multi-resistant Salmonella enterica serovar Isangi, S. typhi, S. enterica serovar Typhimurium, Shigella flexneri type 1b and Sh. sonnei phase II. A qualitative phytochemical screening of the plants extracts was by thin layer chromatography. Plants extracts were screened for antibacterial activity using serial dilution microplate technique and bioautography. The TLC fingerprint indicated the presence of terpenoids and flavonoids in the herbs. Most of the tested organisms were sensitive to the crude acetone extracts with minimum inhibitory concentration (MIC) values ranging from 0.018-2.5 mg/mℓ. Extracts of A. striata, C. uncinulata, E. autumnalis and P. guajava were more active against enteropathogens. S. aureus and Sh. flexneri were the most sensitive isolates to the crude extracts but of significance is the antibacterial activity of A. arborescens and P. guajava against a confirmed extended spectrum betalactamase positive S. enterica serovar Typhimurium. The presence of bioactive compounds and the antibacterial activity of some of the selected herbs against multidrug resistant enteric agents corroborate assertions by traditional healers on their efficacies.

  2. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  3. Resistance to organophosphorus agent toxicity in transgenic mice expressing the G117H mutant of human butyrylcholinesterase

    International Nuclear Information System (INIS)

    Wang Yuxia; Ticu Boeck, Andreea; Duysen, Ellen G.; Van Keuren, Margaret; Saunders, Thomas L.; Lockridge, Oksana

    2004-01-01

    Organophosphorus toxicants (OP) include chemical nerve agents and pesticides. The goal of this work was to find out whether an animal could be made resistant to OP toxicity by genetic engineering. The human butyrylcholinesterase (BChE) mutant G117H was chosen for study because it has the unusual ability to hydrolyze OP as well as acetylcholine, and it is resistant to inhibition by OP. Human G117H BChE, under the control of the ROSA26 promoter, was expressed in all tissues of transgenic mice. A stable transgenic mouse line expressed 0.5 μg/ml of human G117H BChE in plasma as well as 2 μg/ml of wild-type mouse BChE. Intestine, kidneys, stomach, lungs, heart, spleen, liver, brain, and muscle expressed 0.6-0.15 μg/g of G117H BChE. Transgenic mice were normal in behavior and fertility. The LD50 dose of echothiophate for wild-type mice was 0.1 mg/kg sc. This dose caused severe cholinergic signs of toxicity and lethality in wild-type mice, but caused no deaths and only mild toxicity in transgenic animals. The mechanism of protection was investigated by measuring acetylcholinesterase (AChE) and BChE activity. It was found that AChE and endogenous BChE were inhibited to the same extent in echothiophate-treated wild type and transgenic mice. This led to the hypothesis that protection against echothiophate toxicity was not explained by hydrolysis of echothiophate. In conclusion, the transgenic G117H BChE mouse demonstrates the factors required to achieve protection from OP toxicity in a vertebrate animal

  4. Agentes bacterianos enteropatogênicos em suínos de diferentes faixas etárias e perfil de resistência a antimicrobianos de cepas de Escherichia coli e Salmonella spp Enteropathogenic bacterial agents in pigs of different age groups and profile of resistance in strains of Escherichia coli and Salmonella spp. to antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Álvaro Menin

    2008-09-01

    Full Text Available As enterites infecciosas bacterianas provocam severas perdas para a indústria suína em todo o mundo. Os objetivos deste trabalho foram determinar os agentes bacterianos, associados com a ocorrência de diarréia em suínos, em diferentes faixas etárias, no Estado de Santa Catarina, Brasil, e verificar o perfil de resistência das cepas de Escherichia coli e Salmonella spp, frente aos principais antimicrobianos utilizados em granjas de suínos. Os principais gêneros/espécies bacterianos diagnosticados foram Escherichia coli, Clostridium spp, Salmonella spp Brachyspira hyodysenteriae, Brachyspira pilosicoli e Lawsonia intracellularis. Os fatores de virulência de E. coli mais prevalentes na fase de maternidade foram F5 / (K99 20%, F6 / (987P 16,3%, F42 6,8% e F41 5,7%, já nas fases de creche e terminação, predominaram cepas com fimbrias F4 (K88 11,2% e 5,4%, respectivamente. Para E. coli os maiores índices de resistência foram encontrados para oxitetraciclina (94% e tetraciclina (89,5% e os menores índices de resistência para neomicina (55%, ceftiofur (57,4%. Quanto às amostras de Salmonella spp, estas apresentaram maior resistência à oxitetraciclina (77%, e à tetraciclina (42,1% e menor à gentamicina (3,5% e amoxicilina (4,8%.Infectious bacterial enteritis causes severe losses to the swine industry worldwide. The objective of this study was to determine the epidemiology of bacterial agents that are associated with the occurrence of diarrhea in pigs at different age groups, and to verify the profile of resistance of strains of Escherichia coli and Salmonella spp to the main antimicrobial agents. The main bacterial species diagnosed were Escherichia coli, Clostridium spp, Salmonella spp, Brachyspira hyodysenteriae, Brachyspira pilosicoli and Lawsonia intracellularis. The E. coli virulence factors of higher prevalence in preweaning piglets were F5 / (K99 20%, F6 / (987P 16.3%, F42 6.8% and F41 5.7%, whereas at the nursery and with

  5. Identification of Agents Active against Methicillin-Resistant Staphylococcus aureus USA300 from a Clinical Compound Library

    Directory of Open Access Journals (Sweden)

    Hongxia Niu

    2017-09-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA poses a significant threat for effective treatment of several difficult-to-treat infections in humans. To identify potential new treatment options for MRSA infections, we screened a clinical compound library consisting of 1524 compounds using a growth inhibition assay in 96-well plates. We identified 34 agents which are either bacteriostatic or bactericidal against log-phase clinical MRSA strain USA300. Among them, 9 candidates (thonzonium, cetylpyridinium, trilocarban, benzododecinium, bithionol, brilliant green, chlorquinaldol, methylbenzethonium and green violet are known antiseptics, 11 candidates are known antibiotics currently recommended for the treatment of MRSA. We identified 9 new drug candidates, 5 of which (thiostrepton, carbomycin, spiramycin, clofazimine and chloroxine are antibiotics used for treating other infections than S. aureus infections; 4 of which (quinaldine blue, closantel, dithiazanine iodide and pyrvinium pamoate are drugs used for treating parasitic diseases or cancer. We ranked these new drug candidates according to their MICs against the MRSA strain USA300. Our findings may have implications for more effective treatment of MRSA infections.

  6. Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro

    International Nuclear Information System (INIS)

    Ferreira, Paulo; Oliveira, Maria Jose; Beraldi, Eliana; Mateus, Ana Rita; Nakajima, Takashi; Gleave, Martin; Yokota, Jun; Carneiro, Fatima; Huntsman, David; Seruca, Raquel; Suriano, Gianpaolo

    2005-01-01

    Experimental evidence supports a role for E-cadherin in suppressing invasion, metastasis, and proliferation. Germline mutations of the E-cadherin represent the genetic cause of hereditary diffuse gastric cancer (HDGC). In this type of tumor, isolated cancer cells permeate the basal membrane and paradoxically survive in the gastric wall in the absence of contact with neighbor epithelial cells or with the extracellular matrix. This suggests that upon E-cadherin deregulation, cells acquired resistance to apoptosis. To test this hypothesis, CHO cells stably expressing either wild-type E-cadherin or the HDGC-related germline mutations T340A and V832M were seeded either on a thin layer of collagen type I or on plastic and then subjected to the apoptotic agent taxol. We found that in vitro functional E-cadherin renders cells more sensitive to the effect of taxol. Our results also indicate that this effect is associated to decreased level of the anti-apoptotic bcl-2 protein

  7. Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model

    Directory of Open Access Journals (Sweden)

    Sonja Stojković

    2016-06-01

    Full Text Available Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl-1-nitrosourea (BCNU and temozolomide (TMZ. Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.

  8. Optimal causal inference: estimating stored information and approximating causal architecture.

    Science.gov (United States)

    Still, Susanne; Crutchfield, James P; Ellison, Christopher J

    2010-09-01

    We introduce an approach to inferring the causal architecture of stochastic dynamical systems that extends rate-distortion theory to use causal shielding--a natural principle of learning. We study two distinct cases of causal inference: optimal causal filtering and optimal causal estimation. Filtering corresponds to the ideal case in which the probability distribution of measurement sequences is known, giving a principled method to approximate a system's causal structure at a desired level of representation. We show that in the limit in which a model-complexity constraint is relaxed, filtering finds the exact causal architecture of a stochastic dynamical system, known as the causal-state partition. From this, one can estimate the amount of historical information the process stores. More generally, causal filtering finds a graded model-complexity hierarchy of approximations to the causal architecture. Abrupt changes in the hierarchy, as a function of approximation, capture distinct scales of structural organization. For nonideal cases with finite data, we show how the correct number of the underlying causal states can be found by optimal causal estimation. A previously derived model-complexity control term allows us to correct for the effect of statistical fluctuations in probability estimates and thereby avoid overfitting.

  9. Quantitative trait loci for resistance to two fungal pathogens in Quercus robur

    Science.gov (United States)

    Cécile Robin; Amira Mougou-Hamdane; Jean-Marc Gion; Antoine Kremer; Marie-Laure. Desprez-Loustau

    2012-01-01

    Powdery mildew, caused by Erysiphe alphitoides (Ascomycete), is the most frequent disease of oaks, which are also known to be host plants for Phytophthora cinnamomi (Oomycete), the causal agent of ink disease. Components of genetic resistance to these two pathogens, infecting either leaves or root and collar, were...

  10. Enhanced Peroxide Resistance of In Vitro Mutagenized Fluorideresistant Klebsiella pneumoniae Ureases for Catalytic Buffering of Agent Decontamination Reactions

    National Research Council Canada - National Science Library

    Fry, Ilona J; DeFrank, Joseph J

    2004-01-01

    ...) and oxidative surety agent decontamination technologies. Ammonia production from urea by urease neutralizes the production of Oalkylphosphonic acids resulting from the hydrolysis of Nerve agents such as Sarin and VX...

  11. Zinc and copper in animal feed – development of resistance and co-resistance to antimicrobial agents in bacteria of animal origin

    Directory of Open Access Journals (Sweden)

    Siamak Yazdankhah

    2014-09-01

    Full Text Available Farmed animals such as pig and poultry receive additional Zn and Cu in their diets due to supplementing elements in compound feed as well as medical remedies. Enteral bacteria in farmed animals are shown to develop resistance to trace elements such as Zn and Cu. Resistance to Zn is often linked with resistance to methicillin in staphylococci, and Zn supplementation to animal feed may increase the proportion of multiresistant E. coli in the gut. Resistance to Cu in bacteria, in particular enterococci, is often associated with resistance to antimicrobial drugs like macrolides and glycopeptides (e.g. vancomycin. Such resistant bacteria may be transferred from the food-producing animals to humans (farmers, veterinarians, and consumers. Data on dose-response relation for Zn/Cu exposure and resistance are lacking; however, it seems more likely that a resistance-driven effect occurs at high trace element exposure than at more basal exposure levels. There is also lack of data which could demonstrate whether Zn/Cu-resistant bacteria may acquire antibiotic resistance genes/become antibiotics resistant, or if antibiotics-resistant bacteria are more capable to become Zn/Cu resistant than antibiotics-susceptible bacteria. Further research is needed to elucidate the link between Zn/Cu and antibiotic resistance in bacteria.

  12. Lipopolysaccharides of Rhizobium etli strain G12 act in potato roots as an inducing agent of systemic resistance to infection by the cyst nematode Globodera pallida.

    Science.gov (United States)

    Reitz, M; Rudolph, K; Schröder, I; Hoffmann-Hergarten, S; Hallmann, J; Sikora, R A

    2000-08-01

    Recent studies have shown that living and heat-killed cells of the rhizobacterium Rhizobium etli strain G12 induce in potato roots systemic resistance to infection by the potato cyst nematode Globodera pallida. To better understand the mechanisms of induced resistance, we focused on identifying the inducing agent. Since heat-stable bacterial surface carbohydrates such as exopolysaccharides (EPS) and lipopolysaccharides (LPS) are essential for recognition in the symbiotic interaction between Rhizobium and legumes, their role in the R. etli-potato interaction was studied. EPS and LPS were extracted from bacterial cultures, applied to potato roots, and tested for activity as an inducer of plant resistance to the plant-parasitic nematode. Whereas EPS did not affect G. pallida infection, LPS reduced nematode infection significantly in concentrations as low as 1 and 0.1 mg ml(-1). Split-root experiments, guaranteeing a spatial separation of inducing agent and challenging pathogen, showed that soil treatments of one half of the root system with LPS resulted in a highly significant (up to 37%) systemic induced reduction of G. pallida infection of potato roots in the other half. The results clearly showed that LPS of R. etli G12 act as the inducing agent of systemic resistance in potato roots.

  13. Operator ordering and causality

    OpenAIRE

    Plimak, L. I.; Stenholm, S. T.

    2011-01-01

    It is shown that causality violations [M. de Haan, Physica 132A, 375, 397 (1985)], emerging when the conventional definition of the time-normal operator ordering [P.L.Kelley and W.H.Kleiner, Phys.Rev. 136, A316 (1964)] is taken outside the rotating wave approximation, disappear when the amended definition [L.P. and S.S., Annals of Physics, 323, 1989 (2008)] of this ordering is used.

  14. Space, time and causality

    International Nuclear Information System (INIS)

    Lucas, J.R.

    1984-01-01

    Originating from lectures given to first year undergraduates reading physics and philosophy or mathematics and philosophy, formal logic is applied to issues and the elucidation of problems in space, time and causality. No special knowledge of relativity theory or quantum mechanics is needed. The text is interspersed with exercises and each chapter is preceded by a suggested 'preliminary reading' and followed by 'further reading' references. (U.K.)

  15. The phenotypic and genotypic characteristics of antibiotic resistance in Escherichia coli populations isolated from farm animals with different exposure to antimicrobial agents.

    Science.gov (United States)

    Mazurek, Justyna; Pusz, Paweł; Bok, Ewa; Stosik, Michał; Baldy-Chudzik, Katarzyna

    2013-01-01

    The aim of the study was to determine the influence of the presence or the absence of antibiotic input on the emergence and maintenance of resistance in commensal bacteria from food producing animals. The research material constituted E. coli isolates from two animal species: swine at different age from one conventional pig farm with antibiotic input in young pigs and from beef and dairy cattle originated from organic breeding farm. The sensitivity to 16 antimicrobial agents was tested, and the presence of 15 resistance genes was examined. In E. coli from swine, the most prevalent resistance was resistance to streptomycin (88.3%), co-trimoxazole (78.8%), tetracycline (57.3%) ampicillin (49.3%) and doxycycline (44.9%) with multiple resistance in the majority. The most commonly observed resistance genes were: bla(TEM) (45.2%), tetA (35.8%), aadA1 (35.0%), sul3 (29.5%), dfrA1 (20.4%). Differences in phenotypes and genotypes of E. coli between young swine undergoing prevention program and the older ones without the antibiotic pressure occurred. A disparate resistance was found in E. coli from cattle: cephalothin (36.9%), cefuroxime (18.9%), doxycycline (8.2%), nitrofurantoin (7.7%), and concerned mainly dairy cows. Among isolates from cattle, multidrug resistance was outnumbered by resistance to one or two antibiotics and the only found gene markers were: bla(SHV), (3.4%), tetA (1.29%), bla(TEM) (0.43%) and tetC (0.43%). The presented outcomes provide evidence that antimicrobial pressure contributes to resistance development, and enteric microflora constitutes an essential reservoir of resistance genes.

  16. Zinc and copper in animal feed - development of resistance and co-resistance to antimicrobial agents in bacteria of animal origin

    OpenAIRE

    Yazdankhah, Siamak; Rudi, Knut; Bernhoft, Aksel

    2014-01-01

    Farmed animals such as pig and poultry receive additional Zn and Cu in their diets due to supplementing elements in compound feed as well as medical remedies. Enteral bacteria in farmed animals are shown to develop resistance to trace elements such as Zn and Cu. Resistance to Zn is often linked with resistance to methicillin in staphylococci, and Zn supplementation to animal feed may increase the proportion of multiresistant E. coli in the gut. Resistance to Cu in bacteria, in particular ente...

  17. Antibiotic-loaded, silver core-embedded mesoporous silica nanovehicles as a synergistic antibacterial agent for the treatment of drug-resistant infections.

    Science.gov (United States)

    Wang, Yao; Ding, Xiali; Chen, Yuan; Guo, Mingquan; Zhang, Yan; Guo, Xiaokui; Gu, Hongchen

    2016-09-01

    Drug-resistant bacterial infections have become one of the most serious risks in public health as they make the conventional antibiotics less efficient. There is an urgent need for developing new generations of antibacterial agents in this field. In this work, a nanoplatform of LEVO-loaded and silver core-embedded mesoporous silica nanovehicles (Ag@MSNs@LEVO) is demonstrated as a synergistic antibacterial agent for the treatment of drug-resistant infections both in vitro and in vivo. The combination of the inner Ag core and the loaded antibiotic drug in mesopores endows the single-particle nanoplatform with a synergistic effect on killing the drug-resistant bacteria. The nanoplatform of Ag@MSNs@LEVO exhibits superior antibacterial activity to LEVO-loaded MSNs (MSNs@LEVO) and silver core-embedded MSNs (Ag@MSNs) in vitro. In the in vivo acute peritonitis model, the infected drug-resistant Escherichia coli GN102 in peritoneal cavity of the mice is reduced by nearly three orders of magnitude and the aberrant pathological feature of spleen and peritoneum disappears after treatment with Ag@MSNs@LEVO. Importantly, this nanopaltform renders no obvious toxic side effect to the mice during the tested time. There is no doubt that this study strongly indicates a promising potential of Ag@MSNs@LEVO as a synergistic and safety therapy tool for the clinical drug-resistant infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Presença de genes de resistência a agentes antimicrobianos em saliva, biofilme supragengival e canais radiculares infectados

    OpenAIRE

    Ludmila Coutinho Moraes

    2013-01-01

    Embora diferentes estudos indiquem que há um aumento da resistência dos microrganismos aos agentes antimicrobianos prescritos, pouco se sabe a respeito da sua distribuição na cavidade oral. A presente dissertação está dividida em dois capítulos, representados por dois diferentes manuscritos. No manuscrito I, uma revisão sistemática foi realizada e teve como objetivo determinar quais genes de resistência a antimicrobianos foram pesquisados em saliva (S), no biofilme supragengival (SB) e canal ...

  19. Pseudomonas aeruginosa cells adapted to benzalkonium chloride show resistance to other membrane-active agents but not to clinically relevant antibiotics.

    Science.gov (United States)

    Loughlin, M F; Jones, M V; Lambert, P A

    2002-04-01

    Our objective was to determine whether strains of Pseudomonas aeruginosa can adapt to growth in increasing concentrations of the disinfectant benzalkonium chloride (BKC), and whether co-resistance to clinically relevant antimicrobial agents occurs. Attempts were made to determine what phenotypic alterations accompanied resistance and whether these explained the mechanism of resistance. Strains were serially passaged in increasing concentrations of BKC in static nutrient broth cultures. Serotyping and genotyping were used to determine purity of the cultures. Two strains were examined for cross-resistance to other disinfectants and antibiotics by broth dilution MIC determination. Alterations in outer membrane proteins and lipopolysaccharide (LPS) expressed were examined by SDS-PAGE. Cell surface hydrophobicity and charge, uptake of disinfectant and proportion of specific fatty acid content of outer and cytoplasmic membranes were determined. Two P. aeruginosa strains showed a stable increase in resistance to BKC. Co-resistance to other quaternary ammonium compounds was observed in both strains; chloramphenicol and polymyxin B resistance were observed in one and a reduction in resistance to tobramycin observed in the other. However, no increased resistance to other biocides (chlorhexidine, triclosan, thymol) or antibiotics (ceftazidime, imipenem, ciprofloxacin, tobramycin) was detected. Characteristics accompanying resistance included alterations in outer membrane proteins, uptake of BKC, cell surface charge and hydrophobicity, and fatty acid content of the cytoplasmic membrane, although no evidence was found for alterations in LPS. Each of the two strains had different alterations in phenotype, indicating that such adaptation is unique to each strain of P. aeruginosa and does not result from a single mechanism shared by the whole species.

  20. [Alkylating agents].

    Science.gov (United States)

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  1. Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics.

    Science.gov (United States)

    Kuo, David; Yu, Guanping; Hoch, Wyatt; Gabay, Dean; Long, Lisa; Ghannoum, Mahmoud; Nagy, Nancy; Harding, Clifford V; Viswanathan, Rajesh; Shoham, Menachem

    2015-03-01

    The dwindling repertoire of antibiotics to treat methicillin-resistant Staphylococcus aureus (MRSA) calls for novel treatment options. Quorum-quenching agents offer an alternative or an adjuvant to antibiotic therapy. Three biaryl hydroxyketone compounds discovered previously (F1, F12, and F19; G. Yu, D. Kuo, M. Shoham, and R. Viswanathan, ACS Comb Sci 16:85-91, 2014) were tested for efficacy in MRSA-infected animal models. Topical therapy of compounds F1 and F12 in a MRSA murine wound infection model promotes wound healing compared to the untreated control. Compounds F1, F12, and F19 afford significant survival benefits in a MRSA insect larva model. Combination therapy of these quorum-quenching agents with cephalothin or nafcillin, antibiotics to which MRSA is resistant in monotherapy, revealed additional survival benefits. The quorum-quenching agents sensitize MRSA to the antibiotic by a synergistic mode of action that also is observed in vitro. An adjuvant of 1 μg/ml F1, F12, or F19 reduces the MIC of nafcillin and cephalothin about 50-fold to values comparable to those for vancomycin, the antibiotic often prescribed for MRSA infections. These findings suggest that it is possible to resurrect obsolete antibiotic therapies in combination with these novel quorum-quenching agents. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Frequency of resistance to methicillin and other antimicrobial agents among Staphylococcus aureus strains isolated from pigs and their human handlers in Trinidad

    Directory of Open Access Journals (Sweden)

    Annika Gordon

    2014-04-01

    Full Text Available Background: Methicillin-resistant Staphylococcus aureus (MRSA has emerged recently worldwide in production animals, particularly pigs and veal calves, which act as reservoirs for MRSA strains for human infection. The study determined the prevalence of MRSA and other resistant strains of S. aureus isolated from the anterior nares of pigs and human handlers on pig farms in Trinidad. Methods: Isolation of S. aureus was done by concurrently inoculating Baird-Parker agar (BPA and Chromagar MRSA (CHROM with swab samples and isolates were identified using standard methods. Suspect MRSA isolates from Chromagar and BPA were subjected to confirmatory test using Oxoid PBP2 latex agglutination test. The disc diffusion method was used to determine resistance to antimicrobial agents. Results: The frequency of isolation of MRSA was 2.1% (15 of 723 for pigs but 0.0% (0 of 72 for humans. Generally, for isolates of S. aureus from humans there was a high frequency of resistance compared with those from pigs, which had moderate resistance to the following antimicrobials: penicillin G (54.5%, 51.5%, ampicillin (59.1%, 49.5%, and streptomycin (59.1%, 37.1%, respectively. There was moderate resistance to tetracycline (36.4%, 41.2% and gentamycin (27.2%, 23.7% for human and pig S. aureus isolates, respectively, and low resistance to sulfamethoxazole-trimethoprim (4.5%, 6.2% and norfloxacin (9.1%, 12.4%, respectively. The frequency of resistance to oxacillin by the disc method was 36.4 and 34.0% from S. aureus isolates from humans and pigs, respectively. Out of a total of 78 isolates of S. aureus from both human and pig sources that were resistant to oxacillin by the disc diffusion method, only 15 (19.2% were confirmed as MRSA by the PBP'2 latex test kit. Conclusions: The detection of MRSA strains in pigs, albeit at a low frequency, coupled with a high frequency of resistance to commonly used antimicrobial agents in pig and humans could have zoonotic and therapeutic

  3. Evaluation of host resistance to Botrytis bunch rot in Vitis spp. and its correlation with Botrytis leaf spot

    Science.gov (United States)

    Botrytis cinerea, the causal agent of Botrytis bunch rot and gray mold, is the number one postharvest disease of fresh grapes in the United States. Fungicide applications are used to manage the disease, but fungicide-resistant isolates are common and postharvest losses occur annually. Host resistanc...

