Science.gov

Sample records for conditions favoring polyborates

  1. Conditions Favoring a Facilitation Effect in the Learned Helplessness Paradigm.

    ERIC Educational Resources Information Center

    Samuel, William; Nilsen, Paul

    Following a traditional learned helplessness paradigm, subjects initially tried to terminate random bursts of noise using a button-pressing manipulandum and next tried to solve 20 serially-presented anagrams. The noise was broadcast at either a loud or soft intensity, and the subject's button-pressing was either successful (Escape condition) or…

  2. Second Seminole War: Establishing Favorable Conditions for Conflict Resolution

    DTIC Science & Technology

    2013-05-23

    better the nature of the conflict, which informed subsequent campaigns and established conditions for conflict termination. These first campaigns...Seminoles vacated their towns and moved their families into the swamps . On 26 November 1835, Osceola assassinated Charley Emathla to terrorize any...March 1836, advised Scott that European tactics would not work against the Seminoles in the swamps of Florida. While in transit, Scott requested

  3. Assessment of fungal growth on sodium polyborate-treated cellulose insulation.

    PubMed

    Herrera, José

    2005-12-01

    Cellulose insulation has rapidly gained a large market share among general contractors and homeowners. Recent interest regarding health effects of high concentrations of fungi within indoor environments (building-related illnesses or sick building syndrome) has promoted concern about susceptibility of building materials, including wood products (in general) and cellulose insulation (specifically), to fungal attack. This study reports an assessment of fungal growth on cellulose insulation made from recycled paper and treated with varying concentrations of sodium polyborate within half-scale wall units exposed to variable and high ambient temperatures and relative humidities throughout the summer. Boron-treated and untreated (control) cellulose insulation within the wall units were challenged with a suspension containing high concentrations of spores of five fungal species commonly found in indoor environments. Our results suggest that cellulose insulation treated with sodium polyborate (a) precludes the growth of the five common fungal species; (b) harbors fewer fungal species before and after being challenged with the fungal spore suspension; and (c) is likely having a cytotoxic or sporocidal effect on many, if not all, fungal species. These results suggest that cellulose insulation treated with sodium polyborate, when properly applied and installed, precludes fungal growth for at least 124 days at high temperatures and relative humidities.

  4. Molecular Crowding Favors Reactivity of a Human Ribozyme Under Physiological Ionic Conditions

    PubMed Central

    Strulson, Christopher A.; Yennawar, Neela H.; Rambo, Robert P.; Bevilacqua, Philip C.

    2013-01-01

    In an effort to relate RNA folding to function under cellular-like conditions, we monitored the self-cleavage reaction of the human hepatitis delta virus (HDV)-like CPEB3 ribozyme in the background of physiological ionic concentrations and various crowding and cosolute agents. We found that under physiological free Mg2+ concentrations (~0.1 to 0.5 mM Mg2+), both crowders and cosolutes stimulate the rate of self-cleavage, up to ~6-fold, but that in 10 mM Mg2+—conditions widely used for in vitro ribozyme studies—these same additives have virtually no effect on self-cleavage rate. We further observe a dependence of self-cleavage rate on crowder size, wherein rate stimulation is diminished for crowders larger than the size of the unfolded RNA. Monitoring effects of crowding and cosolute agents on rates in biological amounts of urea revealed additive-promoted increases in both low and high Mg2+ concentrations, with a maximal stimulation of more than 10-fold and a rescue of the rate to its urea-free values. Small-angle X-ray scattering (SAXS) experiments reveal a structural basis for this stimulation in that higher molecular weight crowding agents favor a more compact form of the ribozyme in 0.5 mM Mg2+ that is essentially equivalent to the form under standard ribozyme conditions of 10 mM Mg2+ and no crowder. This finding suggests that at least a portion of the rate enhancement arises from favoring the native RNA tertiary structure. We conclude that cellular-like crowding supports ribozyme reactivity by favoring a compact form of the ribozyme, but only under physiological ionic and cosolute conditions. PMID:24187989

  5. Resource allocation in offspring provisioning: An evaluation of the conditions favoring the evolution of matrotrophy

    USGS Publications Warehouse

    Trexler, Joel C.; DeAngelis, Donald L.

    2003-01-01

    We used analytic and simulation models to determine the ecological conditions favoring evolution of a matrotrophic fish from a lecithotrophic ancestor given a complex set of trade‐offs. Matrotrophy is the nourishment of viviparous embryos by resources provided between fertilization and parturition, while lecithotrophy describes embryo nourishment provided before fertilization. In fishes and reptiles, embryo nourishment encompasses a continuum from solely lecithotrophic to primarily matrotrophic. Matrotrophy has evolved independently from lecithotrophic ancestors many times in many groups. We assumed matrotrophy increased the number of offspring a viviparous female could gestate and evaluated conditions of food availability favoring lecithotrophy or matrotrophy. The matrotrophic strategy was superior when food resources exceeded demand during gestation but at a risk of overproduction and reproductive failure if food intake was limited. Matrotrophic females were leaner during gestation than lecithotrophic females, yielding shorter life spans. Our models suggest that matrotrophic embryo nourishment evolved in environments with high food availability, consistently exceeding energy requirements for maintaining relatively large broods. Embryo abortion with some resorption of invested energy is a necessary preadaptation to the evolution of matrotrophy. Future work should explore trade‐offs of age‐specific mortality and reproductive output for females maintaining different levels of fat storage during gestation.

  6. Thermodynamic Conditions Favorable to Superlative Thunderstorm Updraft, Mixed Phase Microphysics and Lightning Flash Rate. Revised

    NASA Technical Reports Server (NTRS)

    Williams, E.; Mushtak, V.; Rosenfeld, D.; Goodman, S.; Boccippio, D.

    2004-01-01

    Satellite observations of lightning flash rate have been merged with proximal surface station thermodynamic observations toward improving the understanding of the response of the updraft and lightning activity in the tropical atmosphere to temperature. The tropical results have led in turn to an examination of thermodynamic climatology over the continental United States in summertime and its comparison with exceptional electrical conditions documented in earlier studies. The tropical and mid-latitude results taken together support an important role for cloud base height in regulating the transfer of Convective Available Potential Energy (CAPE) to updraft kinetic energy in thunderstorms. In the tropics, cloud base height is dominated by the dry bulb temperature over the wet bulb temperature as the lightning-regulating temperature in regions characterized by moist convection. In the extratropics, an elevated cloud base height may enable larger cloud water concentrations in the mixed phase region, a favorable condition for the positive charging of large ice particles that may result in thunderclouds with a reversed polarity of the main cloud dipole. The combined requirements of instability and cloud base height serve to confine the region of superlative electrification to the vicinity of the ridge in moist entropy in the western Great Plains.

  7. Complexation of Nickel Ions by Boric Acid or (Poly)borates.

    PubMed

    Graff, Anais; Barrez, Etienne; Baranek, Philippe; Bachet, Martin; Bénézeth, Pascale

    2017-01-01

    An experiment based on electrochemical reactions and pH monitoring was performed in which nickel ions were gradually formed by oxidation of a nickel metal electrode in a solution of boric acid. Based on the experimental results and aqueous speciation modeling, the evolution of pH showed the existence of significant nickel-boron complexation. A triborate nickel complex was postulated at high boric acid concentrations when polyborates are present, and the equilibrium constants were determined at 25, 50 and 70 °C. The calculated enthalpy and entropy at 25 °C for the formation of the complex from boric acid and Ni(2+) ions are respectively equal to (65.6 ± 3.1) kJ·mol(-1) and (0.5 ± 11.1) J·K(-1)·mol(-1). The results of this study suggest that complexation of nickel ions by borates can significantly enhance the solubility of nickel metal and nickel oxide depending on the concentration of boric acid and pH. First principles calculations were investigated and tend to show that the complex is thermodynamically stable and the nickel cation in solution should interact more strongly with the [Formula: see text] than with boric acid.

  8. The Ecological Conditions That Favor Tool Use and Innovation in Wild Bottlenose Dolphins (Tursiops sp.)

    PubMed Central

    Patterson, Eric M.; Mann, Janet

    2011-01-01

    Dolphins are well known for their exquisite echolocation abilities, which enable them to detect and discriminate prey species and even locate buried prey. While these skills are widely used during foraging, some dolphins use tools to locate and extract prey. In the only known case of tool use in free-ranging cetaceans, a subset of bottlenose dolphins (Tursiops sp.) in Shark Bay, Western Australia habitually employs marine basket sponge tools to locate and ferret prey from the seafloor. While it is clear that sponges protect dolphins' rostra while searching for prey, it is still not known why dolphins probe the substrate at all instead of merely echolocating for buried prey as documented at other sites. By ‘sponge foraging’ ourselves, we show that these dolphins target prey that both lack swimbladders and burrow in a rubble-littered substrate. Delphinid echolocation and vision are critical for hunting but less effective on such prey. Consequently, if dolphins are to access this burrowing, swimbladderless prey, they must probe the seafloor and in turn benefit from using protective sponges. We suggest that these tools have allowed sponge foraging dolphins to exploit an empty niche inaccessible to their non-tool-using counterparts. Our study identifies the underlying ecological basis of dolphin tool use and strengthens our understanding of the conditions that favor tool use and innovation in the wild. PMID:21799801

  9. The ecological conditions that favor tool use and innovation in wild bottlenose dolphins (Tursiops sp.).

    PubMed

    Patterson, Eric M; Mann, Janet

    2011-01-01

    Dolphins are well known for their exquisite echolocation abilities, which enable them to detect and discriminate prey species and even locate buried prey. While these skills are widely used during foraging, some dolphins use tools to locate and extract prey. In the only known case of tool use in free-ranging cetaceans, a subset of bottlenose dolphins (Tursiops sp.) in Shark Bay, Western Australia habitually employs marine basket sponge tools to locate and ferret prey from the seafloor. While it is clear that sponges protect dolphins' rostra while searching for prey, it is still not known why dolphins probe the substrate at all instead of merely echolocating for buried prey as documented at other sites. By 'sponge foraging' ourselves, we show that these dolphins target prey that both lack swimbladders and burrow in a rubble-littered substrate. Delphinid echolocation and vision are critical for hunting but less effective on such prey. Consequently, if dolphins are to access this burrowing, swimbladderless prey, they must probe the seafloor and in turn benefit from using protective sponges. We suggest that these tools have allowed sponge foraging dolphins to exploit an empty niche inaccessible to their non-tool-using counterparts. Our study identifies the underlying ecological basis of dolphin tool use and strengthens our understanding of the conditions that favor tool use and innovation in the wild.

  10. A Combination of Extreme Environmental Conditions Favor the Prevalence of Endospore-Forming Firmicutes

    PubMed Central

    Filippidou, Sevasti; Wunderlin, Tina; Junier, Thomas; Jeanneret, Nicole; Dorador, Cristina; Molina, Veronica; Johnson, David R.; Junier, Pilar

    2016-01-01

    Environmental conditions unsuitable for microbial growth are the rule rather than the exception in most habitats. In response to this, microorganisms have developed various strategies to withstand environmental conditions that limit active growth. Endospore-forming Firmicutes (EFF) deploy a myriad of survival strategies in order to resist adverse conditions. Like many bacterial groups, they can form biofilms and detect nutrient scarcity through chemotaxis. Moreover, within this paraphyletic group of Firmicutes, ecophysiological optima are diverse. Nonetheless, a response to adversity that delimits this group is the formation of wet-heat resistant spores. These strategies are energetically demanding and therefore might affect the biological success of EFF. Therefore, we hypothesize that abundance and diversity of EFF should be maximized in those environments in which the benefits of these survival strategies offsets the energetic cost. In order to address this hypothesis, geothermal and mineral springs and drillings were selected because in these environments of steep physicochemical gradients, diversified survival strategies may become a successful strategy.We collected 71 samples from geothermal and mineral environments characterized by none (null), single or multiple limiting environmental factors (temperature, pH, UV radiation, and specific mineral composition). To measure success, we quantified EFF gene copy numbers (GCN; spo0A gene) in relation to total bacterial GCN (16S rRNA gene), as well as the contribution of EFF to community composition. The quantification showed that relative GCN for EFF reached up to 20% at sites characterized by multiple limiting environmental factors, whereas it corresponded to less than 1% at sites with one or no limiting environmental factor. Pyrosequencing of the 16S rRNA gene supports a higher contribution of EFF at sites with multiple limiting factors. Community composition suggested a combination of phylotypes for which active

  11. A Combination of Extreme Environmental Conditions Favor the Prevalence of Endospore-Forming Firmicutes.

    PubMed

    Filippidou, Sevasti; Wunderlin, Tina; Junier, Thomas; Jeanneret, Nicole; Dorador, Cristina; Molina, Veronica; Johnson, David R; Junier, Pilar

    2016-01-01

    Environmental conditions unsuitable for microbial growth are the rule rather than the exception in most habitats. In response to this, microorganisms have developed various strategies to withstand environmental conditions that limit active growth. Endospore-forming Firmicutes (EFF) deploy a myriad of survival strategies in order to resist adverse conditions. Like many bacterial groups, they can form biofilms and detect nutrient scarcity through chemotaxis. Moreover, within this paraphyletic group of Firmicutes, ecophysiological optima are diverse. Nonetheless, a response to adversity that delimits this group is the formation of wet-heat resistant spores. These strategies are energetically demanding and therefore might affect the biological success of EFF. Therefore, we hypothesize that abundance and diversity of EFF should be maximized in those environments in which the benefits of these survival strategies offsets the energetic cost. In order to address this hypothesis, geothermal and mineral springs and drillings were selected because in these environments of steep physicochemical gradients, diversified survival strategies may become a successful strategy.We collected 71 samples from geothermal and mineral environments characterized by none (null), single or multiple limiting environmental factors (temperature, pH, UV radiation, and specific mineral composition). To measure success, we quantified EFF gene copy numbers (GCN; spo0A gene) in relation to total bacterial GCN (16S rRNA gene), as well as the contribution of EFF to community composition. The quantification showed that relative GCN for EFF reached up to 20% at sites characterized by multiple limiting environmental factors, whereas it corresponded to less than 1% at sites with one or no limiting environmental factor. Pyrosequencing of the 16S rRNA gene supports a higher contribution of EFF at sites with multiple limiting factors. Community composition suggested a combination of phylotypes for which active

  12. Contribution of Nano- to Microscale Roughness to Heterogeneity: Closing the Gap between Unfavorable and Favorable Colloid Attachment Conditions.

    PubMed

    Rasmuson, Anna; Pazmino, Eddy; Assemi, Shoeleh; Johnson, William P

    2017-02-21

    Surface roughness has been reported to both increase as well as decrease colloid retention. In order to better understand the boundaries within which roughness operates, attachment of a range of colloid sizes to glass with three levels of roughness was examined under both favorable (energy barrier absent) and unfavorable (energy barrier present) conditions in an impinging jet system. Smooth glass was found to provide the upper and lower bounds for attachment under favorable and unfavorable conditions, respectively. Surface roughness decreased, or even eliminated, the gap between favorable and unfavorable attachment and did so by two mechanisms: (1) under favorable conditions attachment decreased via increased hydrodynamic slip length and reduced attraction and (2) under unfavorable conditions attachment increased via reduced colloid-collector repulsion (reduced radius of curvature) and increased attraction (multiple points of contact, and possibly increased surface charge heterogeneity). Absence of a gap where these forces most strongly operate for smaller (<200 nm) and larger (>2 μm) colloids was observed and discussed. These observations elucidate the role of roughness in colloid attachment under both favorable and unfavorable conditions.

  13. α-Amylase in Vaginal Fluid: Association With Conditions Favorable to Dominance of Lactobacillus.

    PubMed

    Nasioudis, Dimitrios; Beghini, Joziani; Bongiovanni, Ann Marie; Giraldo, Paulo C; Linhares, Iara M; Witkin, Steven S

    2015-11-01

    Vaginal glycogen is degraded by host α-amylase and then converted to lactic acid by Lactobacilli. This maintains the vaginal pH at ≤4.5 and prevents growth of other bacteria. Therefore, host α-amylase activity may promote dominance of Lactobacilli. We evaluated whether the α-amylase level in vaginal fluid is altered in women with bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) and whether its concentration was associated with levels of lactic acid isomers and host mediators. Vaginal fluid was obtained from 43 women with BV, 50 women with VVC, and 62 women with no vulvovaginal disorders. Vaginal fluid concentrations of α-amylase, secretory leukocyte protease inhibitor (SLPI), hyaluronan, hyaluronidase-1, β-defensin, and elafin were measured by enzyme-linked immunosorbent assay (ELISA). Vaginal concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP) 8, and d- and l-lactic acid levels in these patients were previously reported. The median vaginal fluid α-amylase level was 1.83 mU/mL in control women, 1.45 mU/mL in women with VVC, and 1.07 mU/mL in women with BV. Vaginal levels of α-amylase were correlated with d-lactic acid (P = .003) but not with l-lactic acid (P > .05) and with SLPI (P < .001), hyaluronidase-1 (P < .001), NGAL (P = .001), and MMP-8 (P = .005). The exfoliation of glycogen-rich epithelial cells into the vaginal lumen by hyaluronidase-1 and MMP-8 may increase glycogen availability and promote α-amylase activity. The subsequent enhanced availability of glycogen breakdown products would favor proliferation of Lactobacilli, the primary producers of d-lactic acid in the vagina. Concomitant production of NGAL and SLPI would retard growth of BV-related bacteria.

  14. Greenland englacial drainage: conditions favoring water transport through a fractured aquifer

    NASA Astrophysics Data System (ADS)

    Creyts, T. T.; Fountain, A. G.

    2015-12-01

    Recently, the subglacial hydrology of glaciers and ice sheets has garnered intense interest because of its effects on ice sliding and potential ice sheet responses leading to sea level rise. Less attention has focused on the englacial water system that connects surface meltwater sources to the basal drainage system. Observations of englacial drainage have revealed diametrically opposed behaviors, so that understanding the role of the englacial system is critical to developing knowledge of ice sheet responses. The englacial connections either enhance or limit subglacial processes, including sliding. Some observations show cases where water drainage is mainly through an englacial system of fractures so that water flow at the bed is stunted. Other observations show static englacial water systems that play little role in drainage with primary drainage routes being along the bed. Here, we use a thermomechanical model of englacial water flow to understand the interaction between ice and water along these connections. We assume that water flow is through a series of connected fractures analogous to crevassed Greenland outlet glaciers. The fractures are modified by ice flow, and freezing and melting of the water system. Simple mathematical analyses show trade offs between closure rates and melting rates that determine the englacial flowpaths. From numerical experiments, we show that the dominance of englacial flow follows the locations of both bed overdeepenings and areas where the basal water system is compressed dynamically. The preponderance of overdeependenings in Greenland suggests that englacial systems may be favored in critical areas of ice sheet flow. We conclude by relating the insights from the analytic and numerical results to the broad scale patterns of change of the Greenland Ice Sheet.

  15. Predicting favorable conditions for early leaf spot of peanut using output from the Weather Research and Forecasting (WRF) model.

    PubMed

    Olatinwo, Rabiu O; Prabha, Thara V; Paz, Joel O; Hoogenboom, Gerrit

    2012-03-01

    Early leaf spot of peanut (Arachis hypogaea L.), a disease caused by Cercospora arachidicola S. Hori, is responsible for an annual crop loss of several million dollars in the southeastern United States alone. The development of early leaf spot on peanut and subsequent spread of the spores of C. arachidicola relies on favorable weather conditions. Accurate spatio-temporal weather information is crucial for monitoring the progression of favorable conditions and determining the potential threat of the disease. Therefore, the development of a prediction model for mitigating the risk of early leaf spot in peanut production is important. The specific objective of this study was to demonstrate the application of the high-resolution Weather Research and Forecasting (WRF) model for management of early leaf spot in peanut. We coupled high-resolution weather output of the WRF, i.e. relative humidity and temperature, with the Oklahoma peanut leaf spot advisory model in predicting favorable conditions for early leaf spot infection over Georgia in 2007. Results showed a more favorable infection condition in the southeastern coastline of Georgia where the infection threshold were met sooner compared to the southwestern and central part of Georgia where the disease risk was lower. A newly introduced infection threat index indicates that the leaf spot threat threshold was met sooner at Alma, GA, compared to Tifton and Cordele, GA. The short-term prediction of weather parameters and their use in the management of peanut diseases is a viable and promising technique, which could help growers make accurate management decisions, and lower disease impact through optimum timing of fungicide applications.

  16. Predicting favorable conditions for early leaf spot of peanut using output from the Weather Research and Forecasting (WRF) model

    NASA Astrophysics Data System (ADS)

    Olatinwo, Rabiu O.; Prabha, Thara V.; Paz, Joel O.; Hoogenboom, Gerrit

    2012-03-01

    Early leaf spot of peanut ( Arachis hypogaea L.), a disease caused by Cercospora arachidicola S. Hori, is responsible for an annual crop loss of several million dollars in the southeastern United States alone. The development of early leaf spot on peanut and subsequent spread of the spores of C. arachidicola relies on favorable weather conditions. Accurate spatio-temporal weather information is crucial for monitoring the progression of favorable conditions and determining the potential threat of the disease. Therefore, the development of a prediction model for mitigating the risk of early leaf spot in peanut production is important. The specific objective of this study was to demonstrate the application of the high-resolution Weather Research and Forecasting (WRF) model for management of early leaf spot in peanut. We coupled high-resolution weather output of the WRF, i.e. relative humidity and temperature, with the Oklahoma peanut leaf spot advisory model in predicting favorable conditions for early leaf spot infection over Georgia in 2007. Results showed a more favorable infection condition in the southeastern coastline of Georgia where the infection threshold were met sooner compared to the southwestern and central part of Georgia where the disease risk was lower. A newly introduced infection threat index indicates that the leaf spot threat threshold was met sooner at Alma, GA, compared to Tifton and Cordele, GA. The short-term prediction of weather parameters and their use in the management of peanut diseases is a viable and promising technique, which could help growers make accurate management decisions, and lower disease impact through optimum timing of fungicide applications.

  17. Optimization of fermentation condition favoring butanol production from glycerol by Clostridium pasteurianum DSM 525.

    PubMed

    Sarchami, Tahereh; Johnson, Erin; Rehmann, Lars

    2016-05-01

    Butanol is a promising biofuel and valuable platform chemical that can be produced through fermentative conversion of glycerol. The initial fermentation conditions for butanol production from pure glycerol by Clostridium pasteurianum DSM 525 were optimized via a central composite design. The effect of inoculum age, initial cell density, initial pH of medium and temperature were quantified and a quadratic model was able to predict butanol yield as a function of all four investigated factors. The model was confirmed through additional experiments and via analysis of variance (ANOVA). Subsequently, numerical optimization was used to maximize the butanol yield within the experimental range. Based on these results, batch fermentations in a 7 L bioreactor were performed using pure and crude (residue from biodiesel production) glycerol as substrates at optimized conditions. A butanol yield of 0.34 mole(butanol) mole(-1)(glycerol) was obtained indicating the suitability of this feedstock for fermentative butanol production.

  18. Asymmetric ecological conditions favor Red-Queen type of continued evolution over stasis.

    PubMed

    Nordbotten, Jan Martin; Stenseth, Nils C

    2016-02-16

    Four decades ago, Leigh Van Valen presented the Red Queen's hypothesis to account for evolution of species within a multispecies ecological community [Van Valen L (1973) Evol Theory 1(1):1-30]. The overall conclusion of Van Valen's analysis was that evolution would continue even in the absence of abiotic perturbations. Stenseth and Maynard Smith presented in 1984 [Stenseth NC, Maynard Smith J (1984) Evolution 38(4):870-880] a model for the Red Queen's hypothesis showing that both Red-Queen type of continuous evolution and stasis could result from a model with biotically driven evolution. However, although that contribution demonstrated that both evolutionary outcomes were possible, it did not identify which ecological conditions would lead to each of these evolutionary outcomes. Here, we provide, using a simple, yet general population-biologically founded eco-evolutionary model, such analytically derived conditions: Stasis will predominantly emerge whenever the ecological system contains only symmetric ecological interactions, whereas both Red-Queen and stasis type of evolution may result if the ecological interactions are asymmetrical, and more likely so with increasing degree of asymmetry in the ecological system (i.e., the more trophic interactions, host-pathogen interactions, and the like there are [i.e., +/- type of ecological interactions as well as asymmetric competitive (-/-) and mutualistic (+/+) ecological interactions]). In the special case of no between-generational genetic variance, our results also predict dynamics within these types of purely ecological systems.

  19. Asymmetric ecological conditions favor Red-Queen type of continued evolution over stasis

    PubMed Central

    Nordbotten, Jan Martin; Stenseth, Nils C.

    2016-01-01

    Four decades ago, Leigh Van Valen presented the Red Queen’s hypothesis to account for evolution of species within a multispecies ecological community [Van Valen L (1973) Evol Theory 1(1):1–30]. The overall conclusion of Van Valen’s analysis was that evolution would continue even in the absence of abiotic perturbations. Stenseth and Maynard Smith presented in 1984 [Stenseth NC, Maynard Smith J (1984) Evolution 38(4):870–880] a model for the Red Queen’s hypothesis showing that both Red-Queen type of continuous evolution and stasis could result from a model with biotically driven evolution. However, although that contribution demonstrated that both evolutionary outcomes were possible, it did not identify which ecological conditions would lead to each of these evolutionary outcomes. Here, we provide, using a simple, yet general population-biologically founded eco-evolutionary model, such analytically derived conditions: Stasis will predominantly emerge whenever the ecological system contains only symmetric ecological interactions, whereas both Red-Queen and stasis type of evolution may result if the ecological interactions are asymmetrical, and more likely so with increasing degree of asymmetry in the ecological system (i.e., the more trophic interactions, host–pathogen interactions, and the like there are [i.e., +/− type of ecological interactions as well as asymmetric competitive (−/−) and mutualistic (+/+) ecological interactions]). In the special case of no between-generational genetic variance, our results also predict dynamics within these types of purely ecological systems. PMID:26831108

  20. The Role of Imported Cases and Favorable Meteorological Conditions in the Onset of Dengue Epidemics

    PubMed Central

    Shang, Chuin-Shee; Wen, Tzai-Hung; Tsai, Kun-Hsien

    2010-01-01

    Background Travelers who acquire dengue infection are often routes for virus transmission to other regions. Nevertheless, the interplay between infected travelers, climate, vectors, and indigenous dengue incidence remains unclear. The role of foreign-origin cases on local dengue epidemics thus has been largely neglected by research. This study investigated the effect of both imported dengue and local meteorological factors on the occurrence of indigenous dengue in Taiwan. Methods and Principal Findings Using logistic and Poisson regression models, we analyzed bi-weekly, laboratory-confirmed dengue cases at their onset dates of illness from 1998 to 2007 to identify correlations between indigenous dengue and imported dengue cases (in the context of local meteorological factors) across different time lags. Our results revealed that the occurrence of indigenous dengue was significantly correlated with temporally-lagged cases of imported dengue (2–14 weeks), higher temperatures (6–14 weeks), and lower relative humidity (6–20 weeks). In addition, imported and indigenous dengue cases had a significant quantitative relationship in the onset of local epidemics. However, this relationship became less significant once indigenous epidemics progressed past the initial stage. Conclusions These findings imply that imported dengue cases are able to initiate indigenous epidemics when appropriate weather conditions are present. Early detection and case management of imported cases through rapid diagnosis may avert large-scale epidemics of dengue/dengue hemorrhagic fever. The deployment of an early-warning surveillance system, with the capacity to integrate meteorological data, will be an invaluable tool for successful prevention and control of dengue, particularly in non-endemic countries. PMID:20689820

  1. Climatic and environmental conditions favoring the crossing of the Carpathians by early Neolithic populations

    NASA Astrophysics Data System (ADS)

    Perşoiu, Ioana; Perşoiu, Aurel

    2015-04-01

    The study of the origin and spread of Neolithic has been the subject of heated debate since the early studies of Childe (1942). To what extent the dispersal process was influenced by environmental factors is still debated, one of the issues being whether climatic conditions influencing agricultural practices, could have influenced the dispersal route, "blocking" some of the Neolithic societies in front of ecological barriers. Data from Neolithic sites in SE Europe shows that a continuous stream of people and cultures flowed through the Danube's Iron Gates towards Central Europe, while in the eastern part of Europe this process was delayed, people and cultures "moving" around the Carpathians and crossing them with a delay of ca. 1000 years. One of the possible avenues for this crossing is the floodplain of Someşu Mic River (Transylvanian depression), home to the oldest (~8500 cal. BP) Neolithic settlement in Romania. In this paper, we review the climatic and environmental changes that affected the region at the time of Neolithic dispersal. Pollen and stable isotopes in cave ice indicate an early Holocene rapid warming during summer months, peaking around 7 ka cal. BP; and a delayed warming for autumn and winter months, peaking at 5 ka cal. BP, both followed by a continuous cooling trend towards the present. Someşu Mic River developed and maintained a narrow sinuous channel during the Holocene, with local development of meanders and anabranches, in response to both climatic and geologic controlling factors. Archaeological finds in the floodplain and the lower terraces suggest that human societies in the region responded in sensitive manner to these climatic and environmental changes. During warm and dry periods, with low fluvial activity, the number of settlements increased in the floodplain's perimeter, while during the short cold and humid periods, the number of settlements rapidly increased on the lower terraces and on the valley slopes, disappearing from the

  2. Use of RegCM gridded dataset for thunderstorm favorable conditions analysis over Poland—climatological approach

    NASA Astrophysics Data System (ADS)

    Walawender, Ewelina; Kielar, Rafał; Ustrnul, Zbigniew

    2017-01-01

    The paper analyzes equivalent data for a low density meteorological station network (spatially discontinuous data) and poor temporal homogeneity of thunderstorm observational data. Due to that, a Regional Climate Model (RegCM) dataset was tested. The Most Unstable Convective Available Potential Energy index value (MUCAPE) above the 200 J kg-1 threshold was selected as a predictor describing favorable conditions for the occurrence of thunderstorms. The quality of the dataset was examined through a comparison between model results and soundings from several aerological stations in Central Europe. Good, statistically significant (0.05 significance level) results were obtained through correlation analysis; the value of Pearson's correlation coefficient was above 0.8 in every single case. Then, using methods associated with gridded climatology, data series for 44 weather stations were derived and an analysis of correlation between RegCM modeled data and in situ thunderstorm observations was conducted with coefficients in the range of 0.75-0.90. The possibility of employing the dataset in thunderstorm climatology analysis was checked via a few examples by mapping monthly, seasonal, and annual means. Moreover, long-term variability and trend analysis along with modeled MUCAPE data were tested. As a result, the RegCM modeled MUCAPE gridded dataset was proposed as an easily available, suitable, and valuable predictor for thunderstorm climatology analysis and mapping. Finally, some limitations are discussed and recommendations for further improvements are given.

  3. Timing of favorable conditions, competition and fertility interact to govern recruitment of invasive Chinese tallow tree in stressful environments.

    PubMed

    Gabler, Christopher A; Siemann, Evan

    2013-01-01

    The rate of new exotic recruitment following removal of adult invaders (reinvasion pressure) influences restoration outcomes and costs but is highly variable and poorly understood. We hypothesize that broad variation in average reinvasion pressure of Triadica sebifera (Chinese tallow tree, a major invader) arises from differences among habitats in spatiotemporal availability of realized recruitment windows. These windows are periods of variable duration long enough to permit establishment given local environmental conditions. We tested this hypothesis via a greenhouse mesocosm experiment that quantified how the duration of favorable moisture conditions prior to flood or drought stress (window duration), competition and nutrient availability influenced Triadica success in high stress environments. Window duration influenced pre-stress seedling abundance and size, growth during stress and final abundance; it interacted with other factors to affect final biomass and germination during stress. Stress type and competition impacted final size and biomass, plus germination, mortality and changes in size during stress. Final abundance also depended on competition and the interaction of window duration, stress type and competition. Fertilization interacted with competition and stress to influence biomass and changes in height, respectively, but did not affect Triadica abundance. Overall, longer window durations promoted Triadica establishment, competition and drought (relative to flood) suppressed establishment, and fertilization had weak effects. Interactions among factors frequently produced different effects in specific contexts. Results support our 'outgrow the stress' hypothesis and show that temporal availability of abiotic windows and factors that influence growth rates govern Triadica recruitment in stressful environments. These findings suggest that native seed addition can effectively suppress superior competitors in stressful environments. We also describe

  4. Short-term favorable weather conditions are an important control of interannual variability in carbon and water fluxes.

    PubMed

    Zscheischler, Jakob; Fatichi, Simone; Wolf, Sebastian; Blanken, Peter D; Bohrer, Gil; Clark, Kenneth; Desai, Ankur R; Hollinger, David; Keenan, Trevor; Novick, Kimberly A; Seneviratne, Sonia I

    2016-08-01

    Ecosystem models often perform poorly in reproducing interannual variability in carbon and water fluxes, resulting in considerable uncertainty when estimating the land-carbon sink. While many aggregated variables (growing season length, seasonal precipitation, or temperature) have been suggested as predictors for interannual variability in carbon fluxes, their explanatory power is limited and uncertainties remain as to their relative contributions. Recent results show that the annual count of hours where evapotranspiration (ET) is larger than its 95th percentile is strongly correlated with the annual variability of ET and gross primary production (GPP) in an ecosystem model. This suggests that the occurrence of favorable conditions has a strong influence on the annual carbon budget. Here we analyzed data from eight forest sites of the AmeriFlux network with at least 7 years of continuous measurements. We show that for ET and the carbon fluxes GPP, ecosystem respiration (RE), and net ecosystem production, counting the "most active hours/days" (i.e., hours/days when the flux exceeds a high percentile) correlates well with the respective annual sums, with correlation coefficients generally larger than 0.8. Phenological transitions have much weaker explanatory power. By exploiting the relationship between most active hours and interannual variability, we classify hours as most active or less active and largely explain interannual variability in ecosystem fluxes, particularly for GPP and RE. Our results suggest that a better understanding and modeling of the occurrence of large values in high-frequency ecosystem fluxes will result in a better understanding of interannual variability of these fluxes.

  5. Short-term favorable weather conditions are an important control of interannual variability in carbon and water fluxes

    NASA Astrophysics Data System (ADS)

    Zscheischler, Jakob; Fatichi, Simone; Wolf, Sebastian; Blanken, Peter D.; Bohrer, Gil; Clark, Kenneth; Desai, Ankur R.; Hollinger, David; Keenan, Trevor; Novick, Kimberly A.; Seneviratne, Sonia I.

    2016-08-01

    Ecosystem models often perform poorly in reproducing interannual variability in carbon and water fluxes, resulting in considerable uncertainty when estimating the land-carbon sink. While many aggregated variables (growing season length, seasonal precipitation, or temperature) have been suggested as predictors for interannual variability in carbon fluxes, their explanatory power is limited and uncertainties remain as to their relative contributions. Recent results show that the annual count of hours where evapotranspiration (ET) is larger than its 95th percentile is strongly correlated with the annual variability of ET and gross primary production (GPP) in an ecosystem model. This suggests that the occurrence of favorable conditions has a strong influence on the annual carbon budget. Here we analyzed data from eight forest sites of the AmeriFlux network with at least 7 years of continuous measurements. We show that for ET and the carbon fluxes GPP, ecosystem respiration (RE), and net ecosystem production, counting the "most active hours/days" (i.e., hours/days when the flux exceeds a high percentile) correlates well with the respective annual sums, with correlation coefficients generally larger than 0.8. Phenological transitions have much weaker explanatory power. By exploiting the relationship between most active hours and interannual variability, we classify hours as most active or less active and largely explain interannual variability in ecosystem fluxes, particularly for GPP and RE. Our results suggest that a better understanding and modeling of the occurrence of large values in high-frequency ecosystem fluxes will result in a better understanding of interannual variability of these fluxes.

  6. Favorable alleles for stem water-soluble carbohydrates identified by association analysis contribute to grain weight under drought stress conditions in wheat.

    PubMed

    Li, Weiyu; Zhang, Bin; Li, Runzhi; Chang, Xiaoping; Jing, Ruilian

    2015-01-01

    Drought is a major environmental constraint to crop distribution and productivity. Stem water-soluble carbohydrates (WSC) buffer wheat grain yield against conditions unfavorable for photosynthesis during the grain filling stage. In this study, 262 winter wheat accessions and 209 genome-wide SSR markers were collected and used to undertake association analysis based on a mixed linear model (MLM). The WSC in different internodes at three growth stages and 1000-grain weight (TGW) were investigated under four environmental regimes (well-watered, drought stress during the whole growth period, and two levels of terminal drought stress imposed by chemical desiccation under the well-watered and drought stress during the whole growth period conditions). Under diverse drought stress conditions, WSC in lower internodes showed significant positive correlations with TGW, especially at the flowering stage under well-watered conditions and at grain filling under drought stress. Sixteen novel WSC-favorable alleles were identified, and five of them contributed to significantly higher TGW. In addition, pyramiding WSC favorable alleles was not only effective for obtaining accessions with higher WSC, but also for enhancing TGW under different water regimes. During the past fifty years of wheat breeding, WSC was selected incidentally. The average number of favorable WSC alleles increased from 1.13 in the pre-1960 period to 4.41 in the post-2000 period. The results indicate a high potential for using marker-assisted selection to pyramid WSC favorable alleles in improving WSC and TGW in wheat.

  7. Analysis of the hydrographic conditions and cyst beds in the San Jorge Gulf, Argentina, that favor dinoflagellate population development including toxigenic species and their toxins

    NASA Astrophysics Data System (ADS)

    Krock, Bernd; Borel, C. Marcela; Barrera, Facundo; Tillmann, Urban; Fabro, Elena; Almandoz, Gastón O.; Ferrario, Martha; Garzón Cardona, John E.; Koch, Boris P.; Alonso, Cecilia; Lara, Rubén

    2015-08-01

    The overlay of cooler nutrient enriched Beagle-Magellan water with warmer nutrient depleted shelf water and a strong stratification of the water column in the San Jorge Gulf region, Argentina, coincided with relatively high dinoflagellate abundances in April 2012, up to 34,000 cells L- 1. This dinoflagellate proliferation was dominated by Ceratium spp., but environmental conditions also favored to a lesser amount the occurrence of toxigenic dinoflagellates, such as Alexandrium tamarense and Protoceratium reticulatum, whose toxins were hardly detected in any other areas along the expedition transect of the R/V Puerto Deseado between 38 and 56°S (Ushuaia-Mar del Plata) in March/April 2012. Generally vegetative cells of A. tamarense and P. reticulatum co-occurred with their respective phycotoxins in the water column and their cysts in the upper sediment layers. Two strains of A. tamarense were isolated from the bloom sample and morphologically characterized. Their PSP toxin profiles consisted of C1/2, gonyautoxins 1/4 and to a lesser amount of neosaxitoxin and confirmed earlier data from this region. The ratios between autotrophic picoplankton and heterotrophic bacteria were higher in shelf waters in the north than in Beagle-Magellan waters in the south of San Jorge Gulf.

  8. Using geologic conditions and multiattribute decision analysis to determine the relative favorability of selected areas for siting a high-level radioactive waste repository

    SciTech Connect

    Harrison, W.; Edgar, D.E.; Baker, C.H.; Buehring, W.A.; Whitfield, R.G.; Van Luik, A.E.J.; Sood, M.K.; Flower, M.F.J.; Warren, M.F.; Jusko, M.J.; Peerenboom, J.P.; Bogner, J.E.

    1988-05-01

    A method is presented for determining the relative favorability of geologically complex areas for isolating high-level radioactive wastes. In applying the method to the northeastern region of the United States, seismicity and tectonic activity were the screening criteria used to divide the region into three areas of increasing seismotectonic risk. Criteria were then used to subdivide the area of lowest seismotectonic risk into six geologically distinct subareas including characteristics, surface-water and groundwater hydrology, potential human intrusion, site geometry, surface characteristics, and tectonic environment. Decision analysis was then used to identify the subareas most favorable from a geologic standpoint for further investigation, with a view to selecting a site for a repository. Three subareas (parts of northeastern Vermont, northern New Hampshire, and western Maine) were found to be the most favorable, using this method and existing data. However, because this study assessed relative geologic favorability, no conclusions should be drawn concerning the absolute suitability of individual subareas for high-level radioactive waste isolation. 34 refs., 7 figs., 20 tabs.

  9. Les conditions d’hébergement favorables au rétablissement : perspective des usagers et usagères

    PubMed Central

    Piat, Myra; Boyer, Richard; Cloutier, Simon; Fleury, Marie-Josée; Lesage, Alain

    2016-01-01

    Cette recherche vise à mieux comprendre le rôle de l’hébergement dans le rétablissement des personnes vivant avec une maladie mentale grave. Quarante résidents et résidentes de différents types d’hébergement communautaire structuré ont été interrogés sur les conditions d’hébergement qui favorisent leur rétablissement. Les résultats indiquent qu’aux yeux des résidents et résidentes, les conditions matérielles d’existence ont une influence déterminante sur le rétablissement. Leurs préoccupations s’articulent autour des besoins de base tels que l’alimentation, le coût, les commodités et la qualité de leur hébergement. Les relations sociales avec leur entourage immédiat ont également une grande influence sur le rétablissement des personnes, lesquelles souhaitent d’abord conserver leurs modestes acquis, tant matériels que sociaux. Cette stabilité est prérequise à leur rétablissement. PMID:27099410

  10. Favorable conditions noted for Australia shale oil

    SciTech Connect

    Not Available

    1986-09-01

    After brief descriptions of the Rundle, Condor, and Stuart/Kerosene Creek oil shale projects in Queensland, the competitive advantages of oil shale development and the state and federal governments' attitudes towards an oil shale industry in Australia are discussed. It is concluded that Australia is the ideal country in which to start an oil shale industry.

  11. GRIZZLY/FAVOR Interface Project Report

    SciTech Connect

    Dickson, Terry L; Williams, Paul T; Yin, Shengjun; Klasky, Hilda B; Tadinada, Sashi; Bass, Bennett Richard

    2013-06-01

    As part of the Light Water Reactor Sustainability (LWRS) Program, the objective of the GRIZZLY/FAVOR Interface project is to create the capability to apply GRIZZLY 3-D finite element (thermal and stress) analysis results as input to FAVOR probabilistic fracture mechanics (PFM) analyses. The one benefit of FAVOR to Grizzly is the PROBABILISTIC capability. This document describes the implementation of the GRIZZLY/FAVOR Interface, the preliminary verification and tests results and a user guide that provides detailed step-by-step instructions to run the program.

  12. Minimum Favorable Conditions for Hydrogen-Diesel Combustion

    NASA Astrophysics Data System (ADS)

    Hanson, Jacob Dylan

    A test apparatus was designed and fabricated that allowed very small amounts of diesel fuel to be injected into a hydrogen-air mixture. This apparatus was designed to be able to operate near the limits of diesel fuel injectors. The purpose of this apparatus is to find out if the injectors in diesel engines are capable of igniting a hydrogen-air mixture when operated at their limits and to explore past their limits for further advancement in the field of dual-fuel hydrogen-diesel combustion. The minimum flow rate of diesel fuel the apparatus could produce was 120.46 (cm3)/min and the fastest response time that could be achieved was 1 ms. Both of these parameters at least met the limits of the current diesel injection setups. The smallest mass of diesel fuel that could be injected was 15.7 mg. This mass produced combustion in the hydrogen-air mixture for all hydrogen concentrations and temperatures tested.

  13. New Study Says CAI May Favor Introverts.

    ERIC Educational Resources Information Center

    Hopmeier, George

    1981-01-01

    A personality research study using the Myers-Briggs Type Indicator indicates that computer-assisted instruction programs favor introverts, i.e., those learners who can concentrate on details, memorize facts, and stay with a task until it is completed. (JJD)

  14. To Form a Favorable Idea of Chemistry

    ERIC Educational Resources Information Center

    Heikkinen, Henry W.

    2010-01-01

    "To confess the truth, Mrs. B., I am not disposed to form a very favorable idea of chemistry, nor do I expect to derive much entertainment from it." That 200-year-old statement by Caroline to Mrs. Bryan, her teacher, appeared on the first page of Jane Marcet's pioneering secondary school textbook, "Conversations on Chemistry". It was published 17…

  15. Familial risk factors favoring drug addiction onset.

    PubMed

    Zimić, Jadranka Ivandić; Jukić, Vlado

    2012-01-01

    This study, primarily aimed at identification of familial risk factors favoring drug addiction onset, was carried out throughout 2008 and 2009. The study comprised a total of 146 addicts and 134 control subjects. Based on the study outcome, it can be concluded that in the families the addicts were born into, familial risk factors capable of influencing their psychosocial development and favoring drug addiction onset had been statistically more frequently encountered during childhood and adolescence as compared to the controls. The results also indicated the need for further research into familial interrelations and the structure of the families addicts were born into, as well as the need for the implementation of family-based approaches to both drug addiction prevention and therapy.

  16. On Favorable Thermal Fields for Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Stelian, Carmen; Volz, Martin P.; Derby, Jeffrey J.

    2009-01-01

    The thermal fields of two Bridgman-like configurations, representative of real systems used in prior experiments for the detached growth of CdTe and Ge crystals, are studied. These detailed heat transfer computations are performed using the CrysMAS code and expand upon our previous analyses [14] that posited a new mechanism involving the thermal field and meniscus position to explain stable conditions for dewetted Bridgman growth. Computational results indicate that heat transfer conditions that led to successful detached growth in both of these systems are in accordance with our prior assertion, namely that the prevention of crystal reattachment to the crucible wall requires the avoidance of any undercooling of the melt meniscus during the growth run. Significantly, relatively simple process modifications that promote favorable thermal conditions for detached growth may overcome detrimental factors associated with meniscus shape and crucible wetting. Thus, these ideas may be important to advance the practice of detached growth for many materials.

  17. Children's need for favorable acoustics in schools

    NASA Astrophysics Data System (ADS)

    Nelson, Peggy B.

    2003-10-01

    Children continue to improve their understanding of speech in noise and reverberation throughout childhood and adolescence. They do not typically achieve adult performance levels until their late teenage years. As a result, schools that are designed to be acoustically adequate for adult understanding may be insufficient for full understanding by young children. In addition, children with hearing loss, those with attention problems, and those learning in a non-native language require even more favorable signal-to-noise ratios. This tutorial will review the literature gathered by the ANSl/ASA working group on classroom acoustics that shaped the recommendations of the working group. Special topics will include speech perception data from typically developing infants and children, from children with hearing loss, and from adults and children listening in a non-native language. In addition, the tutorial will overview recommendations contained within ANSI standard 12.60-2002: Acoustical Performance Criteria, Design Requirements, and Guidelines for Schools. The discussion will also include issues related to designing quiet classrooms and working with local schools and professionals.

  18. Habitat heterogeneity favors asexual reproduction in natural populations of grassthrips

    PubMed Central

    Lavanchy, Guillaume; Strehler, Marie; Llanos Roman, Maria Noemi; Lessard‐Therrien, Malie; Humbert, Jean‐Yves; Dumas, Zoé; Jalvingh, Kirsten; Ghali, Karim; Fontcuberta García‐Cuenca, Amaranta; Zijlstra, Bart; Arlettaz, Raphaël; Schwander, Tanja

    2016-01-01

    Explaining the overwhelming success of sex among eukaryotes is difficult given the obvious costs of sex relative to asexuality. Different studies have shown that sex can provide benefits in spatially heterogeneous environments under specific conditions, but whether spatial heterogeneity commonly contributes to the maintenance of sex in natural populations remains unknown. We experimentally manipulated habitat heterogeneity for sexual and asexual thrips lineages in natural populations and under seminatural mesocosm conditions by varying the number of hostplants available to these herbivorous insects. Asexual lineages rapidly replaced the sexual ones, independently of the level of habitat heterogeneity in mesocosms. In natural populations, the success of sexual thrips decreased with increasing habitat heterogeneity, with sexual thrips apparently only persisting in certain types of hostplant communities. Our results illustrate how genetic diversity‐based mechanisms can favor asexuality instead of sex when sexual lineages co‐occur with genetically variable asexual lineages. PMID:27346066

  19. Habitat heterogeneity favors asexual reproduction in natural populations of grassthrips.

    PubMed

    Lavanchy, Guillaume; Strehler, Marie; Llanos Roman, Maria Noemi; Lessard-Therrien, Malie; Humbert, Jean-Yves; Dumas, Zoé; Jalvingh, Kirsten; Ghali, Karim; Fontcuberta García-Cuenca, Amaranta; Zijlstra, Bart; Arlettaz, Raphaël; Schwander, Tanja

    2016-08-01

    Explaining the overwhelming success of sex among eukaryotes is difficult given the obvious costs of sex relative to asexuality. Different studies have shown that sex can provide benefits in spatially heterogeneous environments under specific conditions, but whether spatial heterogeneity commonly contributes to the maintenance of sex in natural populations remains unknown. We experimentally manipulated habitat heterogeneity for sexual and asexual thrips lineages in natural populations and under seminatural mesocosm conditions by varying the number of hostplants available to these herbivorous insects. Asexual lineages rapidly replaced the sexual ones, independently of the level of habitat heterogeneity in mesocosms. In natural populations, the success of sexual thrips decreased with increasing habitat heterogeneity, with sexual thrips apparently only persisting in certain types of hostplant communities. Our results illustrate how genetic diversity-based mechanisms can favor asexuality instead of sex when sexual lineages co-occur with genetically variable asexual lineages.

  20. Salinity inversions in the thermocline under upwelling favorable winds

    NASA Astrophysics Data System (ADS)

    Burchard, Hans; Basdurak, N. Berkay; Gräwe, Ulf; Knoll, Michaela; Mohrholz, Volker; Müller, Selina

    2017-02-01

    This paper discusses and explains the phenomenon of salinity inversions in the thermocline offshore from an upwelling region during upwelling favorable winds. Using the nontidal central Baltic Sea as an easily accessible natural laboratory, high-resolution transect and station observations in the upper layers are analyzed. The data show local salinity minima in the strongly stratified seasonal thermocline during summer conditions under the influence of upwelling favorable wind. A simple analytical box model using parameters (including variation by means of a Monte Carlo method) estimated from a hindcast model for the Baltic Sea is constructed to explain the observations. As a result, upwelled water with high salinity and low temperature is warmed up due to downward surface heat fluxes while it is transported offshore by the Ekman transport. The warming of upwelled surface water allows maintenance of stable stratification despite the destabilizing salinity stratification, such that local salinity minima in the thermocline can be generated. Inspection of published observations from the Benguela, Peruvian, and eastern tropical North Atlantic upwelling systems shows that also there salinity inversions occur in the thermocline, but in these cases thermocline salinity shows local maxima, since upwelled water has a lower salinity than the surface water. It is hypothesized that thermocline salinity inversions should generally occur offshore from upwelling regions whenever winds are steady enough and surface warming is sufficiently strong.

  1. Coevolution of robustness, epistasis, and recombination favors asexual reproduction.

    PubMed

    MacCarthy, Thomas; Bergman, Aviv

    2007-07-31

    The prevalence of sexual reproduction remains one of the most perplexing phenomena in evolutionary biology. The deterministic mutation hypothesis postulates that sexual reproduction will be advantageous under synergistic epistasis, a condition in which mutations cause a greater reduction in fitness when combined than would be expected from their individual effects. The inverse condition, antagonistic epistasis, correspondingly is predicted to favor asexual reproduction. To assess this hypothesis, we introduce a finite population evolutionary process that combines a recombination modifier formalism with a gene-regulatory network model. We demonstrate that when reproductive mode and epistasis are allowed to coevolve, asexual reproduction outcompetes sexual reproduction. In addition, no correlation is found between the level of synergistic epistasis and the fixation time of the asexual mode. However, a significant correlation is found between the level of antagonistic epistasis and asexual mode fixation time. This asymmetry can be explained by the greater reduction in fitness imposed by sexual reproduction as compared with asexual reproduction. Our findings present evidence and suggest plausible explanations that challenge both the deterministic mutation hypothesis and recent arguments asserting the importance of emergent synergistic epistasis in the maintenance of sexual reproduction.

  2. Competition favors elk over beaver in a riparian willow ecosystem

    USGS Publications Warehouse

    Baker, B.W.; Peinetti, H.R.; Coughenour, M.C.; Johnson, T.L.

    2012-01-01

    Beaver (Castor spp.) conservation requires an understanding of their complex interactions with competing herbivores. Simulation modeling offers a controlled environment to examine long-term dynamics in ecosystems driven by uncontrollable variables. We used a new version of the SAVANNA ecosystem model to investigate beaver (C. Canadensis) and elk (Cervus elapses) competition for willow (Salix spp.). We initialized the model with field data from Rocky Mountain National Park, Colorado, USA, to simulate a 4-ha riparian ecosystem containing beaver, elk, and willow. We found beaver persisted indefinitely when elk density was or = 30 elk km_2. The loss of tall willow preceded rapid beaver declines, thus willow condition may predict beaver population trajectory in natural environments. Beaver were able to persist with slightly higher elk densities if beaver alternated their use of foraging sites in a rest-rotation pattern rather than maintained continuous use. Thus, we found asymmetrical competition for willow strongly favored elk over beaver in a simulated montane ecosystem. Finally, we discuss application of the SAVANNA model and mechanisms of competition relative to beaver persistence as metapopulations, ecological resistance and alternative state models, and ecosystem regulation.

  3. 18 CFR 706.303 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... solicit from a person having business with the Council anything of value as a gift, gratuity, loan, entertainment, or favor for himself or another person, particularly one with whom he has family, business,...

  4. Most Americans Favor Larger Health Warnings on Cigarette Packs

    MedlinePlus

    ... html Most Americans Favor Larger Health Warnings on Cigarette Packs Even many smokers think these warnings should ... 31, 2017 FRIDAY, March 31, 2017 (HealthDay News) -- Cigarette packs carry health warnings, but many Americans think ...

  5. Experimental Investigation of a Supersonic Boundary Layer Including Favorable Pressure Gradient Effects

    DTIC Science & Technology

    2011-07-21

    United States Government. EXPERIMENTAL INVESTIGATION OF A SUPERSONIC BOUNDARY LAYER INCLUDING FAVORABLE PRESSURE GRADIENT EFFECTS THESIS Presented to...flow to be disturbed from its original state . Aside from providing a non-intrusive method of measurement, LDV has the advantage of measuring the...providing some useful test of turbulence modeling. 4. Well-defined experimental boundary conditions: All incoming conditions (especially the state of

  6. Short-term oral toxicity study of FAVOR PAC in rats.

    PubMed

    Haselbach, J; Hey, S; Berner, T

    2000-12-01

    A short-term rat feeding study was conducted to evaluate the oral toxicity of FAVOR PAC (CAS Registry No. 9003-04-7), one member of a family of cross-linked sodium polyacrylate polymers developed by Stockhausen GmbH & Co KG (Krefeld, Germany). FAVOR polymers are classified as superabsorbent polymers because of their ability to absorb and retain large volumes of fluid. In this short-term study, three groups of 10 male and 10 female Sprague-Dawley rats were administered 0 (control), 1, or 5% FAVOR PAC in the diet daily for up to 32 days. No significant changes in clinical signs, body weight and food consumption, functional observation battery results, ophthalmoscopy, hematology and clinical chemistries, or absolute and relative organ weights were observed. Significant differences between treated and control animals were limited to increases in water consumption and modifications in urinary ionic excretion. Both findings were likely the result of the relatively high concentration of sodium in the test article, and thus consistent with adaptive physiologic changes, not overt toxicity. In conclusion, levels of up to 5% FAVOR PAC in the diet produced no treatment-related toxicity in rats under the conditions of this short-term test (i.e., a NOAEL of 5% FAVOR PAC in the diet was identified).

  7. Filtering the Net in Libraries: The Case (Mostly) in Favor.

    ERIC Educational Resources Information Center

    Banks, Michael A.

    1998-01-01

    Examines issues and decision-making involved in restricting Internet access in libraries, for the most part favoring filtering devices. Questions to consider when selecting a filtering program are provided. Some of the better filtering programs are described, and Web addresses are included for each. Security risks associated with Java and…

  8. 25 CFR 700.519 - Gifts, entertainment and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employee Responsibility and Conduct § 700.519 Gifts, entertainment and favors. (a) Acceptance of gratuities... individuals with whom Commission employees do business. This prohibition extends to the acceptance of meals and refreshments offered by individuals conducting or seeking business with the Commission...

  9. Preschoolers Reduce Inequality While Favoring Individuals with More

    ERIC Educational Resources Information Center

    Li, Vivian; Spitzer, Brian; Olson, Kristina R.

    2014-01-01

    Inequalities are everywhere, yet little is known about how children respond to people affected by inequalities. This article explores two responses--minimizing inequalities and favoring those who are advantaged by them. In Studies 1a (N = 37) and 1b (N = 38), 4- and 5-year-olds allocated a resource to a disadvantaged recipient, but judged…

  10. Increasing long term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  11. 22 CFR 1203.735-305 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Gifts, entertainment, and favors. 1203.735-305 Section 1203.735-305 Foreign Relations UNITED STATES INTERNATIONAL DEVELOPMENT COOPERATION AGENCY EMPLOYEE... the Constitution and in 5 U.S.C. 7342, and the regulations promulgated thereunder pursuant to...

  12. 22 CFR 1203.735-305 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Gifts, entertainment, and favors. 1203.735-305 Section 1203.735-305 Foreign Relations UNITED STATES INTERNATIONAL DEVELOPMENT COOPERATION AGENCY EMPLOYEE... the Constitution and in 5 U.S.C. 7342, and the regulations promulgated thereunder pursuant to...

  13. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  14. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  15. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  16. 11 CFR 7.8 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Employees or Commissioners § 7.8 Gifts, entertainment, and favors. (a) A Commissioner or employee of the... affected by the performance or nonperformance of the Commissioner or employee's official duty. (b... persons concerned which are the motivating factors; (2) To the acceptance of food, refreshments,...

  17. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  18. 18 CFR 706.202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... EMPLOYEE RESPONSIBILITIES AND CONDUCT Conduct and Responsibilities of Employees § 706.202 Gifts, entertainment, and favors. (a) Except as provided in paragraphs (b) and (c) of this section, an employee shall... to: (1) Obvious family or personal relationships, such as those between the employee and his...

  19. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role.

    PubMed

    Hage, Mirella P; Al-Badri, Marwa R; Azar, Sami T

    2014-08-01

    Hydroxychloroquine (HCQ), a commonly used antimalarial drug in rheumatic diseases, has shown favorable metabolic effects on both glucose control and lipid profiles. We describe a case of a young woman with type 1 diabetes whose glycemic control was optimized with the introduction of HCQ as a treatment for her Sjogren syndrome in addition to a subtle yet measurable improvement in her lipid profile. An increasing body of evidence supports the beneficial impacts of HCQ in various ancillary conditions, including diabetes mellitus and dyslipidemia. However, mechanisms of action responsible for these effects remain ill-defined and may include alterations in insulin metabolism and signaling through cellular receptors. These favorable metabolic effects of HCQ and further understanding of underlying mechanisms may provide an additional rational for its use in rheumatic diseases, conditions associated with an elevated cardiovascular risk.

  20. Multimodality therapy of favorable prognosis non-Hodgkin's lymphoma

    SciTech Connect

    Corder, M.P.; Leimert, J.T.; Tewfik, H.H.; Lovett, J.M.

    1983-07-01

    Twenty-seven previously untreated patients with favorable prognosis non-Hodgkin's lymphoma were treated with a combination of total body irradiation followed by cyclophosphamide - vincristine - prednisone (CVP). The dose of total body irradiation was planned to be 150 rad followed by 6 cycles of chemotherapy. The complete response rate was 59%; the complete plus partial response rate, 93%. The 50% disease-free survival was 8 months. The actuarial projected 5 year survival was 60% and the disease-free survival at 5 years was 27%. The program was well tolerated by the majority of patients. It is possible for some patients with favorable non-Hodgkin's lymphomas to achieve prolonged periods of disesase-free survival when treated with combinations of irradiation plus chemotherapy.

  1. Design integration of favorable geometry, structural support and containment

    SciTech Connect

    Purcell, J.A.; McGehee, G.A.

    1991-07-01

    In designs for fissile processes at Savannah River site, different approaches have been used to provide engineered margins of safety for criticality with containment and seismic resistance as additional requirements. These requirements are frequently at odds in engineered systems. This paper proposes a plan to take advantage of vessels with favorable geometry to provide seismic resistance and to support a glovebox for containment. Thin slab tanks, small diameter pencil tanks, annular tanks, and other novel designs have been used for criticality safety. The requirement for DBE seismic resistance and rigid control of dimensions leads the designer to consider annular tanks for meeting these requirements. The high strength of annular tanks may logically be used to support secondary containment. Hands-on access to all instruments, piping etc. within containment can be provided through gloveports, thus a specialized glovebox. This paper examines the advantages of using an annular tank design to provide favorable geometry, structural support and containment.

  2. Contact line pinning favors the mass production of monodisperse microbubbles.

    NASA Astrophysics Data System (ADS)

    Gordillo, Jose Manuel; Campo-Cortes, Francisco; Riboux, Guillaume

    2015-11-01

    A robust method for the generation of phospholipid covered monodisperse microbubbles of diameters ~10 microns at production rates exceeding 0.1 MHz, is presented here. We show that bubbles are periodically formed from the tip of a long and thin gas ligament stabilized thanks to both the strong favorable pressure gradient existing at the entrance region of a long rectangular PDMS-PDMS channel and to the pinning of the gas-liquid interface at a centered groove of several microns width placed on one of its walls. Moreover, the long exit channel incorporated in our design, favors the transport of phospholipid molecules towards the gas-liquid interface. Our experiments show that the resulting phospholipid shell inhibit both the diffusion of the gas in the surrounding liquid as well as the coalescence between contacting bubbles. These evidences indicate that the proposed method is suitable for the generation of monodisperse microbubbles for diagnosis or therapeutical applications.

  3. Autophagy favors Brucella melitensis survival in infected macrophages.

    PubMed

    Guo, Fei; Zhang, Hui; Chen, Chuangfu; Hu, Shengwei; Wang, Yuanzhi; Qiao, Jun; Ren, Yan; Zhang, Ke; Wang, Yong; Du, Guoqing

    2012-06-01

    This study investigated the role of autophagy in the survival of the invasive bacterium Brucella melitensis strain 16M in murine macrophages. Here, Brucella melitensis 16M was found to trigger autophagosome formation, enhance autophagy flux and increase the expression level of the autophagy marker protein LC3-II. When autophagy was pharmacologically inhibited by 3-methyladenine (3-MA), Brucella replication efficiency was significantly decreased (p < 0.05). These results suggest that autophagy favors Brucella melitensis 16M survival in murine macrophages.

  4. Bioactive, mechanically favorable, and biodegradable copolymer nanocomposites for orthopedic applications.

    PubMed

    Victor, Sunita Prem; Muthu, Jayabalan

    2014-06-01

    We report the synthesis of mechanically favorable, bioactive, and biodegradable copolymer nanocomposites for potential bone applications. The nanocomposites consist of in situ polymerized biodegradable copolyester with hydroxyapatite (HA). Biodegradable copolyesters comprise carboxy terminated poly(propylene fumarate) (CT-PPF) and poly(trimethylol propane fumarate co mannitol sebacate) (TF-Co-MS). Raman spectral imaging clearly reveals a uniform homogenous distribution of HA in the copolymer matrix. The mechanical studies reveal that improved mechanical properties formed when crosslinked with methyl methacrylate (MMA) when compared to N-vinyl pyrrolidone (NVP). The SEM micrographs of the copolymer nanocomposites reveal a serrated structure reflecting higher mechanical strength, good dispersion, and good interfacial bonding of HA in the polymer matrix. In vitro degradation of the copolymer crosslinked with MMA is relatively more than that of NVP and the degradation decreases with an increase in the amount of the HA filler. The mechanically favorable and degradable MMA based nanocomposites also have favorable bioactivity, blood compatibility, cytocompatibility and cell adhesion. The present nanocomposite is a more promising material for orthopedic applications.

  5. Gestational Weight Gain in Japanese Women With Favorable Perinatal Outcomes

    PubMed Central

    Suzuki, Shunji

    2017-01-01

    Background We examined the optimal gestational weight gain (GWG) in the healthy Japanese women with favorable perinatal outcomes of singleton pregnancy. Methods We calculated the average GWG in the women whose height was 150 - 164 cm with favorable perinatal outcomes set for this study. The women were categorized to underweight, normal, overweight and obese based on the pre-pregnancy body mass index categories according to the Institute of Medicine guideline. Results The average GWG in the normal-weight women with the favorable perinatal outcomes was 11.4 ± 3.7 kg. It was not significantly different from that in the underweight and overweight women (12.0 ± 3.4 and 10.0 ± 4.8 kg) by Student’s t-test. The average GWG in the obese women was significantly lower than that in the other three groups (3.2 ± 2.2 kg, P < 0.01). Conclusion Based on the current results, the optimal GWG for the Japanese women without obesity was found to be 10 - 12 kg. PMID:27924177

  6. Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite.

    PubMed

    Giordanengo, Laura; Guiñazú, Natalia; Stempin, Cinthia; Fretes, Ricardo; Cerbán, Fabio; Gea, Susana

    2002-04-01

    We recently demonstrated that humoral immune response to cruzipain, a major antigen of Trypanosoma cruzi parasite, is implicated in the pathogenesis of experimental Chagas' disease. In the present study, the spleen cell phenotype and the cytokine profile induced by cruzipain in immunized mice were analyzed. The results showed that cruzipain increases the number of spleen cells with large size and granularity. Splenocyte populations with CD19(+), Mac-1(+), Gr-1(+) and CD11c(+) positive surface markers significantly increased in immune mice compared to controls ones. Histological study revealed the presence of high number of megacariocyte and granulocyte-macrophage progenitors, indicating extramedullary hemopoiesis in spleens of immune mice. The finding of high levels of IL-4, IL5 and IL-10 and low levels of IFN-gamma and IL-12 in supernatants of immune cells stimulated with cruzipain indicates a preferential activation of T2 type cells in immune animals. To investigate the role of innate immunity cells, the classical and alternative metabolic pathways of spleen macrophages from immune mice stimulated by cruzipain were also studied. The results showed an increase of urea associated with a decrease of nitrite levels, suggesting that cruzipain up-regulates the arginase way. Therefore, cruzipain leads to T2 type cytokine profile which may enhance the arginase via in the macrophages promoting a susceptible mechanism to infection. Thus, we postulate that during T. cruzi infection, cruzipain could be used by the parasite to spread inside the host.

  7. Organic particulate material levels in the atmosphere: conditions favoring sensitivity to varying relative humidity and temperature.

    PubMed

    Pankow, James F

    2010-04-13

    This study examines the sensitivity in predicted levels of atmospheric organic particulate matter (M(o), microg m(-3)) as those levels may potentially be affected by changes in relative humidity and temperature. In a given system, for each partitioning compound, f(g) and f(p) represent the gaseous and particulate fractions (f(g) + f(p) = 1). Sensitivity in the M(o) levels becomes dampened as the compounds contributing significantly to M(o) are increasingly found in the particle phase (f(p) --> 1). Thus, although local maxima in sensitivity can be encountered as M(o) levels increase, because as M(o) increases each f(p) --> 1, then increasing M(o) levels generally tend to reduce sensitivity in M(o) levels to changes in relative humidity and temperature. Experiments designed to elucidate the potential magnitudes of the effects of relative humidity and temperature on M(o) levels must be carried out at M(o) levels that are relevant for the ambient atmosphere: The f(p) values for the important partitioning compounds must not be elevated above ambient-relevant values. Systems in which M(o) levels are low (e.g., 1-2 microg m(-3)) and/or composed of unaged secondary organic aerosol are the ones most likely to show sensitivity to changing relative humidity and temperature. Results from two published chamber studies are examined in the above regard: [Warren B, et al. (2009) Atmos Environ 43:1789-1795] and [Prisle NL, et al. (2010) Geophys Res Lett 37:L01802].

  8. Metabolomic evaluation of conditions favoring mycotoxin production in isolates of Fusarium fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several species of Fusarium have the potential to produce secondary metabolites that have been identified as mycotoxins. Mycotoxins are often found in plants that serve as hosts for invasive fungi. Toxicity can serve as a mechanism for imparting virulence to invasive fungi, and can cause toxicity in...

  9. Do captive conditions favor shedding of parasites in the reared Atlantic bluefin tuna (Thunnus thynnus)?

    PubMed

    Mladineo, I; Segvić, T; Petrić, M

    2011-01-01

    Tuna (Thunnus spp.) has been characterized by long distance migrations, highly predatory behavior and longevity, all of which in turn, enable infections with a wide spectrum of different parasitic groups, reflecting in a remarkable diversity of tuna parasite communities. Since 2003, we have been monitoring parasite communities of Atlantic bluefin tuna (Thunnus thynnus) that are caught from the wild and transferred into cages during spring-summer months, as well as assemblages in fish that exit rearing cycle during the winter harvest period after 1.5 years. Interestingly in reared tuna, parasitic populations exhibit a significant decreasing trend at the end of the rearing cycle, rarely observed in other intensive productions that represent a suitable environment for the emergence, establishment and transmission of pathogens. In order to assess epizootiological behavior of tuna parasites assemblages at the beginning (B group) and at the end (A group) of 1.5 year rearing cycle, we examined data on parasite prevalence and abundance over 4 years. The aim was to evaluate parasite diversity indices and emerging differences between newly caught and harvested fish, as well as community compositions and their nestedness in respect to the event in the rearing cycle (capture or harvest time). In order to be able to predict classification of tuna in two categories (newly caught or heavily infected and harvested or less infected fish), based on empirical didymozoids abundances and year of sampling, we built a decision tree model. Results suggest that specificities of parasite assemblages and their dynamics in tuna before and after farming have no similar precedents in aquaculture. A trend of parasitic pauperization repeating in each rearing cycle over four-years time, in once diverse and species rich parasite communities is observed, however, structures of both B and A group rearing assemblages remain nested, with the same species being core parasites (Didymosulcus katsuwonicola and Koellikerioides intestinalis). The B group exhibited significantly higher total parasite richness and mean parasites abundance, as well as the heteroxenous species richness and abundance in comparison to A group, where monoxenous species were not recorded at all. Eleven parasite species out of 26 taxa were selected as important in discriminating between B and A groups' parasites assemblages, while significantly the most abundant in B group were D. katsuwonicola, Platocystis alalongae, K. intestinalis, Koellikerioides internogastricus, Didymocystis abdominalis and Anisakis sp. It is hard to postulate the combination of factors affecting these parasite populations, but environmental, anthropogenic or host intrinsic influence has to be taken into account for further investigation.

  10. A Favorability Score for Vaginal Hysterectomy in a Statewide Collaborative.

    PubMed

    Skinner, Bethany D; Kamdar, Neil S; Mahnert, Nichole; Lim, Courtney S; Mullard, Andrew J; Campbell, Darrell A; As-Sanie, Sawsan; Morgan, Daniel M

    STUDY OBJECTIVE: Because it is associated with fewer complications and more rapid recovery, the vaginal approach is preferred for benign hysterectomy. Patient characteristics that traditionally favor a vaginal approach include adequate vaginal access, small uterine size, and low suspicion for extrauterine disease. However, the low proportion of hysterectomies performed vaginally in the United States suggests that these data are not routinely applied in clinical practice. We sought to analyze the association of parity, prior pelvic surgery, and uterine weight with the use of the vaginal, laparoscopic, robotic, and abdominal approaches to hysterectomy.

  11. Clinical quality is independently associated with favorable bond ratings.

    PubMed

    Haydar, Ziad; Nicewander, David; Convery, Paul; Black, Michael; Ballard, David

    2010-01-01

    The relation between clinical quality and bond rating for nonprofit hospitals has been proposed but never fully studied. We analyzed the relation between bond rating, clinical quality measures (The Joint Commission/Centers for Medicare and Medicaid Services [CMS] core measures), and balance sheet and income statement financial measures of 236 hospitals across the United States that are rated by Moody's Investors Service and that reported clinical quality measures to CMS during the study period. We found a statistically significant relation between higher quality measures and more favorable bond ratings. This association remained significant after controlling for traditional financial parameters.

  12. Favorable Long-term Prognosis of Cataract Surgery in Herpes Zoster Ophthalmicus

    PubMed Central

    Chaudhary, Kulbhushan Prakash; Mahajan, Deepti; Panwar, Praveen

    2016-01-01

    Purpose: Scleritis is a rare presentation of herpes zoster ophthalmicus, complicated most commonly by iridocyclitis and raised intraocular pressure. These complications can recur in subsequent years, therefore they should be managed well. Case Report: We describe a female patient who developed scleritis, complicated cataract and secondary glaucoma 2 years after being diagnosed by HZO. Secondary glaucoma was managed medically, and the patient underwent extracapsular cataract extraction for the complicated cataract. Final visual acuity was 6/6 and IOP was 22.4 mm Hg. This is a rare report describing favorable long-term (>20 years) prognosis for surgical management of cataract associated with HZO together with scleritis, secondary glaucoma and post-herpetic neuralgia. Conclusion: A favorable outcome may be attained with surgery for complicated cataract associated with HZO if the condition is managed optimally and intraocular inflammation is well controlled. PMID:27413505

  13. HOW MUCH FAVORABLE SELECTION IS LEFT IN MEDICARE ADVANTAGE?

    PubMed

    Newhouse, Joseph P; Price, Mary; McWilliams, J Michael; Hsu, John; McGuire, Thomas G

    2015-01-01

    The health economics literature contains two models of selection, one with endogenous plan characteristics to attract good risks and one with fixed plan characteristics; neither model contains a regulator. Medicare Advantage, a principal example of selection in the literature, is, however, subject to anti-selection regulations. Because selection causes economic inefficiency and because the historically favorable selection into Medicare Advantage plans increased government cost, the effectiveness of the anti-selection regulations is an important policy question, especially since the Medicare Advantage program has grown to comprise 30 percent of Medicare beneficiaries. Moreover, similar anti-selection regulations are being used in health insurance exchanges for those under 65. Contrary to earlier work, we show that the strengthened anti-selection regulations that Medicare introduced starting in 2004 markedly reduced government overpayment attributable to favorable selection in Medicare Advantage. At least some of the remaining selection is plausibly related to fixed plan characteristics of Traditional Medicare versus Medicare Advantage rather than changed selection strategies by Medicare Advantage plans.

  14. HOW MUCH FAVORABLE SELECTION IS LEFT IN MEDICARE ADVANTAGE?

    PubMed Central

    PRICE, MARY; MCWILLIAMS, J. MICHAEL; HSU, JOHN; MCGUIRE, THOMAS G.

    2015-01-01

    The health economics literature contains two models of selection, one with endogenous plan characteristics to attract good risks and one with fixed plan characteristics; neither model contains a regulator. Medicare Advantage, a principal example of selection in the literature, is, however, subject to anti-selection regulations. Because selection causes economic inefficiency and because the historically favorable selection into Medicare Advantage plans increased government cost, the effectiveness of the anti-selection regulations is an important policy question, especially since the Medicare Advantage program has grown to comprise 30 percent of Medicare beneficiaries. Moreover, similar anti-selection regulations are being used in health insurance exchanges for those under 65. Contrary to earlier work, we show that the strengthened anti-selection regulations that Medicare introduced starting in 2004 markedly reduced government overpayment attributable to favorable selection in Medicare Advantage. At least some of the remaining selection is plausibly related to fixed plan characteristics of Traditional Medicare versus Medicare Advantage rather than changed selection strategies by Medicare Advantage plans. PMID:26389127

  15. Donepezil regulates energy metabolism and favors bone mass accrual.

    PubMed

    Eimar, Hazem; Alebrahim, Sharifa; Manickam, Garthiga; Al-Subaie, Ahmed; Abu-Nada, Lina; Murshed, Monzur; Tamimi, Faleh

    2016-03-01

    The autonomous nervous system regulates bone mass through the sympathetic and parasympathetic arms. The sympathetic nervous system (SNS) favors bone loss whereas the parasympathetic nervous system (PNS) promotes bone mass accrual. Donepezil, a central-acting cholinergic agonist, has been shown to down-regulate SNS and up-regulate PNS signaling tones. Accordingly, we hypothesize that the use of donepezil could have beneficial effects in regulating bone mass. To test our hypothesis, two groups of healthy female mice were treated either with donepezil or saline. Differences in body metabolism and bone mass of the treated groups were compared. Body and visceral fat weights as well as serum leptin level were increased in donepezil-treated mice compared to control, suggesting that donepezil effects on SNS influenced metabolic activity. Donepezil-treated mice had better bone quality than controls due to a decrease in osteoclasts number. These results indicate that donepezil is able to affect whole body energy metabolism and favors bone mass in young female WT mice.

  16. Does a Favor Request Increase Liking Toward the Requester?

    PubMed

    Niiya, Yu

    2016-01-01

    Although a request for help can impose a burden on the provider and has the potential of harming a relationship, the theory of amae suggests that in fact it could help promote a stronger relationship. In an experiment, both Japanese and American participants who were asked for help from a confederate increased their liking of the confederate relative to the baseline. Sociable impression of the confederate and perceived closeness of the relationship also increased relative to the baseline. There was, however, no such increase when participants helped the confederate without receiving a direct request. This study suggests that despite the potential risks to relationships, asking favors can provide opportunities for requesters to build and promote relationships.

  17. Reticulate evolution is favored in influenza niche switching

    PubMed Central

    Hill, Nichola J.; Zabilansky, Justin; Yuan, Kyle; Runstadler, Jonathan A.

    2016-01-01

    Reticulate evolution is thought to accelerate the process of evolution beyond simple genetic drift and selection, helping to rapidly generate novel hybrids with combinations of adaptive traits. However, the long-standing dogma that reticulate evolutionary processes are likewise advantageous for switching ecological niches, as in microbial pathogen host switch events, has not been explicitly tested. We use data from the influenza genome sequencing project and a phylogenetic heuristic approach to show that reassortment, a reticulate evolutionary mechanism, predominates over mutational drift in transmission between different host species. Moreover, as host evolutionary distance increases, reassortment is increasingly favored. We conclude that the greater the quantitative difference between ecological niches, the greater the importance of reticulate evolutionary processes in overcoming niche barriers. PMID:27114508

  18. White House Budget Proposal Favorable Overall for Federal Science Agencies

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-02-01

    President Barack Obama's proposed federal budget of 3.8 trillion for fiscal year (FY) 2013, released on 13 February, provides an overall favorable funding picture for federal science agencies in a tight economic environment. However, there are also a number of proposed decreases, including a sharp cut to NASA's Planetary Science account. Overall, the budget proposal includes 140.8 billion for the federal investment in research and development, a 1.4% increase above the FY 2012 enacted level. Funding for federal basic and applied research would be 64 billion, 3.3% above FY 2012 enacted levels. Funding for defense research and development (R&D) would decrease to 75.9 billion, a drop of 1.5%; nondefense R&D would increase 5% to $64.9 billion.

  19. High nevus counts confer a favorable prognosis in melanoma patients.

    PubMed

    Ribero, Simone; Davies, John R; Requena, Celia; Carrera, Cristina; Glass, Daniel; Rull, Ramon; Vidal-Sicart, Sergi; Vilalta, Antonio; Alos, Lucia; Soriano, Virtudes; Quaglino, Pietro; Traves, Victor; Newton-Bishop, Julia A; Nagore, Eduardo; Malvehy, Josep; Puig, Susana; Bataille, Veronique

    2015-10-01

    A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.

  20. Favorable Geochemistry from Springs and Wells in COlorado

    DOE Data Explorer

    Zehner, Richard E.

    2012-02-01

    Citation Information: Originator: Geothermal Development Associates, Reno Nevada Originator: United States Geological Survey (USGS) Originator: Colorado Geological Survey Publication Date: 2012 Title: Favorable Geochemistry Edition: First Publication Information: Publication Place: Reno Nevada Publisher: Geothermal Development Associates, Reno, Nevada Description: This layer contains favorable geochemistry for high-temperature geothermal systems, as interpreted by Richard "Rick" Zehner. The data is compiled from the data obtained from the USGS. The original data set combines 15,622 samples collected in the State of Colorado from several sources including 1) the original Geotherm geochemical database, 2) USGS NWIS (National Water Information System), 3) Colorado Geological Survey geothermal sample data, and 4) original samples collected by R. Zehner at various sites during the 2011 field season. These samples are also available in a separate shapefile FlintWaterSamples.shp. Data from all samples were reportedly collected using standard water sampling protocols (filtering through 0.45 micron filter, etc.) Sample information was standardized to ppm (micrograms/liter) in spreadsheet columns. Commonly-used cation and silica geothermometer temperature estimates are included. Spatial Domain: Extent: Top: 4515595.841032 m Left: 149699.513964 m Right: 757959.309388 m Bottom: 4104156.435530 m Contact Information: Contact Organization: Geothermal Development Associates, Reno, Nevada Contact Person: Richard “Rick” Zehner Address: 3740 Barron Way City: Reno State: NV Postal Code: 89511 Country: USA Contact Telephone: 775-737-7806 Spatial Reference Information: Coordinate System: Universal Transverse Mercator (UTM) WGS’1984 Zone 13N False Easting: 500000.00000000 False Northing: 0.00000000 Central Meridian: -105.00000000 Scale Factor: 0.99960000 Latitude of Origin: 0.00000000 Linear Unit: Meter Datum: World Geodetic System 1984 (WGS ’1984) Prime Meridian: Greenwich

  1. Favorable prognosis for children with Pfeiffer syndrome types 2 and 3: implications for classification.

    PubMed

    Robin, N H; Scott, J A; Arnold, J E; Goldstein, J A; Shilling, B B; Marion, R W; Cohen, M M

    1998-01-23

    Pfeiffer syndrome (PS) is an autosomal dominant condition comprising bilateral coronal craniosynostosis, midface hypoplasia with a beaked nasal tip, and broad and medially deviated thumbs and great toes. It is a clinically variable disorder and has been divided into three subtypes [Cohen, 1993: Am J Med Genet 45:300-307]. Type 1 represents the less severe cases, while types 2 and 3 are the more severe cases. These latter types tend to have a higher risk for neurodevelopmental problems and a reduced life expectancy. Here we review the clinical course of seven children with PS type 3. All of these children had severe manifestations of PS; however, development was essentially normal in three, mild delay was noted in two, and moderate delay in one. Favorable outcomes in children with types 2 and 3 PS were also documented by Moore et al. [1995: Cleft Pal-Craniofac J 32:62-70]. These cases illustrate that while children with PS types 2 and 3 have an increased risk for neurodevelopmental difficulties, a favorable outcome can be achieved in some cases with aggressive medical and surgical management. Finally, although such management should be the rule for PS types 2 and 3, it needs to be remembered that normal outcome is not the rule. The prognosis for favorable neurodevelopmental outcome and/or life expectancy remains guarded in most cases.

  2. Domain expertise insulates against judgment bias by monetary favors through a modulation of ventromedial prefrontal cortex

    PubMed Central

    Kirk, Ulrich; Harvey, Ann; Montague, P. Read

    2011-01-01

    Recent work using an art-viewing paradigm shows that monetary sponsorship of the experiment by a company (a favor) increases the valuation of paintings placed next to the sponsoring corporate logo, an effect that correlates with modulation of the ventromedial prefrontal cortex (VMPFC). We used the same art-viewing paradigm to test a prevailing idea in the domain of conflict-of-interest: that expertise in a domain insulates against judgment bias even in the presence of a monetary favor. Using a cohort of art experts, we show that monetary favors do not bias the experts’ valuation of art, an effect that correlates with a lack of modulation of the VMPFC across sponsorship conditions. The lack of sponsorship effect in the VMPFC suggests the hypothesis that their brains remove the behavioral sponsorship effect by censoring sponsorship-dependent modulation of VMPFC activity. We tested the hypothesis that prefrontal regions play a regulatory role in mediating the sponsorship effect. We show that the dorsolateral prefrontal cortex (DLPFC) is recruited in the expert group. Furthermore, we tested the hypothesis in nonexpert controls by contrasting brain responses in controls who did not show a sponsorship effect to controls who did. Changes in effective connectivity between the DLPFC and VMPFC were greater in nonexpert controls, with an absence of the sponsorship effect relative to those with a presence of the sponsorship effect. The role of the DLPFC in cognitive control and emotion regulation suggests that it removes the influence of a monetary favor by controlling responses in known valuation regions of the brain including the the VMPFC. PMID:21646526

  3. Musical FAVORS: Reintroducing music to adult cochlear implant users.

    PubMed

    Plant, Geoff

    2015-09-01

    Music represents a considerable challenge for many adult users of cochlear implants (CIs). Around half of adult CI users report that they do not find music enjoyable, and, in some cases, despite enhanced speech perception skills, this leads to considerable frustration and disappointment for the CI user. This paper presents suggestions to improve the musical experiences of deafened adults with CIs. Interviews with a number of adult CI users revealed that there were a number of factors which could lead to enhanced music experiences. The acronym FAVORS (familiar music, auditory-visual access, open-mindedness, and simple arrangements) summarizes the factors that have been identified, which can help CI users in their early music listening experiences. Each of these factors is discussed in detail, along with suggestions for how they can be used in therapy sessions. The use of a group approach (music focus groups) is also discussed and an overview of the approach and exercises used is presented. The importance of live music experiences is also discussed.

  4. Gender bias in food intake favors male preschool Guatemalan children.

    PubMed

    Frongillo, E A; Bégin, F

    1993-02-01

    Gender bias in food intake and its subsequent effects on growth and illness were examined using data from rural Guatemalan children. Multiple regression controlled for energy requirements, illness, and maternal and economic factors. Gender bias in energy and protein intake favored boys; the magnitude for ages 2-5 y was 247 kJ/d. Analysis of subsequent effects showed that boys had higher rates of weight gain due to gender bias in energy intake than did girls for ages 1-2 y (0.27-0.97 kg/y), when there were no differences in illness rates due to gender bias in energy intake. For age 3-5 y, boys and girls did not differ in weight gain due to gender bias in energy intake. For ages 1-2 y for weight and stature, the growth rate for boys was faster than that of girls by 6-49% due to gender bias. This study provides evidence of gender bias in food intake in a Latin American population, but more work on the existence of and reasons for gender bias in food intake is needed before advocating that education or health programs should focus on this issue.

  5. Paleozoic unconformities favorable for uranium concentration in northern Appalachian basin

    SciTech Connect

    Dennison, J.M.

    1986-05-01

    Unconformities can redistribute uranium from protore rock as ground water moves through poorly consolidated strata beneath the erosion surface, or later moves along the unconformity. Groundwater could migrate farther than in present-day lithified Paleozoic strata in the Appalachian basin, now locally deformed by the Taconic and Allegheny orogenies. Several paleoaquifer systems could have developed uranium geochemical cells. Sandstone mineralogy, occurrences of fluvial strata, and reduzate facies are important factors. Other possibilities include silcrete developed during desert exposure, and uranium concentrated in paleokarst. Thirteen unconformities are evaluated to determine favorable areas for uranium concentration. Cambrian Potsdam sandstone (New York) contains arkoses and possible silcretes just above crystalline basement. Unconformities involving beveled sandstones and possible fluvial strata include Cambrian Hardyston sandstone (New Jersey), Cambrian Potsdam Sandstone (New York), Ordovician Oswego and Juniata formations (Pennsylvania and New York), Silurian Medina Group (New York), and Silurian Vernon, High Falls, and Longwood formations (New York and New Jersey). Devonian Catskill Formation is beveled by Pennsylvanian strata (New York and Pennsylvania). The pre-Pennsylvanian unconformity also bevels Lower Mississippian Pocono, Knapp, and Waverly strata (Pennsylvania, New York, and Ohio), truncates Upper Mississippian Mauch Chunk Formation (Pennsylvania), and forms paleokarst on Mississippian Loyalhanna Limestone (Pennsylvania) and Maxville Limestone (Ohio). Strata associated with these unconformities contain several reports of uranium. Unconformities unfavorable for uranium concentration occur beneath the Middle Ordovician (New York), Middle Devonian (Ohio and New York), and Upper Devonian (Ohio and New York); these involve marine strata overlying marine strata and probably much submarine erosion.

  6. Phenotypic selection favors missing trait combinations in coexisting annual plants.

    PubMed

    Kimball, Sarah; Gremer, Jennifer R; Huxman, Travis E; Lawrence Venable, D; Angert, Amy L

    2013-08-01

    Trade-offs among traits are important for maintaining biodiversity, but the role of natural selection in their construction is not often known. It is possible that trade-offs reflect fundamental constraints, negative correlational selection, or directional selection operating on costly, redundant traits. In a Sonoran Desert community of winter annual plants, we have identified a trade-off between relative growth rate and water-use efficiency among species, such that species with high relative growth rate have low water-use efficiency and vice versa. We measured selection on water-use efficiency, relative growth rate, and underlying traits within populations of four species at two study sites with different average climates. Phenotypic trait correlations within species did not match the among-species trade-off. In fact, for two species with high water-use efficiency, individuals with high relative growth rate also had high water-use efficiency. All populations experienced positive directional selection for water-use efficiency and relative growth rate. Selection tended to be stronger on water-use efficiency at the warmer and drier site, and selection on relative growth rate tended to be stronger at the cooler and wetter site. Our results indicate that directional natural selection favors a phenotype not observed among species in the community, suggesting that the among-species trade-off could be due to pervasive genetic constraints, perhaps acting in concert with processes of community assembly.

  7. Favorable Selection, Risk Adjustment, and the Medicare Advantage Program

    PubMed Central

    Morrisey, Michael A; Kilgore, Meredith L; Becker, David J; Smith, Wilson; Delzell, Elizabeth

    2013-01-01

    Objectives To examine the effects of changes in payment and risk adjustment on (1) the annual enrollment and switching behavior of Medicare Advantage (MA) beneficiaries, and (2) the relative costliness of MA enrollees and disenrollees. Data From 1999 through 2008 national Medicare claims data from the 5 percent longitudinal sample of Parts A and B expenditures. Study Design Retrospective, fixed effects regression analysis of July enrollment and year-long switching into and out of MA. Similar regression analysis of the costliness of those switching into (out of) MA in the 6 months prior to enrollment (after disenrollment) relative to nonswitchers in the same county over the same period. Findings Payment generosity and more sophisticated risk adjustment were associated with substantial increases in MA enrollment and decreases in disenrollment. Claims experience of those newly switching into MA was not affected by any of the policy reforms, but disenrollment became increasingly concentrated among high-cost beneficiaries. Conclusions Enrollment is very sensitive to payment levels. The use of more sophisticated risk adjustment did not alter favorable selection into MA, but it did affect the costliness of disenrollees. PMID:23088500

  8. Sperm competition favors harmful males in seed beetles.

    PubMed

    Hotzy, Cosima; Arnqvist, Göran

    2009-03-10

    One of the most enigmatic observations in evolutionary biology is the evolution of morphological or physiological traits in one sex that physically injure members of the other sex. Such traits occur in a wide range of taxa and range from toxic ejaculate substances to genital or external spines that wound females during copulation. Current hypotheses for the adaptive evolution of such injurious traits rest entirely on the assumption that they are beneficial to their bearer by aiding in reproductive competition. Here, we assess this key assumption in seed beetles where genital spines in males physically injure females. We demonstrate that male spine length is positively correlated with harm to females during mating but also that males with longer spines are more successful in sperm competition. This is the first complete support for the proposal that sexual selection by sperm competition can favor morphological traits in males that inflict injury upon females. However, our results suggest that harm to females is a pleiotropic by-product, such that genital spines in males elevate success in sperm competition by means other than by causing harm.

  9. Patients with Spinal Cord Injuries Favor Administration of Methylprednisolone

    PubMed Central

    Bowers, Christian A.; Kundu, Bornali; Rosenbluth, Jeffrey; Hawryluk, Gregory W. J.

    2016-01-01

    Methylprednisolone sodium succinate (MPSS) for treatment of acute spinal cord injury (SCI) has been associated with both benefits and adverse events. MPSS administration was the standard of care for acute SCI until recently when its use has become controversial. Patients with SCI have had little input in the debate, thus we sought to learn their opinions regarding administration of MPSS. A summary of the published literature to date on MPSS use for acute SCI was created and adjudicated by 28 SCI experts. This summary was then emailed to 384 chronic SCI patients along with a survey that interrogated the patients’ neurological deficits, communication with physicians and their views on MPSS administration. 77 out of 384 patients completed the survey. 28 respondents indicated being able to speak early after injury and of these 24 reported arriving at the hospital within 8 hours of injury. One recalled a physician speaking to them about MPSS and one patient reported choosing whether or not to receive MPSS. 59.4% felt that the small neurological benefits associated with MPSS were ‘very important’ to them (p<0.0001). Patients had ‘little concern’ for potential side-effects of MPSS (p = 0.001). Only 1.4% felt that MPSS should not be given to SCI patients regardless of degree of injury (p<0.0001). This is the first study to report SCI patients’ preferences regarding MPSS treatment for acute SCI. Patients favor the administration of MPSS for acute SCI, however few had input into whether or not it was administered. Conscious patients should be given greater opportunity to decide their treatment. These results also provide some guidance regarding MPSS administration in patients unable to communicate. PMID:26789007

  10. Mechanical Heterogeneity Favors Fragmentation of Strained Actin Filaments

    PubMed Central

    De La Cruz, Enrique M.; Martiel, Jean-Louis; Blanchoin, Laurent

    2015-01-01

    We present a general model of actin filament deformation and fragmentation in response to compressive forces. The elastic free energy density along filaments is determined by their shape and mechanical properties, which were modeled in terms of bending, twisting, and twist-bend coupling elasticities. The elastic energy stored in filament deformation (i.e., strain) tilts the fragmentation-annealing reaction free-energy profile to favor fragmentation. The energy gradient introduces a local shear force that accelerates filament intersubunit bond rupture. The severing protein, cofilin, renders filaments more compliant in bending and twisting. As a result, filaments that are partially decorated with cofilin are mechanically heterogeneous (i.e., nonuniform) and display asymmetric shape deformations and energy profiles distinct from mechanically homogenous (i.e., uniform), bare actin, or saturated cofilactin filaments. The local buckling strain depends on the relative size of the compliant segment as well as the bending and twisting rigidities of flanking regions. Filaments with a single bare/cofilin-decorated boundary localize energy and force adjacent to the boundary, within the compliant cofilactin segment. Filaments with small cofilin clusters were predicted to fragment within the compliant cofilactin rather than at boundaries. Neglecting contributions from twist-bend coupling elasticity underestimates the energy density and gradients along filaments, and thus the net effects of filament strain to fragmentation. Spatial confinement causes compliant cofilactin segments and filaments to adopt higher deformation modes and store more elastic energy, thereby promoting fragmentation. The theory and simulations presented here establish a quantitative relationship between actin filament fragmentation thermodynamics and elasticity, and reveal how local discontinuities in filament mechanical properties introduced by regulatory proteins can modulate both the severing efficiency

  11. Quantifying favorableness for occurrence of a mineral deposit type using fuzzy logic; an example from Arizona

    USGS Publications Warehouse

    Gettings, Mark E.; Bultman, Mark W.

    1993-01-01

    An application of possibility theory from fuzzy logic to the quantification of favorableness for quartz-carbonate vein deposits in the southern Santa Rita Mountains of southeastern Arizona is described. Three necessary but probably not sufficient conditions for the formation of these deposits were defined as the occurrence of carbonate berain rocks within hypabyssal depths, significant fracturing of the rocks, and proximity to a felsic intrusive. The quality of data available to evaluate these conditions is variable over the study area. The possibility of each condition was represented as a fuzzy set enumerated over the area. The intersection of the sets measures the degree of simultaneous occurrence of hte necessary factors and provides a measure of the possibility of deposit occurrence. Using fuzzy set technicques, the effect of one or more fuzzy sets relative to the others in the intersection can be controlled and logical combinations of the sets can be used to impose a time sequential constraint on the necessary conditions. Other necessary conditions, and supplementary conditions such as variable data quality or intensity of exploration can be included in the analysis by their proper representation as fuzzy sets.

  12. Charcoal kiln relicts - a favorable site for tree growth?

    NASA Astrophysics Data System (ADS)

    Buras, Allan; Hirsch, Florian; van der Maaten, Ernst; Takla, Melanie; Räbiger, Christin; Cruz Garcia, Roberto; Schneider, Anna; Raab, Alexandra; Raab, Thomas; Wilmking, Martin

    2015-04-01

    Soils with incompletely combusted organic material (aka 'black carbon') are considered fertile for plant growth. Considerable enrichment of soils with black carbon is known from Chernozems, from anthropogenic induced altering of soils like the 'Terra Preta' in South America (e.g. Glaser, 2001), and from charcoal kiln relicts. Recent studies have reported a high spatial frequency of charcoal kiln relicts in the Northeastern German lowlands (Raab et al., 2015), which today are often overgrown by forest plantations. In this context the question arises whether these sites are favorable for tree growth. Here we compare the performance of 22 Pinus sylvestris individuals - a commonly used tree species in forestry - growing on charcoal kiln relicts with 22 control trees. Growth performance (height growth and diameter growth) of the trees was determined using dendrochronological techniques, i.e. standard ring-width measurements were undertaken on each two cores per tree and tree height was measured in the field. Several other wood properties such as annual wood density, average resin content, as well as wood chemistry were analyzed. Our results indicate that trees growing on charcoal kiln relicts grow significantly less and have a significantly lower wood density in comparison with control trees. Specific chemical components such as Manganese as well as resin contents were significantly higher in kiln trees. These results highlight that tree growth on charcoal kiln relicts is actually hampered instead of enhanced. Possibly this is a combined effect of differing physical soil properties which alter soil water accessibility for plants and differing chemical soil properties which may negatively affect tree growth either if toxic limits are surpassed or if soil nutrient availability is decreased. Additional soil analyses with respect to soil texture and soil chemistry shall reveal further insight into this hypothesis. Given the frequent distribution of charcoal kiln relicts in

  13. The risk of predation favors cooperation among breeding prey.

    PubMed

    Krams, Indrikis; Krama, Tatjana; Berzins, Arnis; Rantala, Markus J

    2010-05-01

    Empirical studies have shown that animals often focus on short-term benefits under conditions of predation risk, which reduces the likelihood that they will cooperate with others. However, some theoretical studies predict that animals in adverse conditions should not avoid cooperation with their neighbors since it may decrease individual risks and increase long-term benefits of reciprocal help. We experimentally tested these two alternatives to find out whether increased predation risk enhances or diminishes the occurrence of cooperation in mobbing, a common anti-predator behavior, among breeding pied flycatchers, Ficedula hypoleuca. Our results show that birds attended mobs initiated by their neighbors more often, approached the stuffed predator significantly more closely, and mobbed it at a higher intensity in areas where the perceived risk of predation was experimentally increased. This study demonstrates a positive impact of predation risk on cooperation in breeding songbirds, which might help to explain the emergence and evolution of cooperation.