  4. Causal events enter awareness faster than non-causal events

    Directory of Open Access Journals (Sweden)

    Pieter Moors

    2017-01-01

    Full Text Available Philosophers have long argued that causality cannot be directly observed but requires a conscious inference (Hume, 1967. Albert Michotte however developed numerous visual phenomena in which people seemed to perceive causality akin to primary visual properties like colour or motion (Michotte, 1946. Michotte claimed that the perception of causality did not require a conscious, deliberate inference but, working over 70 years ago, he did not have access to the experimental methods to test this claim. Here we employ Continuous Flash Suppression (CFS—an interocular suppression technique to render stimuli invisible (Tsuchiya & Koch, 2005—to test whether causal events enter awareness faster than non-causal events. We presented observers with ‘causal’ and ‘non-causal’ events, and found consistent evidence that participants become aware of causal events more rapidly than non-causal events. Our results suggest that, whilst causality must be inferred from sensory evidence, this inference might be computed at low levels of perceptual processing, and does not depend on a deliberative conscious evaluation of the stimulus. This work therefore supports Michotte’s contention that, like colour or motion, causality is an immediate property of our perception of the world.

  5. PLASMA SPRAYED Al₂O₃-13 WT.%TiO₂ COATING SEALED WITH ORGANIC-INORGANIC HYBRID AGENT AND ITS CORROSION RESISTANCE IN ACID ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Zehua Zhou

    2016-07-01

    Full Text Available A novel organic-inorganic hybrid material of γ-methacryloxypropyltrime-thoxysilane (KH570 -SiO₂ was fabricated by Sol-Gel method. The hybrid material was used as the sealing agent for the plasma sprayed Al₂O₃-13 wt.% TiO₂ coating. Infrared spectrum and grafted mechanism of the hybrid agent (HA were studied. Moreover, morphology and porosity, as well as characteristics of immersion plus electrochemical corrosion in acid environment of the coating with and without sealing treatment were evaluated, compared with those of the coating sealed with the conventional silicone resin agent (SRA. The results reveal that KH570 was successfully grafted onto the surface of SiO₂. The HA film sealed on the surface of the coating presents a little better quality than the SRA film. The porosities of the coatings after the sealing treatment decreased. Furthermore, the sealing treatment can improve efficiently the corrosion resistance of the coating in 5 vol.% HCl solution. The hybrid sealing agent can become a candidate for the plasma sprayed Al₂O₃-13 wt.% TiO₂ coating used in acid environment to overcome some disadvantages of organic agents such as severely environmental pollution.

  6. Causal inference based on counterfactuals

    Directory of Open Access Journals (Sweden)

    Höfler M

    2005-09-01

    Full Text Available Abstract Background The counterfactual or potential outcome model has become increasingly standard for causal inference in epidemiological and medical studies. Discussion This paper provides an overview on the counterfactual and related approaches. A variety of conceptual as well as practical issues when estimating causal effects are reviewed. These include causal interactions, imperfect experiments, adjustment for confounding, time-varying exposures, competing risks and the probability of causation. It is argued that the counterfactual model of causal effects captures the main aspects of causality in health sciences and relates to many statistical procedures. Summary Counterfactuals are the basis of causal inference in medicine and epidemiology. Nevertheless, the estimation of counterfactual differences pose several difficulties, primarily in observational studies. These problems, however, reflect fundamental barriers only when learning from observations, and this does not invalidate the counterfactual concept.

  7. Causal inference in public health.

    Science.gov (United States)

    Glass, Thomas A; Goodman, Steven N; Hernán, Miguel A; Samet, Jonathan M

    2013-01-01

    Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action's consequences rather than the less precise notion of a risk factor's causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world.

  8. Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

    Science.gov (United States)

    Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

    2017-05-01

    AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Causal Diagrams for Empirical Research

    OpenAIRE

    Pearl, Judea

    1994-01-01

    The primary aim of this paper is to show how graphical models can be used as a mathematical language for integrating statistical and subject-matter information. In particular, the paper develops a principled, nonparametric framework for causal inference, in which diagrams are queried to determine if the assumptions available are sufficient for identifiying causal effects from non-experimental data. If so the diagrams can be queried to produce mathematical expressions for causal effects in ter...

  10. Causality Statistical Perspectives and Applications

    CERN Document Server

    Berzuini, Carlo; Bernardinell, Luisa

    2012-01-01

    A state of the art volume on statistical causality Causality: Statistical Perspectives and Applications presents a wide-ranging collection of seminal contributions by renowned experts in the field, providing a thorough treatment of all aspects of statistical causality. It covers the various formalisms in current use, methods for applying them to specific problems, and the special requirements of a range of examples from medicine, biology and economics to political science. This book:Provides a clear account and comparison of formal languages, concepts and models for statistical causality. Addr

  11. Causal electromagnetic interaction equations

    International Nuclear Information System (INIS)

    Zinoviev, Yury M.

    2011-01-01

    For the electromagnetic interaction of two particles the relativistic causal quantum mechanics equations are proposed. These equations are solved for the case when the second particle moves freely. The initial wave functions are supposed to be smooth and rapidly decreasing at the infinity. This condition is important for the convergence of the integrals similar to the integrals of quantum electrodynamics. We also consider the singular initial wave functions in the particular case when the second particle mass is equal to zero. The discrete energy spectrum of the first particle wave function is defined by the initial wave function of the free-moving second particle. Choosing the initial wave functions of the free-moving second particle it is possible to obtain a practically arbitrary discrete energy spectrum.

  12. Structural Equations and Causal Explanations: Some Challenges for Causal SEM

    Science.gov (United States)

    Markus, Keith A.

    2010-01-01

    One common application of structural equation modeling (SEM) involves expressing and empirically investigating causal explanations. Nonetheless, several aspects of causal explanation that have an impact on behavioral science methodology remain poorly understood. It remains unclear whether applications of SEM should attempt to provide complete…

  13. Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.

    Science.gov (United States)

    Suprasert, Prapaporn; Manopunya, Manatsawee; Cheewakriangkrai, Chalong

    2014-01-01

    Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

  14. Expert Causal Reasoning and Explanation.

    Science.gov (United States)

    Kuipers, Benjamin

    The relationship between cognitive psychologists and researchers in artificial intelligence carries substantial benefits for both. An ongoing investigation in causal reasoning in medical problem solving systems illustrates this interaction. This paper traces a dialectic of sorts in which three different types of causal resaoning for medical…

  15. Re-thinking local causality

    NARCIS (Netherlands)

    Friederich, Simon

    There is widespread belief in a tension between quantum theory and special relativity, motivated by the idea that quantum theory violates J. S. Bell's criterion of local causality, which is meant to implement the causal structure of relativistic space-time. This paper argues that if one takes the

  16. Covariation in Natural Causal Induction.

    Science.gov (United States)

    Cheng, Patricia W.; Novick, Laura R.

    1991-01-01

    Biases and models usually offered by cognitive and social psychology and by philosophy to explain causal induction are evaluated with respect to focal sets (contextually determined sets of events over which covariation is computed). A probabilistic contrast model is proposed as underlying covariation computation in natural causal induction. (SLD)

  17. Mounting resistance of uropathogens to antimicrobial agents: A retrospective study in patients with chronic bacterial prostatitis relapse.

    Science.gov (United States)

    Stamatiou, Konstantinos; Pierris, Nikolaos

    2017-07-01

    Despite recent progress in the management of chronic bacterial prostatitis (CBP), many cases relapse. Increased drug resistance patterns of responsible bacteria have been proposed as the most probable causative factor. Driven by the limited number of previous studies addressing this topic, we aimed to study whether antibiotic resistance increases in patients with CBP when relapse occurs. A secondary aim of this study was to determine the resistance patterns of responsible bacteria from patients with CBP. The study material consisted of bacterial isolates from urine and/or prostatic secretions obtained from patients with CBP. Bacterial identification was performed by using the Vitek 2 Compact system and susceptibility testing was performed by disc diffusion and/or the Vitek 2 system. Interpretation of susceptibility results was based on Clinical and Laboratory Standards Institute guidelines. A total of 253 samples from patients diagnosed with CBP for the first time (group A) and 137 samples from relapsing patients with a history of CBP and previous antibiotic treatment (group B) were analyzed. A significant reduction in bacterial resistance to the less used antibiotics (TMP-SMX, tetracyclines, aminoglycosides, penicillins, and macrolides) was noted. An increase in resistance to quinolones of many bacteria that cause CBP was also noted with the increase in resistance of enterococcus strains being alarming. Comparison of the resistance profile of CBP-responsible bacteria between samples from first-time-diagnosed patients and samples from relapsing patients revealed notable differences that could be attributed to previous antibiotic treatment.

  18. O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.

    Science.gov (United States)

    Raj, Nitya; Klimstra, David S; Horvat, Natally; Zhang, Liying; Chou, Joanne F; Capanu, Marinela; Basturk, Olca; Do, Richard Kinh Gian; Allen, Peter J; Reidy-Lagunes, Diane

    2017-07-01

    Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

  19. Managing Phytophthora crown and root rot on tomato by pre-plant treatments with biocontrol agents, resistance inducers, organic and mineral fertilizers under nursery conditions

    Directory of Open Access Journals (Sweden)

    Giovanna GILARDI

    2014-09-01

    Full Text Available Five trials were carried out under greenhouse conditions to test the efficacy of spray programmes based on biocontrol agents, phosphite-based fertilizers and a chemical inducer of resistance (acibenzolar-S-methyl, phosethyl-Al to control crown and root rot of tomato incited by Phytophthora nicotianae. The best disease control, under high disease pressure resulting from artificial inoculation, was obtained with three pre-plant leaf sprays at 7 d intervals with acibenzolar-S-methyl and with two mineral phosphite-based fertilizers. The disease reduction achieved was similar to that obtained with a single application of azoxystrobin and metalaxyl-M. Phosetyl-Al and the biocontrol agents Glomus spp. + Bacillus megaterium + Trichoderma, B. subtilis QST713, B. velezensis IT45 and the mixture T. asperellum ICC012 + T. gamsii ICC080 provided a partial disease control. Brassica carinata pellets did not control the disease.

  20. Paradoxical Behavior of Granger Causality

    Science.gov (United States)

    Witt, Annette; Battaglia, Demian; Gail, Alexander

    2013-03-01

    Granger causality is a standard tool for the description of directed interaction of network components and is popular in many scientific fields including econometrics, neuroscience and climate science. For time series that can be modeled as bivariate auto-regressive processes we analytically derive an expression for spectrally decomposed Granger Causality (SDGC) and show that this quantity depends only on two out of four groups of model parameters. Then we present examples of such processes whose SDGC expose paradoxical behavior in the sense that causality is high for frequency ranges with low spectral power. For avoiding misinterpretations of Granger causality analysis we propose to complement it by partial spectral analysis. Our findings are illustrated by an example from brain electrophysiology. Finally, we draw implications for the conventional definition of Granger causality. Bernstein Center for Computational Neuroscience Goettingen

  1. On causality of extreme events

    Directory of Open Access Journals (Sweden)

    Massimiliano Zanin

    2016-06-01

    Full Text Available Multiple metrics have been developed to detect causality relations between data describing the elements constituting complex systems, all of them considering their evolution through time. Here we propose a metric able to detect causality within static data sets, by analysing how extreme events in one element correspond to the appearance of extreme events in a second one. The metric is able to detect non-linear causalities; to analyse both cross-sectional and longitudinal data sets; and to discriminate between real causalities and correlations caused by confounding factors. We validate the metric through synthetic data, dynamical and chaotic systems, and data representing the human brain activity in a cognitive task. We further show how the proposed metric is able to outperform classical causality metrics, provided non-linear relationships are present and large enough data sets are available.

  2. Neural Correlates of Causal Power Judgments

    Directory of Open Access Journals (Sweden)

    Denise Dellarosa Cummins

    2014-12-01

    Full Text Available Causal inference is a fundamental component of cognition and perception. Probabilistic theories of causal judgment (most notably causal Bayes networks derive causal judgments using metrics that integrate contingency information. But human estimates typically diverge from these normative predictions. This is because human causal power judgments are typically strongly influenced by beliefs concerning underlying causal mechanisms, and because of the way knowledge is retrieved from human memory during the judgment process. Neuroimaging studies indicate that the brain distinguishes causal events from mere covariation, and between perceived and inferred causality. Areas involved in error prediction are also activated, implying automatic activation of possible exception cases during causal decision-making.

  3. Enhanced Peroxide Resistance of In Vitro Mutagenized Fluorideresistant Klebsiella pneumoniae Ureases for Catalytic Buffering of Agent Decontamination Reactions

    National Research Council Canada - National Science Library

    Fry, Ilona J; DeFrank, Joseph J

    2004-01-01

    .... Fluoride-resistant (FR) ureases developed previously in our laboratory were >95% inhibited by 1% hydrogen peroxide. To overcome this problem, the FR mutant urease structural genes of Klebsiella pneumoniae were mutagenized in vitro in an E...

  4. Clear message for causality

    Energy Technology Data Exchange (ETDEWEB)

    Steinberg, Aephraim M. [Institute for Experimental Physics, University of Vienna, Vienna (Austria)

    2003-12-01

    Experiment confirms that information cannot be transmitted faster than the speed of light. Ever since Einstein stated that nothing can travel faster than light, physicists have delighted in finding exceptions. One after another, observations of such 'superluminal' propagation have been made. However, while some image or pattern- such as the motion of a spotlight projected on a distant wall - might have appeared to travel faster than light, it seemed that there was no way to use the superluminal effect to transmit energy or information. In recent years, the superluminal propagation of light pulses through certain media has led to renewed controversy. In 1995, for example, Guenther Nimtz of the University of Cologne encoded Mozart's 40th Symphony on a microwave beam, which he claimed to have transmitted at a speed faster than light. Others maintain that such a violation of Einstein's speed limit would wreak havoc on our most fundamental ideas about causality, allowing an effect to precede its cause. Relativity teaches us that sending a signal faster than light would be equivalent to sending it backwards in time. (U.K.)

  5. Causal Rasch models

    Directory of Open Access Journals (Sweden)

    A. Jackson Stenner

    2013-08-01

    Full Text Available Rasch’s unidimensional models for measurement show how to connect object measures (e.g., reader abilities, measurement mechanisms (e.g., machine-generated cloze reading items, and observational outcomes (e.g., counts correct on reading instruments. Substantive theory shows what interventions or manipulations to the measurement mechanism can be traded off against a change to the object measure to hold the observed outcome constant. A Rasch model integrated with a substantive theory dictates the form and substance of permissible interventions. Rasch analysis, absent construct theory and an associated specification equation, is a black box in which understanding may be more illusory than not. Finally, the quantitative hypothesis can be tested by comparing theory-based trade-off relations with observed trade-off relations. Only quantitative variables (as measured support such trade-offs. Note that to test the quantitative hypothesis requires more than manipulation of the algebraic equivalencies in the Rasch model or descriptively fitting data to the model. A causal Rasch model involves experimental intervention/manipulation on either reader ability or text complexity or a conjoint intervention on both simultaneously to yield a successful prediction of the resultant observed outcome (count correct. We conjecture that when this type of manipulation is introduced for individual reader text encounters and model predictions are consistent with observations, the quantitative hypothesis is sustained.

  6. Causal Rasch models.

    Science.gov (United States)

    Stenner, A Jackson; Fisher, William P; Stone, Mark H; Burdick, Donald S

    2013-01-01

    Rasch's unidimensional models for measurement show how to connect object measures (e.g., reader abilities), measurement mechanisms (e.g., machine-generated cloze reading items), and observational outcomes (e.g., counts correct on reading instruments). Substantive theory shows what interventions or manipulations to the measurement mechanism can be traded off against a change to the object measure to hold the observed outcome constant. A Rasch model integrated with a substantive theory dictates the form and substance of permissible interventions. Rasch analysis, absent construct theory and an associated specification equation, is a black box in which understanding may be more illusory than not. Finally, the quantitative hypothesis can be tested by comparing theory-based trade-off relations with observed trade-off relations. Only quantitative variables (as measured) support such trade-offs. Note that to test the quantitative hypothesis requires more than manipulation of the algebraic equivalencies in the Rasch model or descriptively fitting data to the model. A causal Rasch model involves experimental intervention/manipulation on either reader ability or text complexity or a conjoint intervention on both simultaneously to yield a successful prediction of the resultant observed outcome (count correct). We conjecture that when this type of manipulation is introduced for individual reader text encounters and model predictions are consistent with observations, the quantitative hypothesis is sustained.

  7. Causal Rasch models

    Science.gov (United States)

    Stenner, A. Jackson; Fisher, William P.; Stone, Mark H.; Burdick, Donald S.

    2013-01-01

    Rasch's unidimensional models for measurement show how to connect object measures (e.g., reader abilities), measurement mechanisms (e.g., machine-generated cloze reading items), and observational outcomes (e.g., counts correct on reading instruments). Substantive theory shows what interventions or manipulations to the measurement mechanism can be traded off against a change to the object measure to hold the observed outcome constant. A Rasch model integrated with a substantive theory dictates the form and substance of permissible interventions. Rasch analysis, absent construct theory and an associated specification equation, is a black box in which understanding may be more illusory than not. Finally, the quantitative hypothesis can be tested by comparing theory-based trade-off relations with observed trade-off relations. Only quantitative variables (as measured) support such trade-offs. Note that to test the quantitative hypothesis requires more than manipulation of the algebraic equivalencies in the Rasch model or descriptively fitting data to the model. A causal Rasch model involves experimental intervention/manipulation on either reader ability or text complexity or a conjoint intervention on both simultaneously to yield a successful prediction of the resultant observed outcome (count correct). We conjecture that when this type of manipulation is introduced for individual reader text encounters and model predictions are consistent with observations, the quantitative hypothesis is sustained. PMID:23986726

  8. Causal aspects of diffraction

    International Nuclear Information System (INIS)

    Crawford, G.N.

    1981-01-01

    The analysis is directed at a causal description of photon diffraction, which is explained in terms of a wave exerting real forces and providing actual guidance to each quantum of energy. An undulatory PSI wave is associated with each photon, and this wave is assumed to imply more than an informative probability function, so that it actually carries real energy, in much the same way as does an electro-magnetic wave. Whether or not it may be in some way related to the electromagnetic wave is left as a matter of on-going concern. A novel application of the concept of a minimum energy configuration is utilized; that is, a system of energy quanta seeks out relative positions and orientations of least mutual energy, much as an electron seeks its Bohr radius as a position of least mutual energy. Thus the concept implies more a guiding interaction of the PSI waves than an interfering cancellation of these waves. Similar concepts have been suggested by L. de Broglie and D. Bohm

  9. ["Karoshi" and causal relationships].

    Science.gov (United States)

    Hamajima, N

    1992-08-01

    This paper aims to introduce a measure for use by physicians for stating the degree of probable causal relationship for "Karoshi", ie, a sudden death from cerebrovascular diseases or ischemic heart diseases under occupational stresses, as well as to give a brief description for legal procedures associated with worker's compensation and civil trial in Japan. It is a well-used measure in epidemiology, "attributable risk percent (AR%)", which can be applied to describe the extent of contribution to "Karoshi" of the excess occupational burdens the deceased worker was forced to bear. Although several standards such as average occupational burdens for the worker, average occupational burdens for an ordinary worker, burdens in a nonoccupational life, and a complete rest, might be considered for the AR% estimation, the average occupational burdens for an ordinary worker should normally be utilized as a standard for worker's compensation. The adoption of AR% could be helpful for courts to make a consistent judgement whether "Karoshi" cases are compensatable or not.

  10. Structure and Strength in Causal Induction

    Science.gov (United States)

    Griffiths, Thomas L.; Tenenbaum, Joshua B.

    2005-01-01

    We present a framework for the rational analysis of elemental causal induction--learning about the existence of a relationship between a single cause and effect--based upon causal graphical models. This framework makes precise the distinction between causal structure and causal strength: the difference between asking whether a causal relationship…

  11. P3-10: Crossmodal Perceptual Grouping Modulates Subjective Causality between Action and Outcome

    Directory of Open Access Journals (Sweden)

    Takahiro Kawabe

    2012-10-01

    Full Text Available Agents have to determine which external events their action has causally produced. A sensation of causal relation between action and outcome is called subjective causality. Subjective causality has been linked to the comparator model. This model assumes that the brain compares an internal prediction for action outcome with an actual sensory outcome, distinguishing between self and externally produced outcomes depending on spatiotemporal congruency. However, recent studies have expressed some doubt about the idea that subjective causality arises depending solely on the spatiotemporal congruency, suggesting instead that other perceptual/cognitive factors play a critical role in determining subjective causality. We hypothesized that crossmodal grouping between action and outcome contributed to subjective causality. Crossmodal temporal grouping is an essential factor for crossmodal simultaneity judgments with ungrouped crossmodal signals likely to be judged as non-simultaneous. We predicted that subjective causality would decrease when an agent's action was not temporally grouped with action outcome. In the experiment, observers were asked to press a key in order to trigger a display change with some temporal delay. To disrupt temporal grouping between action and outcome, a task-irrelevant visual flash or tone was sometimes presented synchronously with the button press and/or the display change. Subjective causality was decreased when the flash or the tone was coincided with the button press. This demonstrates that perceptual grouping has a key role in determination of subjective causality, a result that is not accounted for by the standard comparator model.

  12. Impact of medicated feed along with clay mineral supplementation on Escherichia coli resistance to antimicrobial agents in pigs after weaning in field conditions.

    Science.gov (United States)

    Jahanbakhsh, Seyedehameneh; Kabore, Kiswendsida Paul; Fravalo, Philippe; Letellier, Ann; Fairbrother, John Morris

    2015-10-01

    The aim of this study was to examine changes in antimicrobial resistance (AMR) phenotype and virulence and AMR gene profiles in Escherichia coli from pigs receiving in-feed antimicrobial medication following weaning and the effect of feed supplementation with a clay mineral, clinoptilolite, on this dynamic. Eighty E. coli strains isolated from fecal samples of pigs receiving a diet containing chlortetracycline and penicillin, with or without 2% clinoptilolite, were examined for antimicrobial resistance to 15 antimicrobial agents. Overall, an increased resistance to 10 antimicrobials was observed with time. Supplementation with clinoptilolite was associated with an early increase but later decrease in blaCMY-2, in isolates, as shown by DNA probe. Concurrently, a later increase in the frequency of blaCMY-2 and the virulence genes iucD and tsh was observed in the control pig isolates, being significantly greater than in the supplemented pigs at day 28. Our results suggest that, in the long term, supplementation with clinoptilolite could decrease the prevalence of E. coli carrying certain antimicrobial resistance and virulence genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Both the Jasmonic Acid and the Salicylic Acid Pathways Contribute to Resistance to the Biotrophic Clubroot Agent Plasmodiophora brassicae in Arabidopsis.