  14. [Favorable, unfavorable and indifferent side effects of pharmacotherapy of psychoses].

    PubMed

    Gall, H

    1975-01-01

    Not all side-effects are undesirable side-effects of a treatment. Under certain conditions allergic side-effects during the therapy of phasic psychotics affect a turn in the course of the basic illness and bring a premature end to depression. As a result of the observation of a sudden cure of a deep vital depression in a 73 year old patient in direct chronological connection with the appearance of an allergic urticaria, studies were carried out, in the 8 years following, of a total of 18 cases of similar circumstances; during the treatment of an endogenous depression the development of intercurrent allergic skin reactions showed: in 6 cases the psychosis completely disappeared with the development of the urticaria; in 8 cases the symptoms were considerably relieved so that only the remains of vegetative disorders persisted; in 4 cases no effect could be determined. In 2 cases the same allergic reaction was consciously provoked by a reapplication of the medicaments concerned during a following depressive phase; again with favourable results since under these conditions coincidences are not very probable, the conclusion can be made, and experimentally supported, that allergic drug reactions may be employed in the course of depressions, with careful avoidance of complications.

  15. Study the most favorable shapes of electrostatic quadrupole doublet lenses

    NASA Astrophysics Data System (ADS)

    Hussein, O. A.; Sise, O.

    2017-02-01

    The optical properties of an electrostatic quadrupole doublet lens with two different electrode shapes were studied with the aid of computer simulation. The optimal electrode voltages of the electrostatic quadrupole lenses which give the stigmatic image in both planes simultaneously were found for both concave cylindrical electrode shape and plan electrode shape of the operation mode: parallel to point focusing. The effect of electrode shape on the image properties was investigated, and the aberration figures were studied. The results showed that under the same operation condition and the geometrical dimensions, the changing of the electrode shape of the electrostatic quadrupole doublet lenses lead to important differences in the optical properties of the lenses and the characteristics of the systems.

  16. Evaluation Of Levels Of Climate Favorability For Viticulture In Breasta Viticultural Centre

    NASA Astrophysics Data System (ADS)

    Buzatu, Gilda-Diana; Mărăcineanu, Liviu Cristian

    2015-09-01

    The aim of this present research was to evaluate the climatic conditions of a viticultural centre, as there are always needed studies to determine the climate favorability of the vine cultivation and the varieties resistant to heat and water stress, especially when climate change affects globally viticulture. The present research was made using the interpretation of Craiova Regional Weather Centre's meteorological records for the year of 2014, for Breasta viticultural centre. The climatic factors permitted the determination of several indexes used in viticultural climatology for the appreciation of the viticultural biotope characteristics. Assessment of climatic resources through synthetic climatic indexes, clearly express the generous heliothermic offer available for Breasta viticultural centre, the guarantee of quality and specificity of vine products obtained in this area.

  17. Factors for Predicting Favorable Outcome of Percutaneous Epidural Adhesiolysis for Lumbar Disc Herniation

    PubMed Central

    Moon, Sang Ho; Lee, Jae Il; Cho, Hyun Seok; Shin, Jin Woo

    2017-01-01

    Background. Lower back pain is a common reason for disability and the most common cause is lumbar disc herniation. Percutaneous epidural adhesiolysis has been applied to relieve pain and increase the functional capacity of patients who present this condition. Objectives. In this study, we retrospectively evaluated the factors which predict the outcome of percutaneous epidural adhesiolysis in patients who were diagnosed with lumbar disc herniation. Methods. Electronic medical records of patients diagnosed with lumbar disc herniation who have received percutaneous epidural adhesiolysis treatment were reviewed. The primary outcome was the factors that were associated with substantial response of ≥4 points or ≥50% of pain relief in the numerical rating scale pain score 12 months after the treatment. Results. Multivariate logistic regression analysis demonstrated that the presence of high-intensity zone (HIZ) at magnetic resonance imaging was a predictor of substantial response to percutaneous epidural adhesiolysis for 12 months (P = 0.007). The presence of a condition involving the vertebral foramen was a predictor for unsuccessful response after 12 months (P = 0.02). Discussion and Conclusion. The presence of HIZ was a predictor of favorable long-term outcome after percutaneous epidural adhesiolysis for the treatment of lower back pain with radicular pain caused by lumbar disc herniation. PMID:28246488

  18. "Time" and "Newsweek" Favor John F. Kennedy, Criticize Robert and Edward Kennedy.

    ERIC Educational Resources Information Center

    Fedler, Fred; And Others

    1983-01-01

    Finds that the percentage of favorable, neutral, and unfavorable statements about the three Kennedy brothers in two national news magazines was similar and that both magazines published proportionately more favorable statements about John Kennedy than about either of his brothers. (FL)

  19. 45 CFR 73.735-503 - Criminal provisions relating to gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... GENERAL ADMINISTRATION STANDARDS OF CONDUCT Gifts, Entertainment, and Favors § 73.735-503 Criminal provisions relating to gifts, entertainment, and favors. (a) The law provides criminal penalties for whoever... 45 Public Welfare 1 2010-10-01 2010-10-01 false Criminal provisions relating to...

  20. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  1. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  2. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  3. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  4. Favorable effect of in-situ generated platinum in the membrane on fuel cell membrane durability

    NASA Astrophysics Data System (ADS)

    Macauley, Natalia; Wong, Ka Hung; Watson, Mark; Kjeang, Erik

    2015-12-01

    The overall lifetime of polymer electrolyte fuel cells is often determined by the membrane durability. Platinum, which may dissolve from the catalyst layers during fuel cell operation and deposit in the membrane, has been shown to have both positive and negative effects on membrane stability. In the present work, we analyze what specific conditions are required in order to reach a favorable, membrane stabilizing effect with the controlled use of platinum in the membrane. Using accelerated membrane durability testing, field operated membrane samples, and electron microscopy, we demonstrate that a high platinum concentration with specific particle shapes and sizes is essential for enhanced membrane stability. Specifically, star shaped and dendritic particles with high particle density and high surface area are shown to be preferable. These particles contain high levels of Pt(111) and are expected to have high catalytic activity toward peroxide quenching and crossover gas consumption, thereby mitigating chemical membrane degradation. On the other hand, small, dispersed cubic particles are found to have no effect or the opposite, negative effect on membrane stability.

  5. Anticipated detection of favorable periods for wind energy production by means of information theory

    NASA Astrophysics Data System (ADS)

    Vogel, Eugenio; Saravia, Gonzalo; Kobe, Sigismund; Schumann, Rolf; Schuster, Rolf

    Managing the electric power produced by different sources requires mixing the different response times they present. Thus, for instance, coal burning presents large time lags until operational conditions are reached while hydroelectric generation can react in a matter of some seconds or few minutes to reach the desired productivity. Wind energy production (WEP) can be instantaneously fed to the network to save fuels with low thermal inertia (gas burning for instance), but this source presents sudden variations within few hours. We report here for the first time a method based on information theory to handle WEP. This method has been successful in detecting dynamical changes in magnetic transitions and variations of stock markets. An algorithm called wlzip based on information recognition is used to recognize the information content of a time series. We make use of publically available energy data in Germany to simulate real applications. After a calibration process the system can recognize directly on the WEP data the onset of favorable periods of a desired strength. Optimization can lead to a few hours of anticipation which is enough to control the mixture of WEP with other energy sources, thus saving fuels.

  6. Genotypic diversity effects on the performance of Taraxacum officinale populations increase with time and environmental favorability.

    PubMed

    Drummond, Emily B M; Vellend, Mark

    2012-01-01

    Within-population genetic diversity influences many ecological processes, but few studies have examined how environmental conditions may impact these short-term diversity effects. Over four growing seasons, we followed experimental populations of a clonal, ubiquitous weed, Taraxacum officinale, with different numbers of genotypes in relatively favorable fallow field and unfavorable mowed lawn environmental treatments. Population performance (measured as total leaf area, seed production or biomass) clearly and consistently increased with diversity, and this effect became stronger over the course of the experiment. Diversity effects were stronger, and with different underlying mechanisms, in the fallow field versus the mowed lawn. Large genotypes dominated in the fallow field driving overyielding (via positive selection effects), whereas in the mowed lawn, where performance was limited by regular disturbance, there was evidence for complementarity among genotypes (with one compact genotype in particular performing better in mixture than monoculture). Hence, we predict stronger genotypic diversity effects in environments where intense intraspecific competition enhances genotypic differences. Our four-year field experiment plus seedling establishment trials indicate that genotypic diversity effects have far-reaching and context-dependent consequences across generations.

  7. Membrane-anchoring stabilizes and favors secretion of New Delhi Metallo-β-lactamase

    PubMed Central

    González, Lisandro J.; Bahr, Guillermo; Nakashige, Toshiki G.; Nolan, Elizabeth M.; Bonomo, Robert A.; Vila, Alejandro J.

    2016-01-01

    Carbapenems, “last resort” β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, since these enzymes are readily degraded in their non-metallated form. However, the New Delhi Metallo-β-lactamase (NDM-1) is able to persist under conditions of metal depletion. NDM-1 is a lipidated protein anchored to the outer membrane of Gram-negative bacteria. Membrane-anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the blaNDM gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies. PMID:27182662

  8. Designation of less favorable areas by the regionalization of soil degradation on various spatial scales

    NASA Astrophysics Data System (ADS)

    Pásztor, L.; Szabó, J.; Bakacsi, Zs.; Laborczi, A.

    2009-04-01

    One of the main objectives of the EU's Common Agricultural Policy is to encourage maintaining agricultural production in less favorable areas (LFA) in order (among others) to sustain agricultural production and use natural resources, in such a way to secure both stable production and income to farmers and to protect the environment. LFA assignment has both ecological and severe economical aspects. Delimitation of LFAs can be carried out by using biophysical diagnostic criteria on low soil productivity and poor climate conditions. Identification of low-productivity areas requires regionalization of soil functions related to food and other biomass production. This process can be carried out in different scales from national to local level, but always requires map-based pedological and further environmental information with appropriate spatial resolution. For the regionalization of less productive areas in national scale a functional approach was used which integrates the knowledge on soil degradation processes in nationwide level. Specific soil threats were classified into ranked categories. Supposing (quasi)uniform distribution of vulnerability measure along these classes, we introduced a "standardized" value as a ratio of the class order to the maximum class order expressed in percentage. For the overall spatial characterization of degradation status, spatial information was integrated in a result map by summarizing the degradation specific "standardized" cell values. This map in one hand has been used for the delineation of soil degradation regions. On the other hand appropriate spatial aggregation of index values on geographical and administrative regions is suitable for their quantitative comparison thus they can be ranked and this feature can be used for the identification of less favorable areas. At the more detailed, county level the Digital Kreybig Soil Information System was used as a tool of the regionalization of soil functions related to soil

  9. 15 CFR Supplement No. 3 to Part 740 - License Exception ENC Favorable Treatment Countries

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Treatment Countries No. Supplement No. 3 to Part 740 Commerce and Foreign Trade Regulations Relating to... Favorable Treatment Countries Austria Australia Belgium Bulgaria Canada Cyprus Czech Republic Estonia... Turkey United Kingdom...

  10. Catalytic performance and thermostability of chloroperoxidase in reverse micelle: achievement of a catalytically favorable enzyme conformation.

    PubMed

    Wang, Yali; Wu, Jinyue; Ru, Xuejiao; Jiang, Yucheng; Hu, Mancheng; Li, Shuni; Zhai, Quanguo

    2011-06-01

    The catalytic performance of chloroperoxidase (CPO) in peroxidation of 2, 2'-azinobis-(-3 ethylbenzothiazoline-6-sulfononic acid) diammonium salt (ABTS) and oxidation of indole in a reverse micelle composed of surfactant-water-isooctane-pentanol was investigated and optimized in this work. Some positive results were obtained as follows: the peroxidation activity of CPO was enhanced 248% and 263%, while oxidation activity was enhanced 215% and 222% in cetyltrimethylammonium bromide (CTABr) reverse micelle medium and dodecyltrimethylammonium bromide (DTABr) medium, respectively. Thermostability was also greatly improved in reverse micelle: at 40 °C, CPO essentially lost all its activity after 5 h incubation, while 58-76% catalytic activity was retained for both reactions in the two reverse micelle media. At 50 °C, about 44-75% catalytic activity remained for both reactions in reverse micelle after 2 h compared with no observed activity in pure buffer under the same conditions. The enhancement of CPO activity was dependent mainly on the surfactant concentration and structure, organic solvent ratio (V(pentanol)/V(isooctane)), and water content in the reverse micelle. The obtained kinetic parameters showed that the catalytic turnover frequency (k(cat)) was increased in reverse micelle. Moreover, the lower K(m) and higher k(cat)/K(m) demonstrated that both the affinity and specificity of CPO to substrates were improved in reverse micelle media. Fluorescence, circular dichroism (CD) and UV-vis spectra assays indicated that a catalytically favorable conformation of enzyme was achieved in reverse micelle, including the strengthening of the protein α-helix structure, and greater exposure of the heme prosthetic group for easy access of the substrate in bulk solution. These results are promising in view of the industrial applications of this versatile biological catalyst.

  11. Understanding and Mitigating the Effects of Stable Dodecahydro- closo -dodecaborate Intermediates on Hydrogen-Storage Reactions

    DOE PAGES

    White, James L.; Newhouse, Rebecca J.; Zhang, Jin Z.; ...

    2016-10-25

    Alkali metal borohydrides can reversibly store hydrogen; however, the materials display poor cyclability, often times linked to occurrence of stable closo-polyborate intermediate species. In an effort to understand the role of such intermediates on the hydrogen storage properties of metal borohydrides, several alkali metal dodecahydro-closo-dodecaborate salts were isolated in anhydrous form and characterized by diffraction and spectroscopic techniques. Mixtures of Li2B12H12, Na2B12H12, and K2B12H12 with the corresponding alkali metal hydrides were subjected to hydrogenation conditions known to favor partial or full reversibility in metal borohydrides. The stoichiometric mixtures of MH and M2B12H12 salts form the corresponding metal borohydrides MBH4 (M=Li,more » Na, K) in almost quantitative yield at 100 MPa H2 and 500 °C. In addition, stoichiometric mixtures of Li2B12H12 and MgH2 were found to form MgB2 at 500 °C and above upon desorption in vacuum. The two destabilization strategies outlined above suggest that metal polyhydro-closo-polyborate species can be converted into the corresponding metal borohydrides or borides, albeit under rather harsh conditions of hydrogen pressure and temperature.« less

  12. MET receptor variant R970C favors calpain-dependent generation of a fragment promoting epithelial cell scattering.

    PubMed

    Montagne, Rémi; Baranzelli, Anne; Muharram, Ghaffar; Catherine, Leroy; Lesaffre, Marie; Vinchent, Audrey; Kherrouche, Zoulika; Werkmeister, Elisabeth; Cortot, Alexis B; Tulasne, David

    2017-01-04

    The receptor tyrosine kinase MET and its ligand, the hepatocyte growth factor, are essential to embryonic development, whereas deregulation of MET signaling is associated with tumorigenesis leading to various cancers, including lung carcinoma. Mutations in the MET kinase domain lead to constitutive kinase activity and are associated with tumorigenesis. In lung cancer, however, some mutations are found in the juxtamembrane domain, and their functional consequences are unknown. Because the juxtamembrane domain of MET is targeted by several proteolytic cleavages, involved in its degradation during cell death or under steady-state conditions, we evaluated the influence of these mutations on the MET proteolytic cleavages. In stably transfected epithelial cells expressing MET, the juxtamembrane mutations R970C, P991S, and T992I were found not to modify the known caspase or presenilin-dependent regulated intramembrane proteolysis. Yet when overexpressed, the R970C variant caused generation of an as yet undescribed 45-kDa fragment (p45 MET). This fragment was found in the confluent lung cancer cell line NCI-H1437 carrying the R970C mutation and at a lesser extent in cell lines expressing WT MET, suggesting that R970C mutation favors this cleavage. Generation of p45 MET required the activity of the calpain proteases, confirming the involvement of proteolysis. Ectopic expression of reconstituted p45 MET in epithelial cell lines favored cell scattering and invasion indicating active role of this fragment in HGF/SF induced responses. Hence, although the juxtamembrane mutations of MET do not affect its known proteolytic cleavages, the R970C MET variant favors calpain dependent proteolytic cleavage in lung cancer cells.

  13. Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity.

    PubMed

    Contreras, Francisco; Prado, Carolina; González, Hugo; Franz, Dafne; Osorio-Barrios, Francisco; Osorio, Fabiola; Ugalde, Valentina; Lopez, Ernesto; Elgueta, Daniela; Figueroa, Alicia; Lladser, Alvaro; Pacheco, Rodrigo

    2016-05-15

    Dopamine receptor D3 (DRD3) expressed on CD4(+) T cells is required to promote neuroinflammation in a murine model of Parkinson's disease. However, how DRD3 signaling affects T cell-mediated immunity remains unknown. In this study, we report that TCR stimulation on mouse CD4(+) T cells induces DRD3 expression, regardless of the lineage specification. Importantly, functional analyses performed in vivo using adoptive transfer of OVA-specific OT-II cells into wild-type recipients show that DRD3 deficiency in CD4(+) T cells results in attenuated differentiation of naive CD4(+) T cells toward the Th1 phenotype, exacerbated generation of Th2 cells, and unaltered Th17 differentiation. The reciprocal regulatory effect of DRD3 signaling in CD4(+) T cells favoring Th1 generation and impairing the acquisition of Th2 phenotype was also reproduced using in vitro approaches. Mechanistic analysis indicates that DRD3 signaling evokes suppressor of cytokine signaling 5 expression, a negative regulator of Th2 development, which indirectly favors acquisition of Th1 phenotype. Accordingly, DRD3 deficiency results in exacerbated eosinophil infiltration into the airways of mice undergoing house dust mite-induced allergic response. Interestingly, our results show that, upon chronic inflammatory colitis induced by transfer of naive CD4(+) T cells into lymphopenic recipients, DRD3 deficiency not only affects Th1 response, but also the frequency of Th17 cells, suggesting that DRD3 signaling also contributes to Th17 expansion under chronic inflammatory conditions. In conclusion, our findings indicate that DRD3-mediated signaling in CD4(+) T cells plays a crucial role in the balance of effector lineages, favoring the inflammatory potential of CD4(+) T cells.

  14. Reciprocal sign epistasis and truncation selection: When is recombination favorable in a pre-breeding program with a selfing species?

    PubMed

    Vagne, Constance; David, Jacques; Tavaud, Muriel; Fontez, Bénédicte

    2015-12-07

    Since the dawn of agriculture, humans have applied artificial selection on traits of interest, regardless of their genetic architecture. Yet, still today, most models used to study and streamline this process overlook genetic interactions. In this study, we determined the conditions in which a target genotype can be fixed when truncation selection is applied on an epistatic trait. Previous studies have shown that reciprocal sign epistasis with two fitness peaks of unequal height involves multiple equilibrium states, i.e. below one critical parameter value, such as a critical recombination rate, one genotype may be fixed, and above it, another one may be fixed. Using a haploid bi-locus model, we identified which genotype would be fixed, and how quickly, in an infinite population selected for a phenotypic trait subject to reciprocal sign epistasis with unequal peak heights, depending on two criteria: the recombination rate and percentage of selected individuals. The critical parameter values at which bistability sets in, were also calculated. These results were complemented by stochastic simulations in finite populations. Our results confirmed that, in the case of fitness under reciprocal sign epistasis, high recombination rates induce blockage at the local optimum or attainment of an equilibrium state between the two peaks. However, if linkage disequilibrium is negative in the initial population, recombination is necessary to create the most favorable genotype. Therefore, in this case, reciprocal sign epistasis favors non-null recombination rates, particularly if selection is intense.

  15. An ignored but most favorable channel for NCO +C2H2 reaction

    NASA Astrophysics Data System (ADS)

    Xie, Hong-bin; Wang, Jian; Zhang, Shao-wen; Ding, Yi-hong; Sun, Chia-chung

    2006-09-01

    The NCO +C2H2 reaction has been considered as a prototype for understanding the chemical reactivity of the isocyanate radical towards unsaturated hydrocarbons in fuel-rich combustion. It has also been proposed to provide an effective route for formation of oxazole-containing compounds in organic synthesis, and might have potential applications in interstellar processes. Unfortunately, this reaction has met mechanistic controversy both between experiments and between experiments and theoretical calculations. In this paper, detailed theoretical investigations at the Becke's three parameter Lee-Yang-Parr-B3LYP /6-31G(d), B3LYP /6-311++G(d,p), quadratic configuration interaction with single and double excitations QCISD /6-31G(d), and Gaussian-3 levels are performed for the NCO +C2H2 reaction, covering various entrance, isomerization, and decomposition channels. Also, the highly cost-expensive coupled-cluster theory including single and double excitations and perturbative inclusion of triple excitations CCSD(T)/aug-cc-pVTZ single-point energy calculation is performed for the geometries obtained at the Becke's three parameter Lee-Yang-Parr-B3LYP /6-311++G(d,p) level. A previously ignored yet most favorable channel via a four-membered ring intermediate with allyl radical character is found. However, formation of P3 H +HCCNCO and the five-membered ring channel predicted by previous experimental and theoretical studies is kinetically much less competitive. With the new channel, master equation rate constant calculations over a wide range of temperatures (298-1500K) and pressures (10-560Torr) show that the predicted total rate constants exhibit a positive-temperature dependence and no distinct pressure dependence effect. This is in qualitative agreement with available experimental results. Under the experimental conditions, the predicted values are about 50% lower than the latest experimental results. Also, the branching ratio variations of the fragments P2 HCN +HCCO and P5

  16. 48 CFR 53.301-275 - Reinsurance Agreement in Favor of the United States.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Reinsurance Agreement in Favor of the United States. 53.301-275 Section 53.301-275 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-275...

  17. 48 CFR 53.301-275 - Reinsurance Agreement in Favor of the United States.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Reinsurance Agreement in Favor of the United States. 53.301-275 Section 53.301-275 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-275...

  18. 48 CFR 53.301-275 - Reinsurance Agreement in Favor of the United States.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Reinsurance Agreement in Favor of the United States. 53.301-275 Section 53.301-275 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-275...

  19. 48 CFR 53.301-275 - Reinsurance Agreement in Favor of the United States.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Reinsurance Agreement in Favor of the United States. 53.301-275 Section 53.301-275 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-275...

  20. 48 CFR 53.301-275 - Reinsurance Agreement in Favor of the United States.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Reinsurance Agreement in Favor of the United States. 53.301-275 Section 53.301-275 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-275...

  1. Monetary favors and their influence on neural responses and revealed preference.

    PubMed

    Harvey, Ann H; Kirk, Ulrich; Denfield, George H; Montague, P Read

    2010-07-14

    Favors from a sender to a receiver are known to bias decisions made by the recipient, especially when the decision relates to the sender, a feature of social exchange known as reciprocity. Using an art-viewing paradigm possessing no objectively correct answer for preferring one piece of art over another, we show that sponsorship of the experiment by a company endows the logo of the company with the capacity to bias revealed preference for art displayed next to the logo. Merely offering to sponsor the experiment similarly endowed the gesturing logo of the company with the capacity to bias revealed preferences. These effects do not depend upon the size of the displayed art or the proximity of the sponsoring logo to the piece of art. We used functional magnetic resonance imaging to show that such monetary favors do not modulate a special collection of brain responses but instead modulate responses in neural networks normally activated by a wide range of preference judgments. The results raise the important possibility that monetary favors bias judgments in domains seemingly unrelated to the favor but nevertheless act in an implicit way through neural networks that underlie normal, ongoing preference judgments.

  2. 49 CFR 805.735-5 - Receipt of gifts, entertainment, and favors by Members or employees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Members or employees. 805.735-5 Section 805.735-5 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL TRANSPORTATION SAFETY BOARD EMPLOYEE RESPONSIBILITIES AND CONDUCT § 805.735-5 Receipt of gifts, entertainment, and favors by Members or employees. (a) Except as provided in...

  3. 45 CFR 1303.22 - Decision on appeal in favor of grantee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Decision on appeal in favor of grantee. 1303.22 Section 1303.22 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH...

  4. The Art of the Favor: The Connection between Networking and Personal Influence within a College

    ERIC Educational Resources Information Center

    Simplicio, Joseph

    2009-01-01

    This article discusses various strategies for utilizing favors as a means for developing a personal powerbase and influencing individuals within a college setting. Building a personal network of influence centers upon effectively utilizing various strategies including; learning how to control the budget, how to empower others, when to compromise…

  5. Challenging the Courtesy Bias Interpretation of Favorable Clients' Perceptions of Family Planning Delivery

    ERIC Educational Resources Information Center

    Len, Federico R.; Lundgren, Rebecka; Huapaya, Ana; Sinai, Irit; Jennings, Victoria

    2007-01-01

    Favorable client perceptions of provider's interpersonal behavior in contraceptive delivery, documented in clinic exit questionnaires, appear to contradict results from qualitative evaluations and are attributed to clients' courtesy bias. In this study, trained simulated clients requested services from Ministry of Health providers in three…

  6. Evidence from Biochemical Pathways in Favor of Unfinished Evolution Rather than Intelligent Design

    ERIC Educational Resources Information Center

    Behrman, Edward J.; Marzluf, George A.

    2004-01-01

    An argument is made in favor of imperfect or unfinished evolution based on some metabolic pathways in which it seems that intelligent design would have done better. The case studies noted indicate the absence of highly intelligent design and are not intended as comprehensive collection but as a limited sample of inefficient situations in…

  7. Favorable response to aggressive chemotherapy in a patient with primary plasma cell leukemia.

    PubMed

    Lishner, M; Lang, R; Jutrin, I; Ravid, M

    1985-01-01

    Primary plasma cell leukemia was diagnosed in a previously healthy 58-year-old man. The unusual presentation with concomitant multiple osteolytic lesions and hepatosplenomegaly, the favorable response to aggressive chemotherapy with COAP, and the relatively long survival of 22 months prompted this report. This and several other cases recently reported should encourage an aggressive therapeutic approach to this disease.

  8. Does Favorable Selection Among Medicare Advantage Enrollees Affect Measurement of Hospital Readmission Rates?

    PubMed

    Wong, Edwin S; Hebert, Paul L; Maciejewski, Matthew L; Perkins, Mark; Bryson, Chris L; Au, David H; Liu, Chuan-Fen

    2014-08-01

    Literature indicates favorable selection among Medicare Advantage (MA) enrollees compared with fee-for-service (FFS) enrollees. This study examined whether favorable selection into MA affected readmission rates among Medicare-eligible veterans following hospitalization for congestive heart failure in the Veterans Affairs Health System (VA). We measured total (VA + Medicare FFS) 30-day all-cause readmission rates across hospitals and all of VA. We used Heckman's correction to adjust readmission rates to be representative of all Medicare-eligible veterans, not just FFS-enrolled veterans. The adjusted all-cause readmission rate among FFS veterans was 27.1% (95% confidence interval [CI] = 26.5% to 27.7%), while the adjusted readmission rate among Medicare-eligible veterans was 25.3% (95% CI = 23.6% to 27.1%) after correcting for favorable selection. Readmission rate estimates among FFS veterans generalize to all Medicare-eligible veterans only after accounting for favorable selection into MA. Estimation of quality metrics should carefully consider sample selection to produce valid policy inferences.

  9. Frequency Affects Object Relative Clause Processing: Some Evidence in Favor of Usage-Based Accounts

    ERIC Educational Resources Information Center

    Reali, Florencia

    2014-01-01

    The processing difficulty of nested grammatical structure has been explained by different psycholinguistic theories. Here I provide corpus and behavioral evidence in favor of usage-based models, focusing on the case of object relative clauses in Spanish as a first language. A corpus analysis of spoken Spanish reveals that, as in English, the…

  10. Correlates of Perceived Favorability of Online Courses for Quantitative versus Qualitative Undergraduate Business Majors

    ERIC Educational Resources Information Center

    Blau, Gary; Pred, Robert; Drennan, Rob B., Jr.; Kapanjie, Darin

    2016-01-01

    An online survey tested the association among background, technological, and course-related variables with perceived favorability of online courses for two independent samples of fall 2015 and spring 2016 business undergraduates taking at least one online or hybrid course. Results showed that perceived learning was a consistent positive correlate…

  11. Biofilm mode of growth of Streptococcus intermedius favored by a competence-stimulating signaling peptide.

    PubMed

    Petersen, Fernanda C; Pecharki, Daniele; Scheie, Anne A

    2004-09-01

    Gram-positive and gram-negative bacteria use quorum sensing to coordinate population behavior. In several streptococci, quorum sensing mediated by competence-stimulating peptides (CSP) is associated with development of competence for transformation. We show here that a synthetic CSP favored the biofilm mode of growth of Streptococcus intermedius without affecting the rate of culture growth.

  12. Increasing long-term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  13. 49 CFR 805.735-5 - Receipt of gifts, entertainment, and favors by Members or employees.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Members or employees. 805.735-5 Section 805.735-5 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL TRANSPORTATION SAFETY BOARD EMPLOYEE RESPONSIBILITIES AND CONDUCT § 805.735-5 Receipt of gifts, entertainment, and favors by Members or employees. (a) Except as provided in...

  14. Colleges, Fighting U.S. Trade Proposal, Say It Favors For-Profit Distance Education.

    ERIC Educational Resources Information Center

    Foster, Andrea

    2002-01-01

    Describes how many colleges are opposing a U.S. plan that they say favors for-profit distance education. The proposal before the World Trade Organization asks member countries to begin formal negotiations to reduce barriers that keep higher education institutions from offering courses in other countries. (EV)

  15. Conservative Management and Planned Surgery for Periviable Advanced Extrauterine Abdominal Pregnancy with Favorable Outcome: Report of Two Cases

    PubMed Central

    Harirah, Hassan M.; Smith, J. Michael; Dixon, C. Luke; Hankins, Gary D. V.

    2016-01-01

    Advanced abdominal pregnancy is an extremely rare condition that poses diagnostic and management challenges. A high index of suspicion and careful assessment of the patient's symptoms, supplemented with obstetric ultrasound, and magnetic resonance imaging, are crucial for timely diagnosis and management to prevent life-threatening complications. The presence of periviable fetuses in advanced abdominal pregnancies increases the challenge to achieve a balance between maternal and fetal benefits and risks. Early diagnosis and management decisions via a multidisciplinary approach and planned delivery are of paramount importance to minimize complications and achieve favorable maternal and fetal outcomes. Even in the setting of oligohydramnios and suspected preterm premature rupture of membranes, in-patient conservative management and an individualized planned surgical approach that includes removing or leaving the placenta in place are appropriate for managing the periviable abdominal pregnancy. PMID:27595049

  16. Glucose Promotes a Pro-Oxidant and Pro-Inflammatory Stromal Microenvironment Which Favors Motile Properties in Breast Tumor Cells.

    PubMed

    Kallens, Violeta; Tobar, Nicolás; Molina, Jessica; Bidegain, Arantzazú; Smith, Patricio C; Porras, Omar; Martínez, Jorge

    2017-05-01

    Chronic inflammation and metabolic reprogramming have been proposed as hallmarks of cancer development. Currently, many of the functional clues between these two phenomena are studied under the integrative view of functional stroma-epithelia interaction. It has been proposed that stromal cells, due to their abundance and avidity for glucose, are able to modify the metabolic behavior of an entire solid tumor. In the present study, using a mammary stromal cell line derived from healthy tissue subjected to long-term culture in low (5 mM) or high (25 mM) glucose, we found that the hyperglycemic condition favors the establishment of a pro-inflammatory and pro-oxidant environment characterized by the induction of the COX-2/PGE2 axis. In this condition, epithelial migration was stimulated. Moreover, we also found that stromal-derived PGE2, acting as a stimulator of IL-1 epithelial expression was one of the factors that promote the acquisition of motile properties by epithelial cells and the maintenance of a COX-2/PGE2-dependent inflammatory condition. Overall, our work provides experimental evidence that glucose stimulates a tumor inflammatory environment that, as a result of a functional cross-talk between stroma and epithelia, may be responsible for tumor progression. J. Cell. Biochem. 118: 994-1002, 2017. © 2016 Wiley Periodicals, Inc.

  17. Development of Discussion Supporting System Based on the "Value of Favorable Words' Influence"

    NASA Astrophysics Data System (ADS)

    Kotani, Tetsuro; Seki, Kazuya; Matsui, Tatsunori; Okamoto, Toshio

    The importance of the WEB chat in discussion has been well known and used effectively in collaborative learning environment. In order to activate discussions, various functions such as identification of participants' roles, motivation to participate, and resolution of depressed discussions are needed. This research proposes the function to calculate the "values of favorable words' influence" on real time, which are estimated by member of participants' words and their transitive structures. In this paper, firstly we define the "values of favorable wards' influence" as an index for the active direction of discussion and the discussion model based on this index, secondly we introduce an architecture of the discussion supporting system based on this model and its performance and finally through some practical experiments we examine the validity and effectiveness of our discussion model.

  18. Cytoskeleton-centric protein transportation by exosomes transforms tumor-favorable macrophages

    PubMed Central

    Cui, Yizhi; Zhou, Yanlong; Yin, Xingfeng; Guo, Jiahui; Zhang, Gong; Wang, Tong; He, Qing-Yu

    2016-01-01

    The exosome is a key initiator of pre-metastatic niche in numerous cancers, where macrophages serve as primary inducers of tumor microenvironment. However, the proteome that can be exosomally transported from cancer cells to macrophages has not been sufficiently characterized so far. Here, we used colorectal cancer (CRC) exosomes to educate tumor-favorable macrophages. With a SILAC-based mass spectrometry strategy, we successfully traced the proteome transported from CRC exosomes to macrophages. Such a proteome primarily focused on promoting cytoskeleton rearrangement, which was biologically validated with multiple cell lines. We reproduced the exosomal transportation of functional vimentin as a proof-of-concept example. In addition, we found that some CRC exosomes could be recognized by macrophages via Fc receptors. Therefore, we revealed the active and necessary role of exosomes secreted from CRC cells to transform cancer-favorable macrophages, with the cytoskeleton-centric proteins serving as the top functional unit. PMID:27602764

  19. Influences of Mental Illness Stigma on Perceptions of and Responses to Requests for Favors.

    PubMed

    Imai, Tatsuya; Dailey, René

    2016-07-01

    This article examines mental illness stigma effects on a request for a favor from a mentally ill individual. Four hundred and fourteen participants interacted with a hypothetical target on Facebook who was believed to have schizophrenia, depression, or a tooth cavity (i.e., the control group). Participants were asked to rate the favor request in terms of face threat, in addition to writing a response, which was then coded using message design logics. Results indicated that a request by a schizophrenic target threatened participants' positive face more significantly than that of a target with depression or without any mental illness. Participants' responses to the schizophrenic target were more likely to be conventional messages, whereas responses to the depressed target were more likely to be rhetorical messages. Theoretical and practical contributions are considered.

  20. Perceived Distributive Fairness of EU Transfer Payments, Outcome Favorability, Identity, and EU-Tax Compliance.

    PubMed

    Hartner, Martina; Rechberger, Silvia; Kirchler, Erich; Wenzel, Michael

    2011-01-01

    In a representative UK study (N = 1000) the link between distributive fairness perceptions, outcome favorability, identity, and tax compliance was researched in the context of European transfer payments. Results showed that both forms of tax compliance (i.e., individual and collective EU-tax compliance) were influenced by perceived distributive fairness judgments of EU transfer payments. Fairness itself was related to perceived outcome favorability (i.e., whether their own nation benefits from the EU in financial as well as socio-political terms). Additionally, national identifiers (i.e., people identifying with their own nation, but not with Europe) perceived EU membership as unbeneficial in financial as well as in socio-political terms and thus considered the transfer payments as less fair. Dual identifiers (i.e., people identifying with their own nation and with Europe) perceived the socio-political outcomes from EU membership as more beneficial and thus evaluated the transfer payments as fairer.

  1. Detecting Two-Spirit erotics: The fiction of Carole laFavor.

    PubMed

    Tatonetti, Lisa

    2016-01-01

    This article examines the life and novels of Carole laFavor, arguing for her importance to and influence in Two-Spirit studies. Along with being a writer, laFavor was a powerful voice for social justice and Indigenous health sovereignty in Minnesota and the nation. Her two novels, Along the Journey River and Evil Dead Center, which both focus on Anishinaabe lesbian detective protagonist Renee LaRoche, are the first lesbian detective fiction published by a Native author. Renee's embrace of a specifically Two-Spirit erotics anchors her to family and brings her tribal community a powerful healing when she employs her skills to protect her people from instances of racism, abuse, and injustice. This article, then, reads these novels as the first of an emerging genre of texts that claim an overtly Two-Spirit erotic as well as vital precursors to the present embrace of sovereign erotics in Indigenous studies.

  2. Designing convex repulsive pair potentials that favor assembly of kagome and snub square lattices

    NASA Astrophysics Data System (ADS)

    Piñeros, William D.; Baldea, Michael; Truskett, Thomas M.

    2016-08-01

    Building on a recently introduced inverse strategy, isotropic and convex repulsive pair potentials were designed that favor assembly of particles into kagome and equilateral snub square lattices. The former interactions were obtained by a numerical solution of a variational problem that maximizes the range of density for which the ground state of the potential is the kagome lattice. Similar optimizations targeting the snub square lattice were also carried out, employing a constraint that required a minimum chemical potential advantage of the target over select competing structures. This constraint helped to discover isotropic interactions that meaningfully favored the snub square lattice as the ground state structure despite the asymmetric spatial distribution of particles in its coordination shells and the presence of tightly competing structures. Consistent with earlier published results [W. Piñeros et al., J. Chem. Phys. 144, 084502 (2016)], enforcement of greater chemical potential advantages for the target lattice in the interaction optimization led to assemblies with enhanced thermal stability.

  3. Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes

    PubMed Central

    Zhou, Yunli; Zhang, Mi; He, Dan; Hu, Xueyuan; Xiong, Huarong; Wu, Jianyong; Zhu, Biyue; Zhang, Jingqing

    2016-01-01

    Enzyme therapy is an effective strategy to treat diseases. Three strategies were pursued to provide the favorable microenvironments for uricase (UCU) to eventually improve its features: using the right type of buffer to constitute the liquid media where catalyze reactions take place; entrapping UCU inside the selectively permeable lipid vesicle membranes; and entrapping catalase together with UCU inside the membranes. The nanosized alkaline enzymosomes containing UCU/(UCU and catalase) (ESU/ESUC) in bicine buffer had better thermal, hypothermal, acid-base and proteolytic stabilities, in vitro and in vivo kinetic characteristics, and uric acid lowering effects. The favorable microenvironments were conducive to the establishment of the enzymosomes with superior properties. It was the first time that two therapeutic enzymes were simultaneously entrapped into one enzymosome having the right type of buffer to achieve added treatment efficacy. The development of ESU/ESUC in bicine buffer provides valuable tactics in hypouricemic therapy and enzymosomal application. PMID:26823332

  4. Designing convex repulsive pair potentials that favor assembly of kagome and snub square lattices.

    PubMed

    Piñeros, William D; Baldea, Michael; Truskett, Thomas M

    2016-08-07

    Building on a recently introduced inverse strategy, isotropic and convex repulsive pair potentials were designed that favor assembly of particles into kagome and equilateral snub square lattices. The former interactions were obtained by a numerical solution of a variational problem that maximizes the range of density for which the ground state of the potential is the kagome lattice. Similar optimizations targeting the snub square lattice were also carried out, employing a constraint that required a minimum chemical potential advantage of the target over select competing structures. This constraint helped to discover isotropic interactions that meaningfully favored the snub square lattice as the ground state structure despite the asymmetric spatial distribution of particles in its coordination shells and the presence of tightly competing structures. Consistent with earlier published results [W. Piñeros et al., J. Chem. Phys. 144, 084502 (2016)], enforcement of greater chemical potential advantages for the target lattice in the interaction optimization led to assemblies with enhanced thermal stability.

  5. Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism.

    PubMed

    Pfattheicher, Stefan; Schindler, Simon

    2016-01-01

    The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O'Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O'Malley. Overall, small

  6. Secondary Hemophagocytic Lymphohistiocytosis in a Patient With Favorable Histology Wilms Tumor.

    PubMed

    Murphy, Erin P; Mo, Jun; Yoon, Janet M

    2015-11-01

    Secondary hemophagocytic lymphohistiocytosis (HLH) is most commonly associated with malignancy, infection, or an underlying autoimmune disorder. Malignancy-associated hemophagocytic syndrome is responsible for most secondary HLH cases, but it has not been well described in children. We present a case of a 4-year-old female with favorable histology of Wilms tumor who developed secondary HLH after unsuccessful resection of the tumor and initiation of chemotherapy.

  7. Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism

    PubMed Central

    Pfattheicher, Stefan; Schindler, Simon

    2016-01-01

    The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O’Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O’Malley. Overall

  8. Glucagon-like peptide-1 receptor agonists favorably address all components of metabolic syndrome

    PubMed Central

    Chatterjee, Sanjay; Ghosal, Samit; Chatterjee, Saurav

    2016-01-01

    Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiology of cardiovascular disease in diabetes may be divided into hyperglycemia per se and factors operating through components of metabolic syndrome (MetS). Hyperglycemia causes direct injury to vascular endothelium and possibly on cardiac myocytes. MetS is a cluster of risk factors like obesity, hyperglycemia, hypertension and dyslipidemia. The incidence of this syndrome is rising globally. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a group of drugs, which address all components of this syndrome favorably. Experimental evidence suggests that they have favorable actions on myocardium as well. Several compounds belonging to GLP-1RA class are in market now and a large number awaiting their entry. Although, originally this class of drugs emerged as a treatment for type 2 diabetes mellitus, more recent data generated revealed beneficial effects on multiple metabolic parameters. We have studied literature published between 2000 and 2016 to look into effects of GLP-1RA on components of MetS. Results from recently concluded clinical trials suggest that some of the molecules in this class may have favorable effects on cardiovascular outcome. PMID:27795818

  9. [Comparison of the quick Gram stain method to the B&M modified and favor methods].

    PubMed

    Osawa, Kayo; Kataoka, Nobumasa; Maruo, Toshio

    2011-01-01

    The Gram stain is an established method for bacterial identification, but the time needed to carry out this stain is 2-3 min. We attempted to shorten this time and stained a total of 70 clinical specimens isolated from using the Bartholomew & Mittwer (B&M) modified or Favor methods with a 3 s duration for washing and staining steps. Results were plotted and analyzed using a Hue Saturation Intensity (HSI) model. The range based on a plot of the two methods with the HSI model was presented as a reference interval. Our results indicated that 100% (35/35) of strains were Gram positive and 97.1% (34/35) were Gram negative for the quick B&M modified method. In the quick Favor method, 80.0% (28/35) were Gram positive and 68.6% (24/35) of strains were Gram negative. We propose that the quick B&M modified method is equivalent to the standard Gram staining method and is superior to the quick Favor method.

  10. Elongated TCR alpha chain CDR3 favors an altered CD4 cytokine profile

    PubMed Central

    2014-01-01

    Background CD4 T lymphocyte activation requires T cell receptor (TCR) engagement by peptide/MHC (major histocompatibility complex) (pMHC). The TCR complementarity-determining region 3 (CDR3) contains variable α and β loops critical for pMHC recognition. During any immune response, tuning of TCR usage through progressive clonal selection occurs. Th1 and Th2 cells operate at different avidities for activation and display distinct transcriptional programs, although polarization may be plastic, influenced by pathogens and cytokines. We therefore hypothesized that CDR3αβ sequence features may intrinsically influence CD4 phenotype during progression of a response. Results We show that CD4 polarization involves distinct CDR3α usage: Th1 and Th17 cells favored short TCR CDR3α sequences of 12 and 11 amino acids, respectively, while Th2 cells favored elongated CDR3α loops of 14 amino acids, with lower predicted affinity. The dominant Th2- and Th1-derived TCRα sequences with14 amino acid CDR3 loops and 12 amino acid CDR3 loops, respectively, were expressed in TCR transgenics. The functional impact of these TCRα transgenes was assessed after in vivo priming with a peptide/adjuvant. The short, Th1-derived receptor transgenic T cell lines made IFNγ, but not IL-4, 5 or 13, while the elongated, Th2-derived receptor transgenic T cell lines made little or no IFNγ, but increased IL-4, 5 and 13 with progressive re-stimulations, mirrored by GATA-3 up-regulation. T cells from primed Th2 TCRα transgenics selected dominant TCR Vβ expansions, allowing us to generate TCRαβ transgenics carrying the favored, Th2-derived receptor heterodimer. Primed T cells from TCRαβ transgenics made little or no IL-17 or IFNγ, but favored IL-9 after priming with Complete Freund’s adjuvant and IL-4, 5, 9, 10 and 13 after priming with incomplete Freund’s. In tetramer-binding studies, this transgenic receptor showed low binding avidity for pMHC and polarized T cell lines show TCR avidity

  11. Favorable life-style modification and attenuation of cardiovascular risk factors.

    PubMed

    Yamamoto, R; Kawamura, T; Wakai, K; Ichihara, Y; Anno, T; Mizuno, Y; Yokoi, M; Ohta, T; Iguchi, A; Ohno, Y

    1999-03-01

    In order to develop an effective counseling system for prevention of cardiovascular diseases, the association of a favorably changed life-style with improved risk factors was examined. Participants were 7,321 office workers aged 30-69 years from in and around Nagoya city. The age-adjusted odds ratio (OR) and its 95% confidence interval (CI) were calculated to assess the likelihood of risk factor improvement by favorable life-style modifications during a 3-year period. Those who began to eat breakfast and increased their vegetable intake normalized their previously abnormal diastolic blood pressure with more than twice the likelihood (adjusted OR [95% CI] 2.89 [1.29-6.46] and 2.60 [1.18-5.75], respectively). 'Began to eat breakfast' was also significantly associated with normalized total cholesterol (TC) (1.84, [1.05-3.21]). 'Stopped eating till full' significantly normalized the body mass index (2.03; [1.25-3.28]), uric acid (1.65; [1.07-2.52]) and TC (1.43; [1.04-1.97]). Those who started regular exercise significantly normalized their high-density lipoprotein-cholesterol (HDL-C) abnormality with 1.69-times the likelihood (1.69; [1.24-2.29]) and those who began to walk briskly also improved their TC abnormality (1.85; [1.19-2.89]). HDL-C was normalized with 2.55-times the likelihood in those who quit smoking (2.55; [1.68-3.86]). Because favorable life-style modifications can attenuate abnormal cardiovascular risk factors, then proper advice on specific risk factors should be routinely given at each health check-up in order to prevent the onset of cardiovascular diseases in subsequent years.

  12. Tau neutrinos favored over sterile neutrinos in atmospheric muon neutrino oscillations.

    PubMed

    Fukuda, S; Fukuda, Y; Ishitsuka, M; Kajita, T; Kameda, J; Kaneyuki, K; Kobayashi, K; Koshio, Y; Miura, M; Moriyama, S; Nakahata, M; Nakayama, S; Obayashi, Y; Okada, A; Okumura, K; Sakurai, N; Shiozawa, M; Suzuki, Y; Takeuchi, H; Takeuchi, Y; Toshito, T; Totsuka, Y; Yamada, S; Earl, M; Habig, A; Kearns, E; Messier, M D; Scholberg, K; Stone, J L; Sulak, L R; Walter, C W; Goldhaber, M; Barszczak, T; Casper, D; Gajewski, W; Kropp, W R; Mine, S; Price, L R; Smy, M; Sobel, H W; Vagins, M R; Ganezer, K S; Keig, W E; Ellsworth, R W; Tasaka, S; Kibayashi, A; Learned, J G; Matsuno, S; Takemori, D

    2000-11-06

    The previously published atmospheric neutrino data did not distinguish whether muon neutrinos were oscillating into tau neutrinos or sterile neutrinos, as both hypotheses fit the data. Using data recorded in 1100 live days of the Super-Kamiokande detector, we use three complementary data samples to study the difference in zenith angle distribution due to neutral currents and matter effects. We find no evidence favoring sterile neutrinos, and reject the hypothesis at the 99% confidence level. On the other hand, we find that oscillation between muon and tau neutrinos suffices to explain all the results in hand.

  13. Some concepts of favorability for world-class-type uranium deposits in the northeastern United States

    SciTech Connect

    Adler, H.H.

    1981-03-01

    An account is given of concepts of favorability of geologic environments in the eastern United States for uranium deposits of several major types existing elsewhere in the world. The purpose is to convey some initial ideas about the interrelationships of the geology of the eastern United States and the geologic settings of certain of these world-class deposits. The study and report include consideration of uranium deposits other than those generally manifesting the geologic, geochemical and genetic characteristics associated with the conventional sandstone-type ores of the western United States.

  14. Favorable areas for prospecting adjacent to the Roberts Mountains thrust in southern Lander County, Nevada

    USGS Publications Warehouse

    Stewart, John Harris; McKee, Edwin H.

    1968-01-01

    Recent geologic mapping by the U.S. Geological Survey of more than 2,500 square miles of a relatively little-studied part of central Nevada has outlined four areas favorable for the discovery of metallic mineral deposits. In these areas, lower Paleozoic carbonate rocks crop out below the Roberts Mountains thrust, a widespread fault in central and north-central Nevada. These areas have a stratigraphic and structural setting similar to that of the areas where large, open-pit gold deposits have been discovered recently at Carlin and Cortez in north-central Nevada.