    Science.gov (United States)

    Lemarié, Séverine; Robert-Seilaniantz, Alexandre; Lariagon, Christine; Lemoine, Jocelyne; Marnet, Nathalie; Jubault, Mélanie; Manzanares-Dauleux, Maria J; Gravot, Antoine

    2015-11-01

    The role of salicylic acid (SA) and jasmonic acid (JA) signaling in resistance to root pathogens has been poorly documented. We assessed the contribution of SA and JA to basal and partial resistance of Arabidopsis to the biotrophic clubroot agent Plasmodiophora brassicae. SA and JA levels as well as the expression of the SA-responsive genes PR2 and PR5 and the JA-responsive genes ARGAH2 and THI2.1 were monitored in infected roots of the accessions Col-0 (susceptible) and Bur-0 (partially resistant). SA signaling was activated in Bur-0 but not in Col-0. The JA pathway was weakly activated in Bur-0 but was strongly induced in Col-0. The contribution of both pathways to clubroot resistance was then assessed using exogenous phytohormone application and mutants affected in SA or JA signaling. Exogenous SA treatment decreased clubroot symptoms in the two Arabidopsis accessions, whereas JA treatment reduced clubroot symptoms only in Col-0. The cpr5-2 mutant, in which SA responses are constitutively induced, was more resistant to clubroot than the corresponding wild type, and the JA signaling-deficient mutant jar1 was more susceptible. Finally, we showed that the JA-mediated induction of NATA1 drove N(δ)-acetylornithine biosynthesis in infected Col-0 roots. The 35S::NATA1 and nata1 lines displayed reduced or enhanced clubroot symptoms, respectively, thus suggesting that in Col-0 this pathway was involved in the JA-mediated basal clubroot resistance. Overall, our data support the idea that, depending on the Arabidopsis accession, both SA and JA signaling can play a role in partial inhibition of clubroot development in compatible interactions with P. brassicae. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Mounting resistance of uropathogens to antimicrobial agents: A retrospective study in patients with chronic bacterial prostatitis relapse

    Directory of Open Access Journals (Sweden)

    Konstantinos Stamatiou

    2017-07-01

    Full Text Available Purpose: Despite recent progress in the management of chronic bacterial prostatitis (CBP, many cases relapse. Increased drug resistance patterns of responsible bacteria have been proposed as the most probable causative factor. Driven by the limited number of previous studies addressing this topic, we aimed to study whether antibiotic resistance increases in patients with CBP when relapse occurs. A secondary aim of this study was to determine the resistance patterns of responsible bacteria from patients with CBP. Materials and Methods: The study material consisted of bacterial isolates from urine and/or prostatic secretions obtained from patients with CBP. Bacterial identification was performed by using the Vitek 2 Compact system and susceptibility testing was performed by disc diffusion and/or the Vitek 2 system. Interpretation of susceptibility results was based on Clinical and Laboratory Standards Institute guidelines. Results: A total of 253 samples from patients diagnosed with CBP for the first time (group A and 137 samples from relapsing patients with a history of CBP and previous antibiotic treatment (group B were analyzed. A significant reduction in bacterial resistance to the less used antibiotics (TMP-SMX, tetracyclines, aminoglycosides, penicillins, and macrolides was noted. An increase in resistance to quinolones of many bacteria that cause CBP was also noted with the increase in resistance of enterococcus strains being alarming. Conclusions: Comparison of the resistance profile of CBP-responsible bacteria between samples from first-time-diagnosed patients and samples from relapsing patients revealed notable differences that could be attributed to previous antibiotic treatment.

  15. Effect of luting agent on the load to failure and accelerated-fatigue resistance of lithium disilicate laminate veneers

    NARCIS (Netherlands)

    Gresnigt, Marco M. M.; Ozcan, Mutlu; Carualho, Marco; Lazari, Priscilla; Cune, Marco S.; Razavi, Peywand; Magne, Pascal

    2017-01-01

    Objective. The aim of this study was to investigate the influence of the luting agent on the application of laminate veneers (LVs) in an accelerated fatigue and load-to-failure test after thermo-cyclic aging. Methods. Sound maxillary central incisors (N = 40) were randomly divided into four groups

  16. Dynamics of Quantum Causal Structures

    Science.gov (United States)

    Castro-Ruiz, Esteban; Giacomini, Flaminia; Brukner, Časlav

    2018-01-01

    It was recently suggested that causal structures are both dynamical, because of general relativity, and indefinite, because of quantum theory. The process matrix formalism furnishes a framework for quantum mechanics on indefinite causal structures, where the order between operations of local laboratories is not definite (e.g., one cannot say whether operation in laboratory A occurs before or after operation in laboratory B ). Here, we develop a framework for "dynamics of causal structures," i.e., for transformations of process matrices into process matrices. We show that, under continuous and reversible transformations, the causal order between operations is always preserved. However, the causal order between a subset of operations can be changed under continuous yet nonreversible transformations. An explicit example is that of the quantum switch, where a party in the past affects the causal order of operations of future parties, leading to a transition from a channel from A to B , via superposition of causal orders, to a channel from B to A . We generalize our framework to construct a hierarchy of quantum maps based on transformations of process matrices and transformations thereof.

  17. Dynamics of Quantum Causal Structures

    Directory of Open Access Journals (Sweden)

    Esteban Castro-Ruiz

    2018-03-01

    Full Text Available It was recently suggested that causal structures are both dynamical, because of general relativity, and indefinite, because of quantum theory. The process matrix formalism furnishes a framework for quantum mechanics on indefinite causal structures, where the order between operations of local laboratories is not definite (e.g., one cannot say whether operation in laboratory A occurs before or after operation in laboratory B. Here, we develop a framework for “dynamics of causal structures,” i.e., for transformations of process matrices into process matrices. We show that, under continuous and reversible transformations, the causal order between operations is always preserved. However, the causal order between a subset of operations can be changed under continuous yet nonreversible transformations. An explicit example is that of the quantum switch, where a party in the past affects the causal order of operations of future parties, leading to a transition from a channel from A to B, via superposition of causal orders, to a channel from B to A. We generalize our framework to construct a hierarchy of quantum maps based on transformations of process matrices and transformations thereof.

  18. Principal stratification in causal inference.

    Science.gov (United States)

    Frangakis, Constantine E; Rubin, Donald B

    2002-03-01

    Many scientific problems require that treatment comparisons be adjusted for posttreatment variables, but the estimands underlying standard methods are not causal effects. To address this deficiency, we propose a general framework for comparing treatments adjusting for posttreatment variables that yields principal effects based on principal stratification. Principal stratification with respect to a posttreatment variable is a cross-classification of subjects defined by the joint potential values of that posttreatment variable tinder each of the treatments being compared. Principal effects are causal effects within a principal stratum. The key property of principal strata is that they are not affected by treatment assignment and therefore can be used just as any pretreatment covariate. such as age category. As a result, the central property of our principal effects is that they are always causal effects and do not suffer from the complications of standard posttreatment-adjusted estimands. We discuss briefly that such principal causal effects are the link between three recent applications with adjustment for posttreatment variables: (i) treatment noncompliance, (ii) missing outcomes (dropout) following treatment noncompliance. and (iii) censoring by death. We then attack the problem of surrogate or biomarker endpoints, where we show, using principal causal effects, that all current definitions of surrogacy, even when perfectly true, do not generally have the desired interpretation as causal effects of treatment on outcome. We go on to forrmulate estimands based on principal stratification and principal causal effects and show their superiority.

  19. Discrete causal theory emergent spacetime and the causal metric hypothesis

    CERN Document Server

    Dribus, Benjamin F

    2017-01-01

    This book evaluates and suggests potentially critical improvements to causal set theory, one of the best-motivated approaches to the outstanding problems of fundamental physics. Spacetime structure is of central importance to physics beyond general relativity and the standard model. The causal metric hypothesis treats causal relations as the basis of this structure. The book develops the consequences of this hypothesis under the assumption of a fundamental scale, with smooth spacetime geometry viewed as emergent. This approach resembles causal set theory, but differs in important ways; for example, the relative viewpoint, emphasizing relations between pairs of events, and relationships between pairs of histories, is central. The book culminates in a dynamical law for quantum spacetime, derived via generalized path summation.

  20. Causal boundary for stably causal space-times

    International Nuclear Information System (INIS)

    Racz, I.

    1987-12-01

    The usual boundary constructions for space-times often yield an unsatisfactory boundary set. This problem is reviewed and a new solution is proposed. An explicit identification rule is given on the set of the ideal points of the space-time. This construction leads to a satisfactory boundary point set structure for stably causal space-times. The topological properties of the resulting causal boundary construction are examined. For the stably causal space-times each causal curve has a unique endpoint on the boundary set according to the extended Alexandrov topology. The extension of the space-time through the boundary is discussed. To describe the singularities the defined boundary sets have to be separated into two disjoint sets. (D.Gy.) 8 refs

  1. [Biological agents].

    Science.gov (United States)

    Amano, Koichi

    2009-03-01

    There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

  2. Causal boundary for strongly causal spacetimes: Pt. 1

    International Nuclear Information System (INIS)

    Szabados, L.B.

    1989-01-01

    In a previous paper an analysis of the general structure of the causal boundary constructions and a new explicit identification rule, built up from elementary TIP-TIF gluings, were presented. In the present paper we complete our identification by incorporating TIP-TIP and TIF-TIF gluings as well. An asymptotic causality condition is found which, for physically important cases, ensures the uniqueness of the endpoints of the non-spacelike curves in the completed spacetime. (author)

  3. Classical planning and causal implicatures

    DEFF Research Database (Denmark)

    Blackburn, Patrick Rowan; Benotti, Luciana

    In this paper we motivate and describe a dialogue manager (called Frolog) which uses classical planning to infer causal implicatures. A causal implicature is a type of Gricean relation implicature, a highly context dependent form of inference. As we shall see, causal implicatures are important...... to generate clarification requests"; as a result we can model task-oriented dialogue as an interactive process locally structured by negotiation of the underlying task. We give several examples of Frolog-human dialog, discuss the limitations imposed by the classical planning paradigm, and indicate...

  4. Functional equations with causal operators

    CERN Document Server

    Corduneanu, C

    2003-01-01

    Functional equations encompass most of the equations used in applied science and engineering: ordinary differential equations, integral equations of the Volterra type, equations with delayed argument, and integro-differential equations of the Volterra type. The basic theory of functional equations includes functional differential equations with causal operators. Functional Equations with Causal Operators explains the connection between equations with causal operators and the classical types of functional equations encountered by mathematicians and engineers. It details the fundamentals of linear equations and stability theory and provides several applications and examples.

  5. Hypertension resistant to antihypertensive agents commonly occurs with the progression of diabetic nephropathy in Japanese patients with type 2 diabetes mellitus: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Ito Hiroyuki

    2012-06-01

    Full Text Available Abstract Background We investigated 1 the frequency of hypertension in patients with type 2 diabetes graded by the new classification of chronic kidney disease (CKD reported by the Kidney Disease: Improving Global Outcomes (KDIGO and 2 the number of antihypertensive agents needed to achieve treatment goals using a prospective observational study. Methods A population of 2018 patients with type 2 diabetes mellitus was recruited for the study. The CKD stage was classified according to the eGFR and the urinary albumin excretion levels. Results Hypertension was found in 1420 (70% of the patients, and the proportion of subjects showing a blood pressure  Conclusions Hypertension resistant to antihypertensive agents was common in the patients with type 2 diabetes mellitus and increased with the progression of CKD. Although powerful combination therapy using antihypertensive agents is considered necessary for the strict control of blood pressure, this became difficult in individuals who were in advanced stages as graded based on the eGFR and the urinary albumin excretion levels.

  6. Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

    Science.gov (United States)

    Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

    2017-02-01

    Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Androgen receptor expression in Circulating Tumor Cells from castration-resistant prostate cancer patients with novel endocrine agents

    NARCIS (Netherlands)

    Crespo, M.; van Dalum, Guus; Ferraldeschi, R.; Zafeiriou, Z.; Sideris, S.; Lorente, D.; Bianchini, D.; Rodrigues, D.N.; Rijsnaes, R.; Miranda, S.; Figueiredo, I.; Flohr, P.; Nowakowska, K.; de Bono, J.S.; Terstappen, Leonardus Wendelinus Mathias Marie; Attard, G.

    2015-01-01

    Background: Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated

  8. Dual HER2\\PIK3CA targeting overcomes single-agent acquired resistance in HER2 amplified uterine serous carcinoma cell lines in vitro and in vivo

    Science.gov (United States)

    Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L.; English, Diana P.; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D.

    2015-01-01

    HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC), and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA mutated and PIK3CA-wild type HER2/neu amplified USC cell lines. Cell viability and cell cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC-xenografts. We found both single agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long lasting growth inhibition in both USC xenografts when compared to single agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA or pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild type PIK3CA resistant to chemotherapy. PMID:26333383

  9. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.

    Science.gov (United States)

    Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D

    2015-11-01

    HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. ©2015 American Association for Cancer Research.

  10. Causal Modelling in Evaluation Research.

    Science.gov (United States)

    Winteler, Adolf

    1983-01-01

    A study applied path analysis methods, using new techniques of causal analysis, to the problem of predicting the achievement, dropout rate, and satisfaction of university students. Besides providing explanations, the technique indicates possible remedial measures. (MSE)

  11. Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

    Directory of Open Access Journals (Sweden)

    Soraya S Andrade

    2006-11-01

    Full Text Available Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%, followed by Klebsiella spp. (7%, Proteus mirabilis (6.4%, Enterococcus spp. (5.6%, and Pseudomonas aeruginosa (4.6%. Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%, TMP/SMX (40.4%, ciprofloxacin (21.6%, and gatifloxacin (17.1%. Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively, and P. mirabilis (71.8 and 84.6%, respectively. For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

  12. Consciousness and the "Causal Paradox"

    OpenAIRE

    Velmans, Max

    1996-01-01

    Viewed from a first-person perspective consciousness appears to be necessary for complex, novel human activity - but viewed from a third-person perspective consciousness appears to play no role in the activity of brains, producing a "causal paradox". To resolve this paradox one needs to distinguish consciousness of processing from consciousness accompanying processing or causing processing. Accounts of consciousness/brain causal interactions switch between first- and third-person perspectives...

  13. THE EFFECT OF DIFFERENT TB DRUGS AND ANTIMICROBIAL AGENTS ON THE EFFICIENCY OF TREATMENT OF TUBERCULOSIS PATIENTS WITH MULTIPLE DRUG RESISTANCE

    Directory of Open Access Journals (Sweden)

    I. A. Vasilyeva

    2017-01-01

    Full Text Available Objective of the study: to study the effect of specific TB drugs and antimicrobial agents constituting chemotherapy regimens on the efficiency of treatment of tuberculosis patients with various patterns of multiple drug resistance.Subjects and Methods. 412 pulmonary tuberculosis patients with bacillary excretion and various patterns of multiple drug resistance were enrolled into the study (117 patients with MDR TB (non pre-XDR and non-XDR; 120 patients with pre-XDR TB and 175 with XDR TB. Patients in the subgroups were compatible regarding sex and age. The patients were prescribed regimens including 5-6 drugs in accordance with their drug resistance pattern. The time of sputum conversion (by culture versus the year of treatment was selected as a surrogate endpoint. The effect of specific TB drugs and antimicrobial agents on treatment efficiency was assessed through calculation of odds ratio (OR of achieving a surrogate endpoint in the patients receiving and not receiving a certain drug.Results. In the subgroup of pre-XDR TB, the following drugs demonstrated the valid increase of odds of sputum conversion: ethambutol (OR 11.8, pyrazinamide (OR 10.2, moxifloxacin (OR 7.8, capreomicin (OR 4.41. Sputum conversion was achieved in all 11 patients treated with bedaquiline.In the subgroup of XDR TB, the following drugs provided a positive effect on the achievement of sputum conversion: bedaquiline (OR 9.62, linezolid (OR 8.15, cycloserine (OR 7.88, pyrazinamide (OR 7.29, moxifloxacin (OR 7.08, and ethambutol (OR 6.69. Ofloxacin demonstrated a confident negative effect on achieving sputum conversion (95% CI 0.06-0.32. 

  14. Multistep resistance selection and postantibiotic-effect studies of the antipneumococcal activity of LBM415 compared to other agents.

    Science.gov (United States)

    Kosowska-Shick, Klaudia; Credito, Kim L; Pankuch, Glenn A; DeWasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C

    2007-02-01

    LBM415 is a peptide deformylase inhibitor active against gram-positive bacterial species and some gram-negative species. In multiselection studies, LBM415 had low MICs against all Streptococcus pneumoniae strains tested, regardless of their genotype, and selected resistant clones after 14 to 50 days. MIC increases correlated with changes mostly in the 70GXGXAAXQ77 motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h.

  15. Etiology of Infectious Complications and Antibiotic-Resistance of Major Causative Agents in Victims with Severe Injury

    Directory of Open Access Journals (Sweden)

    T. A. Vasina

    2007-01-01

    Full Text Available Objective: to analyze the spectrum of major pathogens of infectious complications in patients with concomitant injury.Materials and methods. 560 biological samples taken from 331 patients were bacteriologically studied. A significant reduction in the isolation frequency of Pseudomonas aeruginosa and an increase in etiological role of Staphylococcus aureus were ascertained in victims with severe injury and concomitant infectious complications during long-term 1982—1984 and 2002—2004 follow-ups.Results. The significant pathogens of infectious complications in concomitant injuries are Staphylococcus aureus, Klebsiella and Escherichia coli. Vancomycin, imipenem/cilastatin, and amikacin are shown to be the most effective drugs for early antibiotic therapy. Thus, the findings reflect structural changes in the leading causative agents of infectious complications in victims with severe injury. If their principal pathogen was Pseudomonas aeruginosa in the 1990s, Staphylococcus aureus and representatives in the colibacillus group prevail today. This supports and generates a need for continuous microbiological monitoring of the causative agents of pyoin-flammatory complications in intensive care units wherein patients with immunosuppression are also present. Pathogen monitoring makes it possible to apply of a well-grounded and rational package of preventive and therapeutic measures and to perform early target antibiotic therapy. 

  16. Improving resistance of high strength concrete (HSC) bridge beams to frost and defrosting salt attack by application of hydrophobic agent

    Science.gov (United States)

    Kolisko, Jiri; Balík, Lukáš; Kostelecka, Michaela; Pokorný, Petr

    2017-09-01

    HSC (High Strength Concrete) is increasingly used for bearing bridge structures nowadays. Bridge structures in the Czech Republic are exposed to severe conditions in winter time and durability of the concrete is therefore a crucial requirement. The high strength and low water absorption of HSC suggests that the material will have high durability. However, the situation may not be so straightforward. We carried out a study of the very poor durability of HSC concrete C70/85 used to produce prestresed beams 37.1 m in length to build a 6-span highway bridge. After the beams were cast, a production control test indicated some problems with the durability of the concrete. There was a danger that 42 of the beams would not be suitable for use. All participants in the bridge project finally decided, after extensive discussions, to attempt to improve the durability of the concrete by applying a hydrophobic agent. Paper will present the results of comparative tests of four hydrophobic agents in order to choose one for real application and describes this application on construction site.

  17. Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy agents.

    Science.gov (United States)

    Xue, Kai; Gu, Juan J; Zhang, Qunling; Mavis, Cory; Hernandez-Ilizaliturri, Francisco J; Czuczman, Myron S; Guo, Ye

    2016-02-01

    Preclinical models of chemotherapy resistance and clinical observations derived from the prospective multicenter phase III collaborative trial in relapsed aggressive lymphoma (CORAL) study demonstrated that primary refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical outcome with current available second-line treatments. Preclinically, we found that rituximab resistance is associated with a deregulation on the mitochondrial potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic stimuli. There is a dire need to develop agents capable to execute alternative pathways of cell death in an attempt to overcome chemotherapy resistance. Posttranscriptional histone modification plays an important role in regulating gene transcription and is altered by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs regulate several key cellular functions, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration, antigen presentation, and/or immune regulation. Given their influence in multiple regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its anti-proliferation activity in cancer cells. To this end, we studied the anti-proliferation activity and mechanisms of action of suberoylanilide hydroxamic acid (SAHA, vorinostat) in rituximab-chemotherapy-resistant preclinical models. A panel of rituximab-chemotherapy-sensitive (RSCL) and rituximab-chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from relapsed/refractory B cell lymphoma patients were exposed to escalating doses of vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle distribution were determined by Alamar blue reduction, Titer-Glo luminescent assays, and flow cytometric, respectively. Protein lysates were isolated from vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle regulatory proteins, and the acetylation status of histone H3 were

  18. Aspects of resistance of flax and linseed (Linum usitatissimum) to Fusarium oxysporum f.sp. lini = Aspecten van de resistentie in vezel- en olievlas (Linum usitatissimum) tegen Fusarium oxysporum f.sp. lini

    NARCIS (Netherlands)

    Kroes, I.

    1997-01-01

    In the thesis aspects have been described of the flax and linseed interaction to Fusarium oxysporum f.sp. lini, the causal agent of flax wilt. Two in vitro tests were established to screen for resistance, to investigate race specificity

  19. Regression to Causality : Regression-style presentation influences causal attribution

    DEFF Research Database (Denmark)

    Bordacconi, Mats Joe; Larsen, Martin Vinæs

    2014-01-01

    of equivalent results presented as either regression models or as a test of two sample means. Our experiment shows that the subjects who were presented with results as estimates from a regression model were more inclined to interpret these results causally. Our experiment implies that scholars using regression...... models – one of the primary vehicles for analyzing statistical results in political science – encourage causal interpretation. Specifically, we demonstrate that presenting observational results in a regression model, rather than as a simple comparison of means, makes causal interpretation of the results...... more likely. Our experiment drew on a sample of 235 university students from three different social science degree programs (political science, sociology and economics), all of whom had received substantial training in statistics. The subjects were asked to compare and evaluate the validity...

  20. Putting a cap on causality violations in causal dynamical triangulations

    International Nuclear Information System (INIS)

    Ambjoern, Jan; Loll, Renate; Westra, Willem; Zohren, Stefan

    2007-01-01

    The formalism of causal dynamical triangulations (CDT) provides us with a non-perturbatively defined model of quantum gravity, where the sum over histories includes only causal space-time histories. Path integrals of CDT and their continuum limits have been studied in two, three and four dimensions. Here we investigate a generalization of the two-dimensional CDT model, where the causality constraint is partially lifted by introducing branching points with a weight g s , and demonstrate that the system can be solved analytically in the genus-zero sector. The solution is analytic in a neighborhood around weight g s = 0 and cannot be analytically continued to g s = ∞, where the branching is entirely geometric and where one would formally recover standard Euclidean two-dimensional quantum gravity defined via dynamical triangulations or Liouville theory

  1. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST.