  15. The development of cambered airfoil sections having favorable lift characteristics at supercritical Mach numbers

    NASA Technical Reports Server (NTRS)

    Graham, Donald J

    1949-01-01

    Several groups of new airfoil sections, designated as the NACA 8-series, are derived analytically to have lift characteristics at supercritical Mach numbers which are favorable in the sense that the abrupt loss of lift, characteristic of the usual airfoil section at Mach numbers above the critical, is avoided. Aerodynamic characteristics determined from two-dimensional wind-tunnel tests at Mach numbers up to approximately 0.9 are presented for each of the derived airfoils. Comparisons are made between the characteristics of these airfoils and the corresponding characteristics of representative NACA 6-series airfoils.

  16. Sex differences favoring women in verbal but not in visuospatial episodic memory.

    PubMed

    Lewin, C; Wolgers, G; Herlitz, A

    2001-04-01

    Sex differences favoring women have been found in a number of studies of episodic memory. This study examined sex differences in verbal, nonverbal, and visuospatial episodic memory tasks. Results showed that although women performed at a higher level on a composite verbal and nonverbal episodic memory score, men performed at a higher level on a composite score of episodic memory tasks requiring visuospatial processing. Thus, men can use their superior visuospatial abilities to excel in highly visuospatial episodic memory tasks, whereas women seem to excel in episodic memory tasks in which a verbalization of the material is possible.

  17. Expectant management with selective delayed intervention for favorable risk prostate cancer.

    PubMed

    Klotz, Laurence

    2002-01-01

    Management options for favorable risk prostate cancer are diverse, varying from a conservative approach (expectant management) to definitive treatment (radical prostatectomy or radiotherapy.) Several studies have suggested that expectant management provides similar 10-year survival rates and quality-adjusted life years compared with radical prostatectomy or radiotherapy. Expectant management alone clearly deprives some patients with potentially curable life-threatening disease of the opportunity for curative therapy. However, every series of conservative management contains a substantial subset of long-term survivors, particularly in the group with favorable clinical parameters. We have conducted a clinical study to evaluate a novel approach in which the choice between a definitive therapy and conservative policy is determined by the rate of PSA increase or the development of early, rapid clinical and/or histologic progression. This strategy, which has never been previously evaluated, offers the powerful attraction of individualizing therapy according to the biological behavior of the cancer. This would mean that patients with slowly growing malignancy would be spared the side effects of radical treatment, while those with more rapidly progressive cancer would still benefit from curative therapy. Doubling time varied widely. In this series of 200 patients, neither grade, stage, nor baseline PSA predicted the PSA doubling time. Thirty-three percent of patients had a PSA doubling time (T(D)) > 10 years. Doubling time appears to be a useful tool to guide treatment intervention for patients managed initially with expectant management. A doubling time of less than 2 years appears to identify patients at high risk for local progression in spite of otherwise favorable prognostic factors. Fifteen to 20% of patients will fall into this category. The remainder have a high chance of remaining free of recurrence and progression for many years. Watchful waiting is clearly

  18. Bound on the Slope of Steady Water Waves with Favorable Vorticity

    NASA Astrophysics Data System (ADS)

    Strauss, Walter A.; Wheeler, Miles H.

    2016-12-01

    We consider the angle {θ} of inclination (with respect to the horizontal) of the profile of a steady two dimensional inviscid symmetric periodic or solitary water wave subject to gravity. Although {θ} may surpass 30° for some irrotational waves close to the extreme wave, Amick (Arch Ration Mech Anal 99(2):91-114, 1987) proved that for any irrotational wave the angle must be less than 31.15°. Is the situation similar for periodic or solitary waves that are not irrotational? The extreme Gerstner wave has infinite depth, adverse vorticity and vertical cusps ( θ = 90°). Moreover, numerical calculations show that even waves of finite depth can overturn if the vorticity is adverse. In this paper, on the other hand, we prove an upper bound of 45° on {θ} for a large class of waves with favorable vorticity and finite depth. In particular, the vorticity can be any constant with the favorable sign. We also prove a series of general inequalities on the pressure within the fluid, including the fact that any overturning wave must have a pressure sink.

  19. High DBC1 (CCAR2) expression in gallbladder carcinoma is associated with favorable clinicopathological factors.

    PubMed

    Won, Kyu Yeoun; Cho, Hyuck; Kim, Gou Young; Lim, Sung-Jig; Bae, Go Eun; Lim, Jun Uk; Sung, Ji-Youn; Park, Yong-Koo; Kim, Youn Wha; Lee, Juhie

    2015-01-01

    There have been several studies on gallbladder carcinogenesis, and mutations of the KRAS, TP53, and CDKN2A genes have been reported in gallbladder carcinoma. The DBC1 gene (deleted in breast cancer 1) was initially cloned from region 8p21, which was homozygously deleted in breast cancer. DBC1 has been implicated in cancer cell proliferation and death. The functional role of DBC1 in normal cells and the role of DBC1 loss in cancer are not entirely clear. And DBC1 expression and its clinical implications in gallbladder carcinoma have yet to be thoroughly elucidated. Therefore, we evaluated DBC1 expression in 104 gallbladder carcinoma tissues in relation to survival and other prognostic factors via immunohistochemical analysis. DBC1 expression was divided into two categories: high DBC1 expression was observed in 32/104 cases (30.8%) and low expression in 72/104 cases (69.2%). High DBC1 expression correlated significantly with favorable clinicopathologic variables. Furthermore, in survival analysis, the high-DBC1 expression group showed a better survival rate compared to the low-DBC1 expression group. In conclusion, high DBC1 expression is associated with several favorable clinicopathologic factors in gallbladder carcinoma. These findings suggest that loss of DBC1 expression plays a role in tumorigenesis and tumor progression in gallbladder carcinoma.

  20. Spatial Heterogeneity in Human Activities Favors the Persistence of Wolves in Agroecosystems

    PubMed Central

    Ahmadi, Mohsen; López-Bao, José Vicente; Kaboli, Mohammad

    2014-01-01

    As human populations expand, there is increasing demand and pressure for land. Under this scenario, behavioural flexibility and adaptation become important processes leading to the persistence of large carnivores in human-dominated landscapes such as agroecosystems. A growing interest has recently emerged on the outcome of the coexistence between wolves and humans in these systems. It has been suggested that spatial heterogeneity in human activities would be a major environmental factor modulating vulnerability and persistence of this contentious species in agroecosystems. Here, we combined information from 35 den sites detected between 2011 and 2012 in agroecosystems of western Iran (Hamedan province), a set of environmental variables measured at landscape and fine spatial scales, and generalized linear models to identify patterns of den site selection by wolves in a highly-modified agroecosystem. On a landscape level, wolves selected a mixture of rangelands with scattered dry-farms on hillsides (showing a low human use) to locate their dens, avoiding areas with high densities of settlements and primary roads. On a fine spatial scale, wolves primarily excavated dens into the sides of elevated steep-slope hills with availability of water bodies in the vicinity of den sites, and wolves were relegated to dig in places with coarse-soil particles. Our results suggest that vulnerability of wolves in human-dominated landscapes could be compensated by the existence of spatial heterogeneity in human activities. Such heterogeneity would favor wolf persistence in agroecosystems favoring a land sharing model of coexistence between wolves and people. PMID:25251567

  1. High Concentrations of H2O2 Make Aerobic Glycolysis Energetically More Favorable for Cellular Respiration

    PubMed Central

    Molavian, Hamid R.; Kohandel, Mohammad; Sivaloganathan, Sivabal

    2016-01-01

    Since the original observation of the Warburg Effect in cancer cells, over 8 decades ago, the major question of why aerobic glycolysis is favored over oxidative phosphorylation has remained unresolved. An understanding of this phenomenon may well be the key to the development of more effective cancer therapies. In this paper, we use a semi-empirical method to throw light on this puzzle. We show that aerobic glycolysis is in fact energetically more favorable than oxidative phosphorylation for concentrations of peroxide (H2O2) above some critical threshold value. The fundamental reason for this is the activation and high engagement of the pentose phosphate pathway (PPP) in response to the production of reactive oxygen species (ROS) H2O2 by mitochondria and the high concentration of H2O2 (produced by mitochondria and other sources). This makes oxidative phosphorylation an inefficient source of energy since it leads (despite high levels of ATP production) to a concomitant high energy consumption in order to respond to the hazardous waste products resulting from cellular processes associated with this metabolic pathway. We also demonstrate that the high concentration of H2O2 results in an increased glucose consumption, and also increases the lactate production in the case of glycolysis. PMID:27601999

  2. Spatial structure favors cooperative behavior in the snowdrift game with multiple interactive dynamics

    NASA Astrophysics Data System (ADS)

    Su, Qi; Li, Aming; Wang, Long

    2017-02-01

    Spatial reciprocity is generally regarded as a positive rule facilitating the evolution of cooperation. However, a few recent studies show that, in the snowdrift game, spatial structure still could be detrimental to cooperation. Here we propose a model of multiple interactive dynamics, where each individual can cooperate and defect simultaneously against different neighbors. We realize individuals' multiple interactions simply by endowing them with strategies relevant to probabilities, and every one decides to cooperate or defect with a probability. With multiple interactive dynamics, the cooperation level in square lattices is higher than that in the well-mixed case for a wide range of cost-to-benefit ratio r, implying that spatial structure favors cooperative behavior in the snowdrift game. Moreover, in square lattices, the most favorable strategy follows a simple relation of r, which confers theoretically the average evolutionary frequency of cooperative behavior. We further extend our study to various homogeneous and heterogeneous networks, which demonstrates the robustness of our results. Here multiple interactive dynamics stabilizes the positive role of spatial structure on the evolution of cooperation and individuals' distinct reactions to different neighbors can be a new line in understanding the emergence of cooperation.

  3. 8 CFR 316.11 - Attachment to the Constitution; favorable disposition towards the good order and happiness.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... disposition towards the good order and happiness. 316.11 Section 316.11 Aliens and Nationality DEPARTMENT OF... the Constitution; favorable disposition towards the good order and happiness. (a) General. An... favorably disposed toward the good order and happiness of the United States. Attachment implies a depth...

  4. 8 CFR 316.11 - Attachment to the Constitution; favorable disposition towards the good order and happiness.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... disposition towards the good order and happiness. 316.11 Section 316.11 Aliens and Nationality DEPARTMENT OF... the Constitution; favorable disposition towards the good order and happiness. (a) General. An... favorably disposed toward the good order and happiness of the United States. Attachment implies a depth...

  5. Low preoperative albumin-globulin score predicts favorable survival in esophageal squamous cell carcinoma

    PubMed Central

    Wang, Zhi-qiang; Wang, De-shen; Wang, Yun; Zhang, Dong-sheng; Wang, Feng-hua; Fu, Jian-hua; Xu, Rui-hua; Li, Yu-hong

    2016-01-01

    This study retrospectively investigated the prognostic significance of the preoperative albumin-globulin score (AGS) and albumin/globulin ratio (AGR) in esophageal squamous cell carcinoma (ESCC). A cohort of 458 newly diagnosed ESCC patients who underwent radical esophagectomy in Sun Yat-sen University Cancer Center (Guangzhou, China) between January 2006 and December 2010 were selected into this study. The optimal cut-off value was identified to be 45.6 g/L, 26.9 g/L and 1.30 for albumin (ALB), globulin (GLB) and AGR in terms of survival, respectively. Patients with low ALB levels (< 45.6 g/L) and high GLB levels (≥ 26.9 g/L) were assigned an AGS of 2, those with only one of the two abnormalities were assigned an AGS of 1, and those with neither of the two abnormalities were assigned an AGS of 0. Univariate survival analysis showed that low AGS (0) was significantly associated with favorable disease free survival (DFS) [hazard ratio (HR), 0.635; 95% confidence interval (CI), 0.441–0.914; P = 0.015] and overall survival (OS) (HR, 0.578; 95% CI, 0.387–0.862; P = 0.007), and it remained an independent predictor for OS (HR, 0.630; 95% CI, 0.418–0.952; P = 0.028), but not for DFS (HR, 0.697; 95% CI, 0.479–1.061; P = 0.060) in multivariate models. High AGR (≥ 1.30) was also correlated with favorable DFS (HR, 0.626; 95% CI, 0.430–0.910; P = 0.014) and OS (HR, 0.622; 95% CI, 0.422–0.916; P = 0.016) in univariate analysis, but it failed to be an independent prognostic indicator for DFS (HR, 0.730; 95% CI, 0.494–1.078; P = 0.114) or OS (HR, 0.759; 95% CI, 0.507–1.137; P = 0.181) by multivariate analysis. Low preoperative AGS could serve as a valuable and convenient biochemical marker to predict favorable long-term survival in ESCC patients. PMID:27105522

  6. Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner.

    PubMed

    Luput, Lavinia; Licarete, Emilia; Sesarman, Alina; Laura, Patras; Alupei, Marius Costel; Banciu, Manuela

    2017-02-17

    The role of tumor-associated macrophages (TAMs) in the development of colon carcinoma is still controversial. Therefore, the present study aimed to investigate the TAM‑driven processes that may affect colon cancer cell proliferation. To achieve this purpose, murine macrophages were co-cultured with C26 murine colon carcinoma cells at a cell density ratio that approximates physiological conditions for colon carcinoma development in vivo. In this respect, the effects of TAM-mediated angiogenesis, inflammation and oxidative stress on the proliferative capacity of C26 murine colon carcinoma cells were studied. To gain insight into the TAM-driven oxidative stress, NADPH oxidase, the main pro-oxidant enzyme in macrophages, was inhibited. Our data revealed that the stimulatory effects of TAMs on C26 cell proliferation may be related mainly to their pro-oxidant actions exerted by NADPH oxidase activity, which maintains the redox status and the angiogenic capacity of the tumor microenvironment. Additionally, the anti-inflammatory and pro-angiogenic effects of TAMs on tumor cells were found to create a favorable microenvironment for C26 colon carcinoma development and progression. In conclusion, our data confirmed the protumor role of TAMs in the development of colon carcinoma in an oxidative stress-dependent manner that potentiates the angiogenic capacity of the tumor microenvironment. These data may offer valuable information for future tumor-targeted therapies based on TAM 're-education' strategies.

  7. Low acetate concentrations favor polyphosphate-accumulating organisms over glycogen-accumulating organisms in enhanced biological phosphorus removal from wastewater.

    PubMed

    Tu, Yunjie; Schuler, Andrew J

    2013-04-16

    Glycogen-accumulating organisms (GAOs) are thought to compete with polyphosphate-accumulating organisms (PAOs) in enhanced biological phosphorus removal (EBPR) wastewater treatment systems. A laboratory sequencing batch reactor (SBR) was operated for one year to test the hypothesis that PAOs have a competitive advantage at low acetate concentrations, with a focus on low pH conditions previously shown to favor GAOs. PAOs dominated the system under conventional SBR operation with rapid acetate addition (producing high in-reactor concentrations) and pH values of 7.4-8.4. GAOs dominated when the pH was decreased (6.4-7.0). Decreasing the acetate addition rate led to very low reactor acetate concentrations, and PAOs recovered, supporting the study hypothesis. When the acetate feed rate was increased, EBPR failed again. Dominant PAOs and GAOs were Candidatus Accumulibacter phosphatis and Defluviicoccus Cluster 2, respectively, according to fluorescent in situ hybridization and 454 pyrosequencing. Surprisingly, GAOs were not the immediate causes of PAO failures, based on functional and population measurements. Pyrosequencing results suggested Dechloromonas and Tetrasphaera spp. may have also been PAOs, and additional potential GAOs were also identified. Full-scale systems typically have lower in-reactor acetate concentrations than laboratory SBRs, and so, previous laboratory studies may have overestimated the practical importance of GAOs as causes of EBPR failure.

  8. Brain glucagon-like peptide–1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage

    PubMed Central

    Knauf, Claude; Cani, Patrice D.; Perrin, Christophe; Iglesias, Miguel A.; Maury, Jean François; Bernard, Elodie; Benhamed, Fadilha; Grémeaux, Thierry; Drucker, Daniel J.; Kahn, C. Ronald; Girard, Jean; Tanti, Jean François; Delzenne, Nathalie M.; Postic, Catherine; Burcelin, Rémy

    2005-01-01

    Intestinal glucagon-like peptide–1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9–39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state. PMID:16322793

  9. Combined phosphate and nitrogen limitation generates a nutrient stress transcriptome favorable for arbuscular mycorrhizal symbiosis in Medicago truncatula.

    PubMed

    Bonneau, Laurent; Huguet, Stéphanie; Wipf, Daniel; Pauly, Nicolas; Truong, Hoai-Nam

    2013-07-01

    Arbuscular mycorrhizal (AM) symbiosis is stimulated by phosphorus (P) limitation and contributes to P and nitrogen (N) acquisition. However, the effects of combined P and N limitation on AM formation are largely unknown. Medicago truncatula plants were cultivated in the presence or absence of Rhizophagus irregularis (formerly Glomus intraradices) in P-limited (LP), N-limited (LN) or combined P- and N-limited (LPN) conditions, and compared with plants grown in sufficient P and N. The highest AM formation was observed in LPN, linked to systemic signaling by the plant nutrient status. Plant free phosphate concentrations were higher in LPN than in LP, as a result of cross-talk between P and N. Transcriptome analyses suggest that LPN induces the activation of NADPH oxidases in roots, concomitant with an altered profile of plant defense genes and a coordinate increase in the expression of genes involved in the methylerythritol phosphate and isoprenoid-derived pathways, including strigolactone synthesis genes. Taken together, these results suggest that low P and N fertilization systemically induces a physiological state of plants favorable for AM symbiosis despite their higher P status. Our findings highlight the importance of the plant nutrient status in controlling plant-fungus interaction.

  10. Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage.

    PubMed

    Knauf, Claude; Cani, Patrice D; Perrin, Christophe; Iglesias, Miguel A; Maury, Jean François; Bernard, Elodie; Benhamed, Fadilha; Grémeaux, Thierry; Drucker, Daniel J; Kahn, C Ronald; Girard, Jean; Tanti, Jean François; Delzenne, Nathalie M; Postic, Catherine; Burcelin, Rémy

    2005-12-01

    Intestinal glucagon-like peptide-1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9-39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state.

  11. Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors

    PubMed Central

    Walz, Amy L.; Ooms, Ariadne; Gadd, Samantha; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jamie M.; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Bowlby, Reanne; Brooks, Denise; Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Schein, Jacqueline; Marra, Marco A.; Huff, Vicki; Dome, Jeffrey S.; Chi, Yueh-Yun; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Jafari, Nadereh; Ross, Nicole; Gastier-Foster, Julie M.; Perlman, Elizabeth J.

    2016-01-01

    SUMMARY We report the most common single nucleotide substitution/deletion mutations in Favorable Histology Wilms Tumors (FHWT) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPG) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG-mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death. PMID:25670082

  12. High temperature favors elimination of toxin-producing Microcystis and degradation of microcystins by mixotrophic Ochromonas.

    PubMed

    Zhang, Lu; Gu, Lei; Wei, Qian; Zhu, Xuexia; Wang, Jun; Wang, Xiaojun; Yang, Zhou

    2017-04-01

    This study aimed to investigate the influence of temperature on the ability of the mixotrophic flagellate Ochromonas to eliminate a toxic Microcystis population and degrade microcystins. We exposed Microcystis to cultures with or without Ochromonas YZ1 at 20, 25, and 30 °C for 10 days. Results showed that increased temperature promoted the growth of Ochromonas YZ1 and Microcystis, with the latter achieving high abundance without grazing. With increased temperature, Ochromonas YZ1 clearance rate increased, and Microcystis populations were earlier eliminated. Importantly, Ochromonas YZ1 degraded both intracellular and extracellular microcystins by grazing effects. The reduction ratios of Microcystis abundances and microcystins were both approximately 100% after 6 days at high temperature. In addition, more microcystins were released outside at 20 °C than at the higher temperatures. Overall, this study showed that high temperature favors elimination of toxin-producing Microcystis and degradation of microcystins by mixotrophic Ochromonas.

  13. Favored configurations for four-quasiparticle K isomerism in the heaviest nuclei

    NASA Astrophysics Data System (ADS)

    Liu, H. L.; Walker, P. M.; Xu, F. R.

    2014-04-01

    Configuration-constrained potential-energy-surface calculations are performed including β6 deformation to investigate high-K isomeric states in nuclei around 254No and 270Ds, the heaviest nuclei where there have been some observations of two-quasiparticle isomers, while data for four-quasiparticle isomers are scarce. We predict the prevalent occurrence of four-quasiparticle isomeric states in these nuclei, together with their favored configurations. The most notable examples, among others, are Kπ=20+ states in 266,268Ds and 268,270Cn having very high K value, relatively low excitation energy, and well-deformed axially symmetric shape. The predicted isomeric states, with hindered spontaneous fission and α decay, could play a significant role in the future study of superheavy nuclei.

  14. Cosmology Favoring Extra Radiation and Sub-eV Mass Sterile Neutrinos as an Option

    SciTech Connect

    Hamann, Jan; Hannestad, Steen; Raffelt, Georg G.; Tamborra, Irene; Wong, Yvonne Y. Y.

    2010-10-29

    Precision cosmology and big-bang nucleosynthesis mildly favor extra radiation in the Universe beyond photons and ordinary neutrinos, lending support to the existence of low-mass sterile neutrinos. We use the WMAP 7-year data, small-scale cosmic microwave background observations from ACBAR, BICEP, and QuAD, the SDSS 7th data release, and measurement of the Hubble parameter from HST observations to derive credible regions for the assumed common mass scale m{sub s} and effective number N{sub s} of thermally excited sterile neutrino states. Our results are compatible with the existence of one or perhaps two sterile neutrinos, as suggested by LSND and MiniBooNE, if m{sub s} is in the sub-eV range.

  15. Prejudice, Social Dominance, and Similarity among People who Favor Integration of Minorities.

    PubMed

    Martínez, Carmen; Saiz, José; Angosto, Josefa

    2016-04-12

    This study examines differences in prejudice, perceived similarity, and social dominance in members of the majority who favor integration as a means of minority acculturation. A total of 342 non-Gypsy Spanish participants filled out a questionnaire about their relationship to one of three outgroups: Maghrebians, Gypsies, and Latin Americans. Hierarchical cluster analysis showed that a three-cluster solution was most fitting for every outgroup. ANOVAs applied to the three clusters indicated significant differences in prejudice, perceived similarity, and social dominance. Referring to Gypsies the largest effect size was observed in manifest prejudice (η2 = .63), in Maghrebians, the largest effect size was observed in subtle prejudice (η2 =.77), while for Latin Americans, perceived similarity had the largest effect size η2 ( = .60). The results reveal a need to modify existing measures of integration; we recommend using questionnaires to measure behaviors that members of the majority would be willing to implement.

  16. Maternal Acceptance: Its Contribution to Children's Favorable Perceptions of Discipline and Moral Identity.

    PubMed

    Patrick, Renee B; Gibbs, John C

    2016-01-01

    The authors examined the contribution of maternal acceptance or warmth to children's and adolescents' perceptions of discipline and formation of moral identity. The sample consisted of 93 male and female students from Grades 5, 8, and 10 and their mothers. Students completed measures pertaining to perceived maternal discipline practices and acceptance-rejection, as well as moral identity. A subsample of mothers reported on their accepting or rejecting actions toward their children. Children were more likely to feel accepted, if their mothers used inductive discipline (vs. power assertion and love withdrawal). Perceived acceptance was also related to more favorable discipline evaluations in certain respects. Specifically, inductive discipline recipients who felt accepted also evaluated induction as appropriate and responded to it with positive and guilt-related emotions. Power assertion was evaluated as appropriate among those children who did feel accepted. Finally, among inductive discipline recipients, those who felt accepted also reported higher moral identity.

  17. Teaching accreditation exams reveal grading biases favor women in male-dominated disciplines in France.

    PubMed

    Breda, Thomas; Hillion, Mélina

    2016-07-29

    Discrimination against women is seen as one of the possible causes behind their underrepresentation in certain STEM (science, technology, engineering, and mathematics) subjects. We show that this is not the case for the competitive exams used to recruit almost all French secondary and postsecondary teachers and professors. Comparisons of oral non-gender-blind tests with written gender-blind tests for about 100,000 individuals observed in 11 different fields over the period 2006-2013 reveal a bias in favor of women that is strongly increasing with the extent of a field's male-domination. This bias turns from 3 to 5 percentile ranks for men in literature and foreign languages to about 10 percentile ranks for women in math, physics, or philosophy. These findings have implications for the debate over what interventions are appropriate to increase the representation of women in fields in which they are currently underrepresented.

  18. The drive to ban the NOEC/LOEC in favor of ECx is misguided and misinformed.

    PubMed

    Green, John W; Springer, Timothy A; Staveley, Jane P

    2013-01-01

    Challenges to the use of the no observed effect concentration (NOEC) in ecotoxicology have appeared over the years, with a recent call for banning its use in favor of the x% effects concentration (ECx). This article presents an opposing view, providing reasons for the continued use of the NOEC, and for hypothesis testing in general. Although the use of ECx values is appropriate in many situations, there are numerous real-world examples where it is not suitable and offers no advantage over the use of hypothesis testing. These examples are presented with recommended data analysis techniques, illustrating the variety of statistical approaches that are meaningful in analyzing ecotoxicity data. Thoughtful consideration of study design and proper analysis and interpretation of the results will go further to advance the science of ecotoxicology than attempting to implement a blanket prohibition or endorsement of any single statistical approach.

  19. Graphitic Nanocarbon-Selenium Cathode with Favorable Rate Capability for Li-Se Batteries.

    PubMed

    Zhang, Shuai-Feng; Wang, Wen-Peng; Xin, Sen; Ye, Huan; Yin, Ya-Xia; Guo, Yu-Guo

    2017-03-15

    A well-organized selenium/carbon nanosheets nanocomposite(Se/CNSs) is prepared by confining chain-like Sen molecules in hierarchically micromesoporous carbon nanosheets. A unique two-dimensional morphology and high graphitization degree of carbon nanosheets benefits fast Li(+)/e(-) access to the active Se, which guarantees a high utilization of Se during the(de)lithiation process. Besides, the chain-like Se molecules confined in the carbon matrix could alleviate the shuttle effect of polyselenides and promise a stable electrochemistry. Therefore, the resultant Se/CNSs delivers a highly reversible capacity, a long cycle life and favorable rate capabilities. Furthermore, a Li-Se pouch cell built from a metallic Li anode and the as-prepared Se/CNSs cathode exhibits an excellent electrochemical performance, demonstrating the potential of Se/CNSs in serving future energy storage devices with high energy density.

  20. mTOR pathway activation is a favorable prognostic factor in human prostate adenocarcinoma

    PubMed Central

    Stelloo, Suzan; Sanders, Joyce; Nevedomskaya, Ekaterina; de Jong, Jeroen; Peters, Dennis; van Leenders, Geert J.L.H.; Jenster, Guido; Bergman, Andries M.; Zwart, Wilbert

    2016-01-01

    Prostate cancer patients with localized disease are treated with curative intent. However, the disease will recur in approximately 30% of patients with a high incidence of morbidity and mortality. Prognostic biomarkers are needed to identify patients with high risk of relapse. mTOR pathway activation is reported in prostate cancer, but clinical trials testing efficacy of mTOR inhibitors were unsuccessful. To explain this clinical observation, we studied the expression and prognostic impact of mTOR-S2448 phosphorylation in localized prostate carcinomas. mTOR-S2448 phosphorylation is indicative for an activated mTOR pathway in prostate cancer. Surprisingly, the mTOR signaling pathway is activated specifically in prostate cancer patients with a favorable outcome. Since tumors from poor-outcome patients have low levels of mTOR-S2448 phosphorylation, this may explain why mTOR inhibitors proved unsuccessful in prostate cancer trials. PMID:27096957

  1. Cosmology favoring extra radiation and sub-eV mass sterile neutrinos as an option.

    PubMed

    Hamann, Jan; Hannestad, Steen; Raffelt, Georg G; Tamborra, Irene; Wong, Yvonne Y Y

    2010-10-29

    Precision cosmology and big-bang nucleosynthesis mildly favor extra radiation in the Universe beyond photons and ordinary neutrinos, lending support to the existence of low-mass sterile neutrinos. We use the WMAP 7-year data, small-scale cosmic microwave background observations from ACBAR, BICEP, and QuAD, the SDSS 7th data release, and measurement of the Hubble parameter from HST observations to derive credible regions for the assumed common mass scale m{s} and effective number N{s} of thermally excited sterile neutrino states. Our results are compatible with the existence of one or perhaps two sterile neutrinos, as suggested by LSND and MiniBooNE, if m{s} is in the sub-eV range.

  2. HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker12

    PubMed Central

    Sconocchia, Giuseppe; Eppenberger-Castori, Serenella; Zlobec, Inti; Karamitopoulou, Eva; Arriga, Roberto; Coppola, Andrea; Caratelli, Sara; Spagnoli, Giulio Cesare; Lauro, Davide; Lugli, Alessandro; Han, Junyi; Iezzi, Giandomenica; Ferrone, Cristina; Ferlosio, Amedeo; Tornillo, Luigi; Droeser, Raoul; Rossi, Piero; Attanasio, Antonio; Ferrone, Soldano; Terracciano, Luigi

    2014-01-01

    The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1β (IL-1β) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1β production by monocytes. PMID:24563618

  3. Pre and Post-copulatory Selection Favor Similar Genital Phenotypes in the Male Broad Horned Beetle

    PubMed Central

    House, Clarissa M.; Sharma, M. D.; Okada, Kensuke; Hosken, David J.

    2016-01-01

    Sexual selection can operate before and after copulation and the same or different trait(s) can be targeted during these episodes of selection. The direction and form of sexual selection imposed on characters prior to mating has been relatively well described, but the same is not true after copulation. In general, when male–male competition and female choice favor the same traits then there is the expectation of reinforcing selection on male sexual traits that improve competitiveness before and after copulation. However, when male–male competition overrides pre-copulatory choice then the opposite could be true. With respect to studies of selection on genitalia there is good evidence that male genital morphology influences mating and fertilization success. However, whether genital morphology affects reproductive success in more than one context (i.e., mating versus fertilization success) is largely unknown. Here we use multivariate analysis to estimate linear and nonlinear selection on male body size and genital morphology in the flour beetle Gnatocerus cornutus, simulated in a non-competitive (i.e., monogamous) setting. This analysis estimates the form of selection on multiple traits and typically, linear (directional) selection is easiest to detect, while nonlinear selection is more complex and can be stabilizing, disruptive, or correlational. We find that mating generates stabilizing selection on male body size and genitalia, and fertilization causes a blend of directional and stabilizing selection. Differences in the form of selection across these bouts of selection result from a significant alteration of nonlinear selection on body size and a marginally significant difference in nonlinear selection on a component of genital shape. This suggests that both bouts of selection favor similar genital phenotypes, whereas the strong stabilizing selection imposed on male body size during mate acquisition is weak during fertilization. PMID:27371390

  4. Metastasis of circulating tumor cells: Favorable soil or suitable biomechanics, or both?

    PubMed Central

    Azevedo, Ana Sofia; Follain, Gautier; Patthabhiraman, Shankar; Harlepp, Sébastien; Goetz, Jacky G

    2015-01-01

    Metastasis is the end product of a multistep process where cancer cells disseminate and home themselves in distant organs. Tumor cell extravasation is a rare, inefficient and transient event in nature and makes its studies very difficult. Noteworthy, little is known about how cancer cells arrest, adhere and pass through the endothelium of capillaries. Moreover, the key events driving metastatic growth in specific organs are not well understood. Thus, although metastasis is the leading cause of cancer-related death, how cancer cells acquire their abilities to colonize distant organs and why they do so in specific locations remain central questions in the understanding of this deadly disease. In this review, we would like to confront 2 concepts explaining the efficiency and location of metastatic secondary tumors. While the “seed and soil” hypothesis states that metastasis occurs at sites where the local microenvironment is favorable, the “mechanical” concept argues that metastatic seeding occurs at sites of optimal flow patterns. In addition, recent evidence suggests that the primary event driving tumor cell arrest before extravasation is mostly controlled by blood circulation patterns as well as mechanical cues during the process of extravasation. In conclusion, the organ tropism displayed by cancer cells during metastatic colonization is a multi-step process, which is regulated by the delivery and survival of circulating tumor cells (CTCs) through blood circulation, the ability of these CTCs to adhere and cross the physical barrier imposed by the endothelium and finally by the suitability of the soil to favor growth of secondary tumors. PMID:26312653

  5. Protein phosphatase methylesterase-1 (PME-1) expression predicts a favorable clinical outcome in colorectal cancer.

    PubMed

    Kaur, Amanpreet; Elzagheid, Adam; Birkman, Eva-Maria; Avoranta, Tuulia; Kytölä, Ville; Korkeila, Eija; Syrjänen, Kari; Westermarck, Jukka; Sundström, Jari

    2015-12-01

    Colorectal cancer (CRC) accounts for high mortality. So far, there is lack of markers capable of predicting which patients are at risk of aggressive course of the disease. Protein phosphatase-2A (PP2A) inhibitor proteins have recently gained interest as markers of more aggressive disease in certain cancers. Here, we report the role of PP2A inhibitor PME-1 in CRC. PME-1 expression was assessed from a rectal cancer patient cohort by immunohistochemistry, and correlations were performed for various clinicopathological variables and patient survival. Rectal cancer patients with higher cytoplasmic PME-1 protein expression (above median) had less recurrences (P = 0.003, n = 195) and better disease-free survival (DFS) than the patients with low cytoplasmic PME-1 protein expression (below median). Analysis of PPME-1 mRNA expression from TCGA dataset of colon and rectal adenocarcinoma (COADREAD) patient cohort confirmed high PPME1 expression as an independent protective factor predicting favorable overall survival (OS) (P = 0.005, n = 396) compared to patients with low PPME1 expression. CRC cell lines were used to study the effect of PME-1 knockdown by siRNA on cell survival. Contrary to other cancer types, PME-1 inhibition in CRC cell lines did not reduce the viability of cells or the expression of active phosphorylated AKT and ERK proteins. In conclusion, PME-1 expression predicts for a favorable outcome of CRC patients. The unexpected role of PME-1 in CRC in contrast with the oncogenic role of PP2A inhibitor proteins in other malignancies warrants further studies of cancer-specific function for each of these proteins.

  6. Does community-based conservation shape favorable attitudes among locals? an empirical study from nepal.

    PubMed

    Mehta, J N; Heinen, J T

    2001-08-01

    Like many developing countries, Nepal has adopted a community-based conservation (CBC) approach in recent years to manage its protected areas mainly in response to poor park-people relations. Among other things, under this approach the government has created new "people-oriented" conservation areas, formed and devolved legal authority to grassroots-level institutions to manage local resources, fostered infrastructure development, promoted tourism, and provided income-generating trainings to local people. Of interest to policy-makers and resource managers in Nepal and worldwide is whether this approach to conservation leads to improved attitudes on the part of local people. It is also important to know if personal costs and benefits associated with various intervention programs, and socioeconomic and demographic characteristics influence these attitudes. We explore these questions by looking at the experiences in Annapurna and Makalu-Barun Conservation Areas, Nepal, which have largely adopted a CBC approach in policy formulation, planning, and management. The research was conducted during 1996 and 1997; the data collection methods included random household questionnaire surveys, informal interviews, and review of official records and published literature. The results indicated that the majority of local people held favorable attitudes toward these conservation areas. Logistic regression results revealed that participation in training, benefit from tourism, wildlife depredation issue, ethnicity, gender, and education level were the significant predictors of local attitudes in one or the other conservation area. We conclude that the CBC approach has potential to shape favorable local attitudes and that these attitudes will be mediated by some personal attributes.

  7. Characterization of a novel N-acetylneuraminic acid lyase favoring N-acetylneuraminic acid synthesis

    PubMed Central

    Ji, Wenyan; Sun, Wujin; Feng, Jinmei; Song, Tianshun; Zhang, Dalu; Ouyang, Pingkai; Gu, Zhen; Xie, Jingjing

    2015-01-01

    N-Acetylneuraminic acid lyase (NAL, E.C. number 4.1.3.3) is a Class I aldolase that catalyzes the reversible aldol cleavage of N-acetylneuraminic acid (Neu5Ac) from pyruvate and N-acetyl-D-mannosamine (ManNAc). Due to the equilibrium favoring Neu5Ac cleavage, the enzyme catalyzes the rate-limiting step of two biocatalytic reactions producing Neu5Ac in industry. We report the biochemical characterization of a novel NAL from a “GRAS” (General recognized as safe) strain C. glutamicum ATCC 13032 (CgNal). Compared to all previously reported NALs, CgNal exhibited the lowest kcat/Km value for Neu5Ac and highest kcat/Km values for ManNAc and pyruvate, which makes CgNal favor Neu5Ac synthesis the most. The recombinant CgNal reached the highest expression level (480 mg/L culture), and the highest reported yield of Neu5Ac was achieved (194 g/L, 0.63 M). All these unique properties make CgNal a promising biocatalyst for industrial Neu5Ac biosynthesis. Additionally, although showing the best Neu5Ac synthesis activity among the NAL family, CgNal is more related to dihydrodipicolinate synthase (DHDPS) by phylogenetic analysis. The activities of CgNal towards both NAL's and DHDPS' substrates are fairly high, which indicates CgNal a bi-functional enzyme. The sequence analysis suggests that CgNal might have adopted a unique set of residues for substrates recognition. PMID:25799411

  8. Dynamic telecytology compares favorably to rapid onsite evaluation of endoscopic ultrasound fine needle aspirates

    PubMed Central

    Buxbaum, James L.; Eloubeidi, Mohamad A.; Lane, Christianne J.; Varadarajulu, Shyam; Linder, Ami; Crowe, Amanda E.; Jhala, Darshana; Jhala, Nirag C.; Crowe, David R.; Eltoum, Isam A.

    2013-01-01

    Background and Aims Rapid onsite evaluation (ROSE) has been demonstrated to correlate with final cytologic interpretations and improves the diagnostic yield of EUS-FNA, however, its availability is variable across centers. The aim of this prospective study was to evaluate whether remote telecytology can substitute for ROSE. Methods Consecutive patients who underwent EUS-FNA for diverse indications at a high volume referral center were enrolled All samples were prospectively evaluated by three methods. ROSE was performed by a cytopathologist in the procedure room; simultaneously dynamic telecytology was done by a different cytopathologist in a remote location at our institution. The third method, final cytologic interpretation in the laboratory, was the gold standard. Telecytology was performed using an Olympus microscope system (BX) which broadcasts live images over the internet. Accuracy of telecytology and agreement with other methods were the principle outcome measurements. Results Twenty-five consecutive samples were obtained from participants 40–87 years (median age =63, 48% male). There was 88% agreement between telecytology and final cytology (p < 0.001) and 92% agreement between ROSE and final cytology (p <0.001). There was consistency between telecytology and ROSE (p-value for McNemar’s χ2 = 1.0). Cohen’s kappa for agreement for telecytology and ROSE was 0.80 (SE = 0.11), confirming favorable correlation. Conclusion Dynamic telecytology compares favorably to ROSE in the assessment of EUS acquired fine needle aspirates. If confirmed by larger trials, this system might obviate the need for onsite interpretation of EUS-FNA specimens. PMID:22729624

  9. Computation assisted design of favored composition for ternary Mg-Cu-Y metallic glass formation.

    PubMed

    Wang, Q; Li, J H; Liu, B X

    2015-06-14

    With the aid of ab initio calculations, a realistic interatomic potential was constructed for the Mg-Cu-Y ternary system under the proposed formalism of smoothed and long-range second-moment approximation of tight-binding. Taking the potential as the starting base, an atomistic computation/simulation route was developed for designing favored and optimized compositions for Mg-Cu-Y metallic glass formation. Simulations revealed that the physical origin of metallic glass formation is the collapse of crystalline lattice when solute concentration exceeds a critical value, thus leading to predict a hexagonal region in the Mg-Cu-Y composition triangle, within which metallic glass formation is energetically favored. It is proposed that the hexagonal region can be defined as the intrinsic glass formation region, or quantitative glass formation ability of the system. Inside the hexagonal region, the driving force for formation of each specific glassy alloy was further calculated and correlated with its forming ability in practice. Calculations pinpointed the optimized stoichiometry in the Mg-Cu-Y system to be Mg64Cu16Y20, at which the formation driving force reaches its maximum, suggesting that metallic glasses designed to have compositions around Mg64Cu16Y20 are most stable or easiest to obtain. The predictions derived directly from the atomistic simulations are supported by experimental observations reported so far in the literature. Furthermore, Honeycutt-Anderson analysis indicated that pentagonal bipyramids (although not aggregating to form icosahedra) dominate in the local structure of the Mg-Cu-Y metallic glasses. A microscopic picture of the medium-range packing can then be described as an extended network of the pentagonal bipyramids, entangled with the fourfold and sixfold disclination lines, jointly fulfilling the space of the metallic glasses.

  10. Observing end-state comfort favorable actions does not modulate action plan recall.

    PubMed

    Seegelke, Christian

    2015-01-01

    A large corpus of work demonstrates that observing other people's actions activates corresponding motor representations in the observer by running an internal simulation of the observed action. Recent evidence suggests that recalled action plans reflect a plan of how the observer would execute that action (based on the specific motor representation) rather than a plan of the actually observed action (based on the visual representation). This study examined whether people would recall an action plan based on a visual representation if the observed movement is biomechanically favorable for their own subsequent action. Participants performed an object manipulation task alongside a confederate. In the intra-individual task, the participant (or confederate) transported a plunger from an outer platform of fixed height to a center target platform located at different heights (home-to-target move), and then the same person transported the plunger back to the outer platform (target-back-to-home move). In the inter-individual task, the sequence was split between the two persons such that the participant (or confederate) performed the home-to-target move and the other person performed the target-back-to-home move. Importantly, the confederate always grasped the plunger at the same height. This grasp height was designated such that if participants would copy the action (i.e., grasp the object at the same height) it would place the participant's arm in a comfortable position at the end of the target-back-to-home move (i.e., end-state comfort). Results show that participants' grasp height was inversely related to center target height and similar regardless of direction (home-to-target vs. target-back-to-home move) and task (intra- vs. inter-individual). In addition, during the inter-individual task, participant's target-back-to-home grasp height was correlated with their own, but not with the confederate's grasp height during the home-to-target moves. These findings provide

  11. Observing end-state comfort favorable actions does not modulate action plan recall

    PubMed Central

    Seegelke, Christian

    2015-01-01

    A large corpus of work demonstrates that observing other people’s actions activates corresponding motor representations in the observer by running an internal simulation of the observed action. Recent evidence suggests that recalled action plans reflect a plan of how the observer would execute that action (based on the specific motor representation) rather than a plan of the actually observed action (based on the visual representation). This study examined whether people would recall an action plan based on a visual representation if the observed movement is biomechanically favorable for their own subsequent action. Participants performed an object manipulation task alongside a confederate. In the intra-individual task, the participant (or confederate) transported a plunger from an outer platform of fixed height to a center target platform located at different heights (home-to-target move), and then the same person transported the plunger back to the outer platform (target-back-to-home move). In the inter-individual task, the sequence was split between the two persons such that the participant (or confederate) performed the home-to-target move and the other person performed the target-back-to-home move. Importantly, the confederate always grasped the plunger at the same height. This grasp height was designated such that if participants would copy the action (i.e., grasp the object at the same height) it would place the participant’s arm in a comfortable position at the end of the target-back-to-home move (i.e., end-state comfort). Results show that participants’ grasp height was inversely related to center target height and similar regardless of direction (home-to-target vs. target-back-to-home move) and task (intra- vs. inter-individual). In addition, during the inter-individual task, participant’s target-back-to-home grasp height was correlated with their own, but not with the confederate’s grasp height during the home-to-target moves. These findings

  12. TRAF4 Is a Novel Phosphoinositide-Binding Protein Modulating Tight Junctions and Favoring Cell Migration

    PubMed Central

    Rousseau, Adrien; McEwen, Alastair G.; Poussin-Courmontagne, Pierre; Rognan, Didier; Nominé, Yves; Rio, Marie-Christine; Tomasetto, Catherine; Alpy, Fabien

    2013-01-01

    Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration. PMID:24311986

  13. Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients.

    PubMed

    Dielmann, Anastasia; Letsch, Anne; Nonnenmacher, Anika; Miller, Kurt; Keilholz, Ulrich; Busse, Antonia

    2016-02-01

    T-box transcription factors, T-box expressed in T cells (T-bet) encoded by Tbx21 and Eomesodermin (Eomes), drive the differentiation of effector/memory T cell lineages and NK cells. The aim of the study was to determine the prognostic influence of the expression of these transcription factors in peripheral blood (pB) in a cohort of 41 metastatic (m) RCC patients before receiving sorafenib treatment and to analyze their association with the immunophenotype in pB. In contrast to Tbx21, in the multivariate analysis including clinical features, Eomes mRNA expression was identified as an independent good prognostic factor for progression-free survival (PFS, p = 0.042) and overall survival (OS, p = 0.001) in addition to a favorable ECOG performance status (p = 0.01 and p = 0.008, respectively). Eomes expression correlated positively not only with expression of Tbx21 and TGFβ1 mRNA, but also with mRNA expression of the activation marker ICOS, and with in vivo activated HLA-DR(+) T cells. Eomes expression was negatively associated with TNFα-producing T cells. On protein level, Eomes was mainly expressed by CD56(+)CD3(-) NK cells in pB. In conclusion, we identified a higher Eomes mRNA expression as an independent good prognostic factor for OS and PFS in mRCC patients treated with sorafenib.

  14. Alginate-polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering.

    PubMed

    Thankam, Finosh G; Muthu, Jayabalan

    2015-11-01

    The physiochemical and biological responses of tissue engineering hydrogels are crucial in determining their desired performance. A hybrid comacromer was synthesized by copolymerizing alginate and poly(mannitol fumarate-co-sebacate) (pFMSA). Three bimodal hydrogels pFMSA-AA, pFMSA-MA and pFMSA-NMBA were synthesized by crosslinking with Ca(2+) and vinyl monomers acrylic acid (AA), methacrylic acid (MA) and N,N'-methylene bisacrylamide (NMBA), respectively. Though all the hydrogels were cytocompatible and exhibited a normal cell cycle profile, pFMSA-AA exhibited superior physiochemical properties viz non-freezable water content (58.34%) and water absorption per unit mass (0.97 g water/g gel) and pore length (19.92±3.91 μm) in comparing with other two hydrogels. The increased non-freezable water content and water absorption of pFMSA-AA hydrogels greatly influenced its biological performance, which was evident from long-term viability assay and cell cycle proliferation. The physiochemical and biological favorability of pFMSA-AA hydrogels signifies its suitability for cardiac tissue engineering.

  15. Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?

    PubMed Central

    Salehipour, Mehdi; Mohammadian, Reza; Malekahmadi, Amir; Hosseinzadeh, Massood; Yadollahi, Mahnaz; Natami, Mohammad; Mohammadian, Mahsa

    2016-01-01

    ABSTRACT Purpose: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. Materials and Methods: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. Results: Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039). Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039). Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. Conclusions: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model. PMID:27256195

  16. FLARE STARS—A FAVORABLE OBJECT FOR STUDYING MECHANISMS OF NONTHERMAL ASTROPHYSICAL PHENOMENA

    SciTech Connect

    Oks, E.; Gershberg, R. E.

    2016-03-01

    We present a spectroscopic method for diagnosing a low-frequency electrostatic plasma turbulence (LEPT) in plasmas of flare stars. This method had been previously developed by one of us and successfully applied to diagnosing the LEPT in solar flares. In distinction to our previous applications of the method, here we use the latest advances in the theory of the Stark broadening of hydrogen spectral lines. By analyzing observed emission Balmer lines, we show that it is very likely that the LEPT was developed in several flares of AD Leo, as well as in one flare of EV Lac. We found the LEPT (though of different field strengths) both in the explosive/impulsive phase and at the phase of the maximum, as well as at the gradual phase of the stellar flares. While for solar flares our method allows diagnosing the LEPT only in the most powerful flares, for the flare stars it seems that the method allows revealing the LEPT practically in every flare. It should be important to obtain new and better spectrograms of stellar flares, allowing their analysis by the method outlined in the present paper. This can be the most favorable way to the detailed understanding of the nature of nonthermal astrophysical phenomena.