    Directory of Open Access Journals (Sweden)

    Neelke C van der Weerd

    Full Text Available Resistance to erythropoiesis stimulating agents (ESA is common in patients undergoing chronic hemodialysis (HD treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF. In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556, the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit. The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [-0.024 to 0.081]; P = 0.29. Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (-2.52% [-4.72 to -0.31]; P = 0.02 and -49 ng/mL [-103 to 4]; P = 0.06 respectively, although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [-0.4 to 14.5]; P = 0.06. In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.ClinicalTrials.gov NCT00205556.

  2. Lipooligosaccharide structure is an important determinant in the resistance of Neisseria gonorrhoeae to antimicrobial agents of innate host defense

    Directory of Open Access Journals (Sweden)

    Jacqueline T Balthazar

    2011-02-01

    Full Text Available The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens. In order to facilitate the identification of gonococcal genes that are important in determining levels of bacterial susceptibility to mediators of innate host defense, we used the Himar I mariner in vitro mutagenesis system to construct a transposon insertion library in strain F62. As proof of principle that this strategy would be suitable for this purpose, we screened the library for mutants expressing decreased susceptibility to the bacteriolytic action of normal human serum (NHS. We found that a transposon insertion in the lgtD gene, which encodes an N-acetylgalactosamine transferase involved in the extension of the α-chain of lipooligosaccharide (LOS, could confer decreased susceptibility of strain F62 to complement-mediated killing by NHS. By complementation and chemical analyses, we demonstrated both linkage of the transposon insertion to the NHS-resistance phenotype and chemical changes in LOS structure that resulted from loss of LgtD production. Further truncation of the LOS α-chain or loss of phosphoethanolamine (PEA from the lipid A region of LOS also impacted levels of NHS-resistance. PEA decoration of lipid A also increased gonococcal resistance to the model cationic antimicrobial polymyxin B. Taken together, we conclude that the Himar I mariner in vitro mutagenesis procedure can facilitate studies on structures involved in gonococcal

  3. Mapping X-Disease Phytoplasma Resistance in Prunus virginiana

    OpenAIRE

    Ryan R. Lenz; Wenhao Dai

    2017-01-01

    Phytoplasmas such as “Candidatus Phytoplasma pruni,” the causal agent of X-disease of stone fruits, lack detailed biological analysis. This has limited the understanding of plant resistance mechanisms. Chokecherry (Prunus virginiana L.) is a promising model to be used for the plant-phytoplasma interaction due to its documented ability to resist X-disease infection. A consensus chokecherry genetic map “Cho” was developed with JoinMap 4.0 by joining two parental maps. The new map contains a com...

  4. Bayesian networks improve causal environmental ...

    Science.gov (United States)

    Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the problem, using this knowledge with probabilistic calculus to combine multiple lines of evidence, and minimizing biases in predicting or diagnosing causal relationships. Too often, sources of uncertainty in conventional weight of evidence approaches are ignored that can be accounted for with Bayesian networks. Specifying and propagating uncertainties improve the ability of models to incorporate strength of the evidence in the risk management phase of an assessment. Probabilistic inference from a Bayesian network allows evaluation of changes in uncertainty for variables from the evidence. The network structure and probabilistic framework of a Bayesian approach provide advantages over qualitative approaches in weight of evidence for capturing the impacts of multiple sources of quantifiable uncertainty on predictions of ecological risk. Bayesian networks can facilitate the development of evidence-based policy under conditions of uncertainty by incorporating analytical inaccuracies or the implications of imperfect information, structuring and communicating causal issues through qualitative directed graph formulations, and quantitatively comparing the causal power of multiple stressors on value

  5. Causality and analyticity in optics

    International Nuclear Information System (INIS)

    Nussenzveig, H.M.

    In order to provide an overall picture of the broad range of optical phenomena that are directly linked with the concepts of causality and analyticity, the following topics are briefly reviewed, emphasizing recent developments: 1) Derivation of dispersion relations for the optical constants of general linear media from causality. Application to the theory of natural optical activity. 2) Derivation of sum rules for the optical constants from causality and from the short-time response function (asymptotic high-frequency behavior). Average spectral behavior of optical media. Applications. 3) Role of spectral conditions. Analytic properties of coherence functions in quantum optics. Reconstruction theorem.4) Phase retrieval problems. 5) Inverse scattering problems. 6) Solution of nonlinear evolution equations in optics by inverse scattering methods. Application to self-induced transparency. Causality in nonlinear wave propagation. 7) Analytic continuation in frequency and angular momentum. Complex singularities. Resonances and natural-mode expansions. Regge poles. 8) Wigner's causal inequality. Time delay. Spatial displacements in total reflection. 9) Analyticity in diffraction theory. Complex angular momentum theory of Mie scattering. Diffraction as a barrier tunnelling effect. Complex trajectories in optics. (Author) [pt

  6. Hierarchical organisation of causal graphs

    International Nuclear Information System (INIS)

    Dziopa, P.

    1993-01-01

    This paper deals with the design of a supervision system using a hierarchy of models formed by graphs, in which the variables are the nodes and the causal relations between the variables of the arcs. To obtain a representation of the variables evolutions which contains only the relevant features of their real evolutions, the causal relations are completed with qualitative transfer functions (QTFs) which produce roughly the behaviour of the classical transfer functions. Major improvements have been made in the building of the hierarchical organization. First, the basic variables of the uppermost level and the causal relations between them are chosen. The next graph is built by adding intermediary variables to the upper graph. When the undermost graph has been built, the transfer functions parameters corresponding to its causal relations are identified. The second task consists in the upwelling of the information from the undermost graph to the uppermost one. A fusion procedure of the causal relations has been designed to compute the QFTs relevant for each level. This procedure aims to reduce the number of parameters needed to represent an evolution at a high level of abstraction. These techniques have been applied to the hierarchical modelling of nuclear process. (authors). 8 refs., 12 figs

  7. Pharmaceutical composition and drug effect of synthetic Bacopa monnieri L. health promoting agent from the perspective of resistance fatigue.

    Science.gov (United States)

    Chen, Zhidan; Yan, Yanqin

    2017-09-01

    Bacopa monnieri has effect on the nervous system, digestive system and blood circulation systems. In this paper, the authors conducted pharmacological analysis on Bacopa monniera and its innovative pharmaceutical preparation of promote motor function. The extract of the drug has some effect on relieving the fatigue and providing the movement function. By analyzing the composition and efficacy of Chinese herbal extracts, it can be seen that these drugs have obvious effect on improving immunity. Experimental results show that the agent can increase the liver glycogen energy reserves, reduce Bla and BUN levels, balance and energy metabolism of muscle cells in the environment, it plays a positive role to improve the exercise capacity and exercise fatigue.

  8. Enhanced Biofilm Formation and Increased Resistance to Antimicrobial Agents and Bacterial Invasion Are Caused by Synergistic Interactions in Multispecies Biofilms

    DEFF Research Database (Denmark)

    Burmølle, Mette; Webb, J.S.; Rao, D.

    2006-01-01

    from the surface of the marine alga Ulva australis, were screened for synergistic interactions within biofilms when present together in different combinations. Four isolates, Microbacterium phyllosphaerae, Shewanella japonica, Dokdonia donghaensis, and Acinetobacter lwoffii, were found to interact......Most biofilms in their natural environments are likely to consist of consortia of species that influence each other in synergistic and antagonistic manners. However, few reports specifically address interactions within multispecies biofilms. In this study, 17 epiphytic bacterial strains, isolated...... synergistically in biofilms formed in 96-well microtiter plates: biofilm biomass was observed to increase by >167% in biofilms formed by the four strains compared to biofilms composed of single strains. When exposed to the antibacterial agent hydrogen peroxide or tetracycline, the relative activity (exposed...

  9. Immunomodulation and disease resistance in postyearling rainbow trout infected with Myxobolus cerebralis, the causative agent of whirling disease

    Science.gov (United States)

    Densmore, Christine L.; Ottinger, C.A.; Blazer, V.S.; Iwanowicz, L.R.; Smith, D.R.

    2004-01-01

    Myxobolus cerebralis, the myxosporean parasite that causes whirling disease, has a number of deleterious effects on its salmonid host. Although it is well established that juvenile salmonids in the active stages of whirling disease mount an immune response to the pathogen, the occurrence and longevity of any related immunomodulatory effects are unknown. In this study, postyearling rainbow trout Oncorhynchus mykiss infected with M. cerebralis were examined for leukocyte functions and for resistance to Yersinia ruckeri, a bacterial pathogen of salmonids. Compared with uninfected controls, M. cerebralis-infected fish showed lower proliferative lymphocyte responses to four mitogens (concanavalin A, pokeweed mitogen, phytohemagglutinin, and lipopolysaccharide). Conversely, M. cerebralis-infected fish displayed greater bactericidal activity of anterior kidney macrophages than did uninfected fish. After bath challenges with K. ruckeri, M. cerebralis-infected fish had slightly lower survival and a more rapid onset of mortality than did the control fish. Renal tissue and fecal samples from M. cerebralis-infected and uninfected survivors were cultured for the presence of K. ruckeri, and no difference in prevalence was noted between the two groups. Because immunomodulatory changes in the M. cerebralis-infected fish involved functional enhancement and suppression of different leukocyte populations, disease resistance among M. cerebralis-infected fish in the later stages of whirling disease will probably vary with the secondary pathogen and the nature of immune response the pathogen evokes.

  10. Entropy for theories with indefinite causal structure

    International Nuclear Information System (INIS)

    Markes, Sonia; Hardy, Lucien

    2011-01-01

    Any theory with definite causal structure has a defined past and future, be it defined by light cones or an absolute time scale. Entropy is a concept that has traditionally been reliant on a definite notion of causality. However, without a definite notion of causality, the concept of entropy is not all lost. Indefinite causal structure results from combining probabilistic predictions and dynamical space-time. The causaloid framework lays the mathematical groundwork to be able to treat indefinite causal structure. In this paper, we build on the causaloid mathematics and define a causally-unbiased entropy for an indefinite causal structure. In defining a causally-unbiased entropy, there comes about an emergent idea of causality in the form of a measure of causal connectedness, termed the Q factor.

  11. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  12. A Causal Theory of Modality

    Directory of Open Access Journals (Sweden)

    José Tomás Alvarado

    2009-08-01

    Full Text Available This work presents a causal conception of metaphysical modality in which a state of affairs is metaphysically possible if and only if it can be caused (in the past, the present or the future by current entities. The conception is contrasted with what is called the “combinatorial” conception of modality, in which everything can co-exist with anything else. This work explains how the notion of ‘causality’ should be construed in the causal theory, what difference exists between modalities thus defined from nomological modality, how accessibility relations between possible worlds should be interpreted, and what is the relation between the causal conception and the necessity of origin.

  13. Introductive remarks on causal inference

    Directory of Open Access Journals (Sweden)

    Silvana A. Romio

    2013-05-01

    Full Text Available One of the more challenging issues in epidemiological research is being able to provide an unbiased estimate of the causal exposure-disease effect, to assess the possible etiological mechanisms and the implication for public health. A major source of bias is confounding, which can spuriously create or mask the causal relationship. In the last ten years, methodological research has been developed to better de_ne the concept of causation in epidemiology and some important achievements have resulted in new statistical models. In this review, we aim to show how a technique the well known by statisticians, i.e. standardization, can be seen as a method to estimate causal e_ects, equivalent under certain conditions to the inverse probability treatment weight procedure.

  14. Causal reasoning with mental models

    Science.gov (United States)

    Khemlani, Sangeet S.; Barbey, Aron K.; Johnson-Laird, Philip N.

    2014-01-01

    This paper outlines the model-based theory of causal reasoning. It postulates that the core meanings of causal assertions are deterministic and refer to temporally-ordered sets of possibilities: A causes B to occur means that given A, B occurs, whereas A enables B to occur means that given A, it is possible for B to occur. The paper shows how mental models represent such assertions, and how these models underlie deductive, inductive, and abductive reasoning yielding explanations. It reviews evidence both to corroborate the theory and to account for phenomena sometimes taken to be incompatible with it. Finally, it reviews neuroscience evidence indicating that mental models for causal inference are implemented within lateral prefrontal cortex. PMID:25389398

  15. Causal reasoning with mental models.

    Science.gov (United States)

    Khemlani, Sangeet S; Barbey, Aron K; Johnson-Laird, Philip N

    2014-01-01

    This paper outlines the model-based theory of causal reasoning. It postulates that the core meanings of causal assertions are deterministic and refer to temporally-ordered sets of possibilities: A causes B to occur means that given A, B occurs, whereas A enables B to occur means that given A, it is possible for B to occur. The paper shows how mental models represent such assertions, and how these models underlie deductive, inductive, and abductive reasoning yielding explanations. It reviews evidence both to corroborate the theory and to account for phenomena sometimes taken to be incompatible with it. Finally, it reviews neuroscience evidence indicating that mental models for causal inference are implemented within lateral prefrontal cortex.

  16. Causal reasoning with mental models

    Directory of Open Access Journals (Sweden)

    Sangeet eKhemlani

    2014-10-01

    Full Text Available This paper outlines the model-based theory of causal reasoning. It postulates that the core meanings of causal assertions are deterministic and refer to temporally-ordered sets of possibilities: A causes B to occur means that given A, B occurs, whereas A enables B to occur means that given A, it is possible for B to occur. The paper shows how mental models represent such assertions, and how these models underlie deductive, inductive, and abductive reasoning yielding explanations. It reviews evidence both to corroborate the theory and to account for phenomena sometimes taken to be incompatible with it. Finally, it reviews neuroscience evidence indicating that mental models for causal inference are implemented within lateral prefrontal cortex.

  17. Development of Self-Healing Coatings Based on Linseed Oil as Autonomous Repairing Agent for Corrosion Resistance

    Directory of Open Access Journals (Sweden)

    Karan Thanawala

    2014-11-01

    Full Text Available In recent years corrosion-resistant self-healing coatings have witnessed strong growth and their successful laboratory design and synthesis categorises them in the family of smart/multi-functional materials. Among various approaches for achieving self-healing, microcapsule embedment through the material matrix is the main one for self-healing ability in coatings. The present work focuses on optimizing the process parameters for developing microcapsules by in-situ polymerization of linseed oil as core and urea-formaldehyde as shell material. Characteristics of these microcapsules with respect to change in processing parameters such as stirring rate and reaction time were studied by using optical microscopy (OM, scanning electron microscopy (SEM and Fourier transform infrared spectroscopy (FT-IR. The effectiveness of these microcapsules in coatings was characterized by studying their adhesion, performance, and mechanical properties.

  18. Concepts in causality: chemically induced human urinary bladder cancer

    International Nuclear Information System (INIS)

    Lower, G.M. Jr.

    1982-01-01

    A significant portion of the incidence of human urinary bladder cancer can be attributed to occupational and cultural (tobacco smoking) situations associated with exposures to various arylamines, many of which represent established human carcinogens. A brief historical overview of research in bladder cancer causality indicates that the identification of causal agents and causal mechanism has been approached and rests upon information gathered at the organismal (geographical/historical), cellular, and molecular levels of biologic organization. This viewpoint speaks of a natural evolution within the biomedical sciences; a natural evolution from descriptive approaches to mechanistic approaches; and a natural evolution from more or less independent discipline-oriented approaches to hierarchically organized multidisciplinary approaches. Available information relevant to bladder cancer causality can be readily integrated into general conceptual frameworks to yield a hierarchial view of the natural history of urinary bladder cancer, a view consistent with contemporary natural systems and information theory and perhaps relevant also to other chemically induced epithelial cancers. Such frameworks are useful in appreciating the spatial and temporal boundaries and interrelationships in causality and the conceptual interrelationships within the biomedical sciences. Recent approaches in molecular epidemiology and the assessment of relative individual susceptibility to bladder cancer indicate that such frameworks are useful in forming hypotheses

  19. Granger Causality and Unit Roots

    DEFF Research Database (Denmark)

    Rodríguez-Caballero, Carlos Vladimir; Ventosa-Santaulària, Daniel

    2014-01-01

    The asymptotic behavior of the Granger-causality test under stochastic nonstationarity is studied. Our results confirm that the inference drawn from the test is not reliable when the series are integrated to the first order. In the presence of deterministic components, the test statistic diverges......, eventually rejecting the null hypothesis, even when the series are independent of each other. Moreover, controlling for these deterministic elements (in the auxiliary regressions of the test) does not preclude the possibility of drawing erroneous inferences. Granger-causality tests should not be used under...

  20. Quantum theory and local causality

    CERN Document Server

    Hofer-Szabó, Gábor

    2018-01-01

    This book summarizes the results of research the authors have pursued in the past years on the problem of implementing Bell's notion of local causality in local physical theories and relating it to other important concepts and principles in the foundations of physics such as the Common Cause Principle, Bell's inequalities, the EPR (Einstein-Podolsky-Rosen) scenario, and various other locality and causality concepts. The book is intended for philosophers of science with an interest in the formal background of sciences, philosophers of physics and physicists working in foundation of physics.

  1. [Causal analysis approaches in epidemiology].

    Science.gov (United States)

    Dumas, O; Siroux, V; Le Moual, N; Varraso, R

    2014-02-01

    Epidemiological research is mostly based on observational studies. Whether such studies can provide evidence of causation remains discussed. Several causal analysis methods have been developed in epidemiology. This paper aims at presenting an overview of these methods: graphical models, path analysis and its extensions, and models based on the counterfactual approach, with a special emphasis on marginal structural models. Graphical approaches have been developed to allow synthetic representations of supposed causal relationships in a given problem. They serve as qualitative support in the study of causal relationships. The sufficient-component cause model has been developed to deal with the issue of multicausality raised by the emergence of chronic multifactorial diseases. Directed acyclic graphs are mostly used as a visual tool to identify possible confounding sources in a study. Structural equations models, the main extension of path analysis, combine a system of equations and a path diagram, representing a set of possible causal relationships. They allow quantifying direct and indirect effects in a general model in which several relationships can be tested simultaneously. Dynamic path analysis further takes into account the role of time. The counterfactual approach defines causality by comparing the observed event and the counterfactual event (the event that would have been observed if, contrary to the fact, the subject had received a different exposure than the one he actually received). This theoretical approach has shown limits of traditional methods to address some causality questions. In particular, in longitudinal studies, when there is time-varying confounding, classical methods (regressions) may be biased. Marginal structural models have been developed to address this issue. In conclusion, "causal models", though they were developed partly independently, are based on equivalent logical foundations. A crucial step in the application of these models is the

  2. Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents.

    Science.gov (United States)

    Thompson, M J; Abdul-Rahman, S; Baker, T G; Rafferty, J A; Margison, G P; Bibby, M C

    2000-07-01

    The O(6)-alkylguanine-DNA alkyltransferase inactivator O(6)-benzylguanine was administered to BALB/c mice either alone or before exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea to study the role of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase in the protection of the testis against anti-cancer O(6)-alkylating agents. Exposure of the mice to 1, 3-bis(2-chloroethyl)-1-nitrosourea or O(6)-benzylguanine alone did not produce any marked testicular toxicity at the times studied. Testicular O(6)-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and 240 min after O(6)-benzylguanine treatment and were shown to be > 95% depleted 15 min after treatment with O(6)-benzylguanine and remained at > 95% at all the times assayed. Histological examination, the reduction in testicular mass and the induction of spermatogenic cell apoptosis showed that this depletion significantly potentiated 1, 3-bis(2-chloroethyl)-1-nitrosourea-induced testicular damage after treatment. Major histological damage was apparent 42 days after treatment, demonstrating that the stem spermatogonia were significantly affected by the combination. These results demonstrate that O(6)-alkylguanine-DNA alkyltransferase plays a significant role in protecting the spermatogenic cells from damage caused by DNA alkylation and indicate that the observed toxicity may result from damage to stem spermatogonia.

  3. Evaluation of the synergistic potential of vancomycin combined with other antimicrobial agents against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp strains

    Directory of Open Access Journals (Sweden)

    Lívia Viganor da Silva

    2011-02-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA and coagulase-negative Staphylococcus spp (CNS are the most common pathogens that cause serious long term infections in patients. Despite the existence of new antimicrobial agents, such as linezolid, vancomycin (VAN remains the standard therapy for the treatment of infections caused by these multidrug-resistant strains. However, the use of VAN has been associated with a high frequency of therapeutic failures in some clinical scenarios, mainly with decreasing concentration of VAN. This work aims to evaluate the synergic potential of VAN plus sulfamethoxazole/trimethoprim (SXT, VAN plus rifampin (RIF and VAN plus imipenem (IPM in sub-minimum inhibitory concentrations against 22 clinical strains of MRSA and CNS. The checkerboard method showed synergism of VAN/RIF and VAN/SXT against two and three of the 22 strains, respectively. The combination of VAN with IPM showed synergistic effects against 21 out of 22 strains by the E-test method. Four strains were analyzed by the time-kill curve method and synergistic activity was observed with VAN/SXT, VAN/RIF and especially VAN/IPM in sub-inhibitory concentrations. It would be interesting to determine if synergy occurs in vivo. Evidence of in vivo synergy could lead to a reduction of the standard VAN dosage or treatment time.

  4. Current status of Colletotrichum capsici strains, causal agents of ...

    African Journals Online (AJOL)

    Gil

    ASIC, 15e Colloque,. Montpellier 7 p. Dabert M (2006). DNA markers in the phylogenetic of the. Acari. Biol. Lett. 43(2):97-107. Damm U, Woudenberg JHC, Cannon PF, Crous PW (2009). Colletotrichum species with curved conidia from herbaceous hosts. Fungal Divers 39:45-87. Emechebe AM (1986). Cowpea pathology.

  5. Diplodia natalensis Pole Evans, the causal agent of citrus gummosis ...

    African Journals Online (AJOL)

    The isolation media used were 1.5 per cent water agar, 1.5 per cent water agar + nystatin, and 1.5 per cent water agar + benomyl. ... When the isolates were tested for pathogenicity, only D. natalensis induced the disease symptoms in the inoculated 18-month-old rough lemon seedlings which were incubated after ...

  6. Pathogenicity and fungicide sensitivity of the causal agent of ...

    African Journals Online (AJOL)

    The pathogenicity of the fungus and its cross-infection potential were determined on mango, avocado, papaya and banana fruits. The sensitivity of the pathogen to fungicides was determined by assessing radial mycelial growth on potato dextrose agar (PDA) amended with nine different fungicides (Bendazim, Funguran, ...

  7. Genetic recombination in Venturia effusa, causal agent of pecan scab

    Science.gov (United States)

    Venturia effusa causes pecan scab, the most prevalent disease of pecan in the southeastern USA. Mating type idiomorphs were recently characterized and the sexual stage was subsequently produced in vitro. To investigate sexual reproduction and recombination of traits in V. effusa, select isolates wer...

  8. In vitro inhibition of pathogenic Verticillium dahliae, causal agent of ...

    African Journals Online (AJOL)

    SAM

    2014-08-13

    Aug 13, 2014 ... In addition, plant pathogens directly affected through antibiosis and ... Trichoderma strains for antagonistic activity on the fungal pathogen V. ... Five soil sub samples were taken from the area around the healthy potato roots ...

  9. Diplodia natalensis , Pole Evans: a causal agent of citrus gummosis ...

    African Journals Online (AJOL)

    Isolations were made from the barks of gummosis-infected citrus trees from orchards of the University of Ghana Agricultural Research Station at Kade. The isolation media used were 1.5% water agar, 1.5% water agar + nystatin and 1.5% water agar + benomyl. Four isolates including Diplodia natalensis Pole Evans, ...

  10. Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis.

    Science.gov (United States)

    Garvey, E P; Hoekstra, W J; Schotzinger, R J; Sobel, J D; Lilly, E A; Fidel, P L

    2015-09-01

    Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Grassberger, C; Paganetti, H

    2016-01-01

    Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumed to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo

  12. WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Grassberger, C; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States)

    2016-06-15

    Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumed to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo

  13. Immobilized WO3 nanoparticles on graphene oxide as a photo-induced antibacterial agent against UV-resistant Bacillus pumilus

    Science.gov (United States)

    Hosseini, Farshad; Rasuli, Reza; Jafarian, Vahab

    2018-04-01

    We present the antibacterial and photo-catalytic activity of immobilized WO3 nanoparticles on graphene oxide sheets. WO3 nanoparticles were immobilized on graphene oxide using the arc discharge method in arc currents of 5, 20, 40 and 60 A. Tauc plots of the UV-visible spectra show that the band gap of the prepared samples decreases (to ~2.7 eV) with respect to the WO3 nanoparticles. Photo-catalytic activity was examined by the degradation of rhodamine B under ultra-violet irradiation and the results show that the photo-catalytic activity of WO3 nanoparticles is increased by immobilizing them on graphene oxide sheets. In addition, the photo-degradation yield of the samples prepared by the 5 A arc current is 84% in 120 min, which is more than that of the other samples. The antibacterial activity of the prepared samples was studied against Bacillus pumilus (B. pumilus) bacteria, showing high resistance to ultra-violet exposure. Our results show that the bare and immobilized WO3 nanoparticles become more active under UV irradiation and their antibacterial properties are comparable with Ag nanoparticles. Besides this, the results show that although the photo-catalytic activity of the post-annealed samples at 500 °C is less than the as-prepared samples, it is, however, more active against B. pumilus bacteria under UV irradiation.

  14. Causal Reasoning with Mental Models

    Science.gov (United States)

    2014-08-08

    The initial rubric is equivalent to an exclusive disjunction between the two causal assertions. It 488 yields the following two mental models: 489...are 575 important, whereas the functions of artifacts are important (Ahn, 1998). A genetic code is 576 accordingly more critical to being a goat than

  15. Identity, causality, and pronoun ambiguity.

    Science.gov (United States)

    Sagi, Eyal; Rips, Lance J

    2014-10-01

    This article looks at the way people determine the antecedent of a pronoun in sentence pairs, such as: Albert invited Ron to dinner. He spent hours cleaning the house. The experiment reported here is motivated by the idea that such judgments depend on reasoning about identity (e.g., the identity of the he who cleaned the house). Because the identity of an individual over time depends on the causal-historical path connecting the stages of the individual, the correct antecedent will also depend on causal connections. The experiment varied how likely it is that the event of the first sentence (e.g., the invitation) would cause the event of the second (the house cleaning) for each of the two individuals (the likelihood that if Albert invited Ron to dinner, this would cause Albert to clean the house, versus cause Ron to clean the house). Decisions about the antecedent followed causal likelihood. A mathematical model of causal identity accounted for most of the key aspects of the data from the individual sentence pairs. Copyright © 2014 Cognitive Science Society, Inc.

  16. Charged singularities: the causality violation

    Energy Technology Data Exchange (ETDEWEB)

    De Felice, F; Nobili, L [Padua Univ. (Italy). Ist. di Fisica; Calvani, M [Padua Univ. (Italy). Ist. di Astronomia

    1980-12-01

    A search is made for examples of particle trajectories which, approaching a naked singularity from infinity, make up for lost time before going back to infinity. In the Kerr-Newman metric a whole family of such trajectories is found showing that the causality violation is indeed a non-avoidable pathology.

  17. Entanglement, holography and causal diamonds

    Science.gov (United States)

    de Boer, Jan; Haehl, Felix M.; Heller, Michal P.; Myers, Robert C.

    2016-08-01

    We argue that the degrees of freedom in a d-dimensional CFT can be reorganized in an insightful way by studying observables on the moduli space of causal diamonds (or equivalently, the space of pairs of timelike separated points). This 2 d-dimensional space naturally captures some of the fundamental nonlocality and causal structure inherent in the entanglement of CFT states. For any primary CFT operator, we construct an observable on this space, which is defined by smearing the associated one-point function over causal diamonds. Known examples of such quantities are the entanglement entropy of vacuum excitations and its higher spin generalizations. We show that in holographic CFTs, these observables are given by suitably defined integrals of dual bulk fields over the corresponding Ryu-Takayanagi minimal surfaces. Furthermore, we explain connections to the operator product expansion and the first law of entanglemententropy from this unifying point of view. We demonstrate that for small perturbations of the vacuum, our observables obey linear two-derivative equations of motion on the space of causal diamonds. In two dimensions, the latter is given by a product of two copies of a two-dimensional de Sitter space. For a class of universal states, we show that the entanglement entropy and its spin-three generalization obey nonlinear equations of motion with local interactions on this moduli space, which can be identified with Liouville and Toda equations, respectively. This suggests the possibility of extending the definition of our new observables beyond the linear level more generally and in such a way that they give rise to new dynamically interacting theories on the moduli space of causal diamonds. Various challenges one has to face in order to implement this idea are discussed.

  18. Entanglement, holography and causal diamonds

    Energy Technology Data Exchange (ETDEWEB)

    Boer, Jan de [Institute of Physics, Universiteit van Amsterdam,Science Park 904, 1090 GL Amsterdam (Netherlands); Haehl, Felix M. [Centre for Particle Theory & Department of Mathematical Sciences, Durham University,South Road, Durham DH1 3LE (United Kingdom); Heller, Michal P.; Myers, Robert C. [Perimeter Institute for Theoretical Physics,31 Caroline Street North, Waterloo, Ontario N2L 2Y5 (Canada)

    2016-08-29

    We argue that the degrees of freedom in a d-dimensional CFT can be re-organized in an insightful way by studying observables on the moduli space of causal diamonds (or equivalently, the space of pairs of timelike separated points). This 2d-dimensional space naturally captures some of the fundamental nonlocality and causal structure inherent in the entanglement of CFT states. For any primary CFT operator, we construct an observable on this space, which is defined by smearing the associated one-point function over causal diamonds. Known examples of such quantities are the entanglement entropy of vacuum excitations and its higher spin generalizations. We show that in holographic CFTs, these observables are given by suitably defined integrals of dual bulk fields over the corresponding Ryu-Takayanagi minimal surfaces. Furthermore, we explain connections to the operator product expansion and the first law of entanglement entropy from this unifying point of view. We demonstrate that for small perturbations of the vacuum, our observables obey linear two-derivative equations of motion on the space of causal diamonds. In two dimensions, the latter is given by a product of two copies of a two-dimensional de Sitter space. For a class of universal states, we show that the entanglement entropy and its spin-three generalization obey nonlinear equations of motion with local interactions on this moduli space, which can be identified with Liouville and Toda equations, respectively. This suggests the possibility of extending the definition of our new observables beyond the linear level more generally and in such a way that they give rise to new dynamically interacting theories on the moduli space of causal diamonds. Various challenges one has to face in order to implement this idea are discussed.

  19. Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy.

    Directory of Open Access Journals (Sweden)

    Wooseong Kim

    Full Text Available Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7. In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

  20. Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy.

    Science.gov (United States)

    Kim, Wooseong; Conery, Annie L; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-01-01

    Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA) persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7). In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

  1. The argumentative impact of causal relations

    DEFF Research Database (Denmark)

    Nielsen, Anne Ellerup

    1996-01-01

    such as causality, explanation and justification. In certain types of discourse, causal relations also imply an intentional element. This paper describes the way in which the semantic and pragmatic functions of causal markers can be accounted for in terms of linguistic and rhetorical theories of argumentation.......The semantic relations between and within utterances are marked by the use of connectors and adverbials. One type of semantic relations is causal relations expressed by causal markers such as because, therefore, so, for, etc. Some of these markers cover different types of causal relations...

  2. Inhibition of phosphatidylinositol 3-kinase promotes tumor cell resistance to chemotherapeutic agents via a mechanism involving delay in cell cycle progression

    International Nuclear Information System (INIS)

    McDonald, Gail T.; Sullivan, Richard; Pare, Genevieve C.; Graham, Charles H.

    2010-01-01

    Approaches to overcome chemoresistance in cancer cells have involved targeting specific signaling pathways such as the phosphatidylinositol 3-kinase (PI3K) pathway, a stress response pathway known to be involved in the regulation of cell survival, apoptosis and growth. The present study determined the effect of PI3K inhibition on the clonogenic survival of human cancer cells following exposure to various chemotherapeutic agents. Treatment with the PI3K inhibitors LY294002 or Compound 15e resulted in increased survival of MDA-MB-231 breast carcinoma cells after exposure to doxorubicin, etoposide, 5-fluorouracil, and vincristine. Increased survival following PI3K inhibition was also observed in DU-145 prostate, HCT-116 colon and A-549 lung carcinoma cell lines exposed to doxorubicin. Increased cell survival mediated by LY294002 was correlated with a decrease in cell proliferation, which was linked to an increase in the proportion of cells in the G 1 phase of the cell cycle. Inhibition of PI3K signaling also resulted in higher levels of the cyclin-dependent kinase inhibitors p21 Waf1/Cip1 and p27 Kip1 ; and knockdown of p27 kip1 with siRNA attenuated resistance to doxorubicin in cells treated with LY294002. Incubation in the presence of LY294002 after exposure to doxorubicin resulted in decreased cell survival. These findings provide evidence that PI3K inhibition leads to chemoresistance in human cancer cells by causing a delay in cell cycle; however, the timing of PI3K inhibition (either before or after exposure to anti-cancer agents) may be a critical determinant of chemosensitivity.

  3. Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

    Science.gov (United States)

    Salomone, Federico; Catania, Maurizio; Montineri, Arturo; Bertino, Gaetano; Godos, Justyna; Rizzo, Leonardo; Magrì, Giovanni; Li Volti, Giovanni

    2017-12-19

    Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199 mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62 ± 7.4 years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5 ± 7.1 vs 102.8 ± 7.2 mg/dL, P = .15) but 2-hour plasma glucose was reduced (165.2 ± 22.7 vs 138.5 ± 21.3 mg/dL, P Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1 ± 0.2% vs 5.7 ± 0.3%, P resistance as assessed by the oral glucose insulin sensitivity index (6.92 ± 1.56 vs 9.52 ± 1.39 mg/kg/min, P  .5). Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii.

    Science.gov (United States)

    Knezevic, Petar; Aleksic, Verica; Simin, Natasa; Svircev, Emilija; Petrovic, Aleksandra; Mimica-Dukic, Neda

    2016-02-03

    Traditional herbal medicine has become an important issue on the global scale during the past decade. Among drugs of natural origin, special place belongs to essential oils, known as strong antimicrobial agents that can be used to combat antibiotic-resistant bacteria. Eucalyptus camaldulensis leaves are traditional herbal remedy used for various purposes, including treatment of infections. The aim of this study was to determine antimicrobial potential of two E. camaldulensis essential oils against multi-drug resistant (MDR) Acinetobacter baumannii wound isolates and to examine possible interactions of essential oils with conventional antimicrobial agents. Chemical composition of essential oils was determined by gas chromatography-mass spectrometry analysis (GC-MS). MIC values of essential oils against A. baumannii strains were estimated by modified broth microdilution method. The components responsible for antimicrobial activity were detected by bioautographic analysis. The potential synergy between the essential oils and antibiotics (ciprofloxacin, gentamicin and polymyxin B) was examined by checkerboard method and time kill curve. The dominant components of both essential oils were spatulenol, cryptone, p-cimene, 1,8-cineole, terpinen-4-ol and β-pinene. The detected MICs for the E. camaldulensis essential oils were in range from 0.5 to 2 μl mL(-1). The bioautographic assay confirmed antibacterial activity of polar terpene compounds. In combination with conventional antibiotics (ciprofloxacin, gentamicin and polymyxin B), the examined essential oils showed synergistic antibacterial effect in most of the cases, while in some even re-sensitized MDR A. baumannii strains. The synergistic interaction was confirmed by time-kill curves for E. camaldulensis essential oil and polymyxin B combination which reduced bacterial count under detection limit very fast, i.e. after 6h of incubation. The detected anti-A. baumannii activity of E. camaldulensis essential oils

  5. Spectral dimension in causal set quantum gravity

    International Nuclear Information System (INIS)

    Eichhorn, Astrid; Mizera, Sebastian

    2014-01-01

    We evaluate the spectral dimension in causal set quantum gravity by simulating random walks on causal sets. In contrast to other approaches to quantum gravity, we find an increasing spectral dimension at small scales. This observation can be connected to the nonlocality of causal set theory that is deeply rooted in its fundamentally Lorentzian nature. Based on its large-scale behaviour, we conjecture that the spectral dimension can serve as a tool to distinguish causal sets that approximate manifolds from those that do not. As a new tool to probe quantum spacetime in different quantum gravity approaches, we introduce a novel dimensional estimator, the causal spectral dimension, based on the meeting probability of two random walkers, which respect the causal structure of the quantum spacetime. We discuss a causal-set example, where the spectral dimension and the causal spectral dimension differ, due to the existence of a preferred foliation. (paper)

  6. On causal nonrelativistic classical electrodynamics

    International Nuclear Information System (INIS)

    Goedecke, G.H.

    1984-01-01

    The differential-difference (DD) motion equations of the causal nonrelativistic classical electrodynamics developed by the author in 1975 are shown to possess only nonrunaway, causal solutions with no discontinuities in particle velocity or position. As an example, the DD equation solution for the problem of an electromagnetic shock incident on an initially stationary charged particle is contrasted with the standard Abraham-Lorentz equation solution. The general Cauchy problem for these DD motion equations is discussed. In general, in order to uniquely determine a solution, the initial data must be more detailed than the standard Cauchy data of initial position and velocity. Conditions are given under which the standard Cauchy data will determine the DD equation solutions to sufficient practical accuracy

  7. Quantum mechanics, relativity and causality

    International Nuclear Information System (INIS)

    Tati, Takao.

    1975-07-01

    In quantum mechanics, the state is prepared by a measurement on a space-like surface sigma. What is that determines the surface sigma on which the measurement prepares the state It is considered either a mechanism proper to the measuring process (apparatus) or a universal property of space-time. In the former case, problems arise, concerning causality or conservation of probability due to that the velocity of reduction of wave-packet is considered to exceed the light velocity. The theory of finite degree of freedom proposed previously belongs to the latter case. In this theory, the surface sigma is restricted to the hyper-plane perpendicular to a universal time-like vector governing causal relations. We propose an experiment to discriminate between the above-mentioned two cases and to test the existence of the universal time-like vector. (auth.)

  8. The Causality of Evolution on Different Fitness Landscapes

    Science.gov (United States)

    Vyawahare, Saurabh; Austin, Robert; Zhang, Qiucen; Kim, Hyunsung; Bestoso, John

    2013-03-01

    Evolution of antibiotic resistance is a growing problem. One major reason why most antibiotics fail is because of mutations on drug targets (e.g. essential enzymes). Sequencing of clinically resistant isolates have shown that multiple mutational-hotspots exist in coding regions, which could potentially prohibit the binding of drugs. However, it is not clear whether the appearance of each mutation is random or influenced by other factors. In this paper, we compare evolution of resistance to ciprofloxacin from two distinct but well characterized genetic backgrounds. By combining our recently developed evolution reactor and deep whole-genome sequencing, we show different alleles of σs factor lead to fixation of different mutations in gyrA gene that confer ciprofloxacin resistance to bacteria Escherichia coli. Such causality of evolution in different genes provides an opportunity to control the evolution of antibiotic resistance. Sponsored by the NCI/NIH Physical Sciences Oncology Centers

  9. Causal Set Generator and Action Computer

    OpenAIRE

    Cunningham, William; Krioukov, Dmitri

    2017-01-01

    The causal set approach to quantum gravity has gained traction over the past three decades, but numerical experiments involving causal sets have been limited to relatively small scales. The software suite presented here provides a new framework for the generation and study of causal sets. Its efficiency surpasses previous implementations by several orders of magnitude. We highlight several important features of the code, including the compact data structures, the $O(N^2)$ causal set generatio...

  10. Modeling of causality with metamaterials

    International Nuclear Information System (INIS)

    Smolyaninov, Igor I

    2013-01-01

    Hyperbolic metamaterials may be used to model a 2 + 1-dimensional Minkowski space–time in which the role of time is played by one of the spatial coordinates. When a metamaterial is built and illuminated with a coherent extraordinary laser beam, the stationary pattern of light propagation inside the metamaterial may be treated as a collection of particle world lines, which represents a complete ‘history’ of this 2 + 1-dimensional space–time. While this model may be used to build interesting space–time analogs, such as metamaterial ‘black holes’ and a metamaterial ‘big bang’, it lacks causality: since light inside the metamaterial may propagate back and forth along the ‘timelike’ spatial coordinate, events in the ‘future’ may affect events in the ‘past’. Here we demonstrate that a more sophisticated metamaterial model may fix this deficiency via breaking the mirror and temporal (PT) symmetries of the original model and producing one-way propagation along the ‘timelike’ spatial coordinate. The resulting 2 + 1-dimensional Minkowski space–time appears to be causal. This scenario may be considered as a metamaterial model of the Wheeler–Feynman absorber theory of causality. (paper)

  11. THE CAUSAL ANALYSIS / DIAGNOSIS DECISION ...

    Science.gov (United States)

    CADDIS is an on-line decision support system that helps investigators in the regions, states and tribes find, access, organize, use and share information to produce causal evaluations in aquatic systems. It is based on the US EPA's Stressor Identification process which is a formal method for identifying causes of impairments in aquatic systems. CADDIS 2007 increases access to relevant information useful for causal analysis and provides methods and tools that practitioners can use to analyze their own data. The new Candidate Cause section provides overviews of commonly encountered causes of impairments to aquatic systems: metals, sediments, nutrients, flow alteration, temperature, ionic strength, and low dissolved oxygen. CADDIS includes new Conceptual Models that illustrate the relationships from sources to stressors to biological effects. An Interactive Conceptual Model for phosphorus links the diagram with supporting literature citations. The new Analyzing Data section helps practitioners analyze their data sets and interpret and use those results as evidence within the USEPA causal assessment process. Downloadable tools include a graphical user interface statistical package (CADStat), and programs for use with the freeware R statistical package, and a Microsoft Excel template. These tools can be used to quantify associations between causes and biological impairments using innovative methods such as species-sensitivity distributions, biological inferenc

  12. Causal structure of analogue spacetimes

    International Nuclear Information System (INIS)

    Barcelo, Carlos; Liberati, Stefano; Sonego, Sebastiano; Visser, Matt

    2004-01-01

    The so-called 'analogue models of general relativity' provide a number of specific physical systems, well outside the traditional realm of general relativity, that nevertheless are well-described by the differential geometry of curved spacetime. Specifically, the propagation of perturbations in these condensed matter systems is described by 'effective metrics' that carry with them notions of 'causal structure' as determined by an exchange of quasi-particles. These quasi-particle-induced causal structures serve as specific examples of what can be done in the presence of a Lorentzian metric without having recourse to the Einstein equations of general relativity. (After all, the underlying analogue model is governed by its own specific physics, not necessarily by the Einstein equations.) In this paper we take a careful look at what can be said about the causal structure of analogue spacetimes, focusing on those containing quasi-particle horizons, both with a view to seeing what is different from standard general relativity, and what the similarities might be. For definiteness, and because the physics is particularly simple to understand, we will phrase much of the discussion in terms of acoustic disturbances in moving fluids, where the underlying physics is ordinary fluid mechanics, governed by the equations of traditional hydrodynamics, and the relevant quasi-particles are the phonons. It must however be emphasized that this choice of example is only for the sake of pedagogical simplicity and that our considerations apply generically to wide classes of analogue spacetimes

  13. Behavioural Pattern of Causality Parameter of Autoregressive ...

    African Journals Online (AJOL)

    In this paper, a causal form of Autoregressive Moving Average process, ARMA (p, q) of various orders and behaviour of the causality parameter of ARMA model is investigated. It is deduced that the behaviour of causality parameter ψi depends on positive and negative values of autoregressive parameter φ and moving ...

  14. Exploring Individual Differences in Preschoolers' Causal Stance

    Science.gov (United States)

    Alvarez, Aubry; Booth, Amy E.

    2016-01-01

    Preschoolers, as a group, are highly attuned to causality, and this attunement is known to facilitate memory, learning, and problem solving. However, recent work reveals substantial individual variability in the strength of children's "causal stance," as demonstrated by their curiosity about and preference for new causal information. In…

  15. Representing Personal Determinants in Causal Structures.

    Science.gov (United States)

    Bandura, Albert

    1984-01-01

    Responds to Staddon's critique of the author's earlier article and addresses issues raised by Staddon's (1984) alternative models of causality. The author argues that it is not the formalizability of causal processes that is the issue but whether cognitive determinants of behavior are reducible to past stimulus inputs in causal structures.…

  16. Causal inference in economics and marketing.

    Science.gov (United States)

    Varian, Hal R

    2016-07-05

    This is an elementary introduction to causal inference in economics written for readers familiar with machine learning methods. The critical step in any causal analysis is estimating the counterfactual-a prediction of what would have happened in the absence of the treatment. The powerful techniques used in machine learning may be useful for developing better estimates of the counterfactual, potentially improving causal inference.

  17. Causal knowledge and reasoning in decision making

    NARCIS (Netherlands)

    Hagmayer, Y.; Witteman, C.L.M.

    2017-01-01

    Normative causal decision theories argue that people should use their causal knowledge in decision making. Based on these ideas, we argue that causal knowledge and reasoning may support and thereby potentially improve decision making based on expected outcomes, narratives, and even cues. We will

  18. Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein.