  17. Asymmetry of glia near central synapses favors presynaptically directed glutamate escape.

    PubMed Central

    Lehre, Knut Petter; Rusakov, Dmitri A

    2002-01-01

    Recent findings demonstrate that synaptically released excitatory neurotransmitter glutamate activates receptors outside the immediate synaptic cleft and that the extent of such extrasynaptic actions is regulated by the high affinity glutamate uptake. The bulk of glutamate transporter systems are evenly distributed in the synaptic neuropil, and it is generally assumed that glutamate escaping the cleft affects pre- and postsynaptic receptors to a similar degree. To test whether this is indeed the case, we use quantitative electron microscopy and establish the stochastic pattern of glial occurrence in the three-dimensional (3D) vicinity of two common types of excitatory central synapses, stratum radiatum synapses in hippocampus and parallel fiber synapses in cerebellum. We find that the occurrence of glia postsynaptically is strikingly higher (3-4-fold) than presynaptically, in both types of synapses. To address the functional consequences of this asymmetry, we simulate diffusion and transport of synaptically released glutamate in these two brain areas using a detailed 3D compartmental model of the extracellular space with glutamate transporters arranged unevenly, in accordance with the obtained experimental data. The results predict that glutamate escaping the synaptic cleft is 2-4 times more likely to activate presynaptic compared to postsynaptic receptors. Simulations also show that postsynaptic neuronal transporters (EAAT4 type) at dendritic spines of cerebellar Purkinje cells exaggerate this asymmetry further. Our data suggest that the perisynaptic environment of these common central synapses favors fast presynaptic feedback in the information flow while preserving the specificity of the postsynaptic input. PMID:12080105

  18. Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation

    PubMed Central

    Bertucci, Paola Y.; Nacht, A. Silvina; Alló, Mariano; Rocha-Viegas, Luciana; Ballaré, Cecilia; Soronellas, Daniel; Castellano, Giancarlo; Zaurin, Roser; Kornblihtt, Alberto R.; Beato, Miguel; Vicent, Guillermo P.; Pecci, Adali

    2013-01-01

    Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined the effect of progestins on the transcription of the bcl-x gene, where only intragenic progesterone receptor-binding sites (PRbs) were identified. We found that in response to hormone treatment, the PR is recruited to these sites along with two histone acetyltransferases CREB-binding protein (CBP) and GCN5, leading to an increase in histone H3 and H4 acetylation and to the binding of the SWI/SNF complex. Concomitant, a more relaxed chromatin was detected along bcl-x gene mainly in the regions surrounding the intragenic PRbs. PR also mediated the recruitment of the positive elongation factor pTEFb, favoring RNA polymerase II (Pol II) elongation activity. Together these events promoted the re-distribution of the active Pol II toward the 3′-end of the gene and a decrease in the ratio between proximal and distal transcription. These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone-dependent genes. PMID:23640331

  19. Intragenomic conflict produces sex ratio dynamics that favor maternal sex ratio distorters.

    PubMed

    Rood, Elaine S; Freedberg, Steven

    2016-11-01

    Maternal sex ratio distorters (MSDs) are selfish elements that enhance their transmission by biasing their host's sex allocation in favor of females. While previous models have predicted that the female-biased populations resulting from sex ratio distortion can benefit from enhanced productivity, these models neglect Fisherian selection for nuclear suppressors, an unrealistic assumption in most systems. We used individual-based computer simulation modeling to explore the intragenomic conflict between sex ratio distorters and their suppressors and explored the impacts of these dynamics on population-level competition between species characterized by MSDs and those lacking them. The conflict between distorters and suppressors was capable of producing large cyclical fluctuations in the population sex ratio and reproductive rate. Despite fitness costs associated with the distorters and suppressors, MSD populations often exhibited enhanced productivity and outcompeted non-MSD populations in single and multiple-population competition simulations. Notably, the conflict itself is beneficial to the success of populations, as sex ratio oscillations limit the competitive deficits associated with prolonged periods of male rarity. Although intragenomic conflict has been historically viewed as deleterious to populations, our results suggest that distorter-suppressor conflict can provide population-level advantages, potentially helping to explain the persistence of sex ratio distorters in a range of taxa.

  20. Evolution of learning in fluctuating environments: when selection favors both social and exploratory individual learning.

    PubMed

    Borenstein, Elhanan; Feldman, Marcus W; Aoki, Kenichi

    2008-03-01

    Cumulative cultural change requires organisms that are capable of both exploratory individual learning and faithful social learning. In our model, an organism's phenotype is initially determined innately (by its genotypic value) or by social learning (copying a phenotype from the parental generation), and then may or may not be modified by individual learning (exploration around the initial phenotype). The environment alternates periodically between two states, each defined as a certain range of phenotypes that can survive. These states may overlap, in which case the same phenotype can survive in both states, or they may not. We find that a joint social and exploratory individual learning strategy-the strategy that supports cumulative culture-is likely to spread when the environmental states do not overlap. In particular, when the environmental states are contiguous and mutation is allowed among the genotypic values, this strategy will spread in either moderately or highly stable environments, depending on the exact nature of the individual learning applied. On the other hand, natural selection often favors a social learning strategy without exploration when the environmental states overlap. We find only partial support for the "consensus" view, which holds that individual learning, social learning, and innate determination of behavior will evolve at short, intermediate, and long environmental periodicities, respectively.

  1. The sequential activation of the mitotic microtubule assembly pathways favors bipolar spindle formation

    PubMed Central

    Cavazza, Tommaso; Malgaretti, Paolo; Vernos, Isabelle

    2016-01-01

    Centrosome maturation is the process by which the duplicated centrosomes recruit pericentriolar components and increase their microtubule nucleation activity before mitosis. The role of this process in cells entering mitosis has been mostly related to the separation of the duplicated centrosomes and thereby to the assembly of a bipolar spindle. However, spindles can form without centrosomes. In fact, all cells, whether they have centrosomes or not, rely on chromatin-driven microtubule assembly to form a spindle. To test whether the sequential activation of these microtubule assembly pathways, defined by centrosome maturation and nuclear envelope breakdown, plays any role in spindle assembly, we combined experiments in tissue culture cells and Xenopus laevis egg extracts with a mathematical model. We found that interfering with the sequential activation of the microtubule assembly pathways compromises bipolar spindle assembly in tissue culture cells but not in X. laevis egg extracts. Our data suggest a novel function for centrosome maturation that determines the contribution of the chromosomal microtubule assembly pathway and favors bipolar spindle formation in most animal cells in which tubulin is in limiting amounts. PMID:27489339

  2. Aerosol deposition favors red tide phytoplankton in the East China Sea

    NASA Astrophysics Data System (ADS)

    Mackey, K. R.; Chien, C.; Chen, Y.; Glover, D. M.; Paytan, A.

    2013-12-01

    Chinese marginal seas support vast fisheries and vital economies, but their productivity is threatened by eutrophication from runoff and atmospheric deposition. The East China Sea is inundated with nitrogen from the Yangtze River and anthropogenic emissions, leading to elevated N:P ratios. We show that aerosol additions approximating one week of moderate deposition to offshore waters favor the growth of red tide phytoplankton, such as Skeletonema costatum, by providing nutrients and trace metals (iron and zinc) needed for growth. In contrast toxin-producing Pseudonitzchia does not benefit from aerosols in this region, possibly due to its preference for lower N:P ratios. A dose-dependent toxic response was observed in Synechococcus at high aerosol loads approximating a week of heavy deposition in the region. In contrast, phytoplankton growth at an onshore station was light limited, and aerosol additions did not have an appreciable effect on phytoplankton growth. Aerosol and chlorophyll observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite have the potential to explore the effect of aerosols on phytoplankton blooms over longer time scales and seasons. This study shows the potential for aerosols to control N:P ratios in offshore waters and to shape the phytoplankton community through fertilization and toxicity, contributing to the occurrence of red tides.

  3. Favorable control of advanced colon adenocarcinoma with severe bone marrow metastasis: A case report

    PubMed Central

    Hanamura, Fumiyasu; Shibata, Yoshihiro; Shirakawa, Tsuyoshi; Kuwayama, Miyuki; Oda, Hisanobu; Ariyama, Hiroshi; Taguchi, Kenichi; Esaki, Taito; Baba, Eishi

    2016-01-01

    Colorectal cancer (CRC) has a propensity to metastasize to the liver, lungs and regional abdominal lymph nodes, but rarely to the bone marrow. A 60-year-old man presented to the National Hospital Organization Kyushu Cancer Center with a 4-week history of persistent lower back pain, anorexia and difficulty defecating. Complete blood count revealed severe thrombocytopenia and erythroblastosis, suggesting a hematological malignancy. However, the bone marrow examination demonstrated involvement by a moderately to poorly differentiated adenocarcinoma, but no hematopoietic abnormalities. A computed tomography scan revealed thickening of the wall of the sigmoid colon, with para-aortic, hilar, mediastinal and supraclavicular lymphadenopathy. The patient was thus diagnosed with sigmoid colon adenocarcinoma with lymph node and bone marrow metastasis. Modified FOLFOX6 was promptly initiated, with concurrent therapy for disseminated intravascular coagulation (DIC). An increased number of thrombocytes was observed on day 6. After 3 cycles of treatment, the patient recovered from DIC and the levels of serum carcinoembryonic antigen and cytokeratin 19 fragment were decreased. Tumor biopsy during colonoscopy following recovery from DIC demonstrated poorly differentiated adenocarcinoma with mucin production, without mutations in the RAS, BRAF or PIK3CA genes, and a cytokeratin (CK) 7-negative, CK20-positive phenotype. The patient has been treated with chemotherapy for 150 days without disease progression. However, the efficacy of chemotherapy for rarely encountered bone marrow metastasis from CRC is poor. The present case was favorably maintained on chemotherapy and survived for 10 months. PMID:27900088

  4. The spreading front of invasive species in favorable habitat or unfavorable habitat

    NASA Astrophysics Data System (ADS)

    Lei, Chengxia; Lin, Zhigui; Zhang, Qunying

    2014-07-01

    Spatial heterogeneity and habitat characteristic are shown to determine the asymptotic profile of the solution to a reaction-diffusion model with free boundary, which describes the moving front of the invasive species. A threshold value R0Fr(D,t) is introduced to determine the spreading and vanishing of the invasive species. We prove that if R0Fr(D,t0)⩾1 for some t0⩾0, the spreading must happen; while if R0Fr(D,0)<1, the spreading is also possible. Our results show that the species in the favorable habitat can establish itself if the diffusion is slow or the occupying habitat is large. In an unfavorable habitat, the species dies out if the initial value of the species is small. However, big initial number of the species is benefit for the species to survive. When the species spreads in the whole habitat, the asymptotic spreading speed is given. Some implications of these theoretical results are also discussed.

  5. The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.

    PubMed

    Huang, Chun-Jie; Yuan, Yi-Feng; Wu, Di; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Huo, Li-Jun

    2017-03-01

    Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.

  6. Heightened exposure to parasites favors the evolution of immunity in brood parasitic cowbirds

    USGS Publications Warehouse

    Hahn, Caldwell; Reisen, William K.

    2011-01-01

    Immunologists and evolutionary biologists are interested in how the immune system evolves to fit an ecological niche. We studied the relationship between exposure to parasites and strength of immunity by investigating the response of two species of New World cowbirds (genus Molothrus, Icteridae), obligate brood parasites with contrasting life history strategies, to experimental arboviral infection. The South American shiny cowbird (M. bonariensis) is an extreme host-generalist that lays its eggs in the nests of >225 different avian species. The Central American bronzed cowbird (M. aeneus) is a relative host-specialist that lays its eggs preferentially in the nests of approximately 12 orioles in a single sister genus. West Nile virus provided a strong challenge and delineated immune differences between these species. The extreme host-generalist shiny cowbird, like the North American host-generalist, the brown-headed cowbird, showed significantly lower viremia to three arboviruses than related icterid species that were not brood parasites. The bronzed cowbird showed intermediate viremia. These findings support the interpretation that repeated exposure to a high diversity of parasites favors the evolution of enhanced immunity in brood parasitic cowbirds and makes them useful models for future studies of innate immunity.

  7. Atherosclerotic Lesion Progression Changes Lysophosphatidic Acid Homeostasis to Favor its Accumulation

    PubMed Central

    Bot, Martine; Bot, Ilze; Lopez-Vales, Rubén; van de Lest, Chris H.A.; Saulnier-Blache, Jean Sébastien; Helms, J. Bernd; David, Samuel; van Berkel, Theo J.C.; Biessen, Erik A.L.

    2010-01-01

    Lysophosphatidic acid (LPA) accumulates in the central atheroma of human atherosclerotic plaques and is the primary platelet-activating lipid constituent of plaques. Here, we investigated the enzymatic regulation of LPA homeostasis in atherosclerotic lesions at various stages of disease progression. Atherosclerotic lesions were induced in carotid arteries of low-density lipoprotein receptor–deficient mice by semiconstrictive collar placement. At 2-week intervals after collar placement, lipids and RNA were extracted from the vessel segments carrying the plaque. Enzymatic-and liquid chromatography-mass spectrometry–based lipid profiling revealed progressive accumulation of LPA species in atherosclerotic tissue preceded by an increase in lysophosphatidylcholine, a precursor in LPA synthesis. Plaque expression of LPA-generating enzymes cytoplasmic phospholipase A2IVA (cPLA2IVA) and calcium-independent PLA2VIA (iPLA2VIA) was gradually increased, whereas that of the LPA-hydrolyzing enzyme LPA acyltransferase α was quenched. Increased expression of cPLA2IVA and iPLA2VIA in advanced lesions was confirmed by immunohistochemistry. Moreover, LPA receptors 1 and 2 were 50% decreased and sevenfold upregulated, respectively. Therefore, key proteins in LPA homeostasis are increasingly dysregulated in the plaque during atherogenesis, favoring intracellular LPA production. This might at least partly explain the observed progressive accumulation of this thrombogenic proinflammatory lipid in human and mouse plaques. Thus, intervention in the enzymatic LPA production may be an attractive measure to lower intraplaque LPA content, thereby reducing plaque progression and thrombogenicity. PMID:20431029

  8. The multiscale factors favorable for a persistent heavy rain event over Hainan Island in October 2010

    NASA Astrophysics Data System (ADS)

    Wang, Huijie; Sun, Jianhua; Zhao, Sixiong; Wei, Jie

    2016-06-01

    A case study is presented of the multiscale characteristics that produced the record-breaking persistent heavy rainfall event (PHRE) over Hainan Island, northern South China Sea (SCS), in autumn 2010. The study documents several key weather systems, from planetary scale to mesoscale, that contributed to the extreme rainfall during this event. The main findings of this study are as follows. First, the convectively active phase of the MJO was favorable for the establishment of a cyclonic circulation and the northward expansion of the Intertropical Convergence Zone (ITCZ). The active disturbances in the northward ITCZ helped direct abundant moisture from adjacent oceans towards Hainan Island continuously throughout the event, where it interacted with cold air from the midlatitudes and caused heavy rain. Second, the 8-day-long PHRE can be divided into three processes according to different synoptic systems: peripheral cloud clusters of a tropical depression-type disturbance over the central SCS in process 1; interactions between the abnormally far north ITCZ and the invading cold air in process 2; and the newly formed tropical depression near Hainan Island in process 3. In the relatively stable synoptic background of each process, meso- α- and meso- β-scale cloud clusters repeatedly traveled along the same path to Hainan Island. Finally, based on these analyses, a conceptual model is proposed for this type of PHRE in autumn over the northern SCS, which demonstrates the influences of multiscale systems.

  9. Social heuristics and social roles: Intuition favors altruism for women but not for men.

    PubMed

    Rand, David G; Brescoll, Victoria L; Everett, Jim A C; Capraro, Valerio; Barcelo, Hélène

    2016-04-01

    Are humans intuitively altruistic, or does altruism require self-control? A theory of social heuristics, whereby intuitive responses favor typically successful behaviors, suggests that the answer may depend on who you are. In particular, evidence suggests that women are expected to behave altruistically, and are punished for failing to be altruistic, to a much greater extent than men. Thus, women (but not men) may internalize altruism as their intuitive response. Indeed, a meta-analysis of 13 new experiments and 9 experiments from other groups found that promoting intuition relative to deliberation increased giving in a Dictator Game among women, but not among men (Study 1, N = 4,366). Furthermore, this effect was shown to be moderated by explicit sex role identification (Study 2, N = 1,831): the more women described themselves using traditionally masculine attributes (e.g., dominance, independence) relative to traditionally feminine attributes (e.g., warmth, tenderness), the more deliberation reduced their altruism. Our findings shed light on the connection between gender and altruism, and highlight the importance of social heuristics in human prosociality.

  10. Li7(BH)5(+): a new thermodynamically favored star-shaped molecule.

    PubMed

    Torres-Vega, Juan J; Vásquez-Espinal, Alejandro; Beltran, Maria J; Ruiz, Lina; Islas, Rafael; Tiznado, William

    2015-07-15

    The potential energy surfaces (PESs) of Lin(BH)5(n-6) systems (where n = 5, 6, and 7) were explored using the gradient embedded genetic algorithm (GEGA) program, in order to find their global minima conformations. This search predicts that the lowest-energy isomers of Li6(BH)5 and Li7(BH)5(+) contain a (BH)5(6-) pentagonal fragment, which is isoelectronic and structurally analogous to the prototypical aromatic hydrocarbon anion C5H5(-). Li7(BH)5(+), along with Li7C5(+), Li7Si5(+) and Li7Ge5(+), joins a select group of clusters that adopt a seven-peak star-shape geometry, which is favored by aromaticity in the central five-membered ring, and by the preference of Li atoms for bridging positions. The theoretical analysis of chemical bonding, based on magnetic criteria, supports the notion that electronic delocalization is an important stabilization factor in all these star-shaped clusters.

  11. Predictors of favorable results in pulmonary tuberculosis treatment (Recife, Pernambuco, Brazil, 2001-2004).

    PubMed

    Sassaki, Cinthia Midori; Scatena, Lucia Marina; Gonzales, Roxana Isabel Cardozo; Ruffino-Netto, Antonio; Hinos, Paula; Villa, Tereza Cristina Scatena

    2010-06-01

    Based on data available in the Information System for Notifiable Diseases, predictive factors of favorable results were identified in the treatment of pulmonary tuberculosis, diagnosed between 2001 and 2004 and living in Recife-PE, Brazil. Uni- and multivariate logistic regression methods were used. In multivariate analysis, the following factors remained: Age (years), 0 to 9 (OR = 4.27; p = 0.001) and 10 to 19 (OR = 1.78; p = 0.011), greater chance of cure than over 60; Education (years), 8 to 11 (OR = 1.52; p = 0.049), greater chance of cure than no education; Type of entry, ne wcase s (OR = 3.31; p < 0.001) and relapse (OR = 3.32; p < 0.001), greater chances of cure than restart after abandonment; Time (months) 2, 5--6 (OR = 9.15; p < 0.001); 6--9 (OR = 27.28; p < 0.001) and More than 9 (OR = 24.78; p < 0.001), greater chances of cure than less than 5; Health Unit District, DSII (OR = 1.60; p = 0.018) and DSIIV (OR = 2.87; p < 0.001), greater chance sof cure than DS II.

  12. Music, clicks, and their imaginations favor differently the event-based timing component for rhythmic movements.

    PubMed

    Bravi, Riccardo; Quarta, Eros; Del Tongo, Claudia; Carbonaro, Nicola; Tognetti, Alessandro; Minciacchi, Diego

    2015-06-01

    The involvement or noninvolvement of a clock-like neural process, an effector-independent representation of the time intervals to produce, is described as the essential difference between event-based and emergent timing. In a previous work (Bravi et al. in Exp Brain Res 232:1663-1675, 2014a. doi: 10.1007/s00221-014-3845-9 ), we studied repetitive isochronous wrist's flexion-extensions (IWFEs), performed while minimizing visual and tactile information, to clarify whether non-temporal and temporal characteristics of paced auditory stimuli affect the precision and accuracy of the rhythmic motor performance. Here, with the inclusion of new recordings, we expand the examination of the dataset described in our previous study to investigate whether simple and complex paced auditory stimuli (clicks and music) and their imaginations influence in a different way the timing mechanisms for repetitive IWFEs. Sets of IWFEs were analyzed by the windowed (lag one) autocorrelation-wγ(1), a statistical method recently introduced for the distinction between event-based and emergent timing. Our findings provide evidence that paced auditory information and its imagination favor the engagement of a clock-like neural process, and specifically that music, unlike clicks, lacks the power to elicit event-based timing, not counteracting the natural shift of wγ(1) toward positive values as frequency of movements increase.

  13. APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles.

    PubMed

    Dussart, Sylvie; Douaisi, Marc; Courcoul, Marianne; Bessou, Gilles; Vigne, Robert; Decroly, Etienne

    2005-01-21

    APOBEC3G is a cytidine deaminase that limits the replication of many retroviruses. This antiviral host factor is packaged into retrovirus particles, where it targets single-stranded DNA generated during reverse transcription and induces up to 2% of G-to-A mutations, which are lethal for the HIV-1 provirus. Vif protein counteracts this antiviral factor by decreasing its packaging into lentivirus particles. Here, we demonstrate that Nedd4-1, an HECT E3 ubiquitin ligase, interacts with APOBEC3G, through its WW2 and WW3 domains. As a result of this interaction, APOBEC3G undergoes post-translational modification by addition of ubiquitin moieties. Accordingly, we demonstrate that the dominant negative Nedd4-1 C/S form prevents APOBEC3G ubiquitination. Moreover, the packaging of APOBEC3G into Pr55 Gag virus-like particles and into HIV-1 virions is reduced when Nedd4-1 C/S is expressed. During HIV-1 viral production in the presence of APOBEC3G, Nedd4-1 C/S restores partially the infectivity of Deltavif HIV-1. We conclude that the ubiquitination of APOBEC3G by Nedd4-1 favors its targeting to the virus assembly site where APOBEC3G interacts with Gag and is packaged into HIV-1 particles in the absence of Vif.

  14. TTK is a favorable prognostic biomarker for triple-negative breast cancer survival

    PubMed Central

    Xu, Qianqian; Xu, Yali; Pan, Bo; Wu, Liangcai; Ren, Xinyu; Zhou, Yidong; Mao, Feng; Lin, Yan; Guan, Jinghong; Shen, Songjie; Zhang, Xiaohui; Wang, Changjun; Zhong, Ying; Zhou, Liangrui; Liang, Zhiyong; Zhao, Haitao; Sun, Qiang

    2016-01-01

    Purpose Previous studies demonstrate that threonine and tyrosine kinase (TTK) is overexpressed in triple-negative breast cancer (TNBC), but there are conflicting results regarding its effect on TNBC survival. The purpose of this study was to assess the prognostic significance of TTK expression in primary TNBC. Results Of 169 consecutive cases eligible for this study, 164 included follow-up information. Cytoplasm and membrane TTK staining was observed in 99.4% of cases, while 5.9% displayed whole cell immunostaining. At a discriminating threshold of 55, elevated TTK expression was associated with prolonged disease free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.024) in primary TNBC and prolonged DFS in individual basal-like (p = 0.001) and non-basal-like (p = 0.001) TNBC subtypes. In addition, Cox regression analysis demonstrated that elevated TTK expression was an independent prognostic factor for DFS in TNBC (p < 0.001). Methods TTK expression of 169 samples was tested by immunohistochemistry (IHC). A receiver operating characteristic (ROC) curve was used to identify a cutpoint for TTK expression, which was analyzed for its association with patients' clinicopathological factors and survival using Chi-square, log-rank, and Cox regression analyses. Conclusions TTK is a favorable prognostic biomarker associated with TNBC survival. PMID:27833085

  15. Superstition predicts favorable weight change in an open-placebo trial: a prospective study.

    PubMed

    Rekhviashvili, Nino; Gupta, Sumati

    2015-09-01

    Given the difficulty of losing weight via adhering to healthy lifestyle choices, this study sought to understand how a placebo may elicit favorable weight change. Specifically, we examined if superstition may be related to increased responsiveness to an open-placebo. In this pilot study of 25 undergraduate participants, it was hypothesized that individuals with higher levels of superstition may be more responsive to a 3-week open-placebo weight change trial. Participants were given once-daily saltine crackers to use as open-placebos for weight change in their preferred direction (gain or loss). The weight of each participant was measured before and after the 3-week open-placebo period. A Pearson's r correlation showed a significant positive relationship between superstition and placebo responsiveness, determined by weight gain or loss in the preferred direction, r (25) = 0.493, p < 0.05. We hope these preliminary results engender future research on open-placebo uses for weight management.

  16. Aquatic pollution may favor the success of the invasive species A. franciscana.

    PubMed

    Varó, I; Redón, S; Garcia-Roger, E M; Amat, F; Guinot, D; Serrano, R; Navarro, J C

    2015-04-01

    The genus Artemia consists of several bisexual and parthenogenetic sibling species. One of them, A. franciscana, originally restricted to the New World, becomes invasive when introduced into ecosystems out of its natural range of distribution. Invasiveness is anthropically favored by the use of cryptobiotic eggs in the aquaculture and pet trade. The mechanisms of out-competition of the autochthonous Artemia by the invader are still poorly understood. Ecological fitness may play a pivotal role, but other underlying biotic and abiotic factors may contribute. Since the presence of toxicants in hypersaline aquatic ecosystems has been documented, our aim here is to study the potential role of an organophosphate pesticide, chlorpyrifos, in a congeneric mechanism of competition between the bisexual A. franciscana (AF), and one of the Old World parthenogenetic siblings, A. parthenogenetica (PD). For this purpose we carried out life table experiments with both species, under different concentrations of the toxicant (0.1, 1 and 5μg/l), and analyzed the cholinesterase inhibition at different developmental stages. The results evidence that both, AF and PD, showed an elevated tolerance to high ranges of chlorpyrifos, but AF survived better and its fecundity was less affected by the exposure to the pesticide than that of PD. The higher fecundity of AF is a selective advantage in colonization processes leading to its establishment as NIS. Besides, under the potential selective pressure of abiotic factors, such as the presence of toxicants, its higher resistance in terms of survival and biological fitness also indicates out-competitive advantages.

  17. Femtomolar inhibitors bind to 5'-methylthioadenosine nucleosidases with favorable enthalpy and entropy.

    PubMed

    Thomas, Keisha; Haapalainen, Antti M; Burgos, Emmanuel S; Evans, Gary B; Tyler, Peter C; Gulab, Shivali; Guan, Rong; Schramm, Vern L

    2012-09-25

    5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the hydrolytic cleavage of adenine from methylthioadenosine (MTA). Inhibitor design and synthesis informed by transition state analysis have developed femtomolar inhibitors for MTANs, among the most powerful known noncovalent enzyme inhibitors. Thermodynamic analyses of the inhibitor binding reveals a combination of highly favorable contributions from enthalpic (-24.7 to -4.0 kcal mol(-1)) and entropic (-10.0 to 6.4 kcal mol(-1)) interactions. Inhibitor binding to similar MTANs from different bacterial species gave distinct energetic contributions from similar catalytic sites. Thus, binding of four transition state analogues to EcMTAN and SeMTAN is driven primarily by enthalpy, while binding to VcMTAN is driven primarily by entropy. Human MTA phosphorylase (hMTAP) has a transition state structure closely related to that of the bacterial MTANs, and it binds tightly to some of the same transition state analogues. However, the thermodynamic signature of binding of an inhibitor to hMTAP differs completely from that with MTANs. We conclude that factors other than first-sphere catalytic residue contacts contribute to binding of inhibitors because the thermodynamic signature differs between bacterial species of the same enzyme.

  18. Fluorescent Pseudomonas Strains with only Few Plant-Beneficial Properties Are Favored in the Maize Rhizosphere

    PubMed Central

    Vacheron, Jordan; Moënne-Loccoz, Yvan; Dubost, Audrey; Gonçalves-Martins, Maximilien; Muller, Daniel; Prigent-Combaret, Claire

    2016-01-01

    Plant Growth-Promoting Rhizobacteria (PGPR) enhance plant health and growth using a variety of traits. Effective PGPR strains typically exhibit multiple plant-beneficial properties, but whether they are better adapted to the rhizosphere than PGPR strains with fewer plant-beneficial properties is unknown. Here, we tested the hypothesis that strains with higher numbers of plant-beneficial properties would be preferentially selected by plant roots. To this end, the co-occurrence of 18 properties involved in enhanced plant nutrition, plant hormone modulation, or pathogen inhibition was analyzed by molecular and biochemical methods in a collection of maize rhizosphere and bulk soil isolates of fluorescent Pseudomonas. Twelve plant-beneficial properties were found among the 698 isolates. Contrarily to expectation, maize preferentially selected pseudomonads with low numbers of plant-beneficial properties (up to five). This selection was not due to the predominance of strains with specific assortments of these properties, or with specific taxonomic status. Therefore, the occurrence of only few plant-beneficial properties appeared favorable for root colonization by pseudomonads. PMID:27610110

  19. Platelet count recovery after intravenous immunoglobulin predicts a favorable outcome in children with immune thrombocytopenia

    PubMed Central

    Ji, Mi Hong; Kim, Sung Jin; Ahn, Hyo Seop

    2016-01-01

    Background Childhood immune thrombocytopenic purpura (ITP) is a common acquired bleeding disorder. Even though most children recover, either spontaneously or with therapy, 10-20% of newly diagnosed ITP cases have a chronic course beyond 12 months. This study evaluated whether clinical and laboratory findings can predict the response to intravenous immunoglobulin (IVIG) and progression to persistent or chronic ITP in children. Methods During the period between March 2003 and June 2015, we retrospectively analyzed 72 children, newly diagnosed with ITP, who received IVIG treatment. Peripheral blood counts were obtained at diagnosis and at 1, 3, 6, and 12 months after IVIG treatment. Results After 6 months of IVIG treatment, 14 of 72 patients (19.4%) had persistent ITP, and after 12 months, 7 of 40 patients (17.5%) had chronic ITP. Age at diagnosis, gender, history of viral infection, or vaccination before disease onset were not statistically correlated with platelet recovery at 6 and 12 months. However, a platelet count recovery of ≥100×103/µL at 1 and 3 months was significantly correlated with platelet recovery at 6 (P<0.001 and P<0.001, respectively) and 12 (P=0.007 and P=0.004, respectively) months. Conclusion This study demonstrated that early platelet count recovery, at 1 and 3 months after IVIG treatment, predicts a short disease duration and a favorable outcome in children with newly diagnosed ITP. Further investigation in a larger group of patients is warranted to validate these findings. PMID:27382553

  20. Prediction of the most favorable configuration in the ACBP-membrane interaction based on electrostatic calculations.

    PubMed

    Vallejo, Diego F; Zamarreño, Fernando; Guérin, Diego M A; Grigera, J Raul; Costabel, Marcelo D

    2009-03-01

    Acyl-CoA binding proteins (ACBPs) are highly conserved 10 kDa cytosolic proteins that bind medium- and long-chain acyl-CoA esters. They act as intracellular carriers of acyl-CoA and play a role in acyl-CoA metabolism, gene regulation, acyl-CoA-mediated cell signaling, transport-mediated lipid synthesis, membrane trafficking and also, ACBPs were indicated as a possible inhibitor of diazepam binding to the GABA-A receptor. To estimate the importance of the non-specific electrostatic energy in the ACBP-membrane interaction, we computationally modeled the interaction of HgACBP with both anionic and neutral membranes. To compute the Free Electrostatic Energy of Binding (dE), we used the Finite Difference Poisson Boltzmann Equation (FDPB) method as implemented in APBS. In the most energetically favorable orientation, ACBP brings charged residues Lys18 and Lys50 and hydrophobic residues Met46 and Leu47 into membrane surface proximity. This conformation suggests that these four ACBP amino acids are most likely to play a leading role in the ACBP-membrane interaction and ligand intake. Thus, we propose that long range electrostatic forces are the first step in the interaction mechanism between ACBP and membranes.

  1. Anthropogenic N Deposition Slows Decay by Favoring Bacterial Metabolism: Insights from Metagenomic Analyses.

    PubMed

    Freedman, Zachary B; Upchurch, Rima A; Zak, Donald R; Cline, Lauren C

    2016-01-01

    Litter decomposition is an enzymatically-complex process that is mediated by a diverse assemblage of saprophytic microorganisms. It is a globally important biogeochemical process that can be suppressed by anthropogenic N deposition. In a northern hardwood forest ecosystem located in Michigan, USA, 20 years of experimentally increased atmospheric N deposition has reduced forest floor decay and increased soil C storage. Here, we paired extracellular enzyme assays with shotgun metagenomics to assess if anthropogenic N deposition has altered the functional potential of microbial communities inhabiting decaying forest floor. Experimental N deposition significantly reduced the activity of extracellular enzymes mediating plant cell wall decay, which occurred concurrently with changes in the relative abundance of metagenomic functional gene pathways mediating the metabolism of carbohydrates, aromatic compounds, as well as microbial respiration. Moreover, experimental N deposition increased the relative abundance of 50 of the 60 gene pathways, the majority of which were associated with saprotrophic bacteria. Conversely, the relative abundance and composition of fungal genes mediating the metabolism of plant litter was not affected by experimental N deposition. Future rates of atmospheric N deposition have favored saprotrophic soil bacteria, whereas the metabolic potential of saprotrophic fungi appears resilient to this agent of environmental change. Results presented here provide evidence that changes in the functional capacity of saprotrophic soil microorganisms mediate how anthropogenic N deposition increases C storage in soil.

  2. Anthropogenic N Deposition Slows Decay by Favoring Bacterial Metabolism: Insights from Metagenomic Analyses

    PubMed Central

    Freedman, Zachary B.; Upchurch, Rima A.; Zak, Donald R.; Cline, Lauren C.

    2016-01-01

    Litter decomposition is an enzymatically-complex process that is mediated by a diverse assemblage of saprophytic microorganisms. It is a globally important biogeochemical process that can be suppressed by anthropogenic N deposition. In a northern hardwood forest ecosystem located in Michigan, USA, 20 years of experimentally increased atmospheric N deposition has reduced forest floor decay and increased soil C storage. Here, we paired extracellular enzyme assays with shotgun metagenomics to assess if anthropogenic N deposition has altered the functional potential of microbial communities inhabiting decaying forest floor. Experimental N deposition significantly reduced the activity of extracellular enzymes mediating plant cell wall decay, which occurred concurrently with changes in the relative abundance of metagenomic functional gene pathways mediating the metabolism of carbohydrates, aromatic compounds, as well as microbial respiration. Moreover, experimental N deposition increased the relative abundance of 50 of the 60 gene pathways, the majority of which were associated with saprotrophic bacteria. Conversely, the relative abundance and composition of fungal genes mediating the metabolism of plant litter was not affected by experimental N deposition. Future rates of atmospheric N deposition have favored saprotrophic soil bacteria, whereas the metabolic potential of saprotrophic fungi appears resilient to this agent of environmental change. Results presented here provide evidence that changes in the functional capacity of saprotrophic soil microorganisms mediate how anthropogenic N deposition increases C storage in soil. PMID:26973633

  3. Chromosomal Conditions

    MedlinePlus

    ... 150 babies is born with a chromosomal condition. Down syndrome is an example of a chromosomal condition. Because ... all pregnant women be offered prenatal tests for Down syndrome and other chromosomal conditions. A screening test is ...

  4. Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex

    PubMed Central

    Hinde, Katie; Carpenter, Abigail J.; Clay, John S.; Bradford, Barry J.

    2014-01-01

    Mammalian females pay high energetic costs for reproduction, the greatest of which is imposed by lactation. The synthesis of milk requires, in part, the mobilization of bodily reserves to nourish developing young. Numerous hypotheses have been advanced to predict how mothers will differentially invest in sons and daughters, however few studies have addressed sex-biased milk synthesis. Here we leverage the dairy cow model to investigate such phenomena. Using 2.39 million lactation records from 1.49 million dairy cows, we demonstrate that the sex of the fetus influences the capacity of the mammary gland to synthesize milk during lactation. Cows favor daughters, producing significantly more milk for daughters than for sons across lactation. Using a sub-sample of this dataset (N = 113,750 subjects) we further demonstrate that the effects of fetal sex interact dynamically across parities, whereby the sex of the fetus being gestated can enhance or diminish the production of milk during an established lactation. Moreover the sex of the fetus gestated on the first parity has persistent consequences for milk synthesis on the subsequent parity. Specifically, gestation of a daughter on the first parity increases milk production by ∼445 kg over the first two lactations. Our results identify a dramatic and sustained programming of mammary function by offspring in utero. Nutritional and endocrine conditions in utero are known to have pronounced and long-term effects on progeny, but the ways in which the progeny has sustained physiological effects on the dam have received little attention to date. PMID:24498270

  5. Epithelial splicing regulatory protein 1 and 2 paralogues correlate with splice signatures and favorable outcome in human colorectal cancer

    PubMed Central

    Deloria, Abigail J.; Höflmayer, Doris; Kienzl, Philip; Łopatecka, Justyna; Sampl, Sandra; Klimpfinger, Martin; Braunschmid, Tamara; Bastian, Fabienne; Lu, Lingeng; Marian, Brigitte; Stättner, Stefan; Holzmann, Klaus

    2016-01-01

    ESRPs are master splice regulators implicated in alternative mRNA splicing programs important for epithelial-mesenchymal transition (EMT) and tumor progression. ESRP1 was identified in some tumors as good or worse predictor of outcome, but in colorectal cancer (CRC) the prognostic value of ESRPs and relation with mesenchymal splice variants is not clear. Here, we studied 68 CRC cases, compared tissue expression of ESRPs with clinical data and with EMT gene splice patterns of conditional CRC cells with deficient ESRP1 expression. Around 72% of patients showed global decreased transcript expression of both ESRPs in tumor as compared to matched non-neoplastic colorectal epithelium. Reduction of ESRP1 in tumor cells was evaluated by immunohistochemistry, associated with microsatellite stability and switch to mesenchymal splice signatures of FGFRs, CD44, ENAH and CTNND1(p120-catenin). Expression of ESRPs was significantly associated with favorable overall survival (log-rank test, P=0.0186 and 0.0408), better than prognostic stratification by tumor staging; and for ESRP1 confirmed with second TCGA cohort (log-rank test, P=0.0435). Prognostic value is independent of the pathological stage and microsatellite instability (ESRP1: HR=0.36, 95%CI 0.15–0.91, P=0.032; ESRP2: HR=0.23, 95%CI 0.08–0.65, P=0.006). Our study supports the role of ESRP1 as tumor suppressor and strongly suggests that ESRPs are candidate markers for early detection, diagnosis, and prognosis of CRC. PMID:27650542

  6. Holsteins favor heifers, not bulls: biased milk production programmed during pregnancy as a function of fetal sex.

    PubMed

    Hinde, Katie; Carpenter, Abigail J; Clay, John S; Bradford, Barry J

    2014-01-01

    Mammalian females pay high energetic costs for reproduction, the greatest of which is imposed by lactation. The synthesis of milk requires, in part, the mobilization of bodily reserves to nourish developing young. Numerous hypotheses have been advanced to predict how mothers will differentially invest in sons and daughters, however few studies have addressed sex-biased milk synthesis. Here we leverage the dairy cow model to investigate such phenomena. Using 2.39 million lactation records from 1.49 million dairy cows, we demonstrate that the sex of the fetus influences the capacity of the mammary gland to synthesize milk during lactation. Cows favor daughters, producing significantly more milk for daughters than for sons across lactation. Using a sub-sample of this dataset (N = 113,750 subjects) we further demonstrate that the effects of fetal sex interact dynamically across parities, whereby the sex of the fetus being gestated can enhance or diminish the production of milk during an established lactation. Moreover the sex of the fetus gestated on the first parity has persistent consequences for milk synthesis on the subsequent parity. Specifically, gestation of a daughter on the first parity increases milk production by ∼ 445 kg over the first two lactations. Our results identify a dramatic and sustained programming of mammary function by offspring in utero. Nutritional and endocrine conditions in utero are known to have pronounced and long-term effects on progeny, but the ways in which the progeny has sustained physiological effects on the dam have received little attention to date.

  7. Al- or Si-decorated graphene oxide: A favorable metal-free catalyst for the N2O reduction

    NASA Astrophysics Data System (ADS)

    Esrafili, Mehdi D.; Sharifi, Fahimeh; Nematollahi, Parisa

    2016-11-01

    The structural and catalytic properties of Al- or Si-decorated graphene oxide (Al-/Si-GO) are studied by means of density functional theory calculations. The relatively large adsorption energy together with the small Alsbnd O or Sisbnd O binding distances indicate that the epoxy groups over the GO surface can strongly stabilize the single Al or Si atom. Hence, Al-GO and Si-GO are stable enough to be utilized in catalytic reduction of N2O by CO molecule. It is found that the adsorption and decomposition of N2O molecule over Si-GO is more favorable than over Al-GO, due to its larger adsorption energy (Eads) and charge transfer (qCT) values. On the other hand, the CO molecule is physically adsorbed over both surfaces, with relatively small Eads and qCT values. Therefore, at the presence of N2O and CO molecules as the reaction gas, the Al or Si atom of the surface should be dominantly covered by N2O molecule. Our results indicate that the N2O decomposition process can take place with a negligible activation energy over Al-/Si-GO surface, where the N2 molecule can be easily released from the surface. Then, the activated oxygen atom (Oads) which remains over the surface reacts with the CO molecule to form the CO2 molecule via the reaction Oads + CO → CO2. Based on the calculated activation energies, it is suggested that both Al-GO and Si-GO can be used as an efficient metal-free catalyst for the reduction of N2O molecule at ambient conditions.

  8. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells.

    PubMed

    Rato, Luís; Alves, Marco G; Duarte, Ana I; Santos, Maria S; Moreira, Paula I; Cavaco, José E; Oliveira, Pedro F

    2015-09-01

    The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus.

  9. Purification and characterization of a novel phloretin-2′-O-glycosyltransferase favoring phloridzin biosynthesis

    PubMed Central

    Zhang, Tingjing; Liang, Jianqiang; Wang, Panxue; Xu, Ying; Wang, Yutang; Wei, Xinyuan; Fan, Mingtao

    2016-01-01

    Phloretin-2′-O-glycosyltransferase (P2′GT) catalyzes the last glycosylation step in the biosynthesis of phloridzin that contributes to the flavor, color and health benefits of apples and processed apple products. In this work, a novel P2′GT of Malus x domestica (MdP2′GT) with a specific activity of 46.82 μkat/Kg protein toward phloretin and uridine diphosphate glucose (UDPG) at an optimal temperature of 30 °C and pH 8.0 was purified from the engineered Pichia pastoris broth to homogeneity by anion exchange chromatography, His-Trap affinity chromatography and gel filtration. The purified MdP2′GT was low N-glycosylated and secreted as a stable dimer with a molecular mass of 70.7 kDa in its native form. Importantly, MdP2′GT also exhibited activity towards quercetin and adenosine diphosphate glucose (ADPG), kaempferol and UDPG, quercetin and UDP-galactose, isoliquiritigenin and UDPG, and luteolin and UDPG, producing only one isoquercitrin, astragalin, hyperoside, isoliquiritin, or cynaroside, respectively. This broad spectrum of activities make MdP2′GT a promising biocatalyst for the industrial preparation of the corresponding polyphenol glycosides, preferably for their subsequent isolation and purification. Besides, MdP2′GT displayed the lowest Km and the highest kcat/Km for phloretin and UDPG compared to all previously reported P2′GTs, making MdP2′GT favor phloridzin synthesis the most. PMID:27731384

  10. UVB radiation as a potential selective factor favoring microcystin producing bloom forming Cyanobacteria.

    PubMed

    Ding, Yi; Song, Lirong; Sedmak, Bojan

    2013-01-01

    Due to the stratospheric ozone depletion, several organisms will become exposed to increased biologically active UVB (280-320 nm) radiation, not only at polar but also at temperate and tropical latitudes. Bloom forming cyanobacteria are exposed to UVB radiation on a mass scale, particularly during the surface bloom and scum formation that can persist for long periods of time. All buoyant species of cyanobacteria are at least periodically exposed to higher irradiation during their vertical migration to the surface that usually occurs several times a day. The aim of this study is to assess the influence on cyanobacteria of UVB radiation at realistic environmental intensities. The effects of two UVB intensities of 0.5 and 0.99 W/m(2) in up to 0.5 cm water depth were studied in vitro on Microcystis aeruginosa strains, two microcystin producing and one non-producing. After UVB exposure their ability to proliferate was estimated by cell counting, while cell fitness and integrity were evaluated using light microscopy, autofluorescence and immunofluorescence. Gene damage was assessed by TUNEL assay and SYBR Green staining of the nucleoide area. We conclude that UVB exposure causes damage to the genetic material, cytoskeletal elements, higher sedimentation rates and consequent cell death. In contrast to microcystin producers (PCC7806 and FACHB905), the microcystin non-producing strain PCC7005 is more susceptible to the deleterious effects of radiation, with weak recovery ability. The ecological relevance of the results is discussed using data from eleven years' continuous UVB radiation measurements within the area of Ljubljana city (Slovenia, Central Europe). Our results suggest that increased solar radiation in temperate latitudes can have its strongest effect during cyanobacterial bloom formation in spring and early summer. UVB radiation in this period may significantly influence strain composition of cyanobacterial blooms in favor of microcystin producers.

  11. UVB Radiation as a Potential Selective Factor Favoring Microcystin Producing Bloom Forming Cyanobacteria

    PubMed Central

    Ding, Yi; Song, Lirong; Sedmak, Bojan

    2013-01-01

    Due to the stratospheric ozone depletion, several organisms will become exposed to increased biologically active UVB (280–320 nm) radiation, not only at polar but also at temperate and tropical latitudes. Bloom forming cyanobacteria are exposed to UVB radiation on a mass scale, particularly during the surface bloom and scum formation that can persist for long periods of time. All buoyant species of cyanobacteria are at least periodically exposed to higher irradiation during their vertical migration to the surface that usually occurs several times a day. The aim of this study is to assess the influence on cyanobacteria of UVB radiation at realistic environmental intensities. The effects of two UVB intensities of 0.5 and 0.99 W/m2 in up to 0.5 cm water depth were studied in vitro on Microcystis aeruginosa strains, two microcystin producing and one non-producing. After UVB exposure their ability to proliferate was estimated by cell counting, while cell fitness and integrity were evaluated using light microscopy, autofluorescence and immunofluorescence. Gene damage was assessed by TUNEL assay and SYBR Green staining of the nucleoide area. We conclude that UVB exposure causes damage to the genetic material, cytoskeletal elements, higher sedimentation rates and consequent cell death. In contrast to microcystin producers (PCC7806 and FACHB905), the microcystin non-producing strain PCC7005 is more susceptible to the deleterious effects of radiation, with weak recovery ability. The ecological relevance of the results is discussed using data from eleven years’ continuous UVB radiation measurements within the area of Ljubljana city (Slovenia, Central Europe). Our results suggest that increased solar radiation in temperate latitudes can have its strongest effect during cyanobacterial bloom formation in spring and early summer. UVB radiation in this period may significantly influence strain composition of cyanobacterial blooms in favor of microcystin producers. PMID

  12. Suboptimal temperature favors reserve formation in biennial carrot (Daucus carota) plants.

    PubMed

    González, María V; Sadras, Victor O; Equiza, María A; Tognetti, Jorge A

    2009-09-01

    In response to suboptimal temperatures, temperate annual plants often increase root:shoot ratios, build-up carbohydrates and display typical morphological and anatomical changes. We know less about the responses of biennials such as carrot. As a model plant, carrot has the additional feature of two functionally and morphologically distinct root parts: the taproot, which stores carbohydrate and other compounds, and the fibrous root system involved in acquisition of water and nutrients. Here, we analyze the effects of temperature (12 vs 25°C) on growth, carbohydrate accumulation and whole-plant morphology in two carrot cultivars. Our working hypothesis is that suboptimal temperature favors active formation of reserve structures, rather than passive accumulation of storage carbohydrates. In comparison with plants grown at 25°C, plants grown at 12°C had: (1) higher fibrous root:shoot ratio (13%) , (2) thicker (10-15%) and smaller (up to two- to three-fold) leaves, (3) lower leaf cuticular permeance (two- to four-fold), (4) higher taproot:shoot ratio (two-fold), (5) higher phloem:xylem ratios in taproot (two- to six-fold), (6) unchanged percentage dry matter content (%DMC) in leaves, petioles or fibrous roots and (7) higher %DMC in taproot (20%). However, %DMC of individual taproot tissues (phloem and xylem) was unaffected by temperatures and was consistently higher in the phloem (up to 30%). Therefore, the higher %DMC of whole taproots at 12°C was attributed solely to the increased development of phloem tissue. Carrot, therefore, shares many of the most conspicuous elements of temperate plant responses to low temperatures. Consistently with our hypothesis, however, carrots grown at suboptimal temperature promoted reserve structures, rather than the increase in carbohydrate concentration typical of most temperate annual species and woody perennials.

  13. ALCOHOL MODULATION OF MMP AND TIMP EXPRESSION IN THE HEART FAVORS COLLAGEN ACCUMULATION

    PubMed Central

    El Hajj, E.C.; El hajj, M.C.; Voloshenyuk, T.G.; Mouton, A.J.; Khoutorova, E.; Molina, P.E.; Gilpin, N.W.; Gardner, J.D.