    Science.gov (United States)

    Liu, Zulong; Zhu, Hengrui; Qu, Shijin; Tang, Lisha; Cao, Lihuan; Yu, Wenbo; Yang, Xianmei; Jiang, Songmin; Zhu, Dayuan; Tan, Changheng; Yu, Long

    2018-01-01

    Multi-drug resistance (MDR) remains a major impediment in cancer therapy. A major goal for scientists is to discover more effective compounds that are able to circumvent MDR and simultaneously have minimal adverse side effects. In the present study, we aim to determine the anti-MDR effects of pyramidatine (Z88), a cinnamic acid-derived bisamide compound isolated from the leaves of Aglaia perviridis, on KB/VCR (vincristineresistant human oral cancer cells) and MCF-7/ADR (adriamycin-resistant human breast adenocarcinoma) cells. Cell viability and average resistant fold (RF) of Z88 were examined by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry, western blot, RT-PCR, Rhodamine 123 accumulation assay and P-glycoprotein (P-gp) ATPase assay were used to demonstrate the anti-MDR activity and mechanism of Z88. The average RF of Z88 is 0.09 and 0.51 in KB/VCR and MCF-7/ADR cells. A CCK-8 assay showed that Z88 could enhance the cytotoxicity of VCR toward KB/VCR cells. A FACS analysis revealed that Z88 could enhance the VCR-induced apoptosis as well as G2/M arrest in a dose-dependent manner in KB/VCR cells. Western blot results showed that the expression levels of PARP, Bax, and cyclin B1 all increased after treatment with 0.2 µmol/L (µM) of VCR combined with 10 µM of Z88 for 24 h in KB/VCR cells. Z88 also could enhance the accumulation of rhodamine 123. Further studies showed that Z88 could inhibit the verapamil stimulated Pgp ATPase activity. Additionally, qPCR detection and western blot assays revealed that Z88 could decrease the expression of P-gp at both RNA and protein level. Z88 exerted potent anti-MDR activity in vitro and its mechanisms are associated with dualinhibition of the function and expression of P-gp. These findings encourage efforts to develop more effective reversal agents to circumvent MDR based on Z88. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Radiocomplexation and biological characterization of the 99mTcN-trovafloxacin dithiocarbamate. A novel methicillin-resistant Staphylococcus aureus infection imaging agent

    International Nuclear Information System (INIS)

    Syed Qaiser Shah; Muhammad Rafiullah Khan

    2011-01-01

    The radiolabeling of trovafloxacin dithiocarbamate (TVND) with technetium-99m using [ 99m Tc-N] 2+ core was investigated and biologically assessed as prospective infection imaging agent. The achievability of the 99m TcN-TVND complex as a future MRSA infection radiotracer was investigated in artificially methicillin-resistant Staphylococcus aureus (MRSA) infected male Sprague-Dawley rats (MSDR). Radiochemically the 99m TcN-TVND complex was characterized in terms of radiochemical purity (RCP) in saline, in vitro permanence in serum, in vitro binding with MRSA and biodistribution in living and heat killed MRSA infected MSDR. Radiochemically the complex showed stability in saline with a 97.90 ± 0.22% yield and serum at 37 deg C up to 4 h. The 99m TcN-TVND complex showed saturated in vitro binding with MRSA. Normal in vivo uptake in the MRSA infected MDRS was observed with a five fold uptake in the infected muscle as compared to inflamed and normal muscles. The high RCP values, in vitro permanence in serum, better in vitro binding with MRSA, biodistribution behavior and the target to non-target (infected to inflamed muscle) ratios posed the 99m TcN-TVND complex as a promising MRSA infection radiotracer. (author)

  20. Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.

    Science.gov (United States)

    Dolton, Michael J; Perera, Vidya; Pont, Lisa G; McLachlan, Andrew J

    2014-01-01

    Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

  1. The key role of causal explanation in the climate change issue

    Directory of Open Access Journals (Sweden)

    Francesca Pongiglione

    2012-06-01

    Full Text Available The basis for adoption of pro-environment behaviour is the understanding of causal passages within climate dynamics. The understanding of the causes of climate change is necessary in order to be able to take mitigation actions  (the subject needs to be aware of his role as a causal agent. Conversely, the understanding of the consequences of climate change is essential in motivating action (the subject must be aware of the risks caused by it in order to prevent them. The case of ozone depletion confirms this view: the understanding of its causal dynamics played a determining role in people’s behavioural response.

  2. A theory of causal learning in children: causal maps and Bayes nets.

    Science.gov (United States)

    Gopnik, Alison; Glymour, Clark; Sobel, David M; Schulz, Laura E; Kushnir, Tamar; Danks, David

    2004-01-01

    The authors outline a cognitive and computational account of causal learning in children. They propose that children use specialized cognitive systems that allow them to recover an accurate "causal map" of the world: an abstract, coherent, learned representation of the causal relations among events. This kind of knowledge can be perspicuously understood in terms of the formalism of directed graphical causal models, or Bayes nets. Children's causal learning and inference may involve computations similar to those for learning causal Bayes nets and for predicting with them. Experimental results suggest that 2- to 4-year-old children construct new causal maps and that their learning is consistent with the Bayes net formalism.

  3. Norms and customs: causally important or causally impotent?

    Science.gov (United States)

    Jones, Todd

    2010-01-01

    In this article, I argue that norms and customs, despite frequently being described as being causes of behavior in the social sciences and ordinary conversation, cannot really cause behavior. Terms like "norms" and the like seem to refer to philosophically disreputable disjunctive properties. More problematically, even if they do not, or even if there can be disjunctive properties after all, I argue that norms and customs still cannot cause behavior. The social sciences would be better off without referring to properties like norms and customs as if they could be causal.

  4. Antibiotics and antibiotic resistance in agroecosystems: State of the science

    Science.gov (United States)

    We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly su...

  5. A theory of causal learning in children: Causal maps and Bayes nets

    OpenAIRE

    Gopnik, A; Glymour, C; Sobel, D M; Schulz, L E; Kushnir, T; Danks, D

    2004-01-01

    The authors outline a cognitive and computational account of causal learning in children. They propose that children use specialized cognitive systems that allow them to recover an accurate "causal map" of the world: an abstract, coherent, learned representation of the causal relations among events. This kind of knowledge can be perspicuously understood in terms of the formalism of directed graphical causal models, or Bayes nets. Children's causal learning and inference may involve computatio...

  6. Causal mediation analysis with multiple causally non-ordered mediators.

    Science.gov (United States)

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  7. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Shuit-Mun Wong

    Full Text Available Chronic myeloid leukemia (CML is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

  8. The Functions of Danish Causal Conjunctions

    Directory of Open Access Journals (Sweden)

    Rita Therkelsen

    2004-01-01

    Full Text Available In the article I propose an analysis of the Danish causal conjunctions fordi, siden and for based on the framework of Danish Functional Grammar. As conjunctions they relate two clauses, and their semantics have in common that it indicates a causal relationship between the clauses. The causal conjunctions are different as far as their distribution is concerned; siden conjoins a subordinate clause and a main clause, for conjoins two main clauses, and fordi is able to do both. Methodologically I have based my analysis on these distributional properties comparing siden and fordi conjoining a subordinate and a main clause, and comparing for and fordi conjoining two main clauses, following the thesis that they would establish a causal relationship between different kinds of content. My main findings are that fordi establishes a causal relationship between the events referred to by the two clauses, and the whole utterance functions as a statement of this causal relationship. Siden presupposes such a general causal relationship between the two events and puts forward the causing event as a reason for assuming or wishing or ordering the caused event, siden thus establishes a causal relationship between an event and a speech act. For equally presupposes a general causal relationship between two events and it establishes a causal relationship between speech acts, and fordi conjoining two main clauses is able to do this too, but in this position it also maintains its event-relating ability, the interpretation depending on contextual factors.

  9. Space and time in perceptual causality

    Directory of Open Access Journals (Sweden)

    Benjamin Straube

    2010-04-01

    Full Text Available Inferring causality is a fundamental feature of human cognition that allows us to theorize about and predict future states of the world. Michotte suggested that humans automatically perceive causality based on certain perceptual features of events. However, individual differences in judgments of perceptual causality cast doubt on Michotte’s view. To gain insights in the neural basis of individual difference in the perception of causality, our participants judged causal relationships in animations of a blue ball colliding with a red ball (a launching event while fMRI-data were acquired. Spatial continuity and temporal contiguity were varied parametrically in these stimuli. We did not find consistent brain activation differences between trials judged as caused and those judged as non-caused, making it unlikely that humans have universal instantiation of perceptual causality in the brain. However, participants were slower to respond to and showed greater neural activity for violations of causality, suggesting that humans are biased to expect causal relationships when moving objects appear to interact. Our participants demonstrated considerable individual differences in their sensitivity to spatial and temporal characteristics in perceiving causality. These qualitative differences in sensitivity to time or space in perceiving causality were instantiated in individual differences in activation of the left basal ganglia or right parietal lobe, respectively. Thus, the perception that the movement of one object causes the movement of another is triggered by elemental spatial and temporal sensitivities, which themselves are instantiated in specific distinct neural networks.

  10. Respuesta al glifosato de un aislamiento de Rhizoctonia solani agente causal del anublo de la vaina del arroz, y de cuatro aislamientos de Trichoderma, bajo condiciones in vitro In vitro response of one isolate of Rhizoctonia solani, the pathogen of the rice sheath blight and four isolates of Trichoderma to glyphosate

    Directory of Open Access Journals (Sweden)

    Vargas de Álvarez Amparo

    2002-08-01

    Full Text Available El añublo de la vaina del arroz (Orysa saliva L., cuyo agente causal es Rhizoctonia solani Kuhn, es una de las enfermedades más importantes en el cultivo del arroz en Colombia. En los cultivos de arroz con frecuencia se aplica glifosato ((ácido N-(fosfonometil glicina para controlar las malezas, particularmente el arroz rojo (O. saliva, antes de la siembra del arroz. Observaciones de campo anteriores parecían indicar relación entre el uso intensivo del glifosato y el incremento en la incidencia del añublo de la vaina del arroz. Por tanto, se propuso el presente trabajo con el fin de dilucidar los posibles efectos del glifosato sobre R. solani y Trichoderma sp., conocido éste como antagonista de R. solani. Se determinó, bajo condiciones de laboratorio, el efecto del glifosato en el crecimiento, en medio líquido y sólido PDA, de R. solani y de Trichoderma. Se encontró que la dosis más alta de glifosato sin efecto detrimental sobre R. solani, fue de 300 mg/L y la dosis más baja del herbicida que
    causó la mayor inhibición del crecimiento del hongo fue
    de 2500 mg/L. Por otra parte, no se encontró que el glifosato
    estimulara el crecimiento de R. solani. En teoría, en una aplicación comercial de glifosato de 1,5 Kg ia/ha y asperjando directamente al suelo sin vegetación, el glifosato en el suelo estaría a una concentración de 0,75 mg/Kg de suelo (suponiendo que la capa arable de una hectárea de suelo pesa 2.000.000 de Kg; por tanto, la concentración de glifosato después de una aplicación comercial, está muy por debajo de la concentración a la cual se inicia la reducción del crecimiento de R. solani. Por su parte, la respuesta de Trichoderma al glifosato fue similar a la de R. solani; además, se encontró que el glifosato no afecta la capacidad antagonista de Trichoderma sobre R. sotaní. Estos resultados no apoyan la hipótesis que el glifosato, bajo las condiciones de uso en cultivos de arroz para el control

  11. Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

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    Zhanyi Li

    2017-01-01

    Full Text Available Background and Objective. The direct-acting antiviral agents (DAAs antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV patients. However, the viral drug resistance-associated variants (RAVs can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88 and D168E in 2.3% isolates (2/88. In NS5A region, we detected Q30R in 93.2% isolates (82/88, L31M in 4.6% isolates (4/88, and H58P in 6.8% isolates (6/88. In NS5B region, we detected A15G in 2.3% isolates (2/88, S96T in 1.1% isolates (1/88, and S282T in 20.7% isolates (17/88 and we detected I482L in 100% isolates (4/4, V494A in 50% isolates (2/4, and V499A in 100% isolates (4/4. Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

  12. Causal diagrams in systems epidemiology

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    Joffe Michael

    2012-03-01

    Full Text Available Abstract Methods of diagrammatic modelling have been greatly developed in the past two decades. Outside the context of infectious diseases, systematic use of diagrams in epidemiology has been mainly confined to the analysis of a single link: that between a disease outcome and its proximal determinant(s. Transmitted causes ("causes of causes" tend not to be systematically analysed. The infectious disease epidemiology modelling tradition models the human population in its environment, typically with the exposure-health relationship and the determinants of exposure being considered at individual and group/ecological levels, respectively. Some properties of the resulting systems are quite general, and are seen in unrelated contexts such as biochemical pathways. Confining analysis to a single link misses the opportunity to discover such properties. The structure of a causal diagram is derived from knowledge about how the world works, as well as from statistical evidence. A single diagram can be used to characterise a whole research area, not just a single analysis - although this depends on the degree of consistency of the causal relationships between different populations - and can therefore be used to integrate multiple datasets. Additional advantages of system-wide models include: the use of instrumental variables - now emerging as an important technique in epidemiology in the context of mendelian randomisation, but under-used in the exploitation of "natural experiments"; the explicit use of change models, which have advantages with respect to inferring causation; and in the detection and elucidation of feedback.

  13. Causal diagrams in systems epidemiology.

    Science.gov (United States)

    Joffe, Michael; Gambhir, Manoj; Chadeau-Hyam, Marc; Vineis, Paolo

    2012-03-19

    Methods of diagrammatic modelling have been greatly developed in the past two decades. Outside the context of infectious diseases, systematic use of diagrams in epidemiology has been mainly confined to the analysis of a single link: that between a disease outcome and its proximal determinant(s). Transmitted causes ("causes of causes") tend not to be systematically analysed.The infectious disease epidemiology modelling tradition models the human population in its environment, typically with the exposure-health relationship and the determinants of exposure being considered at individual and group/ecological levels, respectively. Some properties of the resulting systems are quite general, and are seen in unrelated contexts such as biochemical pathways. Confining analysis to a single link misses the opportunity to discover such properties.The structure of a causal diagram is derived from knowledge about how the world works, as well as from statistical evidence. A single diagram can be used to characterise a whole research area, not just a single analysis - although this depends on the degree of consistency of the causal relationships between different populations - and can therefore be used to integrate multiple datasets.Additional advantages of system-wide models include: the use of instrumental variables - now emerging as an important technique in epidemiology in the context of mendelian randomisation, but under-used in the exploitation of "natural experiments"; the explicit use of change models, which have advantages with respect to inferring causation; and in the detection and elucidation of feedback.

  14. Probabilistic causality and radiogenic cancers

    International Nuclear Information System (INIS)

    Groeer, P.G.

    1986-01-01

    A review and scrutiny of the literature on probability and probabilistic causality shows that it is possible under certain assumptions to estimate the probability that a certain type of cancer diagnosed in an individual exposed to radiation prior to diagnosis was caused by this exposure. Diagnosis of this causal relationship like diagnosis of any disease - malignant or not - requires always some subjective judgments by the diagnostician. It is, therefore, illusory to believe that tables based on actuarial data can provide objective estimates of the chance that a cancer diagnosed in an individual is radiogenic. It is argued that such tables can only provide a base from which the diagnostician(s) deviate in one direction or the other according to his (their) individual (consensual) judgment. Acceptance of a physician's diagnostic judgment by patients is commonplace. Similar widespread acceptance of expert judgment by claimants in radiation compensation cases does presently not exist. Judicious use of the present radioepidemiological tables prepared by the Working Group of the National Institutes of Health or of updated future versions of similar tables may improve the situation. 20 references

  15. Biological Agents

    Science.gov (United States)

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  16. miR-296-3p, miR-298-5p and their downstream networks are causally involved in the higher resistance of mammalian pancreatic α cells to cytokine-induced apoptosis as compared to β cells

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    Barbagallo Davide

    2013-01-01

    Full Text Available Abstract Background The molecular bases of mammalian pancreatic α cells higher resistance than β to proinflammatory cytokines are very poorly defined. MicroRNAs are master regulators of cell networks, but only scanty data are available on their transcriptome in these cells and its alterations in diabetes mellitus. Results Through high-throughput real-time PCR, we analyzed the steady state microRNA transcriptome of murine pancreatic α (αTC1-6 and β (βTC1 cells: their comparison demonstrated significant differences. We also characterized the alterations of αTC1-6 cells microRNA transcriptome after treatment with proinflammatory cytokines. We focused our study on two microRNAs, miR-296-3p and miR-298-5p, which were: (1 specifically expressed at steady state in αTC1-6, but not in βTC1 or INS-1 cells; (2 significantly downregulated in αTC1-6 cells after treatment with cytokines in comparison to untreated controls. These microRNAs share more targets than expected by chance and were co-expressed in αTC1-6 during a 6–48 h time course treatment with cytokines. The genes encoding them are physically clustered in the murine and human genome. By exploiting specific microRNA mimics, we demonstrated that experimental upregulation of miR-296-3p and miR-298-5p raised the propensity to apoptosis of transfected and cytokine-treated αTC1-6 cells with respect to αTC1-6 cells, treated with cytokines after transfection with scramble molecules. Both microRNAs control the expression of IGF1Rβ, its downstream targets phospho-IRS-1 and phospho-ERK, and TNFα. Our computational analysis suggests that MAFB (a transcription factor exclusively expressed in pancreatic α cells within adult rodent islets of Langerhans controls the expression of miR-296-3p and miR-298-5p. Conclusions Altogether, high-throughput microRNA profiling, functional analysis with synthetic mimics and molecular characterization of modulated pathways strongly suggest that specific

  17. Linear causal modeling with structural equations

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

    Emphasizing causation as a functional relationship between variables that describe objects, Linear Causal Modeling with Structural Equations integrates a general philosophical theory of causation with structural equation modeling (SEM) that concerns the special case of linear causal relations. In addition to describing how the functional relation concept may be generalized to treat probabilistic causation, the book reviews historical treatments of causation and explores recent developments in experimental psychology on studies of the perception of causation. It looks at how to perceive causal

  18. Botrytis cinerea Control and the Problem of Fungicide Resistance

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    Brankica Tanović

    2011-01-01

    Full Text Available Botrytis cinerea, the causal agent of grey mould, greatly affects fruit, grapevine, vegetable and ornamental crops production. It is a common causal agent of diseases in plants grown in protected areas, as well as fruit decay during storage and transport. The fungusinvades almost all parts of the plant in all developmental stages, and the symptoms are usually described as grey mould, grey mildew, brown rot and seedling blight. The paper reviews the current knowledge on control possibilities of this necrotrophic pathogen. Theattention is particularly paid to the mode of action of novel fungicides and to the problem of resistance. It is pointed out that by limiting the number of treatments in the growing season, avoiding the use of only one fungicide with a high risk for resistance development,appropriate application rate and timing, using mixtures of pesticides with different modes of action, as well as by alternative use of pesticides from different resistance groups, a longterm preservation of pesticide efficacy is provided.

  19. Causal relationship: a new tool for the causal characterization of Lorentzian manifolds

    International Nuclear Information System (INIS)

    Garcia-Parrado, Alfonso; Senovilla, Jose M M

    2003-01-01

    We define and study a new kind of relation between two diffeomorphic Lorentzian manifolds called a causal relation, which is any diffeomorphism characterized by mapping every causal vector of the first manifold onto a causal vector of the second. We perform a thorough study of the mathematical properties of causal relations and prove in particular that two given Lorentzian manifolds (say V and W) may be causally related only in one direction (say from V to W, but not from W to V). This leads us to the concept of causally equivalent (or isocausal in short) Lorentzian manifolds as those mutually causally related and to a definition of causal structure over a differentiable manifold as the equivalence class formed by isocausal Lorentzian metrics upon it. Isocausality is a more general concept than the conformal relationship, because we prove the remarkable result that a conformal relation φ is characterized by the fact of being a causal relation of the particular kind in which both φ and φ -1 are causal relations. Isocausal Lorentzian manifolds are mutually causally compatible, they share some important causal properties, and there are one-to-one correspondences, which are sometimes non-trivial, between several classes of their respective future (and past) objects. A more important feature is that they satisfy the same standard causality constraints. We also introduce a partial order for the equivalence classes of isocausal Lorentzian manifolds providing a classification of all the causal structures that a given fixed manifold can have. By introducing the concept of causal extension we put forward a new definition of causal boundary for Lorentzian manifolds based on the concept of isocausality, and thereby we generalize the traditional Penrose constructions of conformal infinity, diagrams and embeddings. In particular, the concept of causal diagram is given. Many explicit clarifying examples are presented throughout the paper

  20. Space-time as a causal set

    International Nuclear Information System (INIS)

    Bombelli, L.; Lee, J.; Meyer, D.; Sorkin, R.D.

    1987-01-01

    We propose that space-time at the smallest scales is in reality a causal set: a locally finite set of elements endowed with a partial order corresponding to the macroscopic relation that defines past and future. We explore how a Lorentzian manifold can approximate a causal set, noting in particular that the thereby defined effective dimensionality of a given causal set can vary with length scale. Finally, we speculate briefly on the quantum dynamics of causal sets, indicating why an appropriate choice of action can reproduce general relativity in the classical limit

  1. Amodal causal capture in the tunnel effect.

    Science.gov (United States)

    Bae, Gi Yeul; Flombaum, Jonathan I

    2011-01-01

    In addition to identifying individual objects in the world, the visual system must also characterize the relationships between objects, for instance when objects occlude one another or cause one another to move. Here we explored the relationship between perceived causality and occlusion. Can one perceive causality in an occluded location? In several experiments, observers judged whether a centrally presented event involved a single object passing behind an occluder, or one object causally launching another (out of view and behind the occluder). With no additional context, the centrally presented event was typically judged as a non-causal pass, even when the occluding and disoccluding objects were different colors--an illusion known as the 'tunnel effect' that results from spatiotemporal continuity. However, when a synchronized context event involved an unambiguous causal launch, participants perceived a causal launch behind the occluder. This percept of an occluded causal interaction could also be driven by grouping and synchrony cues in the absence of any explicitly causal interaction. These results reinforce the hypothesis that causality is an aspect of perception. It is among the interpretations of the world that are independently available to vision when resolving ambiguity, and that the visual system can 'fill in' amodally.

  2. Electromagnetic pulses, localized and causal

    Science.gov (United States)

    Lekner, John

    2018-01-01

    We show that pulse solutions of the wave equation can be expressed as time Fourier superpositions of scalar monochromatic beam wave functions (solutions of the Helmholtz equation). This formulation is shown to be equivalent to Bateman's integral expression for solutions of the wave equation, for axially symmetric solutions. A closed-form one-parameter solution of the wave equation, containing no backward-propagating parts, is constructed from a beam which is the tight-focus limit of two families of beams. Application is made to transverse electric and transverse magnetic pulses, with evaluation of the energy, momentum and angular momentum for a pulse based on the general localized and causal form. Such pulses can be represented as superpositions of photons. Explicit total energy and total momentum values are given for the one-parameter closed-form pulse.

  3. Quantum retrodiction and causality principle

    International Nuclear Information System (INIS)

    Shirokov, M.I.

    1994-01-01

    Quantum mechanics is factually a predictive science. But quantum retrodiction may also be needed, e.g., for the experimental verification of the validity of the Schroedinger equation for the wave function in the past if the present state is given. It is shown that in the retrodictive analog of the prediction the measurement must be replaced by another physical process called the retromeasurement. In this process, the reduction of a state vector into eigenvectors of a measured observable must proceed in the opposite direction of time as compared to the usual reduction. Examples of such processes are unknown. Moreover, they are shown to be forbidden by the causality principle stating that the later event cannot influence the earlier one. So quantum retrodiction seems to be unrealizable. It is demonstrated that the approach to the retrodiction given by S.Watanabe and F.Belinfante must be considered as an unsatisfactory ersatz of retrodicting. 20 refs., 3 figs

  4. The gut microbiota and obesity: from correlation to causality.

    Science.gov (United States)

    Zhao, Liping

    2013-09-01

    The gut microbiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gut microbiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.

  5. Causal ubiquity in quantum physics. A superluminal and local-causal physical ontology

    International Nuclear Information System (INIS)

    Neelamkavil, Raphael

    2014-01-01

    A fixed highest criterial velocity (of light) in STR (special theory of relativity) is a convention for a layer of physical inquiry. QM (Quantum Mechanics) avoids action-at-a-distance using this concept, but accepts non-causality and action-at-a-distance in EPR (Einstein-Podolsky-Rosen-Paradox) entanglement experiments. Even in such allegedly [non-causal] processes, something exists processually in extension-motion, between the causal and the [non-causal]. If STR theoretically allows real-valued superluminal communication between EPR entangled particles, quantum processes become fully causal. That is, the QM world is sub-luminally, luminally and superluminally local-causal throughout, and the Law of Causality is ubiquitous in the micro-world. Thus, ''probabilistic causality'' is a merely epistemic term.

  6. Causal ubiquity in quantum physics. A superluminal and local-causal physical ontology

    Energy Technology Data Exchange (ETDEWEB)

    Neelamkavil, Raphael

    2014-07-01

    A fixed highest criterial velocity (of light) in STR (special theory of relativity) is a convention for a layer of physical inquiry. QM (Quantum Mechanics) avoids action-at-a-distance using this concept, but accepts non-causality and action-at-a-distance in EPR (Einstein-Podolsky-Rosen-Paradox) entanglement experiments. Even in such allegedly [non-causal] processes, something exists processually in extension-motion, between the causal and the [non-causal]. If STR theoretically allows real-valued superluminal communication between EPR entangled particles, quantum processes become fully causal. That is, the QM world is sub-luminally, luminally and superluminally local-causal throughout, and the Law of Causality is ubiquitous in the micro-world. Thus, ''probabilistic causality'' is a merely epistemic term.

  7. Antibacterial agents and heavy metal resistance in Gram-negative bacteria isolated from seawater, shrimp and sediment in Iskenderun Bay, Turkey

    Energy Technology Data Exchange (ETDEWEB)

    Matyar, Fatih [Cukurova University, Faculty of Education, Department of Science and Technology Education, 01330 Balcali, Adana (Turkey)], E-mail: fmatyar@cu.edu.tr; Kaya, Aysenur; Dincer, Sadik [Cukurova University, Faculty of Science and Letters, Department of Biology, 01330 Balcali, Adana (Turkey)

    2008-12-15

    The aim of the present study was to determine the level of antibiotic resistance patterns and distribution of heavy metal resistance of bacterial isolates from seawater, sediment and shrimps, and to determine if there is a relationship between antibiotic and heavy metal resistance. We undertook studies in 2007 in the industrially polluted Iskenderun Bay, on the south coast of Turkey. The resistance of 236 Gram-negative bacterial isolates (49 from seawater, 90 from sediment and 97 from shrimp) to 16 different antibiotics, and to 5 heavy metals, was investigated by agar diffusion and agar dilution methods, respectively. A total of 31 species of bacteria were isolated: the most common strains isolated from all samples were Escherichia coli (11.4%), Aeromonas hydrophila (9.7%) and Stenotrophomonas maltophilia (9.3%). There was a high incidence of resistance to ampicillin (93.2%), streptomycin (90.2%) and cefazolin (81.3%), and a low incidence of resistance to imipenem (16.5%), meropenem (13.9%) and cefepime (8.0%). Some 56.8% of all bacteria isolated from seawater, sediment and shrimp were resistant to 7 or more antibiotics. Most isolates showed tolerance to different concentrations of heavy metals, and minimal inhibition concentrations ranged from 12.5 {mu}g/ml to > 3200 {mu}g/ml. The bacteria from seawater, sediment and shrimp showed high resistance to cadmium of 69.4%, 88.9%, and 81.1% respectively, and low resistance to manganese of 2%, 6.7% and 11.3% respectively. The seawater and sediment isolates which were metal resistant also showed a high resistance to three antibiotics: streptomycin, ampicillin and trimethoprim-sulphamethoxazole. In contrast, the shrimp isolates which were metal resistant were resistant to four antibiotics: cefazolin, nitrofurantoin, cefuroxime and ampicillin. Our results show that Iskenderun Bay has a significant proportion of antibiotic and heavy metal resistant Gram-negative bacteria, and these bacteria constitute a potential risk for

  8. Antibacterial agents and heavy metal resistance in Gram-negative bacteria isolated from seawater, shrimp and sediment in Iskenderun Bay, Turkey

    International Nuclear Information System (INIS)

    Matyar, Fatih; Kaya, Aysenur; Dincer, Sadik

    2008-01-01

    The aim of the present study was to determine the level of antibiotic resistance patterns and distribution of heavy metal resistance of bacterial isolates from seawater, sediment and shrimps, and to determine if there is a relationship between antibiotic and heavy metal resistance. We undertook studies in 2007 in the industrially polluted Iskenderun Bay, on the south coast of Turkey. The resistance of 236 Gram-negative bacterial isolates (49 from seawater, 90 from sediment and 97 from shrimp) to 16 different antibiotics, and to 5 heavy metals, was investigated by agar diffusion and agar dilution methods, respectively. A total of 31 species of bacteria were isolated: the most common strains isolated from all samples were Escherichia coli (11.4%), Aeromonas hydrophila (9.7%) and Stenotrophomonas maltophilia (9.3%). There was a high incidence of resistance to ampicillin (93.2%), streptomycin (90.2%) and cefazolin (81.3%), and a low incidence of resistance to imipenem (16.5%), meropenem (13.9%) and cefepime (8.0%). Some 56.8% of all bacteria isolated from seawater, sediment and shrimp were resistant to 7 or more antibiotics. Most isolates showed tolerance to different concentrations of heavy metals, and minimal inhibition concentrations ranged from 12.5 μg/ml to > 3200 μg/ml. The bacteria from seawater, sediment and shrimp showed high resistance to cadmium of 69.4%, 88.9%, and 81.1% respectively, and low resistance to manganese of 2%, 6.7% and 11.3% respectively. The seawater and sediment isolates which were metal resistant also showed a high resistance to three antibiotics: streptomycin, ampicillin and trimethoprim-sulphamethoxazole. In contrast, the shrimp isolates which were metal resistant were resistant to four antibiotics: cefazolin, nitrofurantoin, cefuroxime and ampicillin. Our results show that Iskenderun Bay has a significant proportion of antibiotic and heavy metal resistant Gram-negative bacteria, and these bacteria constitute a potential risk for public

  9. Shear bond strength after dentin bleaching with 10% carbamide peroxide agents Resistência ao cisalhamento da dentina após clareamento com peróxido de carbamida a 10%

    Directory of Open Access Journals (Sweden)

    Roberta Tarkany Basting

    2004-06-01

    Full Text Available This in vitro study evaluated the shear bond strength (SBS of dentin treated with two 10% carbamide peroxide bleaching agents 15 days after bleaching and storage in artificial saliva. Dentin fragments were randomly divided into 3 groups (n = 20 for the treatment with the two different bleaching agents (Rembrandt 10% or Opalescence 10% or with a placebo agent, applied to the tooth surface for 8 hours a day. During the remaining time, the specimens were stored in artificial saliva. After 42 days, the fragments were stored in artificial saliva for 14 days. Another group (n = 20 was exposed to distilled and deionized water for 56 days. An adhesive system and microhybrid composite resin were used to prepare specimens for the SBS test. SBS tests were performed and the fractured surfaces were visually examined using a stereoscope at 30 X magnification. The analysis of variance (ANOVA and SIDAK tests showed higher SBS values for dentin treated with Opalescence 10% than for dentin treated with Rembrandt 10% or placebo. Groups treated with Rembrandt 10%, Opalescence 10% or placebo did not differ from the group treated with distilled and deionized water. Ten percent carbamide peroxide agents or a placebo agent caused no differences in SBS of dentin after 15 days of storage in artificial saliva.Este estudo in vitro avaliou a resistência ao cisalhamento da dentina submetida ao tratamento com dois agentes clareadores contendo peróxido de carbamida a 10% depois de 15 dias de clareamento e armazenagem em saliva artificial. Fragmentos de dentina foram aleatoriamente distribuídos em 3 grupos (n = 20 para receber o tratamento com dois diferentes agentes clareadores (Rembrandt a 10% ou Opalescence a 10% ou com um agente placebo, aplicados na superfície dental por 8 horas diárias. No restante do tempo, os espécimens permaneceram imersos em saliva artificial. Após o tratamento por 42 dias, os fragmentos foram armazenados em saliva artificial por 14 dias. Outro

  10. A Theory of Causal Learning in Children: Causal Maps and Bayes Nets

    Science.gov (United States)

    Gopnik, Alison; Glymour, Clark; Sobel, David M.; Schulz, Laura E.; Kushnir, Tamar; Danks, David

    2004-01-01

    The authors outline a cognitive and computational account of causal learning in children. They propose that children use specialized cognitive systems that allow them to recover an accurate "causal map" of the world: an abstract, coherent, learned representation of the causal relations among events. This kind of knowledge can be perspicuously…

  11. Further properties of causal relationship: causal structure stability, new criteria for isocausality and counterexamples

    International Nuclear Information System (INIS)

    Garcia-Parrado, Alfonso; Sanchez, Miguel

    2005-01-01

    Recently (Garcia-Parrado and Senovilla 2003 Class. Quantum Grav. 20 625-64) the concept of causal mapping between spacetimes, essentially equivalent in this context to the chronological map defined in abstract chronological spaces, and the related notion of causal structure, have been introduced as new tools to study causality in Lorentzian geometry. In the present paper, these tools are further developed in several directions such as (i) causal mappings-and, thus, abstract chronological ones-do not preserve two levels of the standard hierarchy of causality conditions (however, they preserve the remaining levels as shown in the above reference), (ii) even though global hyperbolicity is a stable property (in the set of all time-oriented Lorentzian metrics on a fixed manifold), the causal structure of a globally hyperbolic spacetime can be unstable against perturbations; in fact, we show that the causal structures of Minkowski and Einstein static spacetimes remain stable, whereas that of de Sitter becomes unstable, (iii) general criteria allow us to discriminate different causal structures in some general spacetimes (e.g. globally hyperbolic, stationary standard); in particular, there are infinitely many different globally hyperbolic causal structures (and thus, different conformal ones) on R 2 (iv) plane waves with the same number of positive eigenvalues in the frequency matrix share the same causal structure and, thus, they have equal causal extensions and causal boundaries

  12. Campbell's and Rubin's Perspectives on Causal Inference

    Science.gov (United States)

    West, Stephen G.; Thoemmes, Felix

    2010-01-01

    Donald Campbell's approach to causal inference (D. T. Campbell, 1957; W. R. Shadish, T. D. Cook, & D. T. Campbell, 2002) is widely used in psychology and education, whereas Donald Rubin's causal model (P. W. Holland, 1986; D. B. Rubin, 1974, 2005) is widely used in economics, statistics, medicine, and public health. Campbell's approach focuses on…

  13. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  14. Causal Mediation Analysis: Warning! Assumptions Ahead

    Science.gov (United States)

    Keele, Luke

    2015-01-01

    In policy evaluations, interest may focus on why a particular treatment works. One tool for understanding why treatments work is causal mediation analysis. In this essay, I focus on the assumptions needed to estimate mediation effects. I show that there is no "gold standard" method for the identification of causal mediation effects. In…

  15. A General Approach to Causal Mediation Analysis

    Science.gov (United States)

    Imai, Kosuke; Keele, Luke; Tingley, Dustin

    2010-01-01

    Traditionally in the social sciences, causal mediation analysis has been formulated, understood, and implemented within the framework of linear structural equation models. We argue and demonstrate that this is problematic for 3 reasons: the lack of a general definition of causal mediation effects independent of a particular statistical model, the…

  16. A Causal Model of Faculty Research Productivity.

    Science.gov (United States)

    Bean, John P.

    A causal model of faculty research productivity was developed through a survey of the literature. Models of organizational behavior, organizational effectiveness, and motivation were synthesized into a causal model of productivity. Two general types of variables were assumed to affect individual research productivity: institutional variables and…

  17. Counterfactual overdetermination vs. the causal exclusion problem.

    Science.gov (United States)

    Sparber, Georg

    2005-01-01

    This paper aims to show that a counterfactual approach to causation is not sufficient to provide a solution to the causal exclusion problem in the form of systematic overdetermination. Taking into account the truthmakers of causal counterfactuals provides a strong argument in favour of the identity of causes in situations of translevel, causation.

  18. Causal Indicators Can Help to Interpret Factors

    Science.gov (United States)

    Bentler, Peter M.

    2016-01-01

    The latent factor in a causal indicator model is no more than the latent factor of the factor part of the model. However, if the causal indicator variables are well-understood and help to improve the prediction of individuals' factor scores, they can help to interpret the meaning of the latent factor. Aguirre-Urreta, Rönkkö, and Marakas (2016)…

  19. Quasi-Experimental Designs for Causal Inference

    Science.gov (United States)

    Kim, Yongnam; Steiner, Peter

    2016-01-01

    When randomized experiments are infeasible, quasi-experimental designs can be exploited to evaluate causal treatment effects. The strongest quasi-experimental designs for causal inference are regression discontinuity designs, instrumental variable designs, matching and propensity score designs, and comparative interrupted time series designs. This…

  20. Determining Directional Dependency in Causal Associations

    Science.gov (United States)

    Pornprasertmanit, Sunthud; Little, Todd D.

    2012-01-01

    Directional dependency is a method to determine the likely causal direction of effect between two variables. This article aims to critique and improve upon the use of directional dependency as a technique to infer causal associations. We comment on several issues raised by von Eye and DeShon (2012), including: encouraging the use of the signs of…

  1. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  2. Heterogeneous Causal Effects and Sample Selection Bias

    DEFF Research Database (Denmark)

    Breen, Richard; Choi, Seongsoo; Holm, Anders

    2015-01-01

    The role of education in the process of socioeconomic attainment is a topic of long standing interest to sociologists and economists. Recently there has been growing interest not only in estimating the average causal effect of education on outcomes such as earnings, but also in estimating how...... causal effects might vary over individuals or groups. In this paper we point out one of the under-appreciated hazards of seeking to estimate heterogeneous causal effects: conventional selection bias (that is, selection on baseline differences) can easily be mistaken for heterogeneity of causal effects....... This might lead us to find heterogeneous effects when the true effect is homogenous, or to wrongly estimate not only the magnitude but also the sign of heterogeneous effects. We apply a test for the robustness of heterogeneous causal effects in the face of varying degrees and patterns of selection bias...

  3. Repair of Partly Misspecified Causal Diagrams.

    Science.gov (United States)

    Oates, Chris J; Kasza, Jessica; Simpson, Julie A; Forbes, Andrew B

    2017-07-01

    Errors in causal diagrams elicited from experts can lead to the omission of important confounding variables from adjustment sets and render causal inferences invalid. In this report, a novel method is presented that repairs a misspecified causal diagram through the addition of edges. These edges are determined using a data-driven approach designed to provide improved statistical efficiency relative to de novo structure learning methods. Our main assumption is that the expert is "directionally informed," meaning that "false" edges provided by the expert would not create cycles if added to the "true" causal diagram. The overall procedure is cast as a preprocessing technique that is agnostic to subsequent causal inferences. Results based on simulated data and data derived from an observational cohort illustrate the potential for data-assisted elicitation in epidemiologic applications. See video abstract at, http://links.lww.com/EDE/B208.

  4. Causality, spin, and equal-time commutators

    International Nuclear Information System (INIS)

    Abdel-Rahman, A.M.

    1975-01-01

    We study the causality constraints on the structure of the Lorentz-antisymmetric component of the commutator of two conserved isovector currents between fermion states of equal momenta. We discuss the sum rules that follow from causality and scaling, using the recently introduced refined infinite-momentum technique. The complete set of sum rules is found to include the spin-dependent fixed-mass sum rules obtained from light-cone commutators. The causality and scaling restrictions on the structure of the electromagnetic equal-time commutators are discussed, and it is found, in particular, that causality requires the spin-dependent part of the matrix element for the time-space electromagnetic equal-time commutator to vanish identically. It is also shown, in comparison with the electromagnetic case, that the corresponding matrix element for the time-space isovector current equal-time commutator is required, by causality, to have isospin-antisymmetric tensor and scalar operator Schwinger terms

  5. Single- and multistep resistance selection studies on the activity of retapamulin compared to other agents against Staphylococcus aureus and Streptococcus pyogenes.

    Science.gov (United States)

    Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bogdanovich, Tatiana; Appelbaum, Peter C

    2006-02-01

    Retapamulin had the lowest rate of spontaneous mutations by single-step passaging and the lowest parent and selected mutant MICs by multistep passaging among all drugs tested for all Staphylococcus aureus strains and three Streptococcus pyogenes strains which yielded resistant clones. Retapamulin has a low potential for resistance selection in S. pyogenes, with a slow and gradual propensity for resistance development in S. aureus.

  6. A Causal Model of Career Development and Quality of Life of College Students with Disabilities

    Science.gov (United States)

    Chun, Jina

    2017-01-01

    Researchers have assumed that social cognitive factors play significant roles in the career development of transition youth and young adults with disabilities and those without disabilities. However, research on the influence of the career decision-making process as a primary causal agent in one's psychosocial outcomes such as perceived level of…

  7. Summarizing Simulation Results using Causally-relevant States

    Science.gov (United States)

    Parikh, Nidhi; Marathe, Madhav; Swarup, Samarth

    2016-01-01

    As increasingly large-scale multiagent simulations are being implemented, new methods are becoming necessary to make sense of the results of these simulations. Even concisely summarizing the results of a given simulation run is a challenge. Here we pose this as the problem of simulation summarization: how to extract the causally-relevant descriptions of the trajectories of the agents in the simulation. We present a simple algorithm to compress agent trajectories through state space by identifying the state transitions which are relevant to determining the distribution of outcomes at the end of the simulation. We present a toy-example to illustrate the working of the algorithm, and then apply it to a complex simulation of a major disaster in an urban area. PMID:28042620

  8. Causal ubiquity in quantum physics a superluminal and local-causal physical ontology

    CERN Document Server

    Neelamkavil, Raphael

    2014-01-01

    A fixed highest criterial velocity (of light) in STR (special theory of relativity) is a convention for a layer of physical inquiry. QM (Quantum Mechanics) avoids action-at-a-distance using this concept, but accepts non-causality and action-at-a-distance in EPR (Einstein-Podolsky-Rosen-Paradox) entanglement experiments. Even in such allegedly non-causal processes, something exists processually in extension-motion, between the causal and the non-causal. If STR theoretically allows real-valued superluminal communication between EPR entangled particles, quantum processes become fully causal. That

  9. Causality violations in Lovelock theories

    Science.gov (United States)

    Brustein, Ram; Sherf, Yotam

    2018-04-01

    Higher-derivative gravity theories, such as Lovelock theories, generalize Einstein's general relativity (GR). Modifications to GR are expected when curvatures are near Planckian and appear in string theory or supergravity. But can such theories describe gravity on length scales much larger than the Planck cutoff length scale? Here we find causality constraints on Lovelock theories that arise from the requirement that the equations of motion (EOM) of perturbations be hyperbolic. We find a general expression for the "effective metric" in field space when Lovelock theories are perturbed around some symmetric background solution. In particular, we calculate explicitly the effective metric for a general Lovelock theory perturbed around cosmological Friedman-Robertson-Walker backgrounds and for some specific cases when perturbed around Schwarzschild-like solutions. For the EOM to be hyperbolic, the effective metric needs to be Lorentzian. We find that, unlike for GR, the effective metric is generically not Lorentzian when the Lovelock modifications are significant. So, we conclude that Lovelock theories can only be considered as perturbative extensions of GR and not as truly modified theories of gravity. We compare our results to those in the literature and find that they agree with and reproduce the results of previous studies.

  10. The causal relation between turbulent particle flux and density gradient

    Energy Technology Data Exchange (ETDEWEB)

    Milligen, B. Ph. van; Martín de Aguilera, A.; Hidalgo, C. [CIEMAT - Laboratorio Nacional de Fusión, Avda. Complutense 40, 28040 Madrid (Spain); Carreras, B. A. [BACV Solutions, 110 Mohawk Road, Oak Ridge, Tennessee 37830 (United States); García, L.; Nicolau, J. H. [Universidad Carlos III, 28911 Leganés, Madrid (Spain)

    2016-07-15

    A technique for detecting the causal relationship between fluctuating signals is used to investigate the relation between flux and gradient in fusion plasmas. Both a resistive pressure gradient driven turbulence model and experimental Langmuir probe data from the TJ-II stellarator are studied. It is found that the maximum influence occurs at a finite time lag (non-instantaneous response) and that quasi-periodicities exist. Furthermore, the model results show very long range radial influences, extending over most of the investigated regions, possibly related to coupling effects associated with plasma self-organization. These results clearly show that transport in fusion plasmas is not local and instantaneous, as is sometimes assumed.

  11. CRISPR/Cas9/sgRNA-mediated targeted gene modification confirms the cause-effect relationship between gyrA mutation and quinolone resistance in Escherichia coli.

    Science.gov (United States)

    Qiu, Haixiang; Gong, Jiansen; Butaye, Patrick; Lu, Guangwu; Huang, Ke; Zhu, Guoqiang; Zhang, Jilei; Hathcock, Terri; Cheng, Darong; Wang, Chengming

    2018-05-14

    Quinolones are broad-spectrum antibiotics that have been used for decades in treating bacterial infections in humans and animals, and subsequently bacterial resistance to these agents has increased. While studies indicated the relationship between gyrA mutations and bacterial resistance to quinolones, CRISPR/Cas9 was used in this study to investigate causal role of gyrA mutation in the quinolone resistance. In this study, 818 clinical Escherichia coli isolates were analyzed for gyrA mutations and their resistance to quinolones. The CRISPR/Cas9 system was used to generate gyrA mutations in quinolone-susceptible E. coli ATCC 25922, and quinolone-resistant clinical E. coli. The antimicrobial resistance prevalence rate in E. coli against nalidixic acid, ciprofloxacin and enrofloxacin was 77.1% (631/818), 51.1% (418/818) and 49.8% (407/818), respectively. The gyrA mutations were identified in nucleotide positions 248, 255, 259, 260, 261, 273 and 300, and mutations at positions 248 and 259 resulting in amino acid changes at positions 83 and 87 were associated with quinolone resistance. Double-site amino acid mutations increase resistance to quinolones. The gyrA mutations causing changes at amino acids 83 and 87 reversed the features of quinolone resistance in ATCC and clinical strains, verifying the causal role of gyrA mutation in the quinolone resistance of E. coli.

  12. Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

    NARCIS (Netherlands)

    Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

    Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

  13. Genetic modification of haematopoietic cells for combined resistance to podophyllotoxins, other agents covered by MDR1-mediated efflux activity and nitrosoureas.

    Science.gov (United States)

    Baum, C; Peinert, S; Carpinteiro, A; Eckert, H G; Fairbairn, L J

    2000-05-01

    Genetic transfer and expression of drug-resistance functions into haematopoietic stem and progenitor cells is a promising means to overcome both the acute and longterm side-effects of cytotoxic drugs in bone marrow. Here, we describe a functional analysis of a retroviral vector that co-expresses human cDNAs for multidrug resistance 1/P-glycoprotein (MDR1) and a double mutant of O(6)-alkylguanine-alkyltransferase (hATPA/GA) to high levels. The hATPA/GA protein contains two amino acid substitutions that render it resistant to compounds such as O(6)-benzylguanine that inhibit the wild-type protein which is often overexpressed in resistant tumour cells. Evidence for simultaneous drug resistance of genetically modified primary murine progenitor cells to colchicine or the podophyllotoxin etoposide, both covered by MDR1-mediated efflux activity, and the nitrosourea BCNU, which is counteracted by hATPA/GA, is presented using in vitro colony assays.