    2013-01-01

    Background Chronic alcohol consumption has been shown in human and animal studies to result in collagen accumulation, myocardial fibrosis, and heart failure. Cardiac fibroblasts produce collagen and regulate extracellular matrix (ECM) homeostasis through the synthesis and activity of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP), with the balance of MMPs/TIMPs determining the rate of collagen turnover. Dynamic changes of MMP and TIMP expression were reported in alcohol induced hepatic fibrosis; however, the effect of alcohol on MMP/TIMP balance in the heart and cardiac fibroblasts is unknown. We hypothesized that alcohol exposure alters cardiac fibroblast MMP and TIMP expression to promote collagen accumulation in the heart. Methods Cardiac fibroblasts isolated from adult rats were cultured in the presence of alcohol (12.5–200 mM) for 48 hrs. MMP, TIMP, and collagen type I and III expression were assayed by Western blot analysis. Hydroxyproline (HPro) was used as a marker of collagen production. The in vivo cardiac effects of ethanol were determined using rats exposed to ethanol vapor for two weeks, resulting in blood alcohol levels of 150–200 mg/dl. Cardiac collagen volume fraction (CVF), as well as MMP, TIMP and collagen expression, was assessed. Results Ethanol exposed rats exhibited upregulation of TIMP-1, -3 and -4 in the heart, with no significant increases in MMPs. Cardiac fibroblasts exhibited transformation to a profibrotic phenotype following exposure to alcohol. These changes were reflected by increased α-smooth muscle actin and collagen I and III expression, as well as increased collagen secretion. In vivo ethanol exposure also produced fibrosis, indicated by increased CVF and expression of collagens. Conclusion Alcohol exposure modulates cardiac fibroblast MMP/TIMP expression favoring a profile associated with collagen accumulation. Our data suggest that this disrupted MMP/TIMP profile may contribute to the development of

  14. Professional development programs in health promotion: tools and processes to favor new practices.

    PubMed

    Torres, Sara; Richard, Lucie; Guichard, Anne; Chiocchio, François; Litvak, Eric; Beaudet, Nicole

    2015-10-15

    Developing innovative interventions that are in sync with a health promotion paradigm often represents a challenge for professionals working in local public health organizations. Thus, it is critical to have both professional development programs that favor new practices and tools to examine these practices. In this case study, we analyze the health promotion approach used in a pilot intervention addressing children's vulnerability that was developed and carried out by participants enrolled in a public health professional development program. More specifically, we use a modified version of Guichard and Ridde's (Une grille d'analyse des actions pour lutter contre les inégalités sociales de santé. In Potvin, L., Moquet, M.-J. and Jones, C. M. (eds), Réduire les Inégalités Sociales en Santé. INPES, Saint-Denis Cedex, pp. 297-312, 2010) analytical grid to assess deductively the program participants' use of health promotion practices in the analysis and planning, implementation, evaluation, sustainability and empowerment phases of the pilot intervention. We also seek evidence of practices involving (empowerment, participation, equity, holism, an ecological approach, intersectorality and sustainability) in the intervention. The results are mixed: our findings reveal evidence of the application of several dimensions of health promotion (equity, holism, an ecological approach, intersectorality and sustainability), but also a lack of integration of two key dimensions; that is, empowerment and participation, during various phases of the pilot intervention. These results show that the professional development program is associated with the adoption of a pilot intervention integrating multiple but not all dimensions of health promotion. We make recommendations to facilitate a more complete integration. This research also shows that the Guichard and Ridde grid proves to be a thorough instrument to document the practices of participants.

  15. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats

    PubMed Central

    Godfrey, Jessica; Jeanguenin, Lisa; Castro, Norma; Olney, Jeffrey J.; Dudley, Jason; Pipkin, Joseph; Walls, Stanley M.; Wang, Wei; Herr, Deron R.; Harris, Greg L.; Brasser, Susan M.

    2015-01-01

    alcohol-preferring P rats as a result of chronic voluntary exposure may have favorable vs. detrimental effects on lipid profiles in this genetic line, consistent with data supporting beneficial cardioprotective and neuroprotective effects of moderate ethanol consumption. PMID:26405804

  16. Somatic Mutations Favorable to Patient Survival Are Predominant in Ovarian Carcinomas

    PubMed Central

    Zhang, Wensheng; Edwards, Andrea; Flemington, Erik; Zhang, Kun

    2014-01-01

    Somatic mutation accumulation is a major cause of abnormal cell growth. However, some mutations in cancer cells may be deleterious to the survival and proliferation of the cancer cells, thus offering a protective effect to the patients. We investigated this hypothesis via a unique analysis of the clinical and somatic mutation datasets of ovarian carcinomas published by the Cancer Genome Atlas. We defined and screened 562 macro mutation signatures (MMSs) for their associations with the overall survival of 320 ovarian cancer patients. Each MMS measures the number of mutations present on the member genes (except for TP53) covered by a specific Gene Ontology (GO) term in each tumor. We found that somatic mutations favorable to the patient survival are predominant in ovarian carcinomas compared to those indicating poor clinical outcomes. Specially, we identified 19 (3) predictive MMSs that are, usually by a nonlinear dose-dependent effect, associated with good (poor) patient survival. The false discovery rate for the 19 “positive” predictors is at the level of 0.15. The GO terms corresponding to these MMSs include “lysosomal membrane” and “response to hypoxia”, each of which is relevant to the progression and therapy of cancer. Using these MMSs as features, we established a classification tree model which can effectively partition the training samples into three prognosis groups regarding the survival time. We validated this model on an independent dataset of the same disease (Log-rank p-value <2.3×10-4) and a dataset of breast cancer (Log-rank p-value <9.3×10−3). We compared the GO terms corresponding to these MMSs and those enriched with expression-based predictive genes. The analysis showed that the GO term pairs with large similarity are mainly pertinent to the proteins located on the cell organelles responsible for material transport and waste disposal, suggesting the crucial role of these proteins in cancer mortality. PMID:25390899

  17. Identification of a vibration regime favorable for bone healing and muscle in estrogen-deficient rats.

    PubMed

    Komrakova, Marina; Sehmisch, Stephan; Tezval, Mohammad; Ammon, Jan; Lieberwirth, Peggy; Sauerhoff, Cordula; Trautmann, Lukas; Wicke, Michael; Dullin, Christian; Stuermer, Klaus M; Stuermer, Ewa K

    2013-06-01

    Numerous whole-body vibration (WBV) devices of various forces are available on the market, although their influence on the musculoskeletal system is not yet understood. The effect of different WBVs on bone healing and muscle function was evaluated in rats ovariectomized at 3 months of age. 2 months after ovariectomy, bilateral metaphyseal tibia osteotomy and T-plate osteosynthesis were performed. Rats were divided into groups: intact, OVX, and OVX exposed to vertical WBVs of 35, 50, 70, or 90 Hz (experiment 1) or horizontal WBVs of 30, 50, 70, or 90 Hz (experiment 2) 5 days after osteotomy (0.5 mm, 15 min/day for 30 days). The tibia and gastrocnemius and soleus muscles were collected. Vertical vibrations (>35 Hz) improved cortical and callus densities, enlarged callus area and width, suppressed the tartrate-resistant acid phosphatase gene, enhanced citrate synthase activity, accelerated osteotomy bridging (35 and 50 Hz), upregulated the osteocalcin (Oc) gene (70 Hz), and increased relative muscle weight (50 Hz). Horizontal vibrations reduced cortical width (<90 Hz) and callus density (30 Hz), enhanced alkaline phosphatase (Alp) gene expression (50 Hz), decreased the size of oxidative fibers (35 and 70 Hz), and increased capillary density (70, 90 Hz). Biomechanical data; serum Oc, Alp, and creatine kinase activities; body weight; and food intake did not change after WBVs. Vertical WBVs of 35 and 50 Hz produced more favorable results than the higher frequencies. Horizontal WBV showed no positive or negative effects. Further studies are needed to elucidate the effects of WBV on different physiological systems, and precautions must be taken when implementing WBV in the treatment of patients.

  18. Both soybean and kudzu phytoestrogens modify favorably the blood lipoprotein profile in ovariectomized and castrated hamsters.

    PubMed

    Guan, Lei; Yeung, Sai Ying Venus; Huang, Yu; Chen, Zhen-Yu

    2006-06-28

    The present study compared the hypolipidemic activity of kudzu phytoestrogens with that of soybean phytoestrogen in estrogen- and androgen-deficient hamsters. In the first experiment, ovariectomized hamsters (n = 37) were randomly divided into four groups (n = 9-10 each group). The first group was the control group, whereas the second group had the time-releasing estradiol-17beta subcutaneous (pellet) implants as a positive control. The third and fourth groups were orally administered soybean or kudzu phytoestrogen extracts (30 mg/kg of body weight) per day. In the second experiments, the first group of male hamsters (n = 9) received a sham operation, whereas the other three groups of male hamsters (n = 9 each) were castrated. The castrated control group received orally distilled water, whereas the second and third castrated groups were orally given 30 mg/kg soybean or kudzu phytoestrogen extracts. The results for the first experiment showed that the ovariectomized hamsters orally given soybean and kudzu phytoestrogen extracts had significantly decreased serum total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) with HDL cholesterol (HDL-C) being unaffected. The data from the second experiment demonstrated that administration of soybean but not kudzu phytoestrogen extracts decreased significantly serum TC. However, administration of kudzu phytoestrogens caused redistribution of cholesterol among lipoproteins, leading to a significant decrease in the ratio of non-HDL-C to HDL-C. It was concluded that both soybean and kudzu phytoestrogens could modify favorably lipoprotein profiles in ovariectomized and castrated hamsters.

  19. Leishmania donovani-Induced Increase in Macrophage Bcl-2 Favors Parasite Survival

    PubMed Central

    Pandey, Rajeev Kumar; Mehrotra, Sanjana; Sharma, Smriti; Gudde, Ramachandra Subbaraya; Sundar, Shyam; Shaha, Chandrima

    2016-01-01

    Members of the Bcl-2 family are major regulators of apoptosis in mammalian cells, and hence infection-induced perturbations in their expression could result into elimination of the parasites or creation of a niche favoring survival. In this investigation, we uncover a novel role of host Bcl-2 in sustaining Leishmania donovani infection. A rapid twofold increase in Bcl-2 expression occurred in response to parasite challenge. Downregulation of post infection Bcl-2 increase using siRNA or functional inhibition using Bcl-2 small molecule inhibitors interfered with intracellular parasite survival confirming the necessity of elevated Bcl-2 during infection. An increased nitric oxide (NO) response and reduced parasitic burden was observed upon Bcl-2 inhibition, where restitution of the NO response accounted for parasite mortality. Mechanistic insights revealed a major role of elevated Th2 cytokine IL-13 in parasite-induced Bcl-2 expression via the transcription factor STAT-3, where blocking at the level of IL-13 receptor or downstream kinase JAK-2 dampened Bcl-2 induction. Increase in Bcl-2 was orchestrated through Toll like receptor (TLR)-2-MEK-ERK signaling, and changes in TLR-2 levels affected parasite uptake. In a mouse model of visceral leishmaniasis (VL), Bcl-2 inhibitors partially restored the antimicrobial NO response by at least a twofold increase that resulted in significantly reduced parasite burden. Interestingly, monocytes derived from the peripheral blood of six out of nine human VL subjects demonstrated Bcl-2 expression at significantly higher levels, and sera from these patients showed only marginally quantifiable nitrites. Collectively, our study for the first time reveals a pro-parasitic role of host Bcl-2 and the capacity of host-derived IL-13 to modulate NO levels during infection via Bcl-2. Here, we propose Bcl-2 inhibition as a possible therapeutic intervention for VL. PMID:27826299

  20. Overexpression of the chemokine receptor CXCR3 and its correlation with favorable prognosis in gastric cancer.

    PubMed

    Hu, Min; Li, Kai; Maskey, Ninu; Xu, Zhigao; Yu, Fang; Peng, ChunWei; Li, Yan; Yang, Guifang

    2015-12-01

    Chemokine receptor, CXCR3, has been increasingly reported to be involved in tumorigenesis and tumor progression, but limited data are available regarding the expression of CXCR3 in gastric cancer (GC). In the present study, the expressions of CXCR3 and its variants were detected in 96 GC and corresponding nontumor gastric tissues by immunohistochemical staining, in 40 freshly frozen GC and nontumor gastric tissues by reverse-transcription polymerase chain reaction and quantitative real-time polymerase chain reaction, and in 10 freshly frozen GC and nontumor gastric tissues by Western blotting. Results revealed that an overexpression of CXCR3 occurs in GC tissues as compared to the nontumor gastric tissues. High level of CXCR3 expression was found to be inversely associated with invasion depth and metastasis (P = .030 and P = .019, respectively) and directly associated with improved overall survival (log-rank test, P < .001). Furthermore, multivariate analysis showed that high CXCR3 expression acts an independent prognostic factor for GC patients (hazard ratio, 0.379 [0.196-0.734]; P = .004). The messenger RNA expression of both the CXCR3 variants, CXCR3-A and CXCR3-B, were up-regulated in GC tissues (P = .006 and P = .002, respectively), although CXCR3-B messenger RNA expression was significantly higher than CXCR3-A, with an average CXCR3-B to CXCR3-A ratio of 1.80. CXCR3-B protein expression was also up-regulated in GC tissues (P = .023). In conclusion, our study suggested a potential use of CXCR3 overexpression as a prognostic marker for GC and involvement of the up-regulation of CXCR3-B in favorable prognosis of GC patients.

  1. Albumin dialysis has a favorable effect on amino acid profile in hepatic encephalopathy.

    PubMed

    Koivusalo, Anna-Maria; Teikari, Taru; Höckerstedt, Krister; Isoniemi, Helena

    2008-12-01

    According to one popular theory, hepatic encephalopathy (HE) is partly caused by an imbalance in plasma amino acid levels. The Fischer's ratio between branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) correlates with the degree of HE; the lower Fischer's ratio, the higher the grade of HE. Extra-corporeal liver support systems, like MARS(R)-albumin dialysis (Molecular Adsorbents Recirculating System), can improve HE. The MARS(R) system uses a hyperosmolar albumin circuit to remove both water-soluble and albumin-bound substances. Plasma levels of neuroactive amino acids were analyzed in 82 consecutive patients with life-threatening liver failure admitted to our ICU. All patients fulfilled our indications for MARS treatment and most also fulfilled the criteria for liver transplantation (LTx). In patients with acute liver failure (ALF), as compared to those with acute decompensation of chronic liver failure (AcOChr), levels of leucine and isoleucine were significantly higher before MARS(R) treatment. In all patients, before MARS(R) treatment the higher the grade of HE grade the lower was the Fischer's ratio and higher were the levels of inhibitory neuroactive amino acids. During MARS(R) treatments the Fischer's ratio increased, and the grade of HE decreased. The increase in Fischer's ratio was mainly due to the decrease in AAAs. The plasma levels of neuroactive amino acids, methionine, glutamine, glutamate, histidine and taurine decreased during MARS(R)-treatment. In this study MARS(R)-albumin dialysis had a favorable effect on the plasma amino acid profile of patients with HE.

  2. CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer

    PubMed Central

    2012-01-01

    Introduction Tumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes. Methods Immunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival. Results Among 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes. Conclusions CD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic

  3. Resection of ictal high-frequency oscillations leads to favorable surgical outcome in pediatric epilepsy

    PubMed Central

    Fujiwara, Hisako; Greiner, Hansel M.; Lee, Ki Hyeong; Holland-Bouley, Katherine D.; Seo, Joo Hee; Arthur, Todd; Mangano, Francesco T.; Leach, James L.; Rose, Douglas F.

    2012-01-01

    Summary Purpose Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure-onset zone is near eloquent cortex. Determining the seizure-onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High-frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown. Methods We identified 48 patients who underwent surgical treatment after the surgical evaluation with intracranial EEG, and 44 patients met criteria for this retrospective study. Results were not used in surgical decision making. Intracranial EEG recordings were collected with a sampling rate of 2,000 Hz. Recordings were first inspected visually to determine ictal onset and then analyzed further with time-frequency analysis. Forty-one (93%) of 44 patients had ictal HFOs determined with time-frequency analysis of intracranial EEG. Key Findings Twenty-two (54%) of the 41 patients with ictal HFOs had complete resection of HFO regions, regardless of frequency bands. Complete resection of HFOs (n = 22) resulted in a seizure-free outcome in 18 (82%) of 22 patients, significantly higher than the seizure-free outcome with incomplete HFO resection (4/19, 21%). Significance Our study shows that ictal HFOs are commonly found with intracranial EEG in our population largely of children with cortical dysplasia, and have localizing value. The use of ictal HFOs may add more promising information compared to interictal HFOs because of the evidence of ictal propagation and followed by clinical aspect of seizures. Complete resection of HFOs is a favorable prognostic indicator for surgical outcome. PMID

  4. A better surgical resectability of WHO grade II gliomas is independent of favorable molecular markers.

    PubMed

    Cordier, Dominik; Gozé, Catherine; Schädelin, Sabine; Rigau, Valérie; Mariani, Luigi; Duffau, Hugues

    2015-01-01

    A higher extent of resection (EOR) in WHO grade II gliomas (GIIG) is correlated with longer survival. However, the molecular markers also feature prognostic relevance. Here, we examined whether maximal EOR was related to the genetic profile. We retrospectively investigated the predictive value of 1p19q, IDH1, 53 expression and Ki67 index for the EOR in 200 consecutive GIIGs (2007-2013). Data were modeled in a linear model. The analysis was performed with two statistical methods (arcsin-sqrt and Beta-regression model with logit link). There was no deletion 1p19q in 118 cases, codeletion 1p19q (57 cases), single deletion 1p (4 cases) or19q (16 cases). 155 patients had a mutation of IDH1. p53 was graded in 4 degrees (0:92 cases, 1:52 cases, 2:31 cases, 3:8 cases). Mean Ki67 index was 5.2 % (range 1-20 %). Mean preoperative tumor volume was 60.8 cm(3) (range 3.3-250 cm(3)) and mean EOR was 0.917 (range 0.574-1). The statistical analysis was significant for a lower EOR in patients with codeletion 1p19q (OR 0.738, p = 0.0463) and with a single deletion 19q (OR 0.641, p = 0.0168). There was no significant correlation between IDH1 or p53 and the EOR. Higher Ki67 was marginally associated with higher EOR (p = 0.0603). The study demonstrates in a large cohort of GIIG that a higher EOR is not attributable to favorable genetic markers. This original result supports maximal surgical resection as an important therapeutic factor per se to optimize prognosis, independently of the molecular pattern.

  5. Favorable environments for the occurrence of overshooting tops in tropical cyclones

    NASA Astrophysics Data System (ADS)

    Sun, Liangxiao; Zhuge, Xiaoyong; Wang, Yuan

    2017-04-01

    Based on Multifunctional Transport Satellite data and the infrared window-texture detection algorithm, the level of overshooting top (OT) activity within a tropical cyclone (TC), which is defined as the hourly mean number of OT occurrence, was statistically investigated in the western North Pacific basin for the period 2005-12. Based on the level of OT activity, the samples were divided into OT and non-OT cases or high-activity-OT (HA-OT) and low-activity-OT (LA-OT) cases. The differences in large-scale environmental variables between OT (HA-OT) and non-OT (LA-OT) cases were examined 12 hours prior to the OT occurrence. Statistical analysis showed that environmental differences did exist between the OT and non-OT cases. The OTs were more skewed towards the early stage of the TC life cycle, and mostly concentrated in low latitudes. Meanwhile, a sufficiently deep warm-water layer, large temperature difference between the upper- and lower-level troposphere, large humidity at the middle and upper levels, and large atmospheric instability, were favorable for OT occurrence. The differences in large-scale environmental characteristics between HA-OTs and LA-OTs were not as significant as those between OTs and non-OTs, but the HA-OT samples tended to occur when the vertical shear was weak and the TC intensity was low. Finally, statistical models were designed to predict the OT and HA-OT. When at least three OT (HA-OT) predictor thresholds were satisfied, the Peirce skill score reached a maximum value of 0.49 (0.30).

  6. Design of a novel chimeric tissue plasminogen activator with favorable Vampire bat plasminogen activator properties.

    PubMed

    Kazemali, MohammadReza; Majidzadeh-A, Keivan; Sardari, Soroush; Saadatirad, Amir Hossein; Khalaj, Vahid; Zarei, Najmeh; Barkhordari, Farzaneh; Adeli, Ahmad; Mahboudi, Fereidoun

    2014-12-01

    Fibrinolytic agents are widely used in treatment of the thromboembolic disorders. The new generations like recombinant tissue plasminogen activator (t-PA, alteplase) are not showing promising results in clinical practice in spite of displaying specific binding to fibrin in vitro. Vampire bat plasminogen activator (b-PA) is a plasminogen activator with higher fibrin affinity and specificity in comparison to t-PA resulting in reduced probability of hemorrhage. b-PA is also resistant to plasminogen activator inhibitor-1 (PAI-1) showing higher half-life compared to other variants of t-PA. However, its non-human origin was a driving force to design a human t-PA with favorable properties of b-PA. In the present study, we designed a chimeric t-PA with desirable b-PA properties and this new molecule was called as CT-b. The construct was prepared through kringle 2 domain removal and replacement of t-PA finger domain with b-PA one. In addition, the KHRR sequence at the initial part of protease domain was replaced by four alanine residues. The novel construct was integrated in Pichia pastoris genome by electroporation. Catalytic activity was investigated in the presence and absence of fibrin. The purified protein was analyzed by western blot. Fibrin binding and PAI resistance assays were also conducted. The activity of the recombinant protein in the presence of fibrin was 1560 times more than its activity in the absence of fibrin, showing its higher specificity to fibrin. The fibrin binding of CT-b was 1.2 fold more than t-PA. In addition, it was inhibited by PAI enzyme 44% less than t-PA. Although the presented data demonstrate a promising in vitro activity, more in vivo studies are needed to confirm the therapeutic advantage of this novel plasminogen activator.

  7. Time-Based Partitioning Model for Predicting Neurologically Favorable Outcome among Adults with Witnessed Bystander Out-of-Hospital CPA

    PubMed Central

    Abe, Toshikazu; Tokuda, Yasuharu; Cook, E. Francis

    2011-01-01

    Background Optimal acceptable time intervals from collapse to bystander cardiopulmonary resuscitation (CPR) for neurologically favorable outcome among adults with witnessed out-of-hospital cardiopulmonary arrest (CPA) have been unclear. Our aim was to assess the optimal acceptable thresholds of the time intervals of CPR for neurologically favorable outcome and survival using a recursive partitioning model. Methods and Findings From January 1, 2005 through December 31, 2009, we conducted a prospective population-based observational study across Japan involving consecutive out-of-hospital CPA patients (N = 69,648) who received a witnessed bystander CPR. Of 69,648 patients, 34,605 were assigned to the derivation data set and 35,043 to the validation data set. Time factors associated with better outcomes: the better outcomes were survival and neurologically favorable outcome at one month, defined as category one (good cerebral performance) or two (moderate cerebral disability) of the cerebral performance categories. Based on the recursive partitioning model from the derivation dataset (n = 34,605) to predict the neurologically favorable outcome at one month, 5 min threshold was the acceptable time interval from collapse to CPR initiation; 11 min from collapse to ambulance arrival; 18 min from collapse to return of spontaneous circulation (ROSC); and 19 min from collapse to hospital arrival. Among the validation dataset (n = 35,043), 209/2,292 (9.1%) in all patients with the acceptable time intervals and 1,388/2,706 (52.1%) in the subgroup with the acceptable time intervals and pre-hospital ROSC showed neurologically favorable outcome. Conclusions Initiation of CPR should be within 5 min for obtaining neurologically favorable outcome among adults with witnessed out-of-hospital CPA. Patients with the acceptable time intervals of bystander CPR and pre-hospital ROSC within 18 min could have 50% chance of neurologically favorable outcome. PMID:22194860

  8. High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis

    PubMed Central

    2011-01-01

    Background Human Leukocyte Antigen (HLA)-E is a non-classical class I HLA molecule that can be stabilized by ligands donated by other classical (HLA-A, -B, -C) and non-classical (HLA-G) family members. HLA-E engages a variety of immune receptors expressed by cytotoxic T lymphocytes (CTLs), Natural killer (NK) cells and NK-CTLs. In view of the opposing outcomes (activation or inhibition) of the different HLA-E receptors, the preferred role (if any) of HLA-E expressed in vivo on tumor cells remains to be established. Methods Taking advantage of MEM-E/02, a recently characterized antibody to denatured HLA-E molecules, HLA-E expression was assessed by immunohistochemistry on an archival collection (formalin-fixed paraffin-embedded) of 149 colorectal primary carcinoma lesions paired with their morphologically normal mucosae. Lymphoid infiltrates were assessed for the expression of the HLA-E-specific, inhibitory, non-rearranging receptor NKG2A. Results High HLA-E expression did not significantly correlate with the expression of classical HLA-B and HLA-C molecules, but it did correlate with high expression of its preferential ligand donor HLA-A. In addition, it correlated with lymphoid cell infiltrates expressing the inhibitory NKG2A receptor, and was an independent predictor of good prognosis, particularly in a subset of patients whose tumors express HLA-A levels resembling those of their paired normal counterparts (HLA-A). Thus, combination phenotypes (HLA-Elo-int/HLA-AE and HLA-Ehi/HLA-AE) of classical and non-classical class I HLA molecules mark two graded levels of good prognosis. Conclusions These results suggest that HLA-E favors activating immune responses to colorectal carcinoma. They also provide evidence in humans that tumor cells entertain extensive negotiation with the immune system until a compromise between recognition and escape is reached. It is implied that this process occurs stepwise, as predicted by the widely accepted 'immunoediting' model. PMID

  9. Long-term prognosis of clinically early IgA nephropathy is not always favorable

    PubMed Central

    2014-01-01

    Background The long-term prognosis of clinically early IgA nephropathy (IgAN) patients remains to be clarified. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival. Methods We included patients with biopsy-proven IgAN who had estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2, normal blood pressure, and proteinuria <0.5 g/day at the time of biopsy. The primary outcome was progression to end-stage renal disease (ESRD). The secondary outcome was a 50% increase in serum creatinine level or an increase in proteinuria to >1 g/day. Results The analysis included 153 patients who met the inclusion criteria. At diagnosis, their median systolic blood pressure was 120 (110–130) mmHg, eGFR was 85.9 (74.9–100.1) mL/min/1.73 m2, and proteinuria was 0.25 (0.13–0.38) g/day. Of these, 4 patients died and 6 reached ESRD. The 30-year renal survival rate was 85.5%. Three patients had increased serum creatinine levels and 11 developed proteinuria. Remission was observed in 35 (22.9%) patients. A moderate or severe degree of interstitial fibrosis (adjusted odd ratio [OR] 5.93, 95% confidence interval [CI] 1.44–24.45, P = 0.014) and hypoalbuminemia (adjusted OR 6.18, 95% CI 1.20–31.79, P = 0.029) were independent predictors of the secondary outcome. Conclusions This study showed that the prognosis of early IgAN was not always favorable, even resulting in progression to ESRD in some cases. Hypoalbuminemia and interstitial fibrosis should also be considered important prognostic factors in clinically early IgAN patients. PMID:24946688

  10. Favorable pressure gradient turbulent flow over straight and inclined ribs on both channel walls

    NASA Astrophysics Data System (ADS)

    Tachie, Mark F.; Shah, Mohammad K.

    2008-09-01

    This paper reports on experimental study of turbulent flows over straight and inclined transverse ribs of square and triangular cross sections attached to the bottom and top walls of an asymmetric converging channel. The pitch-to-height ratio of the ribs was 10. A particle image velocimetry technique was used to conduct extensive velocity measurements at channel midspan and in planes close to the leading and trailing edges of the inclined ribs. From these measurements, spatial averaged profiles of the mean velocity and higher order statistics were obtained to study the effects of rib geometry, pressure gradient, spanwise plane, and rib inclination on the flow characteristics. The results show that rib geometry has no significant effects on the mean flow and turbulent quantities. The roughness effects produced by the straight ribs outweighed pressure gradient effects in the inner region of the flow. As a result, the skin friction coefficient is nearly independent of pressure gradient. The Reynolds shear stress and turbulent transport of the shear stress are also independent of pressure gradient. On the contrary, favorable pressure gradient decreased the Reynolds normal stresses in the outer region and increased the magnitudes of the triple velocity correlations and transport of turbulent kinetic energy (TKE). The three-dimensional secondary motion produced by the inclined ribs distorted the mean flow pattern and substantially diminished the ribs' effectiveness to augment skin friction and turbulence. For example, the skin friction over the inclined ribs is only 50%-70% of the value measured over the straight ribs. Furthermore, the size of equivalent sand grain required to produce the same amount of drag is one-tenth to one-third of the rib height for the inclined ribs compared to two- to fourfold for the straight ribs. The inclined ribs also reduced the level of the Reynolds stresses, triple velocity correlations, and transport of both the turbulent kinetic energy

  11. Are human embryos Kantian persons?: Kantian considerations in favor of embryonic stem cell research

    PubMed Central

    Manninen, Bertha Alvarez

    2008-01-01

    paper by drawing from Allen Wood's work in Kantian philosophy in order to generate an argument in favor of hESCR. PMID:18237425

  12. Fault barriers favor activation of backthrusts near segment ends of megathrust ruptures

    NASA Astrophysics Data System (ADS)

    Xu, S.; Fukuyama, E.; Ben-Zion, Y.; Ampuero, J. P.

    2013-12-01

    Increasing evidence indicates that backthrusts may become active during or after megathrust ruptures in subduction zones, such as in Chile and Sumatra areas (Melnick et al., 2012; Singh et al., 2011). Previous studies on relevant mechanisms mainly focused on the interaction between forethrusts and the megathrust. Here we aim to investigate through dynamic rupture simulations how backthrusts may be activated by megathrust ruptures in subduction zone environment. Assuming a single backthrust branch, our preliminary results show that the activation of backthrust is difficult if the megathrust rupture can easily pass through the fault junction, owing to a quickly established stress shadow zone in the wake of the megathrust rupture front. In contrast, if the megathrust rupture is arrested or delayed around the junction, a resultant backward stress lobe of the type discussed by Xu and Ben-Zion (2013) can load the backthrust over a considerable amount of time and facilitates rupture activation along the backthrust. A number of candidates can serve to arrest or delay megathrust ruptures, such as the velocity-strengthening frictional behavior and off-fault weak materials in the shallow portion of subduction zones, fault bend or ramp, and subducted seamount. Moreover, these features are also found capable of generating backthrusts during the long-term quasi-static process, which provide pre-existing weakness to be reactivated by later dynamic ruptures. Our results agree, from a different point of view, with the study based on the critical taper theory (Cubas et al., 2013) that an increase of friction towards the trench favors the activation of backthrusts near the up-dip limit of megathrust ruptures. The results highlight the role of fault geometric or strength heterogeneities in controlling the strain partitioning on and off the main fault plane. Accordingly, activated backthrusts may be treated as markers that reflect the limits of seismogenic zones, and thus may be used

  13. Fire disturbance disrupts an acacia ant-plant mutualism in favor of a subordinate ant species.

    PubMed

    Sensenig, Ryan L; Kimuyu, Duncan K; Ruiz Guajardo, Juan Carlos; Veblen, Kari E; Riginos, Corinna; Young, Truman P

    2017-03-08

    Although disturbance theory has been recognized as a useful framework in examining the stability of ant-plant mutualisms, very few studies have examined the effects of fire disturbance on these mutualisms. In myrmecophyte-dominated savannas, fire and herbivory are key drivers that could influence ant-plant mutualisms by causing complete colony mortality and/or decreasing colony size, which potentially could alter dominance hierarchies if subordinate species are more fire resilient. We used a large-scale, replicated fire experiment to examine long-term effects of fire on acacia-ant community composition. To determine if fire shifted ant occupancy from a competitive dominant to a subordinate ant species we surveyed the acacia-ant community in 6-7-year-old burn sites and examined how the spatial scale of these burns influenced ant community responses. We then used two short-term fire experiments to explore possible mechanisms for the shifts in community patterns observed. Because survival of ant colonies is largely dependent on their ability to detect and escape an approaching fire, we first tested the evacuation response of all four ant species when exposed to smoke (fire signal). Then to better understand how fire and its interaction with large mammal herbivory affect the density of ants per tree, we quantified ant worker density in small prescribed burns within herbivore exclusion plots. We found clear evidence suggesting that fire disturbance favored the subordinate ant Crematogaster nigriceps more than the dominant and strong mutualist ant C. mimosae, whereby C. nigriceps: 1) was the only species to occupy a greater proportion of trees in 6-7 year old burn sites compared to unburned sites, 2) had higher burn/unburn tree ratios with increasing burn size; and 3) evacuated significantly faster than C. mimosae in the presence of smoke. Fire and herbivory had opposite effects on ant density per meter of branch for both C. nigriceps and C. mimosae, with fire decreasing

  14. Are human embryos Kantian persons?: Kantian considerations in favor of embryonic stem cell research.

    PubMed

    Manninen, Bertha Alvarez

    2008-01-31

    paper by drawing from Allen Wood's work in Kantian philosophy in order to generate an argument in favor of hESCR.

  15. Oxygen limitation favors the production of protein with antimicrobial activity in Pseudoalteromonas sp

    PubMed Central

    López, Ruth; Monteón, Víctor; Chan, Ernesto; Montejo, Rubí; Chan, Manuel

    2012-01-01

    This study examined the effect of dissolved oxygen concentration on the production of biomass and metabolites with antimicrobial activity of Pseudoalteromonas sp cultured at 0, 150, 250, or 450 revolutions per minute (rev. min-1). Dissolved oxygen (D.O) was monitored during the fermentation process, biomass was quantified by dry weight, and antimicrobial activity was assessed using the disk diffusion method. The bacterium Pseudoalteromonas reached similar concentration of biomass under all experimental agitation conditions, whereas antimicrobial activity was detected at 0 and 150 rev. min-1 registering 0% and 12% of D.O respectively corresponding to microaerophilic conditions. Antibiotic activity was severely diminished when D.O was above 20% of saturation; this corresponded to 250 or 450 rev. min-1. SDS-PAGE electrophoresis revealed a protein with a molecular weight of approximately 80 kilodaltons (kDa) with antimicrobial activity. Pseudoalteromonas is capable of growing under oxic and microaerophilic conditions but the metabolites with antimicrobial activity are induced under microaerophilic conditions. The current opinion is that Pseudoalteromonas are aerobic organisms; we provide additional information on the amount of dissolved oxygen during the fermentation process and its effect on antimicrobial activity. PMID:24031945

  16. [Social politics against poverty and in favor of health in Mexico].

    PubMed

    Hamui-Sutton, Alicia; Irigoyen-Coria, Arnulfo; Gómez-Clavelina, Francisco Javier; Fernández-Ortega, Miguel Angel

    2006-01-01

    One of the biggest challenges that Mexico faces is to fight against the poverty. The transition of a characteristic welfare model from the government in a closed economy, to an open economy where the functions of the State are limited, has modified the modalities of the social politics against poverty. Six indispensable conditions are identified for poverty's reduction: 1. Economic development with stability in order to generate more and better jobs for poor people. 2. To improve regional economies. 3. To improve home conditions of poor people. 4. To elevate education levels (to encourage an authentic heath education). 5. To diminish catastrophic expenses for health problems. 6. Technical training for all workers. The impact of poverty over health can provide valuable elements to establish effective preventive strategies on health workers.

  17. Early selection of black spruce seedlings and global change: Which genotypes should we favor

    SciTech Connect

    Wang, Z.M.; Lechowicz, M.J.; Potvin, C. )

    1994-08-01

    The effects of both soil fertility and predicted changes in climate on growth of different families of black spruce, Picea mariana (Mill.) B.S.P., during the first growing season was studied. The results were used to examine whether reforestation programs should consider changing their preferred family lines in anticipation of altered performance given global climate change. We grew seedlings of 16 open-pollinated maternal families of black spruce under phytotron conditions simulating present and mid-21st century climatic conditions during the growing season. The realistic, simulated future climate included both elevated CO[sub 2] levels and seasonally appropriate increases in mean daily temperature. To explore the dependence of climatic responses on site quality, seedlings were irrigated with solutions having either 5 or 100 mg/L of nitrogen. The lower nitrogen level represents a poor site for black spruce growth and survival, but the higher level provides ample nitrogen. We also recorded seed size for each seedling to evaluate the degree to which maternal investments might buffer responses to future climate and fertility during the first year on the seedbed. Seedling survival and growth increase both under the future climate regime and with nitrogen fertilization. The two factors interacted synergistically, with nitrogen enrichment significantly enhancing the positive effects of the future climate regime. Nitrogen-poor conditions, however, did not preclude a positive seedling response to the future climate. Our results indicate that seedling survival and height growth are highly dependent upon initial seed mass, seed germination, and seedling, survival and growth, but their relative performances did not vary significantly among the treatments. These results suggest that black spruce families selected for rapid growth under present conditions will also do well in the future, at least in terms of early establishment and performance on sites regenerated by seeding.

  18. Transmission advantage favors selfing allele in experimental populations of self-incompatible Witheringia solanacea (solanaceae).

    PubMed

    Stone, Judy L; VanWyk, Emily J; Hale, Jennifer R

    2014-07-01

    The evolution of self-fertilization is one of the most commonly traversed transitions in flowering plants, with profound implications for population genetic structure and evolutionary potential. We investigated factors influencing this transition using Witheringia solanacea, a predominantly self-incompatible (SI) species within which self-compatible (SC) genotypes have been identified. We showed that self-compatibility in this species segregates with variation at the S-locus as inherited by plants in F1 and F2 generations. To examine reproductive assurance and the transmission advantage of selfing, we placed SC and SI genotypes in genetically replicated gardens and monitored male and female reproductive success, as well as selfing rates of SC plants. Self-compatibility did not lead to increased fruit or seed set, even under conditions of pollinator scarcity, and the realized selfing rate of SC plants was less than 10%. SC plants had higher fruit abortion rates, consistent with previous evidence showing strong inbreeding depression at the embryonic stage. Although the selfing allele did not provide reproductive assurance under observed conditions, it also did not cause pollen discounting, so the transmission advantage of selfing should promote its spread. Given observed numbers of S-alleles and selfing rates, self-compatibility should spread even under conditions of exceedingly high initial inbreeding depression.

  19. Transmission advantage favors selfing allele in experimental populations of self-incompatible Witheringia solanacea (Solanaceae)

    PubMed Central

    Stone, Judy L.; VanWyk, Emily J.; Hale, Jennifer R.

    2014-01-01

    The evolution of self-fertilization is one of the most commonly traversed transitions in flowering plants, with profound implications for population genetic structure and evolutionary potential. We investigated factors influencing this transition using Witheringia solanacea, a predominantly self-incompatible species within which self-compatible genotypes have been identified. We showed that self-compatibility in this species segregates with variation at the S-locus as inherited by plants in F1 and F2 generations. To examine reproductive assurance and the transmission advantage of selfing, we placed self-compatible and self-incompatible genotypes in genetically replicated gardens and monitored male and female reproductive success, as well as selfing rates of self-compatible plants. Self-compatibility did not lead to increased fruit or seed set, even under conditions of pollinator scarcity, and the realized selfing rate of self-compatible plants was less than 10%. Self-compatible plants had higher fruit abortion rates, consistent with previous evidence showing strong inbreeding depression at the embryonic stage. Although the selfing allele did not provide reproductive assurance under observed conditions, it also did not cause pollen discounting, so the transmission advantage of selfing should promote its spread. Given observed numbers of S-alleles and selfing rates, self-compatibility should spread even under conditions of exceedingly high initial inbreeding depression. PMID:24713065

  20. The response of inorganic carbon distributions and dynamics to upwelling-favorable winds on the northern Gulf of Mexico during summer

    NASA Astrophysics Data System (ADS)

    Huang, W.-J.; Cai, W.-J.; Wang, Y.; Hu, X.; Chen, B.; Lohrenz, S. E.; Chakraborty, S.; He, R.; Brandes, J.; Hopkinson, C. S.

    2015-12-01

    Upwelling-favorable winds and an offshore-distributed Mississippi and Atchafalaya River plume trajectory were observed in summer 2009 in contrast to the mean conditions from 2002 to 2010 (upwelling-unfavorable winds and an alongshore river plume trajectory), a set of conditions which was also observed in summer 2007. The responses of dissolved inorganic carbon (DIC) distributions and dynamics to upwelling-favorable winds are studied by comparing the contrasting conditions between summer 2009 and summer 2007 on the northern Gulf of Mexico. Patterns of surface water partial pressure of CO2 (pCO2), DIC, δ13C in DIC, and total alkalinity (TA) determined in July 2009 and August 2007 were strongly related to river plume trajectories, and differed between the two summers. The slope of the relationship between dissolved oxygen (DO) and DIC in summer 2007 was comparable to the Redfield O/C ratio of 1.3, which was attributed to respiration of organic matter in the bottom water. The slope of the DO and DIC relationship and δ13CDIC values in bottom waters during July 2009 were clearly affected by mixing since their salinities were <35. A three end-member mixing model was used to remove mixing effects in (1) δ13CDIC, to estimate the organic source of respiration, and (2) in DIC concentrations, to calculate DIC removal and release. δ13CDIC results in both summers were consistent with an apparent release of DIC in hypoxic waters (DO less than 2 mg L-1) associated with respiration of surface organic matter. The area-weighted surface DIC removal (i.e., biological production) was lower in 2009 than in 2007 on the shelf, as the plume was distributed offshore. The release of DIC in bottom waters was higher over the shelf in 2009 and was surmised to be related to stronger mixing, which was favorable for the DO supply for respiration. Overall, surface waters on the continental shelf in the region of study in July 2009 acted as a weak CO2 source to the atmosphere, but a weak CO2 sink

  1. A case of isolated neck extensor myopathy responding favorably to immunotherapy.

    PubMed

    Larsen, Håvard; Bogaard, Pauline W; Oppel, Lorenz

    2013-12-01

    We report on a case of a 79-year-old man with dropped head syndrome, where diagnostic tests, ruling out other differential diagnoses, confirmed the relatively rarely occurring condition known as isolated neck extensor myopathy. Biopsy of the neck extensor musculature was with classical pronounced fibrosis, without signs of myositis. The patient was treated with 3 cycles of corticosteroids with pronounced clinical improvement of his symptoms. This emphasizes the importance of considering isolated neck extensor myopathy as a differential diagnosis when encountered with a patient with dropped head syndrome and the importance of trying therapy with corticosteroids even when myositis is absent.

  2. Understanding and Mitigating the Effects of Stable Dodecahydro- closo -dodecaborate Intermediates on Hydrogen-Storage Reactions

    SciTech Connect

    White, James L.; Newhouse, Rebecca J.; Zhang, Jin Z.; Udovic, Terrence J.; Stavila, Vitalie

    2016-10-25

    Alkali metal borohydrides can reversibly store hydrogen; however, the materials display poor cyclability, often times linked to occurrence of stable closo-polyborate intermediate species. In an effort to understand the role of such intermediates on the hydrogen storage properties of metal borohydrides, several alkali metal dodecahydro-closo-dodecaborate salts were isolated in anhydrous form and characterized by diffraction and spectroscopic techniques. Mixtures of Li2B12H12, Na2B12H12, and K2B12H12 with the corresponding alkali metal hydrides were subjected to hydrogenation conditions known to favor partial or full reversibility in metal borohydrides. The stoichiometric mixtures of MH and M2B12H12 salts form the corresponding metal borohydrides MBH4 (M=Li, Na, K) in almost quantitative yield at 100 MPa H2 and 500 °C. In addition, stoichiometric mixtures of Li2B12H12 and MgH2 were found to form MgB2 at 500 °C and above upon desorption in vacuum. The two destabilization strategies outlined above suggest that metal polyhydro-closo-polyborate species can be converted into the corresponding metal borohydrides or borides, albeit under rather harsh conditions of hydrogen pressure and temperature.

  3. Aging impairs osteoblast differentiation of mesenchymal stem cells grown on titanium by favoring adipogenesis

    PubMed Central

    ABUNA, Rodrigo Paolo Flores; STRINGHETTA-GARCIA, Camila Tami; FIORI, Leonardo Pimentel; DORNELLES, Rita Cassia Menegati; ROSA, Adalberto Luiz; BELOTI, Marcio Mateus

    2016-01-01

    ABSTRACT Aging negatively affects bone/titanium implant interactions. Our hypothesis is that the unbalance between osteogenesis and adipogenesis induced by aging may be involved in this phenomenon. Objective We investigated the osteoblast and adipocyte differentiation of mesenchymal stem cells (MSCs) from young and aged rats cultured on Ti. Material and Methods Bone marrow MSCs derived from 1-month and 21-month rats were cultured on Ti discs under osteogenic conditions for periods of up to 21 days and osteoblast and adipocyte markers were evaluated. Results Cell proliferation, alkaline phosphatase (ALP) activity, extracellular matrix mineralization and gene expression of RUNX2, osterix, ALP, bone sialoprotein, osteopontin, and osteocalcin were reduced in cultures of 21-month rats compared with 1-month rats grown on Ti. Gene expression of PPAR-γ , adipocyte protein 2, and resistin and lipid accumulation were increased in cultures of 21-month rats compared with 1-month rats grown on the same conditions. Conclusions These results indicate that the lower osteogenic potential of MSCs derived from aged rats compared with young rats goes along with the higher adipogenic potential in cultures grown on Ti surface. This unbalance between osteoblast and adipocyte differentiation should be considered in dental implant therapy to the elderly population. PMID:27556209

  4. The Bias in Favor of Venture Capital Finance in U.S. Entrepreneurial Education: At the Expense of Trade Credit

    ERIC Educational Resources Information Center

    Clement, Thomas; LeMire, Steven; Silvernagel, Craig

    2015-01-01

    The authors examine whether U.S. college-level entrepreneurship education demonstrates a bias favoring venture capital (VC) financing while marginalizing trade credit financing, and the resulting impact on entrepreneurship students. A sample of U.S. business textbooks and survey data from entrepreneurship students reveals a significant bias toward…

  5. 8 CFR 316.11 - Attachment to the Constitution; favorable disposition towards the good order and happiness.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... been and continues to be attached to the principles of the Constitution of the United States and favorably disposed toward the good order and happiness of the United States. Attachment implies a depth of... to the basic form of government of the United States, or who disbelieve in the principles of...

  6. 8 CFR 316.11 - Attachment to the Constitution; favorable disposition towards the good order and happiness.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... been and continues to be attached to the principles of the Constitution of the United States and favorably disposed toward the good order and happiness of the United States. Attachment implies a depth of... to the basic form of government of the United States, or who disbelieve in the principles of...

  7. Explaining financial and prosocial biases in favor of attractive people: Interdisciplinary perspectives from economics, social psychology, and evolutionary psychology.

    PubMed

    Maestripieri, Dario; Henry, Andrea; Nickels, Nora

    2017-01-01

    Financial and prosocial biases in favor of attractive adults have been documented in the labor market, in social transactions in everyday life, and in studies involving experimental economic games. According to the taste-based discrimination model developed by economists, attractiveness-related financial and prosocial biases are the result of preferences or prejudices similar to those displayed toward members of a particular sex, racial, ethnic, or religious group. Other explanations proposed by economists and social psychologists maintain that attractiveness is a marker of personality, intelligence, trustworthiness, professional competence, or productivity. Evolutionary psychologists have argued that attractive adults are favored because they are preferred sexual partners. Evidence that stereotypes about attractive people are causally related to financial or prosocial biases toward them is weak or nonexistent. Consistent with evolutionary explanations, biases in favor of attractive women appear to be more consistent or stronger than those in favor of attractive men, and biases are more consistently reported in interactions between opposite-sex than same-sex individuals. Evolutionary explanations also account for increased prosocial behavior in situations in which attractive individuals are simply bystanders. Finally, evolutionary explanations are consistent with the psychological, physiological, and behavioral changes that occur when individuals are exposed to potential mates, which facilitate the expression of courtship behavior and increase the probability of occurrence of mating. Therefore, multiple lines of evidence suggest that mating motives play a more important role in driving financial and prosocial biases toward attractive adults than previously recognized.

  8. Development of intelligent model to determine favorable wheelchair tilt and recline angles for people with spinal cord injury.

    PubMed

    Fu, Jicheng; Jan, Yih-Kuen; Jones, Maria

    2011-01-01

    Machine-learning techniques have found widespread applications in bioinformatics. Such techniques provide invaluable insight on understanding the complex biomedical mechanisms and predicting the optimal individualized intervention for patients. In our case, we are particularly interested in developing an individualized clinical guideline on wheelchair tilt and recline usage for people with spinal cord injury (SCI). The current clinical practice suggests uniform settings to all patients. However, our previous study revealed that the response of skin blood flow to wheelchair tilt and recline settings varied largely among patients. Our finding suggests that an individualized setting is needed for people with SCI to maximally utilize the residual neurological function to reduce pressure ulcer risk. In order to achieve this goal, we intend to develop an intelligent model to determine the favorable wheelchair usage to reduce pressure ulcers risk for wheelchair users with SCI. In this study, we use artificial neural networks (ANNs) to construct an intelligent model that can predict whether a given tilt and recline setting will be favorable to people with SCI based on neurological functions and SCI injury history. Our results indicate that the intelligent model significantly outperforms the traditional statistical approach in accurately classifying favorable wheelchair tilt and recline settings. To the best of our knowledge, this is the first study using intelligent models to predict the favorable wheelchair tilt and recline angles. Our methods demonstrate the feasibility of using ANN to develop individualized wheelchair tilt and recline guidance for people with SCI.

  9. Preferential uptake of ribose by primitive cells might explain why RNA was favored over its analogs

    NASA Astrophysics Data System (ADS)

    Pohorille, Andrew; Wei, Chenyu

    perme-ation, even though it is non-negligibly populated in aqueous solution. The differences in free energy barrier between ribose and arabinose or xylose are due to stronger, highly cooperative, intramolecular interactions between consecutive exocyclic hydroxyl groups, which are stable in non-polar media, but rare in water. Most recently, we extended calculations of permeations to ribonucleosides and their anomers. We determined that, in contrast to sugars, permeation of membranes to these species is nearly identical. This is because sugars of nucleotides exist in the furanose rather than pyranose form. In this form intermolecular interactions between hydroxyl groups are not nearly as efficient for sterical reasons. Our results contribute to the discussion about autotrophic vs. heterotrophic origins of life. Chemical reactions inside protobiological vesicle required supply of organic material from the environment. What was the inventory of organics that must have been delivered to primitive cells is still being debated. According to the autotrophic hypothesis, ancestors of cells pro-duced complex organic molecules from simple substrates. In contrast, the heterotrophic model implies that protocells were able to utilize complex organics delivered from external sources. A possibility of sufficiently efficient uptake of molecules needed to build biopolymers provides an important argument supporting the heterotrophic hypothesis [3]. Viewed in the context of the "RNA world" hypothesis [4], which states that RNA molecules were the first biological poly-mers and acted as both catalysts of biochemical reactions and information storage systems, our results demonstrate that, in the absence of sophisticated mechanisms available to contemporary organisms for achieving selectivity during synthesis and transmembrane transport, preferential uptake of ribose by primitive cells might have provided a kinetic mechanism that favored its selective incorporation into nucleic acids and

  10. Use of generalized regression tree models to characterize vegetation favoring Anopheles albimanus breeding.

    PubMed

    Hernandez, J E; Epstein, L D; Rodriguez, M H; Rodriguez, A D; Rejmankova, E; Roberts, D R

    1997-03-01

    We propose the use of generalized tree models (GTMs) to analyze data from entomological field studies. Generalized tree models can be used to characterize environments with different mosquito breeding capacity. A GTM simultaneously analyzes a set of predictor variables (e.g., vegetation coverage) in relation to a response variable (e.g., counts of Anopheles albimanus larvae), and how it varies with respect to a set of criterion variables (e.g., presence of predators). The algorithm produces a treelike graphical display with its root at the top and 2 branches stemming down from each node. At each node, conditions on the value of predictors partition the observations into subgroups (environments) in which the relation between response and criterion variables is most homogeneous.

  11. Aridity, not fire, favors nitrogen-fixing plants across tropical savanna and forest biomes.

    PubMed

    Pellegrini, Adam F A; Staver, A Carla; Hedin, Lars O; Charles-Dominique, Tristan; Tourgee, Amy

    2016-09-01

    Tropical savannas are hypothesized to be hot spots of nitrogen-fixer diversity and activity because of the high disturbance and low nitrogen characteristic of savanna landscapes. Here we compare the abundances of nitrogen-fixing and non-fixing trees in both tropical savannas and tropical forests under climatically equivalent conditions, using plant inventory studies across 566 plots in South America and Africa. A single factor, aridity, explained 19-54% of the variance in fixer abundance, and unexpectedly was more important than fire frequency, biome, and continent. Nitrogen fixers were more abundant in arid environments; as a result, African savannas, which tend to be drier, were richer in nitrogen fixers than South American savannas. Fixer abundance converged on similar levels in forests in both continents. We conclude that climate plays a greater role than fire in determining the distribution of nitrogen fixers across tropical savanna and forest biomes.

  12. Nocturnal Propagating Thunderstorms May Favor Urban "Hot-Spots": A Model-Based Study over Minneapolis

    NASA Technical Reports Server (NTRS)

    Ganeshan, Manisha; Murtugudde, Raghu

    2015-01-01

    High-resolution WRF model sensitivity experiments are carried out (with and without urban land cover) to study urban impacts on nocturnal propagating thunderstorms over the city of Minneapolis. It is found that the storm spatial characteristics, especially the position of the storm cell, are appreciably altered by the presence of urban land cover. The most robust urban instability during stormy conditions is the enhanced surface convergence due to increased frictional drag. No urban impact is visible on the rainfall intensity simulated by the model. The frictional convergence, aided by the nocturnal Urban Heat Island (UHI), appears to be responsible for attracting propagating storms towards the urban center. Advanced modeling experiments are needed to quantify the mechanical and thermal influence along with similar studies in other cities to further investigate the urban impact on the frequency and trajectory of nocturnal propagating storms.

  13. Cheatgrass is favored by warming but not CO2 enrichment in a semi-arid grassland.

    PubMed

    Blumenthal, Dana M; Kray, Julie A; Ortmans, William; Ziska, Lewis H; Pendall, Elise

    2016-09-01

    Elevated CO2 and warming may alter terrestrial ecosystems by promoting invasive plants with strong community and ecosystem impacts. Invasive plant responses to elevated CO2 and warming are difficult to predict, however, because of the many mechanisms involved, including modification of phenology, physiology, and cycling of nitrogen and water. Understanding the relative and interactive importance of these processes requires multifactor experiments under realistic field conditions. Here, we test how free-air CO2 enrichment (to 600 ppmv) and infrared warming (+1.5 °C day/3 °C night) influence a functionally and phenologically distinct invasive plant in semi-arid mixed-grass prairie. Bromus tectorum (cheatgrass), a fast-growing Eurasian winter annual grass, increases fire frequency and reduces biological diversity across millions of hectares in western North America. Across 2 years, we found that warming more than tripled B. tectorum biomass and seed production, due to a combination of increased recruitment and increased growth. These results were observed with and without competition from native species, under wet and dry conditions (corresponding with tenfold differences in B. tectorum biomass), and despite the fact that warming reduced soil water. In contrast, elevated CO2 had little effect on B. tectorum invasion or soil water, while reducing soil and plant nitrogen (N). We conclude that (1) warming may expand B. tectorum's phenological niche, allowing it to more successfully colonize the extensive, invasion-resistant northern mixed-grass prairie, and (2) in ecosystems where elevated CO2 decreases N availability, CO2 may have limited effects on B. tectorum and other nitrophilic invasive species.

  14. Parvalbumin-Positive Inhibitory Interneurons Oppose Propagation But Favor Generation of Focal Epileptiform Activity.

    PubMed

    Sessolo, Michele; Marcon, Iacopo; Bovetti, Serena; Losi, Gabriele; Cammarota, Mario; Ratto, Gian Michele; Fellin, Tommaso; Carmignoto, Giorgio

    2015-07-01

    Parvalbumin (Pv)-positive inhibitory interneurons effectively control network excitability, and their optogenetic activation has been reported to block epileptic seizures. An intense activity in GABAergic interneurons, including Pv interneurons, before seizures has been described in different experimental models of epilepsy, raising the hypothesis that an increased GABAergic inhibitory signal may, under certain conditions, initiate seizures. It is therefore unclear whether the activity of Pv interneurons enhances or opposes epileptiform activities. Here we use a mouse cortical slice model of focal epilepsy in which the epileptogenic focus can be identified and the role of Pv interneurons in the generation and propagation of seizure-like ictal events is accurately analyzed by a combination of optogenetic, electrophysiological, and imaging techniques. We found that a selective activation of Pv interneurons at the focus failed to block ictal generation and induced postinhibitory rebound spiking in pyramidal neurons, enhancing neuronal synchrony and promoting ictal generation. In contrast, a selective activation of Pv interneurons distant from the focus blocked ictal propagation and shortened ictal duration at the focus. We revealed that the reduced ictal duration was a direct consequence of the ictal propagation block, probably by preventing newly generated afterdischarges to travel backwards to the original focus of ictal initiation. Similar results were obtained upon individual Pv interneuron activation by intracellular depolarizing current pulses. The functional dichotomy of Pv interneurons here described opens new perspectives to our understanding of how local inhibitory circuits govern generation and spread of focal epileptiform activities.

  15. Characterizing acrylic pressure-sensitive adhesive tapes favoring diverse biomedical applications

    NASA Astrophysics Data System (ADS)

    Alhijji, Saleh Mohammed S.

    Strong, self-adhesive acrylic polymer-based tapes have been identified as FDA-approved medical device construction components that might also serve in diverse biological locations as artificial muscles, ligaments, or compressive support discs. After assuring that the tapes themselves were not cytotoxic, they were evaluated as possible low-tension muscle substitutes for eyelids, jaws, and other modest body re-closing needs, and well as for higher-tension applications as artificial ligaments. Self-adhesion of the tapes to representative biomaterials, before and after radio-frequency glow discharge treatment for surface energy modification, illustrated the conditions for maximum attachment strength to nonphysiologic substances. Attachment to bony host parts was challenging but apparently met by the application of acrylic-composite-to-dentin bonding systems that has shown good long-term experience in the mouth. Above all, the compression-relaxation properties of the tape materials were superior and their uses in potential Nucleus Pulposus applications for spinal disc repair were most completely explored. Tests included tape-disc performance longevity, both dry and wet, for over 5000 load-relaxation cycles, with no apparent changes in results for the most dense of the tapes evaluated. Direct abrasion was avoided by insertion of rigid polymeric layers. It is recommended that the compressive loading properties of acrylic tapes be further evaluated for spine repair applications.

  16. The spread of alphabetical writing may have favored the latest variant of the ASPM gene.

    PubMed

    Frost, Peter

    2008-01-01

    ASPM, a gene that regulates brain growth, has evolved considerably in the primate lineage that leads to humans. It continued to evolve even after the emergence of modern humans, with the latest ASPM variant arising about 6000 years ago somewhere in the Middle East. The new variant then proliferated within and outside this region, reaching higher incidences in the Middle East (37-52%) and in Europe (38-50%) than in East Asia (0-25%). Despite its apparent selective advantage, this variant does not seem to improve cognitive performance, at least not on standard IQ tests. At present, we can only say that it probably assists performance on a task that exhibited the same geographic expansion from a Middle Eastern origin roughly 6000 years ago. The closest match seems to be the invention of alphabetical writing, specifically the task of transcribing speech and copying texts into alphabetical script. Though more easily learned than ideographs, alphabetical characters place higher demands on mental processing, especially under premodern conditions (continuous text with little or no punctuation, real-time stenography, absence of automated assistance for publishing or copying, etc.). This task was largely delegated to scribes of various sorts who enjoyed privileged status and probably superior reproductive success. Such individuals may have served as vectors for spreading the new ASPM variant.

  17. Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress

    PubMed Central

    Martinez, Vicente; Mestre, Teresa C.; Rubio, Francisco; Girones-Vilaplana, Amadeo; Moreno, Diego A.; Mittler, Ron; Rivero, Rosa M.

    2016-01-01

    Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance. PMID:27379130

  18. Lactobacillus plantarum favors the early emergence of fit and fertile adult Drosophila upon chronic undernutrition

    PubMed Central

    Téfit, Mélisandre A.

    2017-01-01

    ABSTRACT Animals are naturally surrounded by a variety of microorganisms with which they constantly interact. Among these microbes, some live in close association with a host and form its microbiota. These communities are being extensively studied, owing to their contributions to shaping various aspects of animal physiology. One of these commensal species, Lactobacillus plantarum, and in particular the L.p.WJL strain, has been shown to promote the growth of Drosophila larvae upon nutrient scarcity, allowing earlier metamorphosis and adult emergence compared with axenic individuals. As for many insects, conditions surrounding the post-embryonic development dictate key adult life history traits in Drosophila, and adjusting developmental timing according to the environment is essential for adult fitness. Thus, we wondered whether the growth acceleration induced by L.p.WJL in a context of poor nutrition could adversely impact the fitness of Drosophila adults. Here, we show that the L.p.WJL-mediated acceleration of growth is not deleterious; adults emerging after an accelerated development are as fit as their axenic siblings. Additionally, the presence of L.p.WJL even leads to a lifespan extension in nutritionally challenged males. These results demonstrate that L.p.WJL is a beneficial partner for Drosophila melanogaster through its entire life cycle. Thus, commensal bacteria allow the earlier emergence and longer survival of fit and fertile individuals and might represent one of the factors contributing to the ecological success of Drosophila. PMID:28062579

  19. Are hard lenses superior to soft? Arguments in favor of hard lenses.

    PubMed

    Key, J E

    1990-01-01

    The overriding consideration in choosing between soft contact lenses (SCLs) and rigid gas-permeable (RGP) lenses is the severity of the changes each induces in the corneal epithelium, endothelium, and conjunctival structures. Lens-related epithelial changes are largely the consequence of relative oxygen deprivation and consequent corneal edema. Factors such as lower oxygen transmissibility, minimal tear exchange capacity, and large diameters may explain why SCL wearers show a higher rate of corneal infiltrates, sterile ulcers, and irregular staining patterns than users of RGP lenses. The greater association of hydrogels with infectious keratitis may reflect their tendency to accumulate proteinaceous deposits, harbor bacteria in the polymer matrix, and resist easy disinfection. SCL wear has been linked to endothelial polymegethism, a largely irreversible condition that may cause more rapid corneal swelling and slower deswelling after periods of hypoxic stress. Among the conjunctival problems more often seen in SCL wearers are superficial neovascularization, contact lens-related superior limbic keratoconjunctivitis, and giant papillary conjunctivitis. Mechanical irritation from large-diameter lenses, a tendency to build up mucoproteinaceous deposits, corneal draping, and hypersensitivity to preservatives in SCL care products may play a role in these problems.

  20. Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress.

    PubMed

    Martinez, Vicente; Mestre, Teresa C; Rubio, Francisco; Girones-Vilaplana, Amadeo; Moreno, Diego A; Mittler, Ron; Rivero, Rosa M

    2016-01-01

    Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance.

  1. The Case in Favor of E-Cigarettes for Tobacco Harm Reduction

    PubMed Central

    Nitzkin, Joel L.

    2014-01-01

    A carefully structured Tobacco Harm Reduction (THR) initiative, with e-cigarettes as a prominent THR modality, added to current tobacco control programming, is the most feasible policy option likely to substantially reduce tobacco-attributable illness and death in the United States over the next 20 years. E-cigarettes and related vapor products are the most promising harm reduction modalities because of their acceptability to smokers. There are about 46 million smokers in the United States, and an estimated 480,000 deaths per year attributed to cigarette smoking. These numbers have been essentially stable since 2004. Currently recommended pharmaceutical smoking cessation protocols fail in about 90% of smokers who use them as directed, even under the best of study conditions, when results are measured at six to twelve months. E-cigarettes have not been attractive to non-smoking teens or adults. Limited numbers non-smokers have experimented with them, but hardly any have continued their use. The vast majority of e-cigarette use is by current smokers using them to cut down or quit cigarettes. E-cigarettes, even when used in no-smoking areas, pose no discernable risk to bystanders. Finally, addition of a THR component to current tobacco control programming will likely reduce costs by reducing the need for counseling and drugs. PMID:25003176

  2. St. John's Wort Has Metabolically Favorable Effects on Adipocytes In Vivo

    PubMed Central

    Richard, Allison J.; Ribnicky, David M.; Mynatt, Randall; Stephens, Jacqueline M.

    2014-01-01

    In addition to serving as a storage site for reserve energy, adipocytes play a critical role in whole-body insulin sensitivity and glucose metabolism. St. John's Wort (SJW) is a botanical supplement widely used as an over-the-counter treatment of depression and a variety of other conditions associated with anxiety and nerve pain. Previous studies in our laboratory demonstrated that SJW inhibits insulin-stimulated glucose uptake and adipocyte differentiation in cultured murine and mature human adipocytes. To investigate the effects of SJW on adipocyte function in vivo, we utilized C57BL/6J mice. In our studies, mice were administered SJW extract (200 mg/kg) once daily by gavage for two weeks. In contrast to our in vitro studies, mice treated with SJW extract showed increased levels of adiponectin in white adipose tissue in a depot specific manner (P < 0.01). SJW also exerted an insulin-sensitizing effect as indicated by a significant increase in insulin-stimulated Akt serine phosphorylation in epididymal white adipose tissue (P < 0.01). Food intake, body weight, fasting blood glucose, and fasting insulin did not differ between the two groups. These results are important as they indicate that SJW does not promote metabolic dysfunction in adipose tissue in vivo. PMID:25136373

  3. St. John's Wort Has Metabolically Favorable Effects on Adipocytes In Vivo.

    PubMed

    Fuller, Scott; Richard, Allison J; Ribnicky, David M; Beyl, Robbie; Mynatt, Randall; Stephens, Jacqueline M

    2014-01-01

    In addition to serving as a storage site for reserve energy, adipocytes play a critical role in whole-body insulin sensitivity and glucose metabolism. St. John's Wort (SJW) is a botanical supplement widely used as an over-the-counter treatment of depression and a variety of other conditions associated with anxiety and nerve pain. Previous studies in our laboratory demonstrated that SJW inhibits insulin-stimulated glucose uptake and adipocyte differentiation in cultured murine and mature human adipocytes. To investigate the effects of SJW on adipocyte function in vivo, we utilized C57BL/6J mice. In our studies, mice were administered SJW extract (200 mg/kg) once daily by gavage for two weeks. In contrast to our in vitro studies, mice treated with SJW extract showed increased levels of adiponectin in white adipose tissue in a depot specific manner (P < 0.01). SJW also exerted an insulin-sensitizing effect as indicated by a significant increase in insulin-stimulated Akt serine phosphorylation in epididymal white adipose tissue (P < 0.01). Food intake, body weight, fasting blood glucose, and fasting insulin did not differ between the two groups. These results are important as they indicate that SJW does not promote metabolic dysfunction in adipose tissue in vivo.

  4. Exopolysaccharides favor the survival of Erwinia amylovora under copper stress through different strategies.

    PubMed

    Ordax, Mónica; Marco-Noales, Ester; López, María M; Biosca, Elena G

    2010-09-01

    Erwinia amylovora causes fire blight, a destructive disease of rosaceous plants very difficult to control. We demonstrated that copper, employed to control plant diseases, induces the "viable-but-nonculturable" (VBNC) state in E. amylovora. Moreover, it was previously reported that copper increases production of its main exopolysaccharide (EPS), amylovoran. In this work, the copper-complexing ability of amylovoran and levan, other major EPS of E. amylovora, was demonstrated. Following this, EPS-deficient mutants were used to determine the role of these EPSs in survival of this bacterium in AB mineral medium with copper, compared to their wild type strain and AB without copper. Total, viable and culturable counts of all strains were monitored for six months. With copper, a larger fraction of the viable population of EPS mutants entered into the VBNC state, and earlier than their wild type strain, showing the contribution of both EPSs to long-term survival in a culturable state. Further, we demonstrated that both EPSs can be used as carbon source by E. amylovora under deprivation conditions. Overall, these previously unreported functions of amylovoran and levan provide survival advantages for E. amylovora, which could contribute to its enhanced persistence in nature.

  5. Rhinocerebral zygomycosis: an increasingly frequent challenge: update and favorable outcomes in two cases.

    PubMed

    Islam, Mohammed N; Cohen, Donald M; Celestina, Leslie J; Ojha, Junu; Claudio, Reinaldo; Bhattacharyya, Indraneel B

    2007-11-01

    Zygomycosis or mucormycosis is an increasingly frequent life-threatening infection caused by opportunistic fungal organisms of the class Zygomycetes. The pathognomonic feature is the presence of invasive aseptate mycelia that are larger than other filamentous fungi with the hyphae exhibiting right angle and haphazard branching. Usually classified as rhinocerebral, disseminated, and cutaneous types, this classification serves as important predictor of pathogenesis and outcome. These occur mostly in immunosuppressed patients including individuals with diabetes (43% exhibit the rhino-cerebral form) and patients with organ transplants and hematologic malignancies. Without early aggressive treatment, the disease follows a dismal and fatal course. The prognosis has not shown any appreciable change in the past 40 years with a stagnant mortality rate of 44%. We present 2 cases of rhinocerebral zygomycosis (RCZ), in a 58-year-old male and a 63-year-old female; both were poorly controlled diabetic patients with maxillary lesions suggestive of osteomyelitis. The patients were leading a near normal life with minimal discomfort or signs and symptoms of underlying mycosis. Most of the health care professionals treating these patients often overlooked the disease or recommended inadequate therapy. Despite long delays and inadequate initial therapy these patients survived with little outward morbidity. The prognosis for this condition may therefore be considered less dire than previously thought.

  6. Further evidence in favor of prior entry from endogenous attention to a location in space.

    PubMed

    Redden, Ralph S; d'Entremont, Ghislain; Klein, Raymond M

    2017-03-09

    Titchener's (1908) law of prior entry states that "the object of attention comes to consciousness more quickly than the objects which we are not attending to," or otherwise, that attended stimuli are perceived earlier than unattended stimuli. Shore, Spence, and Klein (Psychological Science, 12, 205-212. doi: 10.1111/1467-9280.00337 , 2001) showed that endogenous visuospatial orienting does in fact elicit prior-entry effects, albeit to a smaller degree than does exogenous visuospatial orienting. In disagreement with this finding, Schneider and Bavelier (Cognitive Psychology, 47, 333-366. doi: 10.1016/S0010-0285(03)00035-5 , 2003) found no effect of their instruction to attend. They concluded that nonattentional effects could masquerade as prior entry, which could account for findings such as those in Shore et al.'s endogenous condition. We investigated this empirical and theoretical discord by replicating the temporal-order judgment task used by Shore, Spence, and Klein, while manipulating and measuring endogenous orienting by way of an orthogonal color probe task. We showed evidence of prior entry as a consequence of endogenous orienting, supporting the conclusions of Shore, Spence, and Klein.

  7. Polling Students about Conditions of Learning

    ERIC Educational Resources Information Center

    Strom, Paris; Strom, Robert; Wing, Charlotte

    2008-01-01

    Online polling was examined as a procedure for decision makers to find out how students perceive conditions of learning at their school. Students in Grades 7-12 from eight schools completed online polls about learning on the Internet, time management, and tutoring. Principals favorably evaluated polling as a method for gathering information and…

  8. Heat Stress Reduces Intestinal Barrier Integrity and Favors Intestinal Glucose Transport in Growing Pigs

    PubMed Central

    Pearce, Sarah C.; Mani, Venkatesh; Boddicker, Rebecca L.; Johnson, Jay S.; Weber, Thomas E.; Ross, Jason W.; Rhoads, Robert P.; Baumgard, Lance H.; Gabler, Nicholas K.

    2013-01-01

    Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P = 0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na+/K+ ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P = 0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport. PMID:23936392

  9. Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum

    PubMed Central

    Prata, Rhana Berto da Silva; Barbosa, Mayara Garcia de Mattos; Mendes, Mayara Abud; Brandão, Sheila Santos; Amadeu, Thaís Porto; Rodrigues, Luciana Silva; Ferreira, Helen; Costa, Fabrício da Mota Ramalho; dos Santos, Jessica Brandão; Pacheco, Fabiana dos Santos; Machado, Alice de Miranda; Nery, José Augusto da Costa; Hacker, Mariana de Andrea; Sales, Anna Maria; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes

    2016-01-01

    Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates—a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably

  10. Autophagy Inhibition Favors Survival of Rubrospinal Neurons After Spinal Cord Hemisection.

    PubMed

    Bisicchia, Elisa; Latini, Laura; Cavallucci, Virve; Sasso, Valeria; Nicolin, Vanessa; Molinari, Marco; D'Amelio, Marcello; Viscomi, Maria Teresa

    2016-08-11

    Spinal cord injuries (SCIs) are devastating conditions of the central nervous system (CNS) for which there are no restorative therapies. Neuronal death at the primary lesion site and in remote regions that are functionally connected to it is one of the major contributors to neurological deficits following SCI.Disruption of autophagic flux induces neuronal death in many CNS injuries, but its mechanism and relationship with remote cell death after SCI are unknown. We examined the function and effects of the modulation of autophagy on the fate of axotomized rubrospinal neurons in a rat model of spinal cord dorsal hemisection (SCH) at the cervical level. Following SCH, we observed an accumulation of LC3-positive autophagosomes (APs) in the axotomized neurons 1 and 5 days after injury. Furthermore, this accumulation was not attributed to greater initiation of autophagy but was caused by a decrease in AP clearance, as demonstrated by the build-up of p62, a widely used marker of the induction of autophagy. In axotomized rubrospinal neurons, the disruption of autophagic flux correlated strongly with remote neuronal death and worse functional recovery. Inhibition of AP biogenesis by 3-methyladenine (3-MA) significantly attenuated remote degeneration and improved spontaneous functional recovery, consistent with the detrimental effects of autophagy in remote damage after SCH. Collectively, our results demonstrate that autophagic flux is blocked in axotomized neurons on SCI and that the inhibition of AP formation improves their survival. Thus, autophagy is a promising target for the development of therapeutic interventions in the treatment of SCIs.

  11. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  12. Visualization of turbulent wedges under favorable pressure gradients using shear-sensitive and temperature-sensitive liquid crystals.

    PubMed

    Chong, Tze-Pei; Zhong, Shan; Hodson, Howard P

    2002-10-01

    Turbulent wedges induced by a three-dimensional surface roughness placed on a flat plate were studied using both shear sensitive and temperature sensitive liquid crystals, respectively denoted by SSLC and TSLC. The experiments were carried out at a free-stream velocity of 28 m/sec at three different favorable pressure gradients. The purpose of this investigation was to examine the spreading angles of the turbulent wedges, as indicated by their associated surface shear stresses and heat transfer characteristics, and to obtain more insight about the behavior of transitional momentum and thermal boundary layers when a streamwise pressure gradient exists. It was shown that under a zero pressure gradient the spreading angles indicated by the two types of liquid crystals are the same, but the difference increases as the level of the favorable pressure gradient increases. The result from the present study is important for modelling the transition of thermal boundary layers over gas turbine blades.

  13. Favorable effect of rehabilitation on balance in ankylosing spondylitis: a quasi-randomized controlled clinical trial.

    PubMed

    Demontis, Alessandra; Trainito, Sabina; Del Felice, Alessandra; Masiero, Stefano

    2016-03-01

    Balance impairment is a frequent and undertreated manifestation in ankylosing spondylitis, leading to increased risk of falls and lower quality of life. Our aim was to assess supervised training and home-based rehabilitation efficacy on balance improvement in ankylosing spondylitis subjects on biologic agents. This was a single-blinded, quasi-randomized parallel study in a single outpatient Rehabilitation Clinic of a tertiary referral center. Subjects with ankylosing spondylitis on biologic agents were assigned either to supervised training and home-based rehabilitation program (rehabilitation group) plus educational-behavioral therapy, or to educational-behavioral therapy alone (educational groups). The same therapist provided therapy. Outcome measures were assessed at baseline (T0), end of treatment (T1) and at 7-month follow-up (T2). Rheumatologic outcomes were Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Disease Activity Index. Balance parameters (anterior-posterior oscillation, latero-lateral oscillation, sway area, sway density and sway path) were evaluated by stabilometry in a condition of open and closed eyes. Forty-six subjects (36 M, 10 F) were enrolled. Demographic data and clinical status at baseline were comparable between the two groups (22 rehabilitation group, 20 educational group). Primary outcome was sway density that improved both at T1 (SDy: open eyes p = 0.003, closed eyes p = 0.004) and at T2 (SDx: open eyes p = 0.0015, closed eyes p = 0.032). A trend toward improvement in the rehabilitation group rather than in the educational group emerged for balance parameters, especially those measured with closed eyes (0.004 < p < 0.048 at T1 and 0.004 < p < 0.036 at T2). Supervised training and home exercise lead to balance improvement in people with ankylosing spondylitis. Eyes-closed trials show a more marked trend toward improvement, and this may suggest a

  14. Predictive Factors of Survival and 6-Month Favorable Outcome of Very Severe Head Trauma Patients; a Historical Cohort Study

    PubMed Central

    Vathanalaoha, Karin; Oearsakul, Thakul; Tunthanathip, Thara

    2017-01-01

    Introduction: Very severe head trauma cases, defined as Glasgow Coma Scale (GCS) scores of less than 6, have a higher mortality rate and poorer outcome. The purpose of this study was to recognize factors associated with survival and 6-month favorable outcome of very severe head trauma patients presenting to emergency department. Methods: In this historical cohort study, the authors retrospectively reviewed medical records of head trauma patients who were admitted to the emergency department with post-resuscitation GCS scores of less than 6. Both univariate and multivariate analyses were used to test the association between various parameters with survival and 6-month outcome. Results: 103 cases with the mean age of 39 ± 16.5 years were studied (80% male). The overall survival rate was 41.7% and the rate of 6-month favorable outcome was 28.2%. In multivariate analysis, brisk pupil light reaction on admission and patent basal cistern on brain computed tomography (CT) scan were significant factors associated with both survival (OR 5.20, 95% CI 1.57-17.246, p = 0.007 and OR 3.65, 95% CI 1.22-10.91, p=0.02 respectively) and favorable outcome (OR 4.07, 95% CI 1.35-12.24, p=0.01 and OR 3.54, 95% CI 1.22-10.26, p 0.02), respectively. Conclusion: Based on the results of present study, the survival rate of patients with very severe head trauma (GCS < 6) was 41.7%. The strong predictors of survival and 6-month favorable outcome of these patients were brisk pupillary reactivity and patent cistern on brain CT scan. It seems that very severe head trauma patients still have a reasonable chance to survive and aggressive management should be continued. PMID:28286831

  15. When do college students have less favorable views of drinking? Evaluations of alcohol experiences and positive and negative consequences.

    PubMed

    Fairlie, Anne M; Ramirez, Jason J; Patrick, Megan E; Lee, Christine M

    2016-08-01

    College students experience numerous positive and negative consequences from drinking alcohol, although the extent to which these consequences influence perceptions of their drinking experiences is poorly understood. A better understanding of the impact of experiencing specific consequences, and how they are evaluated, on college students' perceptions of the overall drinking experience and subsequent alcohol use is crucial for advancing intervention efforts. The current study used daily data to examine (a) whether experiencing specific consequences and (b) whether ratings of the most favorable and most aversive consequences predicted overall evaluations of the drinking experience and perceptions that drinking was worth it; and (c) whether overall evaluations and perceptions that drinking was worth it predicted next-day drinking. College student drinkers (N = 349, 53.3% female) completed daily reports on drinking, consequences, evaluations of consequences, and evaluations of the drinking experience during four 2-week periods across 1 year. Findings from generalized estimating equations demonstrated that experiencing any of the positive consequences predicted more favorable overall evaluations and perceptions that drinking was worth it, whereas the majority of the negative consequences predicted less favorable overall evaluations. Ratings of the most favorable positive consequence and the most aversive negative consequence were also associated with overall evaluations. Perceiving that drinking was more worth it was associated with an increased likelihood of next-day drinking. Current findings reinforce the need to address the experience of both positive and negative consequences in interventions, while simultaneously considering the extent to which students perceived the negative consequences as aversive. (PsycINFO Database Record

  16. One-Step Targeted Minimum Loss-based Estimation Based on Universal Least Favorable One-Dimensional Submodels

    PubMed Central

    van der Laan, Mark; Gruber, Susan

    2016-01-01

    Consider a study in which one observes n independent and identically distributed random variables whose probability distribution is known to be an element of a particular statistical model, and one is concerned with estimation of a particular real valued pathwise differentiable target parameter of this data probability distribution. The targeted maximum likelihood estimator (TMLE) is an asymptotically efficient substitution estimator obtained by constructing a so called least favorable parametric submodel through an initial estimator with score, at zero fluctuation of the initial estimator, that spans the efficient influence curve, and iteratively maximizing the corresponding parametric likelihood till no more updates occur, at which point the updated initial estimator solves the so called efficient influence curve equation. In this article we construct a one-dimensional universal least favorable submodel for which the TMLE only takes one step, and thereby requires minimal extra data fitting to achieve its goal of solving the efficient influence curve equation. We generalize these to universal least favorable submodels through the relevant part of the data distribution as required for targeted minimum loss-based estimation. Finally, remarkably, given a multidimensional target parameter, we develop a universal canonical one-dimensional submodel such that the one-step TMLE, only maximizing the log-likelihood over a univariate parameter, solves the multivariate efficient influence curve equation. This allows us to construct a one-step TMLE based on a one-dimensional parametric submodel through the initial estimator, that solves any multivariate desired set of estimating equations. PMID:27227728

  17. Does Environmental Instability Favor the Production and Horizontal Transmission of Knowledge regarding Medicinal Plants? A Study in Southeast Brazil.

    PubMed

    Soldati, Gustavo Taboada; Hanazaki, Natália; Crivos, Marta; Albuquerque, Ulysses Paulino

    2015-01-01

    Greater socio-environmental instability favors the individual production of knowledge because innovations are adapted to new circumstances. Furthermore, instability stimulates the horizontal transmission of knowledge because this mechanism disseminates adapted information. This study investigates the following hypothesis: Greater socio-environmental instability favors the production of knowledge (innovation) to adapt to new situations, and socio-environmental instability stimulates the horizontal transmission of knowledge, which is a mechanism that diffuses adapted information. In addition, the present study describes "how", "when", "from whom" and the "stimulus/context", in which knowledge regarding medicinal plants is gained or transferred. Data were collected through semi-structured interviews from three groups that represented different levels of socio-environmental instability. Socio-environmental instability did not favor individual knowledge production or any cultural transmission modes, including vertical to horizontal, despite increasing the frequency of horizontal pathways. Vertical transmission was the most important knowledge transmission strategy in all of the groups in which mothers were the most common models (knowledge sources). Significantly, childhood was the most important learning stage, although learning also occurred throughout life. Direct teaching using language was notable as a knowledge transmission strategy. Illness was the main stimulus that triggered local learning. Learning modes about medicinal plants were influenced by the knowledge itself, particularly the dynamic uses of therapeutic resources.

  18. Does Environmental Instability Favor the Production and Horizontal Transmission of Knowledge regarding Medicinal Plants? A Study in Southeast Brazil

    PubMed Central

    Soldati, Gustavo Taboada; Hanazaki, Natália; Crivos, Marta; Albuquerque, Ulysses Paulino

    2015-01-01

    Greater socio-environmental instability favors the individual production of knowledge because innovations are adapted to new circumstances. Furthermore, instability stimulates the horizontal transmission of knowledge because this mechanism disseminates adapted information. This study investigates the following hypothesis: Greater socio-environmental instability favors the production of knowledge (innovation) to adapt to new situations, and socio-environmental instability stimulates the horizontal transmission of knowledge, which is a mechanism that diffuses adapted information. In addition, the present study describes “how”, “when”, “from whom” and the “stimulus/context”, in which knowledge regarding medicinal plants is gained or transferred. Data were collected through semi-structured interviews from three groups that represented different levels of socio-environmental instability. Socio-environmental instability did not favor individual knowledge production or any cultural transmission modes, including vertical to horizontal, despite increasing the frequency of horizontal pathways. Vertical transmission was the most important knowledge transmission strategy in all of the groups in which mothers were the most common models (knowledge sources). Significantly, childhood was the most important learning stage, although learning also occurred throughout life. Direct teaching using language was notable as a knowledge transmission strategy. Illness was the main stimulus that triggered local learning. Learning modes about medicinal plants were influenced by the knowledge itself, particularly the dynamic uses of therapeutic resources. PMID:25992578

  19. Steps to reduce favorable risk selection in medicare advantage largely succeeded, boding well for health insurance exchanges.

    PubMed

    Newhouse, Joseph P; Price, Mary; Huang, Jie; McWilliams, J Michael; Hsu, John

    2012-12-01

    Within Medicare, the Medicare Advantage program has historically attracted better risks-healthier, lower-cost patients-than has traditional Medicare. The disproportionate enrollment of lower-cost patients and avoidance of higher-cost ones during the 1990s-known as favorable selection-resulted in Medicare's spending more per beneficiary who enrolled in Medicare Advantage than if the enrollee had remained in traditional Medicare. We looked at two measures that can indicate whether favorable selection is taking place-predicted spending on beneficiaries and mortality-and studied whether policies that Medicare implemented in the past decade succeeded in reducing favorable selection in Medicare Advantage. We found that these policies-an improved risk adjustment formula and a prohibition on monthly disenrollment by beneficiaries-largely succeeded. Differences in predicted spending between those switching from traditional Medicare to Medicare Advantage relative to those who remained in traditional Medicare markedly narrowed, as did adjusted mortality rates. Because insurance exchanges set up under the Affordable Care Act will employ similar policies to combat risk selection, our results give reason for optimism about managing competition among health plans.

  20. A multi-criteria approach to identify favorable areas for goat production systems in Veracruz, México.

    PubMed

    Ramírez-Rivera, Emmanuel de Jesús; Lopez-Collado, Jose; Díaz-Rivera, Pablo; Ortega-Jiménez, Eusebio; Torres-Hernández, Glafiro; Jacinto-Padilla, Jazmín; Herman-Lara, Erasmo

    2017-04-01

    This research identifies favorable areas for goat production systems in the state of Veracruz, Mexico. Through the use of the analytic hierarchy process, layers of biophysical and soil information were combined to generate a model of favorability. Model validation was performed by calculating the area under the curve, the true skill statistic, and a qualitative comparison with census records. The results showed the existence of regions with high (4494.3 km(2)) and moderate (2985.8 km(2)) favorability, and these areas correspond to 6.25 and 4.15%, respectively, of the state territory and are located in the regions of Sierra de Huayacocotla, Perote, and Orizaba. These regions are characterized as mountainous and having predominantly temperate-wet or cold climates, and having montane mesophilic forests, containing pine, fir, and desert scrub. The reliability of the distribution model was supported by the area under the curve value (0.96), the true skill statistic (0.86), and consistency with census records.

  1. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    PubMed Central

    Muralidhar, Vinayak; Xiang, Michael; Orio, Peter F.; Martin, Neil E.; Beard, Clair J.; Feng, Felix Y.; Hoffman, Karen E.

    2016-01-01

    Purpose Recent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA < 10 ng/ml or T1c, Gleason 6, PSA > 20 ng/ml). Material and methods We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022). Conclusions Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease. PMID:26985191

  2. Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension and heart disease

    PubMed Central

    Yaghootkar, Hanieh; Lotta, Luca A.; Tyrrell, Jessica; Smit, Roelof A. J.; Jones, Sam E.; Donnelly, Louise; Beaumont, Robin; Campbell, Archie; Tuke, Marcus A.; Hayward, Caroline; Ruth, Katherine S.; Padmanabhan, Sandosh; Jukema, J. Wouter; Palmer, Colin C.; Hattersley, Andrew; Freathy, Rachel M.; Langenberg, Claudia; Wareham, Nicholas J.; Wood, Andrew R.; Murray, Anna; Weedon, Michael N.; Sattar, Naveed; Pearson, Ewan; Scott, Robert A.; Frayling, Timothy M.

    2017-01-01

    Recent genetic studies have identified some alleles associated with higher BMI but lower risk of type 2 diabetes, hypertension and heart disease. These “favorable adiposity” alleles are collectively associated with lower insulin levels and higher subcutaneous-to-visceral adipose tissue ratio and may protect from disease through higher adipose storage capacity. We aimed to use data from 164,609 individuals from the UK Biobank and five other studies to replicate associations between a genetic score of 11 favorable adiposity variants and adiposity and risk of disease, test for interactions between BMI and favorable adiposity genetics and test effects separately in men and women. In the UK Biobank the 50% of individuals carrying the most favorable adiposity alleles had higher BMIs (0.120 Kg/m2 [0.066,0.174]; p=1E-5) and higher body fat percentage (0.301 % [0.230,0.372]; p=1E-16) compared to the 50% of individuals carrying the fewest alleles. For a given BMI, the 50% of individuals carrying the most favourable adiposity alleles were at: 0.837 OR [0.784,0.894] lower risk of type 2 diabetes (p=1E-7), -0.859 mmHg [-1.099,-0.618] lower systolic (p=3E-12) and -0.394 mmHg [-0.534,-0.254] lower diastolic blood pressure (p=4E-8), 0.935 OR [0.911,0.958] lower risk of hypertension (p=1E-7) and 0.921 OR [0.872,0.973] lower risk of heart disease (p=3E-3). In women, these associations could be explained by the observation that the alleles associated with higher BMI but lower risk of disease were also associated with a favourable body fat distribution, with a lower waist-hip ratio (-0.004 [-0.005,-0.003] 50% vs 50%; p=3E-14) but in men, the favourable adiposity alleles were associated with higher waist circumference (0.454 cm [0.267,0.641] 50% vs 50%; p=2E-6) and higher waist-hip ratio (0.0013 [0.0003,0.0024] 50% vs 50%; p=0.01). Results were strengthened when meta-analysing with five additional studies. There was no evidence of interaction between a genetic score consisting of

  3. Vegetation-hydrology dynamics in complex terrain of semiarid areas: 2. Energy-water controls of vegetation spatiotemporal dynamics and topographic niches of favorability

    NASA Astrophysics Data System (ADS)

    Ivanov, Valeriy Y.; Bras, Rafael L.; Vivoni, Enrique R.

    2008-03-01

    Ecosystems of dry climates are a particularly interesting subject for ecohydrological studies, as water is generally considered to be the key limiting resource. This work focuses on vegetation-water-energy dynamics occurring on the complex terrain of a semiarid area characteristic of central New Mexico. The study employs a mechanistic model of coupled interactions to construct a set of numerical experiments carried out for two small-scale synthetic domains that exhibit particular hillslope curvatures. The linkages between terrain attributes and patterns of C4 grass productivity and water balance components are examined for three generic soil types. It is argued that in conditions of negligible moisture exchange, aspect and slope are the key determinants of both the hydrologic behavior and the degree of site "favorability" to vegetation. Certain topographic locations are more favorable to vegetation, as compared to a flat horizontal surface not influenced by lateral effects. These locations are associated with sites of northerly aspect with surface slopes within a narrow range of magnitudes. Contributions from both rainfall and radiation forcings are discussed to explain the existence of these topographic niches. The sensitivity of results is investigated by modifying the dominant mechanism of lateral water transfer. Two additional controlling topographic features are explored, corresponding to the contiguous and global terrain convergence levels. It is argued that their effects on vegetation-hydrology dynamics at a given location are characteristically superimposed with the impact of site-specific terrain attributes. Furthermore, the results lead to a conceptual relationship linking vegetation-hydrology quantities at different landscape locations.

  4. Lumpectomy Plus Tamoxifen or Anastrozole With or Without Whole Breast Irradiation in Women With Favorable Early Breast Cancer

    SciTech Connect

    Poetter, Richard . E-mail: Richard.Poetter@meduniwien.ac.at; Gnant, Michael; Kwasny, Werner; Tausch, Christoph; Handl-Zeller, Leonore; Pakisch, Brigitte; Taucher, Susanne; Hammer, Josef; Luschin-Ebengreuth, Gero; Schmid, Marianne; Kapp, Karin; Sedlmayer, Felix; Stierer, Michael; Reiner, Georg; Hofbauer, Friedrich; Rottenfusser, Andrea; Poestlberger, Sabine; Haider, Karin; Draxler, Wolfgang; Jakesz, Raimund

    2007-06-01

    Purpose: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. Methods and Material: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy {+-} boost (n 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. Results: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. Conclusion: Breast radiotherapy {+-} boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse.

  5. Application of a general boundary layer analysis to turbulent boundary layers subjected to strong favorable pressure gradients

    NASA Technical Reports Server (NTRS)

    Kreskovsky, J. P.; Shamroth, S. J.; Mcdonald, H.

    1975-01-01

    Theoretical predictions of turbulent boundary layer development under the influence of strong favorable pressure gradients made using a finite-difference calculation procedure are compared to experimental data. Comparisons are presented for low speed flows with and without wall heat transfer as well as for supersonic flows with adiabatic walls. The turbulence model used is governed by an integral form of the turbulence kinetic energy equation and the results are compared with predictions made using a conventional equilibrium turbulence model based upon Prandtl's mixing length, a Clauser-type eddy viscosity model used by Cebecci and Mosinskis, and a two-equation turbulence energy model of Launder and Jones.

  6. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors | Office of Cancer Genomics

    Cancer.gov

    We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations.

  7. Cervical neuroblastoma in eleven infants--a tumor with favorable prognosis. Clinical and radiologic (US, CT, MRI) findings.

    PubMed

    Abramson, S J; Berdon, W E; Ruzal-Shapiro, C; Stolar, C; Garvin, J

    1993-01-01

    Cervical neuroblastoma, a disease primarily of infants, has a favorable prognosis. Eleven patients are reported. Clinical presentations (other than mass) included stridor and swallowing problems. Masses when felt were commonly mistaken for infectious adenitis. Imaging studies (US, CT, MRI) showed solid masses with vascular displacement and narrowing; intraspinal extension was absent though extension into the adjacent sites of mediastinum and skull occurred. Horner syndrome was seen in five patients with accompanying heterochromia iridis in one. Five tumors had calcification. A high index of suspicion will lead to biopsy and less delay in diagnosis once a mass is felt or imaged.

  8. Considerations in the Diagnosis and Management of Pediatric Patients With Favorable Histology Wilms Tumor Who Present With Only Pulmonary Nodules.

    PubMed

    Green, Daniel M

    2016-04-01

    More than 70% of children with stage IV, favorable histology (FH) Wilms tumor will be relapse-free survivors 16 years after diagnosis. Successful treatment generally includes whole lung radiation therapy and doxorubicin. Such therapy is associated with adverse, long-term effects, including impaired pulmonary function, congestive heart failure, and second malignant neoplasms, especially breast cancer. Cooperative groups have adopted a risk-based approach to the treatment of these patients. It is important to recall the good overall prognosis for this group before recommendations for intensification are made based on preliminary data and in the absence of histological confirmation of persistent malignant disease.

  9. A Favorable Prognosis

    ERIC Educational Resources Information Center

    Stewart, Pearl

    2006-01-01

    Dr. Keith Amos' undying support for his undergrad alma mater, Xavier University of Louisiana, took an unusual turn last year in the aftermath of Hurricane Katrina. Amos, who graduated from Harvard Medical School after earning his bachelor's from Xavier, also served as a mentor and advisor for Xavier students whose plans for applying to medical…

  10. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer

    PubMed Central

    Yoo, So Young; Bang, Seo Young; Jeong, Su-Nam; Kang, Dae Hwan; Heo, Jeong

    2016-01-01

    Stem cell-like colon cancer cells (SCCs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. Oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on SCCs are not well studied yet. Here, we engineered a cancer-favoring oncolytic vaccinia virus (CVV) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing SCCs. CVV is an evolved Wyeth strain vaccinia virus (EVV) lacking the viral thymidine kinase. SCC models were established using human or mouse colon cancer spheres, which continuously expressed stemness markers. The cancer-favoring characteristics and different cytotoxic pathways for killing cancer cells successfully overrode general drug resistance, thereby killing colon cancer cells regardless of the presence of SCCs. Subcutaneously injected HT29 spheres showed lower growth in CVV-treated models than in 5-Fu-treated models. Intraperitoneally injected CT26 spheres induced tumor masses in the abdominal region. CVV-treated groups showed higher survival rates and smaller tumor mass formation, compared to 5-Fu-treated groups. Interestingly, the combined treatment of CVV with 5-Fu showed improved survival rates and complete suppression of tumor mass. The CVV developed in this study, thus, effectively suppresses SCCs, which can be synergistically enhanced by simultaneous treatment with the anticancer drug 5-Fu. Our novel CVV is highly advantageous as a next-generation therapeutic for treating colon cancer. PMID:26918725

  11. Coexpression of SFRP1 and WIF1 as a Prognostic Predictor of Favorable Outcomes in Patients with Colorectal Carcinoma

    PubMed Central

    Huang, Shiyong; Zhong, XiaoMing; Gao, Jun; Song, Rongfeng; Wu, Hongyu; Zi, Shuming; Yang, Shijie; Du, Peng; Cui, Long; Yang, Chun; Li, Zikang

    2014-01-01

    Colorectal tumorigenesis is ascribed to the activity of Wnt signaling pathway in a ligand-independent manner mainly through APC and CTNNB1 gene mutations and in a ligand-dependent manner through low expression of Wnt inhibitors such as WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 1 (SFRP1). In this study we found that WIF1 protein expression was increased and SFRP1 was decreased significantly in CRC tissue versus normal tissue, and high expression of WIF1 was associated with big tumor diameters and deep invasion, and loss of SFRP1 expression was associated with the left lesion site, deep invasion, and high TNM stage. Among the four expression patterns (WIF+/SFRP1+, WIF+/SFRP1−, WIF−/SFRP1+, and WIF−/SFRP1−) only coexpression of WIF1 and SFRP1 (WIF+/SFRP1+) was associated with favorable overall survival, together with low TNM stage, as an independent prognostic factor as shown in a multivariate survival model. The results indicated that WIF1 seemed to play an oncogenic role, while SFRP1 seemed to play an oncosuppressive role although both of them are secreted Wnt antagonists. Coexpression of SFRP1 and WIF1, rather than SFRP1 or WIF1 alone, could be used, together with low TNM stage, as a prognostic predictor of favorable outcomes in CRC. PMID:24949429

  12. Testing the directed dispersal hypothesis: are native ant mounds (Formica sp.) favorable microhabitats for an invasive plant?

    PubMed

    Berg-Binder, Moni C; Suarez, Andrew V

    2012-07-01

    Ant-mediated seed dispersal may be a form of directed dispersal if collected seeds are placed in a favorable microhabitat (e.g., in or near an ant nest) that increases plant establishment, growth, and/or reproduction relative to random locations. We investigated whether the native ant community interacts with invasive leafy spurge (Euphorbia esula) in a manner consistent with predictions of the directed dispersal hypothesis. Resident ants quickly located and dispersed 60% of experimentally offered E. esula seeds. Additionally, 40% of seeds whose final deposition site was observed were either brought inside or placed on top of an ant nest. Seed removal was 100% when seeds were placed experimentally on foraging trails of mound-building Formica obscuripes, although the deposition site of these seeds is unknown. Natural density and above-ground biomass of E. esula were greater on Formica mound edges compared to random locations. However, seedling recruitment and establishment from experimentally planted E. esula seeds was not greater on mound edges than random locations 3 m from the mound. Soil from Formica mound edges was greater in available nitrogen and available phosphorus relative to random soil locations 3 m from the mound. These results suggest Formica ant mounds are favorable microhabitats for E. esula growth following seedling establishment, a likely consequence of nutrient limitation during plant growth. The results also indicate positive species interactions may play an important role in biological invasions.

  13. Examining the Role of Abstainer Prototype Favorability as a Mediator of the Abstainer Norms-Drinking Behavior Relationship

    PubMed Central

    Litt, Dana M.; Lewis, Melissa A.