  14. CONFERENCE REPORT ANTIRETROVIRAL RESISTANCE

    African Journals Online (AJOL)

    2004-08-02

    Aug 2, 2004 ... development of new agents with potential clinical utility for treating resistant ... data on the emergence of resistance among Thai women given zidovudine ... had achieved full virological suppression (viral load. < 50 copies/ml).

  15. Mi-1.2, an R gene for aphid resistance in tomato, has direct negative effects on a zoophytophagous biocontrol agent, Orius insidiosus.

    Science.gov (United States)

    Pallipparambil, Godshen R; Sayler, Ronald J; Shapiro, Jeffrey P; Thomas, Jean M G; Kring, Timothy J; Goggin, Fiona L

    2015-02-01

    Mi-1.2 is a single dominant gene in tomato that confers race-specific resistance against certain phloem-feeding herbivores including aphids, whiteflies, psyllids, and root-knot nematodes. Few prior studies have considered the potential non-target effects of race-specific resistance genes (R genes), and this paper evaluates the compatibility of Mi-mediated resistance in tomato with a beneficial zoophytophagous predator, Orius insidiosus (Say). In addition to preying on aphids and other pests, this piercing-sucking insect also feeds from the xylem, epidermis, and/or mesophyll, and oviposits within plant tissues. Comparison of O. insidiosus confined to isogenic tomato plants with and without Mi-1.2 revealed that immatures of O. insidiosus had lower survival on resistant plants even when the immatures were provisioned with prey that did not feed on the host plant. Molecular gut content analysis confirmed that adults and immatures of O. insidiosus feed on both resistant (Mi-1.2+) and susceptible (Mi-1.2-) genotypes, and bioassays suggest that resistance does not affect oviposition rates, plant sampling, or prey acceptance by O. insidiosus adults. These results demonstrate a direct negative impact of R-gene-mediated host plant resistance on a non-target beneficial species, and reveal that Mi-mediated resistance can impact organisms that do not feed on phloem sap. Through laser capture microdissection and RT-PCR, Mi-1.2 transcripts were detected in the epidermis and mesophyll as well as the phloem of tomato plants, consistent with our observations that Mi-mediated resistance is active outside the phloem. These results suggest that the mode of action and potential ecological impacts of Mi-mediated resistance are broader than previously assumed. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  16. Causal localizations in relativistic quantum mechanics

    Science.gov (United States)

    Castrigiano, Domenico P. L.; Leiseifer, Andreas D.

    2015-07-01

    Causal localizations describe the position of quantum systems moving not faster than light. They are constructed for the systems with finite spinor dimension. At the center of interest are the massive relativistic systems. For every positive mass, there is the sequence of Dirac tensor-localizations, which provides a complete set of inequivalent irreducible causal localizations. They obey the principle of special relativity and are fully Poincaré covariant. The boosters are determined by the causal position operator and the other Poincaré generators. The localization with minimal spinor dimension is the Dirac localization. Thus, the Dirac equation is derived here as a mere consequence of the principle of causality. Moreover, the higher tensor-localizations, not known so far, follow from Dirac's localization by a simple construction. The probability of localization for positive energy states results to be described by causal positive operator valued (PO-) localizations, which are the traces of the causal localizations on the subspaces of positive energy. These causal Poincaré covariant PO-localizations for every irreducible massive relativistic system were, all the more, not known before. They are shown to be separated. Hence, the positive energy systems can be localized within every open region by a suitable preparation as accurately as desired. Finally, the attempt is made to provide an interpretation of the PO-localization operators within the frame of conventional quantum mechanics attributing an important role to the negative energy states.

  17. Causal inference, probability theory, and graphical insights.

    Science.gov (United States)

    Baker, Stuart G

    2013-11-10

    Causal inference from observational studies is a fundamental topic in biostatistics. The causal graph literature typically views probability theory as insufficient to express causal concepts in observational studies. In contrast, the view here is that probability theory is a desirable and sufficient basis for many topics in causal inference for the following two reasons. First, probability theory is generally more flexible than causal graphs: Besides explaining such causal graph topics as M-bias (adjusting for a collider) and bias amplification and attenuation (when adjusting for instrumental variable), probability theory is also the foundation of the paired availability design for historical controls, which does not fit into a causal graph framework. Second, probability theory is the basis for insightful graphical displays including the BK-Plot for understanding Simpson's paradox with a binary confounder, the BK2-Plot for understanding bias amplification and attenuation in the presence of an unobserved binary confounder, and the PAD-Plot for understanding the principal stratification component of the paired availability design. Published 2013. This article is a US Government work and is in the public domain in the USA.

  18. Can chance cause cancer? A causal consideration.

    Science.gov (United States)

    Stensrud, Mats Julius; Strohmaier, Susanne; Valberg, Morten; Aalen, Odd Olai

    2017-04-01

    The role of randomness, environment and genetics in cancer development is debated. We approach the discussion by using the potential outcomes framework for causal inference. By briefly considering the underlying assumptions, we suggest that the antagonising views arise due to estimation of substantially different causal effects. These effects may be hard to interpret, and the results cannot be immediately compared. Indeed, it is not clear whether it is possible to define a causal effect of chance at all. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Dual Causality and the Autonomy of Biology.

    Science.gov (United States)

    Bock, Walter J

    2017-03-01

    Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.

  20. Mathematical implications of Einstein-Weyl causality

    International Nuclear Information System (INIS)

    Borchers, H.J.; Sen, R.N.

    2006-01-01

    The present work is the first systematic attempt at answering the following fundamental question: what mathematical structures does Einstein-Weyl causality impose on a point-set that has no other previous structure defined on it? The authors propose an axiomatization of Einstein-Weyl causality (inspired by physics), and investigate the topological and uniform structures that it implies. Their final result is that a causal space is densely embedded in one that is locally a differentiable manifold. The mathematical level required of the reader is that of the graduate student in mathematical physics. (orig.)

  1. The mistake of the causal relationship

    Directory of Open Access Journals (Sweden)

    О. Д. Комаров

    2015-03-01

    Full Text Available The article deals with issues of the mistake of the causal relationship. The modern criminal law science approaches to the content of the mistake of the causal relationship and its significance to the qualification of the crime are described. It is proved that in cases of dolus generalis different mental attitude of the guilty person to two separate acts of his conduct exist. Consequently, in mentioned above cases mistake of the causal relationship does not have place. The rules of qualification of the crimes commited with the mistake of causation and in cases of dolus generalis are proposed .

  2. Transfer of human genes conferring resistance to methylating mutagens, but not to UV irradiation and cross-linking agents, into Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Kaina, B.; Van Zeeland, A.A.; Backendorf, C.; Thielmann, H.W.; Van de Putte, P.

    1987-01-01

    Chinese hamster ovary cells were transfected by human DNA ligated to the bacterial gpt (xanthine-guanine-phosphoribosyltransferase) gene which was used either in its native form or after partial inactivation with methylnitrosourea. The gpt+ transfectants were screened for resistance to high doses of N-methyl-N'-nitro-N-nitrosoguanidine. Using this approach, we showed that Chinese hamster ovary cells can acquire N-methyl-N'-nitro-N-nitrosoguanidine resistance upon transfection with DNA from diploid human fibroblasts, that this resistance is transferable by secondary transfection and is specific for methylating mutagens, and that it is not caused by increased removal of O6-methylguanine, 3-methyladenine, and 7-methylguanine from DNA

  3. Response surface optimization of low-fat ice cream production by using resistant starch and maltodextrin as a fat replacing agent.

    Science.gov (United States)

    Azari-Anpar, Mojtaba; Khomeiri, Morteza; Ghafouri-Oskuei, Hamed; Aghajani, Narjes

    2017-04-01

    In this research, maltodextrin (0, 1 and 2% w/w) and resistant starch (0, 1 and 2% w/w) were used in the formulation of low-fat ice cream (4% fat) and their effects on the physicochemical and sensory properties were investigated. The optimum levels of maltodextrin and resistant starch were determined by response surface methodology. Increment of maltodextrin and resistant starch increased acidity, viscosity, melting rate, time of dripping and overrun but decreased melting rate of ice cream. Results showed that the incorporation of maltodextrin and resistant starch at 0 and 2% w/w respectively, resulted into ice cream with suitable viscosity, melting rate, first dripping time, overrun and acidity.

  4. Comparative mapping of Phytophthora resistance loci in pepper germplasm: evidence for conserved resistance loci across Solanaceae and for a large genetic diversity.

    Science.gov (United States)

    Thabuis, A; Palloix, A; Pflieger, S; Daubèze, A-M; Caranta, C; Lefebvre, V

    2003-05-01

    Phytophthora capsici Leonian, known as the causal agent of the stem, collar and root rot, is one of the most serious problems limiting the pepper crop in many areas in the world. Genetic resistance to the parasite displays complex inheritance. Quantitative trait locus (QTL) analysis was performed in three intraspecific pepper populations, each involving an unrelated resistant accession. Resistance was evaluated by artificial inoculations of roots and stems, allowing the measurement of four components involved in different steps of the plant-pathogen interaction. The three genetic maps were aligned using common markers, which enabled the detection of QTLs involved in each resistance component and the comparison of resistance factors existing among the three resistant accessions. The major resistance factor was found to be common to the three populations. Another resistance factor was found conserved between two populations, the others being specific to a single cross. This comparison across intraspecific germplasm revealed a large variability for quantitative resistance loci to P. capsici. It also provided insights both into the allelic relationships between QTLs across pepper germplasm and for the comparative mapping of resistance factors across the Solanaceae.

  5. NethMap 2017: Consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria in the Netherlands / MARAN 2017: Monitoring of antimicrobial resistance and antibiotic usage in animals in the Netherlands in 2016

    NARCIS (Netherlands)

    de Greeff SC; Mouton JW; ZIA; I&V

    2017-01-01

    The number of bacteria that are resistant to antimicrobials is increasing worldwide. In the Netherlands, the number of resistant bacteria that can cause infections in humans has remained broadly stable. Nevertheless there is cause for concern and caution. Compared to 2015, in 2016 more 'outbreaks'

  6. Assessing students' beliefs, emotions and causal attribution ...

    African Journals Online (AJOL)

    Keywords: academic emotion; belief; causal attribution; statistical validation; students' conceptions of learning ... Sadi & Lee, 2015), through their effect on motivation and learning strategies .... to understand why they may or may not be doing.

  7. Granger Causality Testing with Intensive Longitudinal Data.

    Science.gov (United States)

    Molenaar, Peter C M

    2018-06-01

    The availability of intensive longitudinal data obtained by means of ambulatory assessment opens up new prospects for prevention research in that it allows the derivation of subject-specific dynamic networks of interacting variables by means of vector autoregressive (VAR) modeling. The dynamic networks thus obtained can be subjected to Granger causality testing in order to identify causal relations among the observed time-dependent variables. VARs have two equivalent representations: standard and structural. Results obtained with Granger causality testing depend upon which representation is chosen, yet no criteria exist on which this important choice can be based. A new equivalent representation is introduced called hybrid VARs with which the best representation can be chosen in a data-driven way. Partial directed coherence, a frequency-domain statistic for Granger causality testing, is shown to perform optimally when based on hybrid VARs. An application to real data is provided.

  8. Causality Between Urban Concentration and Environmental Quality

    Directory of Open Access Journals (Sweden)

    Amin Pujiati

    2015-08-01

    Full Text Available Population is concentrated in urban areas can cause the external diseconomies on environment if it exceeds the carrying capacity of the space and the urban economy. Otherwise the quality of the environment is getting better, led to the concentration of population in urban areas are increasingly high. This study aims to analyze the relationship of causality between the urban concentration and environmental quality in urban agglomeration areas. The data used in the study of secondary data obtained from the Central Bureau of statistics and the City Government from 2000 to 2013. The analytical method used is the Granger causality and descriptive. Granger causality study results showed no pattern of reciprocal causality, between urban concentration and the quality of the environment, but there unidirectional relationship between the urban concentration and environmental quality. This means that increasing urban concentration led to decreased environmental quality.

  9. Selecting appropriate cases when tracing causal mechanisms

    DEFF Research Database (Denmark)

    Beach, Derek; Pedersen, Rasmus Brun

    2016-01-01

    The last decade has witnessed resurgence in the interest in studying the causal mechanisms linking causes and outcomes in the social sciences. This article explores the overlooked implications for case selection when tracing mechanisms using in-depth case studies. Our argument is that existing case...... selection guidelines are appropriate for research aimed at making cross-case claims about causal relationships, where case selection is primarily used to control for other causes. However, existing guidelines are not in alignment with case-based research that aims to trace mechanisms, where the goal...... is to unpack the causal mechanism between X and Y, enabling causal inferences to be made because empirical evidence is provided for how the mechanism actually operated in a particular case. The in-depth, within-case tracing of how mechanisms operate in particular cases produces what can be termed mechanistic...

  10. Rate-Agnostic (Causal) Structure Learning.

    Science.gov (United States)

    Plis, Sergey; Danks, David; Freeman, Cynthia; Calhoun, Vince

    2015-12-01

    Causal structure learning from time series data is a major scientific challenge. Extant algorithms assume that measurements occur sufficiently quickly; more precisely, they assume approximately equal system and measurement timescales. In many domains, however, measurements occur at a significantly slower rate than the underlying system changes, but the size of the timescale mismatch is often unknown. This paper develops three causal structure learning algorithms, each of which discovers all dynamic causal graphs that explain the observed measurement data, perhaps given undersampling. That is, these algorithms all learn causal structure in a "rate-agnostic" manner: they do not assume any particular relation between the measurement and system timescales. We apply these algorithms to data from simulations to gain insight into the challenge of undersampling.

  11. K-causality and degenerate spacetimes

    Science.gov (United States)

    Dowker, H. F.; Garcia, R. S.; Surya, S.

    2000-11-01

    The causal relation K+ was introduced by Sorkin and Woolgar to extend the standard causal analysis of C2 spacetimes to those that are only C0. Most of their results also hold true in the case of metrics with degeneracies which are C0 but vanish at isolated points. In this paper we seek to examine K+ explicitly in the case of topology-changing `Morse histories' which contain degeneracies. We first demonstrate some interesting features of this relation in globally Lorentzian spacetimes. In particular, we show that K+ is robust and the Hawking and Sachs characterization of causal continuity translates into a natural condition in terms of K+. We then examine K+ in topology-changing Morse spacetimes with the degenerate points excised and then for the Morse histories in which the degenerate points are reinstated. We find further characterizations of causal continuity in these cases.

  12. Manipulating Morality: Third-Party Intentions Alter Moral Judgments by Changing Causal Reasoning.

    Science.gov (United States)

    Phillips, Jonathan; Shaw, Alex

    2015-08-01

    The present studies investigate how the intentions of third parties influence judgments of moral responsibility for other agents who commit immoral acts. Using cases in which an agent acts under some situational constraint brought about by a third party, we ask whether the agent is blamed less for the immoral act when the third party intended for that act to occur. Study 1 demonstrates that third-party intentions do influence judgments of blame. Study 2 finds that third-party intentions only influence moral judgments when the agent's actions precisely match the third party's intention. Study 3 shows that this effect arises from changes in participants' causal perception that the third party was controlling the agent. Studies 4 and 5, respectively, show that the effect cannot be explained by changes in the distribution of blame or perceived differences in situational constraint faced by the agent. © 2014 Cognitive Science Society, Inc.

  13. Efficient nonparametric estimation of causal mediation effects

    OpenAIRE

    Chan, K. C. G.; Imai, K.; Yam, S. C. P.; Zhang, Z.

    2016-01-01

    An essential goal of program evaluation and scientific research is the investigation of causal mechanisms. Over the past several decades, causal mediation analysis has been used in medical and social sciences to decompose the treatment effect into the natural direct and indirect effects. However, all of the existing mediation analysis methods rely on parametric modeling assumptions in one way or another, typically requiring researchers to specify multiple regression models involving the treat...

  14. Inference of Boundaries in Causal Sets

    OpenAIRE

    Cunningham, William

    2017-01-01

    We investigate the extrinsic geometry of causal sets in $(1+1)$-dimensional Minkowski spacetime. The properties of boundaries in an embedding space can be used not only to measure observables, but also to supplement the discrete action in the partition function via discretized Gibbons-Hawking-York boundary terms. We define several ways to represent a causal set using overlapping subsets, which then allows us to distinguish between null and non-null bounding hypersurfaces in an embedding space...

  15. The Continuum Limit of Causal Fermion Systems

    OpenAIRE

    Finster, Felix

    2016-01-01

    This monograph introduces the basic concepts of the theory of causal fermion systems, a recent approach to the description of fundamental physics. The theory yields quantum mechanics, general relativity and quantum field theory as limiting cases and is therefore a candidate for a unified physical theory. From the mathematical perspective, causal fermion systems provide a general framework for describing and analyzing non-smooth geometries and "quantum geometries." The dynamics is described by...

  16. The Reactive-Causal Architecture: Introducing an Emotion Model along with Theories of Needs

    Science.gov (United States)

    Aydin, Ali Orhan; Orgun, Mehmet Ali

    In the entertainment application area, one of the major aims is to develop believable agents. To achieve this aim, agents should be highly autonomous, situated, flexible, and display affect. The Reactive-Causal Architecture (ReCau) is proposed to simulate these core attributes. In its current form, ReCau cannot explain the effects of emotions on intelligent behaviour. This study aims is to further improve the emotion model of ReCau to explain the effects of emotions on intelligent behaviour. This improvement allows ReCau to be emotional to support the development of believable agents.

  17. Causal strength induction from time series data.

    Science.gov (United States)

    Soo, Kevin W; Rottman, Benjamin M

    2018-04-01

    One challenge when inferring the strength of cause-effect relations from time series data is that the cause and/or effect can exhibit temporal trends. If temporal trends are not accounted for, a learner could infer that a causal relation exists when it does not, or even infer that there is a positive causal relation when the relation is negative, or vice versa. We propose that learners use a simple heuristic to control for temporal trends-that they focus not on the states of the cause and effect at a given instant, but on how the cause and effect change from one observation to the next, which we call transitions. Six experiments were conducted to understand how people infer causal strength from time series data. We found that participants indeed use transitions in addition to states, which helps them to reach more accurate causal judgments (Experiments 1A and 1B). Participants use transitions more when the stimuli are presented in a naturalistic visual format than a numerical format (Experiment 2), and the effect of transitions is not driven by primacy or recency effects (Experiment 3). Finally, we found that participants primarily use the direction in which variables change rather than the magnitude of the change for estimating causal strength (Experiments 4 and 5). Collectively, these studies provide evidence that people often use a simple yet effective heuristic for inferring causal strength from time series data. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  18. Causality violation, gravitational shockwaves and UV completion

    Energy Technology Data Exchange (ETDEWEB)

    Hollowood, Timothy J.; Shore, Graham M. [Department of Physics, Swansea University,Swansea, SA2 8PP (United Kingdom)

    2016-03-18

    The effective actions describing the low-energy dynamics of QFTs involving gravity generically exhibit causality violations. These may take the form of superluminal propagation or Shapiro time advances and allow the construction of “time machines”, i.e. spacetimes admitting closed non-spacelike curves. Here, we discuss critically whether such causality violations may be used as a criterion to identify unphysical effective actions or whether, and how, causality problems may be resolved by embedding the action in a fundamental, UV complete QFT. We study in detail the case of photon scattering in an Aichelburg-Sexl gravitational shockwave background and calculate the phase shifts in QED for all energies, demonstrating their smooth interpolation from the causality-violating effective action values at low-energy to their manifestly causal high-energy limits. At low energies, these phase shifts may be interpreted as backwards-in-time coordinate jumps as the photon encounters the shock wavefront, and we illustrate how the resulting causality problems emerge and are resolved in a two-shockwave time machine scenario. The implications of our results for ultra-high (Planck) energy scattering, in which graviton exchange is modelled by the shockwave background, are highlighted.

  19. Domain-specific perceptual causality in children depends on the spatio-temporal configuration, not motion onset

    Directory of Open Access Journals (Sweden)

    Anne eSchlottmann

    2013-07-01

    Full Text Available Humans, even babies, perceive causality when one shape moves briefly and linearly after another. Motion timing is crucial in this and causal impressions disappear with short delays between motions. However, the role of temporal information is more complex: It is both a cue to causality and a factor that constrains processing. It affects ability to distinguish causality from non-causality, and social from mechanical causality. Here we study both issues with 3- to 7-year-olds and adults who saw two computer-animated squares and chose if a picture of mechanical, social or non-causality fit each event best. Prior work fit with the standard view that early in development, the distinction between the social and physical domains depends mainly on whether or not the agents make contact, and that this reflects concern with domain-specific motion onset, in particular, whether the motion is self-initiated or not. The present experiments challenge both parts of this position. In Experiments 1 and 2, we showed that not just spatial, but also animacy and temporal information affect how children distinguish between physical and social causality. In Experiments 3 and 4 we showed that children do not seem to use spatio-temporal information in perceptual causality to make inferences about self- or other-initiated motion onset. Overall, spatial contact may be developmentally primary in domain-specific perceptual causality in that it is processed easily and is dominant over competing cues, but it is not the only cue used early on and it is not used to infer motion onset. Instead, domain-specific causal impressions may be automatic reactions to specific perceptual configurations, with a complex role for temporal information.

  20. Inhibition of Hyphal Growth of Azole-Resistant Strains of Candida albicans by Triazole Antifungal Agents in the Presence of Lactoferrin-Related Compounds

    Science.gov (United States)

    Wakabayashi, Hiroyuki; Abe, Shigeru; Teraguchi, Susumu; Hayasawa, Hirotoshi; Yamaguchi, Hideyo

    1998-01-01

    The effects of bovine lactoferrin (LF) or the LF-derived antimicrobial peptide lactoferricin B (LFcin B) on the growth of Candida albicans hyphae, including those of three azole-resistant strains, were investigated by a crystal violet staining method. The hyphae of two highly azole-resistant strains were more susceptible to inhibition by LF or LFcin B than the azole-susceptible strains tested. One moderately azole-resistant strain was defective in the formation of hyphae and showed a susceptibility to LF greater than that of the susceptible strains but a susceptibility to LFcin B similar to that of the susceptible strains. The highly azole-resistant strain TIMM3317 showed trailing growth in the presence of fluconazole or itraconazole, while the extent of growth was reduced by the addition of LF or LFcin B at a sub-MIC. Thus, the addition of LF or LFcin B at a sub-MIC resulted in a substantial decrease in the MICs of fluconazole and itraconazole for two highly azole-resistant strains; e.g., the MIC of fluconazole for TIMM3317 was shifted from >256 to 0.25 μg/ml by LF, but the MICs were not decreased for the susceptible strains. The combination effects observed with triazoles and LF-related compounds in the case of the two highly azole-resistant strains were confirmed to be synergistic by the fractional inhibitory concentration index. These results demonstrate that for some azole-resistant C. albicans strains, LF-related compounds combined with triazoles can inhibit the growth of hyphae, an important form of this organism in pathogenesis. PMID:9660988