    2014-01-01

    Past research has indicated that peer influence is associated with risky health behaviors, such as alcohol and other substance use (e.g., Maxwell, 2002; Santor, Messevey, & Kusumakar, 2000). Specifically, research has indicated that believing that more of one's peers use alcohol predicts more favorable prototypes (risk images) of the typical alcohol user (Litt & Stock, 2011; Teunnisen et al., 2014). However, it is unclear if this same relationship would hold when considering abstainer (i.e. people who don't use alcohol) cognitions. The primary goal of the present study was to determine whether normative perceptions of peer abstinence from alcohol predict alcohol consumption, and whether this relationship is mediated by abstainer prototypes. Results from 2,095 college students (42% male) indicated that the relation between abstainer norms and drinking behavior was mediated by abstainer prototypes such that believing that more peers abstained from alcohol use predicted more favorable prototypes of the typical alcohol abstainer, which in turn predicted lower alcohol use. Results from this study provide important first steps to delineating the relationship between abstainer cognitions and alcohol use. PMID:25437152

  14. Localization of post-transplant lymphoproliferative disorders to the stomach might be associated with favorable outcome: a systematic review.

    PubMed

    Khedmat, Hossein; Ghamar-Chehreh, Mohammad Ebrahim; Amini, Mohsen; Agah, Shahram; Taheri, Saeed

    2014-03-01

    Gastric localization of post-transplant lymphoproliferative disorders (PTLDs) is very rare. In this study, we aimed to accumulate existing data in the current literature to reveal the clinical, histopathological and prognostic specificities associated with gastric PTLDs and to find the best treatment strategies in this patient population. A comprehensive search was conducted for the available data in the current literature using Pubmed and Google scholar search engines for reports on gastric PTLD in renal transplant recipients. Data of different studies were standardized and entered into a database and analyzed. No statistically significant difference was found between gastric and non-gastric PTLD. Gastric PTLD was relatively more prevalent in female patients (P = 0.08) and showed a trend toward better outcome (P = 0.1) and less metastasis (P = 0.07). Surgical intervention and rituximab therapy were associated with a more favorable outcome (17% mortality). Our study showed that organ transplant recipients having gastric PTLD develop metastasis less frequently and tend to have a relatively more favorable outcome. Prospective studies with larger patient populations are needed to confirm or modify our results.

  15. Pedagogical Conditions of Interethnic Relations Correction in Educational Environment

    ERIC Educational Resources Information Center

    Shibankova, Lyutsia A.; Dolganovskaya, Natalia V.; Ishmuradova, Alfiya M.; Matveeva, Elena S.; Vlasova, Tatiana; Chistyakov, Alexey A.

    2016-01-01

    The research urgency is conditioned by the strengthening of the role of educational institutions in the process of interaction between representatives of different cultures and religions, by the creation of favorable socio-psychological climate. Within the study of the educational environment, the authors identify its properties, conditioning the…

  16. Platelet-Rich Plasma Favors Proliferation of Canine Adipose-Derived Mesenchymal Stem Cells in Methacrylate-Endcapped Caprolactone Porous Scaffold Niches

    PubMed Central

    Rodríguez-Jiménez, Francisco Javier; Valdes-Sánchez, Teresa; Carrillo, José M.; Rubio, Mónica; Monleon-Prades, Manuel; García-Cruz, Dunia Mercedes; García, Montserrat; Cugat, Ramón; Moreno-Manzano, Victoria

    2012-01-01

    Osteoarticular pathologies very often require an implementation therapy to favor regeneration processes of bone, cartilage and/or tendons. Clinical approaches performed on osteoarticular complications in dogs constitute an ideal model for human clinical translational applications. The adipose-derived mesenchymal stem cells (ASCs) have already been used to accelerate and facilitate the regenerative process. ASCs can be maintained in vitro and they can be differentiated to osteocytes or chondrocytes offering a good tool for cell replacement therapies in human and veterinary medicine. Although ACSs can be easily obtained from adipose tissue, the amplification process is usually performed by a time consuming process of successive passages. In this work, we use canine ASCs obtained by using a Bioreactor device under GMP cell culture conditions that produces a minimum of 30 million cells within 2 weeks. This method provides a rapid and aseptic method for production of sufficient stem cells with potential further use in clinical applications. We show that plasma rich in growth factors (PRGF) treatment positively contributes to viability and proliferation of canine ASCs into caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) scaffolds. This biomaterial does not need additional modifications for cASCs attachment and proliferation. Here we propose a framework based on a combination of approaches that may contribute to increase the therapeutical capability of stem cells by the use of PRGF and compatible biomaterials for bone and connective tissue regeneration. PMID:24955632

  17. Platelet-rich plasma favors proliferation of canine adipose-derived mesenchymal stem cells in methacrylate-endcapped caprolactone porous scaffold niches.

    PubMed

    Rodríguez-Jiménez, Francisco Javier; Valdes-Sánchez, Teresa; Carrillo, José M; Rubio, Mónica; Monleon-Prades, Manuel; García-Cruz, Dunia Mercedes; García, Montserrat; Cugat, Ramón; Moreno-Manzano, Victoria

    2012-08-09

    Osteoarticular pathologies very often require an implementation therapy to favor regeneration processes of bone, cartilage and/or tendons. Clinical approaches performed on osteoarticular complications in dogs constitute an ideal model for human clinical translational applications. The adipose-derived mesenchymal stem cells (ASCs) have already been used to accelerate and facilitate the regenerative process. ASCs can be maintained in vitro and they can be differentiated to osteocytes or chondrocytes offering a good tool for cell replacement therapies in human and veterinary medicine. Although ACSs can be easily obtained from adipose tissue, the amplification process is usually performed by a time consuming process of successive passages. In this work, we use canine ASCs obtained by using a Bioreactor device under GMP cell culture conditions that produces a minimum of 30 million cells within 2 weeks. This method provides a rapid and aseptic method for production of sufficient stem cells with potential further use in clinical applications. We show that plasma rich in growth factors (PRGF) treatment positively contributes to viability and proliferation of canine ASCs into caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) scaffolds. This biomaterial does not need additional modifications for cASCs attachment and proliferation. Here we propose a framework based on a combination of approaches that may contribute to increase the therapeutical capability of stem cells by the use of PRGF and compatible biomaterials for bone and connective tissue regeneration.

  18. BMP-2, Hypoxia, and COL1A1/HtrA1 siRNAs Favor Neo-Cartilage Hyaline Matrix Formation in Chondrocytes

    PubMed Central

    Ollitrault, David; Legendre, Florence; Drougard, Carole; Briand, Mélanie; Benateau, Hervé; Goux, Didier; Chajra, Hanane; Poulain, Laurent; Hartmann, Daniel; Vivien, Denis; Shridhar, Vijayalakshmi; Baldi, Alfonso; Mallein-Gerin, Frédéric; Boumediene, Karim; Demoor, Magali

    2015-01-01

    Osteoarthritis (OA) is an irreversible pathology that causes a decrease in articular cartilage thickness, leading finally to the complete degradation of the affected joint. The low spontaneous repair capacity of cartilage prevents any restoration of the joint surface, making OA a major public health issue. Here, we developed an innovative combination of treatment conditions to improve the human chondrocyte phenotype before autologous chondrocyte implantation. First, we seeded human dedifferentiated chondrocytes into a collagen sponge as a scaffold, cultured them in hypoxia in the presence of a bone morphogenetic protein (BMP), BMP-2, and transfected them with small interfering RNAs targeting two markers overexpressed in OA dedifferentiated chondrocytes, that is, type I collagen and/or HtrA1 serine protease. This strategy significantly decreased mRNA and protein expression of type I collagen and HtrA1, and led to an improvement in the chondrocyte phenotype index of differentiation. The effectiveness of our in vitro culture process was also demonstrated in the nude mouse model in vivo after subcutaneous implantation. We, thus, provide here a new protocol able to favor human hyaline chondrocyte phenotype in primarily dedifferentiated cells, both in vitro and in vivo. Our study also offers an innovative strategy for chondrocyte redifferentiation and opens new opportunities for developing therapeutic targets. PMID:24957638

  19. No aging bias favoring memory for positive material: evidence from a heterogeneity-homogeneity list paradigm using emotionally toned words.

    PubMed

    Grühn, Daniel; Smith, Jacqui; Baltes, Paul B

    2005-12-01

    Some authors argue for a memory advantage of older adults for positively toned material. To investigate the contribution of selective processing to a positivity effect, the authors investigated young (n = 72, aged 18 to 31) and older (n = 72, aged 64 to 75) adults' memory for emotionally toned words using a multitrial paradigm that compares performance for heterogeneous (mixed valence) and homogeneous (single valence) lists. Regarding the age comparison, there was no evidence for an aging bias favoring positive material. Moreover, older adults' memory was less affected by emotion-based processing prioritization. Although there was no support for age-specific processing biases in memory for emotionally toned words, the findings are consistent with proposals that negative information receives processing priority in some contexts. Possible limits to the generalizability of the present findings (e.g., to nonverbal material) are discussed.

  20. Residual structure of Streptococcus mutans biofilm following complete disinfection favors secondary bacterial adhesion and biofilm re-development.

    PubMed

    Ohsumi, Tatsuya; Takenaka, Shoji; Wakamatsu, Rika; Sakaue, Yuuki; Narisawa, Naoki; Senpuku, Hidenobu; Ohshima, Hayato; Terao, Yutaka; Okiji, Takashi

    2015-01-01

    Chemical disinfection of oral biofilms often leaves biofilm structures intact. This study aimed to examine whether the residual structure promotes secondary bacterial adhesion. Streptococcus mutans biofilms generated on resin-composite disks in a rotating disc reactor were disinfected completely with 70% isopropyl alcohol, and were again cultured in the same reactor after resupplying with the same bacterial solution. Specimens were subjected to fluorescence confocal laser scanning microscopy, viable cell counts and PCR-Invader assay in order to observe and quantify secondarily adhered cells. Fluorescence microscopic analysis, particularly after longitudinal cryosectioning, demonstrated stratified patterns of viable cells on the disinfected biofilm structure. Viable cell counts of test specimens were significantly higher than those of controls, and increased according to the amount of residual structure and culture period. Linear regression analysis exhibited a high correlation between viable and total cell counts. It was concluded that disinfected biofilm structures favored secondary bacterial adhesion.

  1. The effect of sire selection on cow mortality and early lactation culling in adverse and favorable cow survival environments.

    PubMed

    Dechow, C D; Goodling, R C; Rhode, S P

    2012-02-01

    The objective of this study was to determine the extent that genetic selection can help reduce dairy cow mortality and early lactation culling in adverse cow survival environments. Two datasets were constructed. The first contained 100,911 mortality records and 171,178 sixty-day culling records from 1467 herds. Cows that left the herd (culled or died) from 21 days prior to a due date through 60 days in milk were considered a 60-day cull. Cows were classified as belonging to herds with adverse cow survival environments (≥ 4.4% mortality rate and ≥ 7.1% 60-day cull rate) or favorable cow survival environments (<4.4% mortality rate and <7.1% 60-day cull rate). The second dataset included 20,438 mortality records and 34,942 sixty-day culling records from 314 herds with a known herd management system. Cows from both datasets were stratified into quartiles based on their sire's predicted transmitting ability (PTA) for productive life and other traits. Cows in the first dataset were also stratified into high (>50th percentile) and low (≤ 50th percentile) groups based on their sire's PTA for daughter calving ease and daughter stillbirth rates. Mortality and 60-day culling in the first dataset were evaluated with logistic regression models with the independent effects of sire PTA quartile, cow survival environment (adverse or favorable), the interaction of sire PTA quartile with cow survival environment, lactation number, age within lactation number, and herd-calving-cluster. The second dataset was analyzed in the same manner, but with cow survival environment replaced by herd management system. The estimated proportion of lactations that ended in death declined from 9.0% to 6.8% and 60-day culling incidence from 7.6% to 4.9% as sire productive life PTA went from the lowest to highest quartile in adverse cow survival environments. The corresponding reduction in mortality (0.7%) and 60-day culling (0.9%) were also significant in favorable cow survival environments

  2. Favorable effects of VEGF gene transfer on a rat model of Parkinson disease using adeno-associated viral vectors.

    PubMed

    Tian, You-yong; Tang, Cui-Ju; Wang, Jia-ning; Feng, Yuan; Chen, Xiao-wu; Wang, Lan; Qiao, Xian; Sun, Sheng-gang

    2007-06-29

    Vascular endothelial growth factor (VEGF) is a specific angiogenic peptide, which has been identified to play a critical role in neurodegeneration, and has beneficial effects on neurons. In this study, we investigated whether neurodegeneration in a rat model of Parkinson disease could be prevented by VEGF gene transfer mediated by adeno-associated virus (AAV) vectors. Our results demonstrated that a single injection of a VEGF-expressing AAV vector into striatum improved the rotational behavior of rat Parkinson disease models, and promoted the survival of dopaminergic neurons and fibers. Meanwhile, AAV-VEGF injection significantly increased the reactive astrocytes and the levels of glial cell line-derived neurotrophic factor in striatum, but did not induce extra angiogenesis and remarkable disorder of blood-brain barrier. We thus conclude that intrastriatal delivery of VEGF gene mediated by AAV has favorable effects on the dopaminergic neurons in a rat Parkinson disease model.

  3. Indirect effects of habitat disturbance on invasion: nutritious litter from a grazing resistant plant favors alien over native Collembola

    PubMed Central

    Leinaas, Hans Petter; Bengtsson, Jan; Janion-Scheepers, Charlene; Chown, Steven L

    2015-01-01

    Biological invasions are major threats to biodiversity, with impacts that may be compounded by other forms of environmental change. Observations of high density of the invasive springtail (Collembola), Hypogastrura manubrialis in heavily grazed renosterveld vegetation in the Western Cape, South Africa, raised the question of whether the invasion was favored by changes in plant litter quality associated with habitat disturbance in this vegetation type. To examine the likely mechanisms underlying the high abundance of H. manubrialis, cages with three types of naturally occurring litter with different nutrient content were placed out in the area and collected after different periods of time. Hypogastrura manubrialis was mainly found in the nutrient-rich litter of the yellowbush (Galenia africana), which responds positively to disturbance in the form of overgrazing. This suggests that invasion may have been facilitated by a positive interaction with this grazing resistant plant. By contrast, indigenous Collembola were least abundant in yellowbush litter. Negative correlations between high abundance of H. manubrialis and the abundance and diversity of other species suggest that competitive interactions might underlie low abundance of these other species at the patch level. Group behavior enables H. manubrialis to utilize efficiently this ephemeral, high quality resource, and might improve its competitive ability. The results suggest that interactions among environmental change drivers may lead to unforeseen invasion effects. H. manubrialis is not likely to be very successful in un-grazed renosterveld, but in combination with grazing, favoring the nutrient-rich yellowbush, it may become highly invasive. Field manipulations are required to fully verify these conclusions. PMID:26380678

  4. Indirect effects of habitat disturbance on invasion: nutritious litter from a grazing resistant plant favors alien over native Collembola.

    PubMed

    Leinaas, Hans Petter; Bengtsson, Jan; Janion-Scheepers, Charlene; Chown, Steven L

    2015-08-01

    Biological invasions are major threats to biodiversity, with impacts that may be compounded by other forms of environmental change. Observations of high density of the invasive springtail (Collembola), Hypogastrura manubrialis in heavily grazed renosterveld vegetation in the Western Cape, South Africa, raised the question of whether the invasion was favored by changes in plant litter quality associated with habitat disturbance in this vegetation type. To examine the likely mechanisms underlying the high abundance of H. manubrialis, cages with three types of naturally occurring litter with different nutrient content were placed out in the area and collected after different periods of time. Hypogastrura manubrialis was mainly found in the nutrient-rich litter of the yellowbush (Galenia africana), which responds positively to disturbance in the form of overgrazing. This suggests that invasion may have been facilitated by a positive interaction with this grazing resistant plant. By contrast, indigenous Collembola were least abundant in yellowbush litter. Negative correlations between high abundance of H. manubrialis and the abundance and diversity of other species suggest that competitive interactions might underlie low abundance of these other species at the patch level. Group behavior enables H. manubrialis to utilize efficiently this ephemeral, high quality resource, and might improve its competitive ability. The results suggest that interactions among environmental change drivers may lead to unforeseen invasion effects. H. manubrialis is not likely to be very successful in un-grazed renosterveld, but in combination with grazing, favoring the nutrient-rich yellowbush, it may become highly invasive. Field manipulations are required to fully verify these conclusions.

  5. Preoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer.

    PubMed

    Zhang, Jian; Huang, Shao-Hong; Li, Hui; Li, Yun; Chen, Xiu-Ling; Zhang, Wei-Qing; Chen, Hui-Guo; Gu, Li-Jia

    2013-03-01

    Recently, the prognostic value of cancer-related inflammatory response has been revealed. Previous studies showed that peripheral neutrophils and lymphocytes had significant impact on the prognosis of advanced and early-node-negative non-small-cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic value of preoperative lymphocyte and neutrophil counts in patients with NSCLC who underwent lobectomy and lymph node dissection and adjuvant chemotherapy. Retrospective analyses were performed to examine the impact of preoperative peripheral lymphocyte and neutrophil counts on disease-free survival (DFS) and overall survival (OS) and to analyze the relationships of these factors to clinicopathological factors. A total of 142 patients with NSCLC were evaluated of which 57 (40.1 %) patients had local recurrence or metastasis. Multivariate analyses revealed that peripheral lymphocyte count was an independent favorable prognostic factor of DFS (hazard ratio 0.548; 95 % confidence interval 0.351-0.857; P = 0.008) but not OS (P = 0.164). The maximum logrank statistical value was 9.504 (P = 0.002) when the cutoff value of lymphocyte was 1,800 mm(-3). The median DFS was 318.0 days (95 % confidence interval 226.0-410.0) for lymphocyte ≤1,800 mm(-3) group and 669.0 days (95 % confidence interval 0.0-1,431.0) for lymphocyte >1,800 mm(-3) group. Low lymphocyte count was related with lymphatic invasion (P = 0.012) and recurrence of NSCLC (P = 0.022). Peripheral neutrophil count had no impact on DFS or OS when analysis included all the 142 patients. Preoperative peripheral lymphocyte count, which is related with lymphatic invasion, is an independent favorable prognostic factor of DFS in patients with NSCLC who underwent lobectomy and lymph node dissection and adjuvant chemotherapy.

  6. Factors favoring regain of the lost vertical spinal height through posterior spinal fusion in adolescent idiopathic scoliosis

    PubMed Central

    Shi, Benlong; Mao, Saihu; Xu, Leilei; Sun, Xu; Liu, Zhen; Zhu, Zezhang; Lam, Tsz Ping; Cheng, Jack CY; Ng, Bobby; Qiu, Yong

    2016-01-01

    Height gain is a common beneficial consequence following correction surgery in adolescent idiopathic scoliosis (AIS), yet little is known concerning factors favoring regain of the lost vertical spinal height (SH) through posterior spinal fusion. A consecutive series of AIS patients from February 2013 to August 2015 were reviewed. Surgical changes in SH (ΔSH), as well as the multiple coronal and sagittal deformity parameters were measured and correlated. Factors associated with ΔSH were identified through Pearson correlation analysis and multivariate regression analysis. A total of 172 single curve and 104 double curve patients were reviewed. The ΔSH averaged 2.5 ± 0.9 cm in single curve group and 2.9 ± 1.0 cm in double curve group. The multivariate regression analysis revealed the following pre-operative variables contributed significantly to ΔSH: pre-op Cobb angle, pre-op TK (single curve group only), pre-op GK (double curve group only) and pre-op LL (double curve group only) (p < 0.05). Thus change in height (in cm) = 0.044 × (pre-op Cobb angle) + 0.012 × (pre-op TK) (Single curve, adjusted R2 = 0.549) or 0.923 + 0.021 × (pre-op Cobb angle1) + 0.028 × (pre-op Cobb angle2) + 0.015 × (pre-op GK)-0.012 × (pre-op LL) (Double curve, adjusted R2 = 0.563). Severer pre-operative coronal Cobb angle and greater sagittal curves were beneficial factors favoring more contribution to the surgical lengthening effect in vertical spinal height in AIS. PMID:27373798

  7. Detection of Favorable QTL Alleles and Candidate Genes for Lint Percentage by GWAS in Chinese Upland Cotton.

    PubMed

    Su, Junji; Fan, Shuli; Li, Libei; Wei, Hengling; Wang, Caixiang; Wang, Hantao; Song, Meizhen; Zhang, Chi; Gu, Lijiao; Zhao, Shuqi; Mao, Guangzhi; Wang, Chengshe; Pang, Chaoyou; Yu, Shuxun

    2016-01-01

    Improving cotton yield is a major breeding goal for Chinese upland cotton. Lint percentage is an important yield component and a critical economic index for cotton cultivars, and raising the lint percentage has a close relationship to improving cotton lint yield. To investigate the genetic architecture of lint percentage, a diversity panel consisting of 355 upland cotton accessions was grown, and the lint percentage was measured in four different environments. Genotyping was performed with specific-locus amplified fragment sequencing (SLAF-seq). Twelve single-nucleotide polymorphisms (SNPs) associated with lint percentage were detected via a genome-wide association study (GWAS), in which five SNP loci distributed on chromosomes At3 (A02) and At4 (A08) and contained two major-effect QTLs, which were detected in the best linear unbiased predictions (BLUPs) and in more than three environments simultaneously. Furthermore, favorable haplotypes (FHs) of two major-effect QTLs and 47 putative candidate genes in the two linkage disequilibrium (LD) blocks of these associated loci were identified. The expression levels of these putative candidate genes were estimated using RNA-seq data from ten upland cotton tissues. We found that Gh_A02G1268 was very highly expressed during the early fiber development stage, whereas the gene was poorly expressed in the seed. These results implied that Gh_A02G1268 may determine the lint percentage by regulating seed and fiber development. The favorable QTL alleles and candidate genes for lint percentage identified in this study will have high potential for improving lint yield in future Chinese cotton breeding programs.

  8. Detection of Favorable QTL Alleles and Candidate Genes for Lint Percentage by GWAS in Chinese Upland Cotton

    PubMed Central

    Su, Junji; Fan, Shuli; Li, Libei; Wei, Hengling; Wang, Caixiang; Wang, Hantao; Song, Meizhen; Zhang, Chi; Gu, Lijiao; Zhao, Shuqi; Mao, Guangzhi; Wang, Chengshe; Pang, Chaoyou; Yu, Shuxun

    2016-01-01

    Improving cotton yield is a major breeding goal for Chinese upland cotton. Lint percentage is an important yield component and a critical economic index for cotton cultivars, and raising the lint percentage has a close relationship to improving cotton lint yield. To investigate the genetic architecture of lint percentage, a diversity panel consisting of 355 upland cotton accessions was grown, and the lint percentage was measured in four different environments. Genotyping was performed with specific-locus amplified fragment sequencing (SLAF-seq). Twelve single-nucleotide polymorphisms (SNPs) associated with lint percentage were detected via a genome-wide association study (GWAS), in which five SNP loci distributed on chromosomes At3 (A02) and At4 (A08) and contained two major-effect QTLs, which were detected in the best linear unbiased predictions (BLUPs) and in more than three environments simultaneously. Furthermore, favorable haplotypes (FHs) of two major-effect QTLs and 47 putative candidate genes in the two linkage disequilibrium (LD) blocks of these associated loci were identified. The expression levels of these putative candidate genes were estimated using RNA-seq data from ten upland cotton tissues. We found that Gh_A02G1268 was very highly expressed during the early fiber development stage, whereas the gene was poorly expressed in the seed. These results implied that Gh_A02G1268 may determine the lint percentage by regulating seed and fiber development. The favorable QTL alleles and candidate genes for lint percentage identified in this study will have high potential for improving lint yield in future Chinese cotton breeding programs. PMID:27818672

  9. A comparison of two parasitoids (Hymenoptera: Encyrtidae) of the vine mealybug: rapid, non-discriminatory oviposition is favored when ants tend the host.

    PubMed

    Sime, Karen R; Daane, Kent M

    2014-08-01

    The encyrtid parasitoids Coccidoxenoides perminutus Girault and Anagyrus nr. sp. pseudococci (Girault) were compared in the laboratory as parasitoids of the mealybug Planococcus ficus (Signoret). Female C. perminutus preferred second-instar P. ficus for oviposition, and produced more adult offspring (149.3 per female) than A. nr. sp. pseudococci (54.1 per female). The development time, from egg to adult emergence, of C. perminutus decreased with increasing constant temperatures between 18.5 and 30.1°C; at lower (12.0 and 15.0°C) and higher (31.1, 32.7, and 34.2°C) temperatures, the parasitoid did not develop. The lower threshold was calculated by linear methods to be 10.97°C, and the thermal constant was calculated to be 507.98 degree-days. The development times of C. perminutus were longer than those of A. nr. sp. pseudococci, and C. perminutus had narrower temperature tolerances than P. ficus or A. pseudococci. Argentine ants (Linepithema humile (Mayr)) reduced the amount of time C. perminutus foraged on mealybug-infested squash, but did not affect the number of oviposition attempts or offspring produced, whereas Argentine ants reduced A. nr. sp. pseudococci foraging time, oviposition attempts, and number of offspring obtained. Overall, the results suggest that under certain conditions, including optimal conditions of temperature and host-stage availability, C. perminutus outperforms A. nr. sp. pseudococci, and may be an effective augmentative control agent even when ants are tending the hosts. However, temperature limitations and host-stage selection behaviors would reduce C. perminutus performance in the field, and in the absence of ants, other parasitoids may be favored.

  10. LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

    PubMed Central

    2012-01-01

    Background Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. Methods A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. Results We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Conclusion Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration. PMID:23039186

  11. Phlebotominae fauna (Diptera: Psychodidae) in an urban district of Belo Horizonte, Brazil, endemic for visceral leishmaniasis: characterization of favored locations as determined by spatial analysis.

    PubMed

    Saraiva, Lara; Andrade Filho, José Dilermando; Falcão, Alda Lima; de Carvalho, Deborah Aparecida Alves; de Souza, Carina Margonari; Freitas, Christian Rezende; Gomes Lopes, Camila Ragonezi; Moreno, Elizabeth Castro; Melo, Maria Norma

    2011-02-01

    Belo Horizonte, the capital of the southeastern state of Minas Gerais, Brazil, and the fourth-largest city in the country, has the highest incidence of human visceral leishmaniasis (VL) together with a high prevalence of canine VL. The Northeast Sanitary District (NSD) of Belo Horizonte has the largest historical average of human VL cases in the metropolitan region, and is classified as a priority area for epidemiological and entomological monitoring of the disease. The objectives of the present study were to determine the seasonal variation in phlebotomine fauna and to describe the environmental situations in the NSD through characterization of peri-domiciles and application of geographical information system analysis. Entomological captures were performed every two weeks during the period July 2006 to June 2007 using HP light traps placed at 16 locations where cases of human VL had been reported in 2005. The environmental characterization of these locations was accomplished using forms and photographic images. Spatial analyses was used to determine the influence of vegetation, hydrography, altitude and pockets of poverty on the occurrence of cases of human and canine VL, and of phlebotomine vectors. A total of 633 phlebotomines belonging to the subtribes Psychodopygina and Lutzomyina were captured and, of these, 75% were identified as Nyssomyia whitmani and 11% as Lutzomyia longipalpis. The majority of the studied peri-domiciles presented inadequate hygienic conditions that would favor the development of phlebotomines. No significant correlations could be established between biogeographical aspects and either the incidence of human and canine VL or the occurrence of phlebotomines. The proximity of areas with vegetation, villages, slums and open watercourses exerted little influence on the incidence of VL. These findings reinforce the urbanization of the VL profile since the disease occurred in locations where conditions that have been classically related to its

  12. Isolation and Characterization of Microbes Mediating Thermodynamically Favorable Coupling of Anaerobic Oxidation of Methane and Metal Reduction

    NASA Astrophysics Data System (ADS)

    Glass, J. B.; Reed, B. C.; Sarode, N. D.; Kretz, C. B.; Bray, M. S.; DiChristina, T. J.; Stewart, F. J.; Fowle, D. A.; Crowe, S.

    2014-12-01

    Methane is the third most reduced environmentally relevant electron donor for microbial metabolisms after organic carbon and hydrogen. In anoxic ecosystems, the major sink for methane is anaerobic oxidation of methane (AOM) mediated by syntrophic microbial consortia that couple AOM to reduction of an oxidized electron acceptor to yield free energy. In marine sediments, AOM is generally coupled to reduction of sulfate despite an extremely small amount of free energy yield because sulfate is the most abundant electron acceptor in seawater. While AOM coupled to Fe(III) and Mn(IV) reduction (Fe- and Mn-AOM) is 10-30x more thermodynamically favorable than sulfate-AOM, and geochemical data suggests that it occurs in diverse environments, the microorganisms mediating Fe- and Mn-AOM remain unknown. Lake Matano, Indonesia is an ideal ecosystem to enrich for Fe- and Mn-AOM microbes because its anoxic ferruginous deep waters and sediments contain abundant Fe(III), Mn(IV) and methane, and extremely low sulfate and nitrate. Our research aims to isolate and characterize the microbes mediating Fe- and Mn-AOM from three layers of Lake Matano sediments through serial enrichment cultures in minimal media lacking nitrate and sulfate. 16S rRNA amplicon sequencing of sediment inoculum revealed the presence of the Fe(III)-reducing bacterium Geobacter (5-10% total microbial community in shallow sediment and 35-60% in deeper sediment) as well as 1-2% Euryarchaeota implicated in methane cycling, including ANME-1 and 2d and Methanosarcinales. After 90 days of primary enrichment, all three sediment layers showed high levels of Fe(III) reduction (60-90 μM Fe(II) d-1) in the presence of methane compared to no methane and heat-killed controls. Treatments with added Fe(III) as goethite contained higher abundances of Geobacter than the inoculum (60-80% in all layers), suggesting that Geobacter may be mediating Fe(III) reduction in these enrichments. Quantification of AOM rates is underway, and

  13. High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

    SciTech Connect

    Barkati, Maroie; Williams, Scott G.; Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat; Dyk, Sylvia van; See, Andrew; Duchesne, Gillian M.

    2012-04-01

    Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

  14. Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer

    PubMed Central

    Tosoian, Jeffrey J.; Mamawala, Mufaddal; Epstein, Jonathan I.; Landis, Patricia; Wolf, Sacha; Trock, Bruce J.; Carter, H. Ballentine

    2015-01-01

    Purpose To assess long-term outcomes of men with favorable-risk prostate cancer in a prospective, active-surveillance program. Methods Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy. Primary outcomes were overall, cancer-specific, and metastasis-free survival. Secondary outcomes were the cumulative incidence of reclassification and curative intervention. Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model. Results A total of 1,298 men (median age, 66 years) with a median follow-up of 5 years (range, 0.01 to 18.00 years) contributed 6,766 person-years of follow-up since 1995. Overall, cancer-specific, and metastasis-free survival rates were 93%, 99.9%, and 99.4%, respectively, at 10 years and 69%, 99.9%, and 99.4%, respectively, at 15 years. The cumulative incidence of grade reclassification was 26% at 10 years and was 31% at 15 years; cumulative incidence of curative intervention was 50% at 10 years and was 57% at 15 years. The median treatment-free survival was 8.5 years (range, 0.01 to 18 years). Factors associated with grade reclassification were older age (hazard ratio [HR], 1.03 for each additional year; 95% CI, 1.01 to 1.06), prostate-specific antigen density (HR, 1.21 per 0.1 unit increase; 95% CI, 1.12 to 1.46), and greater number of positive biopsy cores (HR, 1.47 for each additional positive core; 95% CI, 1.26 to 1.69). Factors associated with intervention were prostate-specific antigen density (HR, 1.38 per 0.1 unit increase; 95% CI, 1.22 to 1.56) and a greater number of positive biopsy cores (HR, 1.35 for one additional positive core; 95% CI, 1.19 to 1.53). Conclusion Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention. PMID:26324359

  15. YMO1 suppresses invasion and metastasis by inhibiting RhoC signaling and predicts favorable prognosis in hepatocellular carcinoma

    PubMed Central

    Chang, Rui-Min; Pei, Lei; Fang, Feng; Xu, Jiang-Feng; Yang, Hao; Zuo, Chao-Hui; Zhou, Jian-Hua; Luo, Geng-Qiu; Yang, Lian-Yue

    2016-01-01

    Previous studies have shown that 4.1 proteins, which are deregulated in many cancers, contribute to cell adhesion and motility. Yurt/Mosaic eyes-like 1 (YMO1) is a member of 4.1 protein family but it is unclear whether YMO1 plays a role in tumor invasion. This study aimed to investigate the effects of YMO1 on hepatocellular carcinoma (HCC) and attempted to elucidate the underlying molecular mechanisms. YMO1 expression in HCC tissues and its correlation with clinicopathological features and postoperative prognosis was analyzed. The results showed that YMO1 was down-regulated in the highly metastatic HCC cell line and in human tumor tissues. Underexpression of YMO1 indicated poor prognosis of HCC patients. Restoration of YMO1 expression caused a significant decrease in cell migration and invasiveness in vitro. In vivo study showed that YMO1 reduced liver tumor invasion and metastasis in xenograft mice. YMO1 directly inhibited RhoC activation. YMO1 expression in HCC was regulated by PAX5. Analysis of YMO1 expression levels in human HCC patients revealed a significant correlation of YMO1 expression with PAX5 and RhoC. Our findings revealed that YMO1 predicts favorable prognosis and the data suggest that YMO1 suppresses tumor invasion and metastasis by inhibiting RhoC activity. PMID:27487132

  16. Danish Holsteins Favor Bull Offspring: Biased Milk Production as a Function of Fetal Sex, and Calving Difficulty

    PubMed Central

    Græsbøll, Kaare; Kirkeby, Carsten; Nielsen, Søren Saxmose; Christiansen, Lasse Engbo

    2015-01-01

    In a previous study from 2014 it was found that US Holstein cows that gave birth to heifer calves produced more milk than cows having bull calves. We wanted to assess whether this is also true for Danish cattle. Data from 578 Danish Holstein herds were analysed with a mixed effect model and contrary to the findings in the US, we found that cows produced higher volumes of milk if they had a bull calf compared to a heifer calf. We found a significantly higher milk production of 0.28% in the first lactation period for cows giving birth to a bull calf, compared to a heifer calf. This difference was even higher when cows gave birth to another bull calf, so having two bull calves resulted in a difference of 0.52% in milk production compared to any other combination of sex of the offspring. Furthermore, we found that farmer assisted calvings were associated with a higher milk yield. Cows with no farmer assistance or with veterinary assistance during the most recent calving produced less milk. There were also indications that dams would favor a bull fetus by decreasing milk production during the second pregnancy if the calf born in the first parity was a heifer. We hypothesize that size of calves is a confounding factor for milk production. However, calving weight was not available in the present data set to test this hypothesis. PMID:25874441

  17. A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis.

    PubMed

    Guo, Qiu; Sahoo, Soumya P; Wang, Pei-Ran; Milot, Denise P; Ippolito, Marc C; Wu, Margaret S; Baffic, Joanne; Biswas, Chhabi; Hernandez, Melba; Lam, My-Hanh; Sharma, Neelam; Han, Wei; Kelly, Linda J; MacNaul, Karen L; Zhou, Gaochao; Desai, Ranjit; Heck, James V; Doebber, Thomas W; Berger, Joel P; Moller, David E; Sparrow, Carl P; Chao, Yu-Sheng; Wright, Samuel D

    2004-04-01

    Patients with type 2 diabetes mellitus exhibit hyperglycemia and dyslipidemia as well as a markedly increased incidence of atherosclerotic cardiovascular disease. Here we report the characterization of a novel arylthiazolidinedione capable of lowering both glucose and lipid levels in animal models. This compound, designated TZD18, is a potent agonist with dual human peroxisome proliferator-activated receptor (PPAR)-alpha/gamma activities. In keeping with its PPARgamma activity, TZD18 caused complete normalization of the elevated glucose in db/db mice and Zucker diabetic fatty rats. TZD18 lowered both cholesterol and triglycerides in hamsters and dogs. TZD18 inhibited cholesterol biosynthesis at steps before mevalonate and reduced hepatic levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Moreover, TZD18 significantly suppressed gene expression of fatty acid synthesis and induced expression of genes for fatty acid degradation and triglyceride clearance. Studies on 17 additional PPARalpha or PPARalpha/gamma agonists showed that lipid lowering in hamsters correlated with the magnitude of hepatic gene expression changes. Importantly, the presence of PPARgamma agonism did not affect the relationship between hepatic gene expression and lipid lowering. Taken together, these data suggest that PPARalpha/gamma agonists, such as TZD18, affect lipid homeostasis, leading to an antiatherogenic plasma lipid profile. Agents with these properties may provide favorable means for treatment of type 2 diabetes and dyslipidemia and the prevention of atherosclerotic cardiovascular disease.

  18. Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome.

    PubMed

    Martínez-Trillos, Alejandra; Pinyol, Magda; Navarro, Alba; Aymerich, Marta; Jares, Pedro; Juan, Manel; Rozman, María; Colomer, Dolors; Delgado, Julio; Giné, Eva; González-Díaz, Marcos; Hernández-Rivas, Jesús M; Colado, Enrique; Rayón, Consolación; Payer, Angel R; Terol, Maria José; Navarro, Blanca; Quesada, Victor; Puente, Xosé S; Rozman, Ciril; López-Otín, Carlos; Campo, Elías; López-Guillermo, Armando; Villamor, Neus

    2014-06-12

    Mutations in Toll-like receptor (TLR) and myeloid differentiation primary response 88 (MYD88) genes have been found in chronic lymphocytic leukemia (CLL) at low frequency. We analyzed the incidence, clinicobiological characteristics, and outcome of patients with TLR/MYD88 mutations in 587 CLL patients. Twenty-three patients (3.9%) had mutations, 19 in MYD88 (one with concurrent IRAK1 mutation), 2 TLR2 (one with concomitant TLR6 mutation), 1 IRAK1, and 1 TLR5. No mutations were found in IRAK2 and IRAK4. TLR/MYD88-mutated CLL overexpressed genes of the nuclear factor κB pathway. Patients with TLR/MYD88 mutations were significantly younger (83% age ≤50 years) than those with no mutations. TLR/MYD88 mutations were the most frequent in young patients. Patients with mutated TLR/MYD88 CLL had a higher frequency of mutated IGHV and low expression of CD38 and ZAP-70. Overall survival (OS) was better in TLR/MYD88-mutated than unmutated patients in the whole series (10-year OS, 100% vs 62%; P = .002), and in the subset of patients age ≤50 years (100% vs 70%; P = .02). In addition, relative OS of TLR/MYD88-mutated patients was similar to that in the age- and gender-matched population. In summary, TLR/MYD88 mutations identify a population of young CLL patients with favorable outcome.

  19. The effect of iconicity of visual displays on statistical reasoning: evidence in favor of the null hypothesis.

    PubMed

    Sirota, Miroslav; Kostovičová, Lenka; Juanchich, Marie

    2014-08-01

    Knowing which properties of visual displays facilitate statistical reasoning bears practical and theoretical implications. Therefore, we studied the effect of one property of visual diplays - iconicity (i.e., the resemblance of a visual sign to its referent) - on Bayesian reasoning. Two main accounts of statistical reasoning predict different effect of iconicity on Bayesian reasoning. The ecological-rationality account predicts a positive iconicity effect, because more highly iconic signs resemble more individuated objects, which tap better into an evolutionary-designed frequency-coding mechanism that, in turn, facilitates Bayesian reasoning. The nested-sets account predicts a null iconicity effect, because iconicity does not affect the salience of a nested-sets structure-the factor facilitating Bayesian reasoning processed by a general reasoning mechanism. In two well-powered experiments (N = 577), we found no support for a positive iconicity effect across different iconicity levels that were manipulated in different visual displays (meta-analytical overall effect: log OR = -0.13, 95% CI [-0.53, 0.28]). A Bayes factor analysis provided strong evidence in favor of the null hypothesis-the null iconicity effect. Thus, these findings corroborate the nested-sets rather than the ecological-rationality account of statistical reasoning.

  20. FADO: a statistical method to detect favored or avoided distances between occurrences of motifs using the Hawkes' model.

    PubMed

    Gusto, Gaelle; Schbath, Sophie

    2005-01-01

    We propose an original statistical method to estimate how the occurrences of a given process along a genome, genes or motifs for instance, may be influenced by the occurrences of a second process. More precisely, the aim is to detect avoided and/or favored distances between two motifs, for instance, suggesting possible interactions at a molecular level. For this, we consider occurrences along the genome as point processes and we use the so-called Hawkes' model. In such model, the intensity at position t depends linearly on the distances to past occurrences of both processes via two unknown profile functions to estimate. We perform a non parametric estimation of both profiles by using B-spline decompositions and a constrained maximum likelihood method. Finally, we use the AIC criterion for the model selection. Simulations show the excellent behavior of our estimation procedure. We then apply it to study (i) the dependence between gene occurrences along the E. coli genome and the occurrences of a motif known to be part of the major promoter for this bacterium, and (ii) the dependence between the yeast S. cerevisiae genes and the occurrences of putative polyadenylation signals. The results are coherent with known biological properties or previous predictions, meaning this method can be of great interest for functional motif detection, or to improve knowledge of some biological mechanisms.

  1. Hepatitis C virus strategies to evade the specific-T cell response: a possible mission favoring its persistence.

    PubMed

    Quarleri, Jorge Fabián; Oubiña, José Raúl

    2016-01-01

    Hepatitis C virus (HCV) is a small, enveloped RNA virus. The number of HCV-infected individuals worldwide is estimated to be approximately 200 million. The vast majority of HCV infections persist, with up to 80% of all cases leading to chronic hepatitis associated with liver fibrosis, cirrhosis, and hepatocellular carcinoma. The interaction between HCV and the host have a pivotal role in viral fitness, persistence, pathogenicity, and disease progression. The control of HCV infection requires both effective innate and adaptive immune responses. The HCV clearance during acute infection is associated with an early induction of the innate and a delayed initiation of the adaptive immune responses. However, in the vast majority of acute HCV infections, these responses are overcome and the virus persistence almost inexorably occurs. Recently, several host- and virus-related mechanisms responsible for the failure of both the innate and the adaptive immune responses have been recognized. Among the latter, the wide range of escape mutations to evade the specific-T-and B-cell responses as well as the T cell anergy and the CD8+ T cell exhaustion together with the interference with its function after prolonged virus exposure hold a pivotal role. Other HCV strategies include the modification or manipulation of molecules playing key roles in the induction of the interferon response and its induced effector proteins. In this review, we attempt to gain insights on the main T cell immune evasion strategies used by the virus in order to favor its persistence.

  2. Early tumor shrinkage as a predictor of favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX

    PubMed Central

    Kubota, Yutaro; Tagawa, Teppei; Yamamoto, Taikan; Ikusue, Toshikazu; Uto, Yu; Miyashita, Kouichirou; Toshima, Hirokazu; Kobayashi, Kouji; Hisamatsu, Atsushi; Ichikawa, Wataru; Sekikawa, Takashi; Shimada, Ken; Sasaki, Yasutsuna

    2016-01-01

    There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in pancreatic cancer. We therefore investigated whether the ETS will predict outcomes in 59 patients with advanced pancreatic cancer treated with FOLFIRINOX therapy. The association of ETS with progression-free survival (PFS) and overall survival (OS) was evaluated but also we addressed to the correlation between outcomes and DpR. ETS was defined as a reduction ≥ 20% of target lesions' diameters measured at 6 to 8 weeks from treatment start. DpR was percentage of maximal tumor shrinkage observed at the nadir diameter compared with baseline. Among 47 evaluable patients for the ETS, 12 (25.5%) patients experienced ETS. The ETS was significantly associated with better PFS (9.0 vs. 4.2 months) as well as OS (24.0 vs. 9.1 months); moreover, the association had a statistically significance for PFS but a strong trend for OS in multivariate analysis. The DpR was statistically significantly but weakly associated with OS. In conclusion, this is the first report that the early response to chemotherapy may predict favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX therapy. PMID:27634903

  3. No evidence for strong recent positive selection favoring the 7 repeat allele of VNTR in the DRD4 gene.

    PubMed

    Naka, Izumi; Nishida, Nao; Ohashi, Jun

    2011-01-01

    The human dopamine receptor D4 (DRD4) gene contains a 48-bp variable number of tandem repeat (VNTR) in exon 3, encoding the third intracellular loop of this dopamine receptor. The DRD4 7R allele, which seems to have a single origin, is commonly observed in various human populations and the nucleotide diversity of the DRD4 7R haplotype at the DRD4 locus is reduced compared to the most common DRD4 4R haplotype. Based on these observations, previous studies have hypothesized that positive selection has acted on the DRD4 7R allele. However, the degrees of linkage disequilibrium (LD) of the DRD4 7R allele with single nucleotide polymorphisms (SNPs) outside the DRD4 locus have not been evaluated. In this study, to re-examine the possibility of recent positive selection favoring the DRD4 7R allele, we genotyped HapMap subjects for DRD4 VNTR, and conducted several neutrality tests including long range haplotype test and iHS test based on the extended haplotype homozygosity. Our results indicated that LD of the DRD4 7R allele was not extended compared to SNP alleles with the similar frequency. Thus, we conclude that the DRD4 7R allele has not been subjected to strong recent positive selection.

  4. Simulating the 'other-race' effect with autoassociative neural networks: further evidence in favor of the face-space model.

    PubMed

    Caldara, Roberto; Hervé, Abdi

    2006-01-01

    Other-race (OR) faces are less accurately recognized than same-race (SR) faces, but faster classified by race. This phenomenon has often been reported as the 'other-race' effect (ORE). Valentine (1991 Quarterly Journal of Experimental Psychology A: Human Experimental Psychology 43 161-204) proposed a theoretical multidimensional face-space model that explained both of these results, in terms of variations in exemplar density between races. According to this model, SR faces are more widely distributed across the dimensions of the space than OR faces. However, this model does not quantify nor state the dimensions coded within this face space. The aim of the present study was to test the face-space explanation of the ORE with neural network simulations by quantifying its dimensions. We found the predicted density properties of Valentine's framework in the face-projection spaces of the autoassociative memories. This was supported by an interaction for exemplar density between the race of the learned face set and the race of the faces. In addition, the elaborated face representations showed optimal responses for SR but not for OR faces within SR face spaces when explored at the individual level, as gender errors occurred significantly more often in OR than in SR face-space representations. Altogether, our results add further evidence in favor of a statistical exemplar density explanation of the ORE as suggested by Valentine, and question the plausibility of such coding for faces in the framework of recent neuroimaging studies.

  5. Should we change targets and methods of early intervention in autism, in favor of a strengths-based education?

    PubMed

    Mottron, Laurent

    2017-02-08

    Early intensive behavioral intervention (EIBI) and its recent variant, naturalist developmental behavioral intervention (NDBI) aim to increase socialization and communication, and to decrease repetitive and challenging behaviors in preschool age autistic children. These behaviorist techniques are based on the precocity and intensity of the intervention, face-to-face interaction, errorless learning, and information fragmentation. Once considered to be "scientifically proven", the efficacy of these approaches has been called into question in the last decade due to poor-quality data, small effects, low cost-efficiency, and the evolution of ethical and societal standards. Grounded on a reappraisal of the genetic and cognitive neuroscience of autism, we question three aspects of EIBI/NDBI: their focus on prerequisites for typical socio-communicative behaviors, their lack of consideration of autistic language development and learning modes, and their negative view of repetitive behaviors and restricted interests. We propose alternative predictions for empirical validation, based on the strengths of prototypical autistic children: (a) their non-verbal intelligence should be normally distributed and within the normal range; (b) improving access to non-communicative verbal and written auditory language material should favor their subsequent speech development and

  6. Tumor-infiltrating macrophages express interleukin-25 and predict a favorable prognosis in patients with gastric cancer after radical resection

    PubMed Central

    Li, Jinqing; Liao, Yuan; Ding, Tong; Wang, Bo; Yu, Xingjuan; Chu, Yifan; Xu, Jing; Zheng, Limin

    2016-01-01

    Interleukin-25 (IL-25) is a recently identified member of the proinflammatory IL-17 cytokine family; however, its role in human tumors remains largely unknown. The aim of this study was to investigate the cellular source and clinical significance of IL-25 in gastric cancer (GC) in situ. The results demonstrated that macrophages (Mφs) were the primary IL-25-expressing cells (IL-25+) in GC in situ. Moreover, IL-25+ cells were highly enriched in the intra-tumoral (IT) region of GC tissues (p < 0.001). The production of IL-25 in Mφs exposed to culture supernatant from gastric cancer cell line SGC7901 in vitro was induced by transforming growth factor-β1, and their density in the IT region was positively associated with those of other effector immune cells, namely, CD4+ T cells, CD8+ T cells and CD103+T cells (p < 0.01). This suggested that macrophages might produce IL-25 to create an antitumor micromilieu in GC tissues. The level of IL-25+IT cells was positively associated with histological grade (p < 0.001) and found to be an independent predictor of favorable survival (p = 0.024) in patients with GC after radical resection. These findings suggest that IL-25+IT cells may be a novel therapeutic target in those patients. PMID:26840565

  7. Human longevity is associated with regular sleep patterns, maintenance of slow wave sleep, and favorable lipid profile

    PubMed Central

    Mazzotti, Diego Robles; Guindalini, Camila; Moraes, Walter André dos Santos; Andersen, Monica Levy; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Tufik, Sergio

    2014-01-01

    Some individuals are able to successfully reach very old ages, reflecting higher adaptation against age-associated effects. Sleep is one of the processes deeply affected by aging; however few studies evaluating sleep in long-lived individuals (aged over 85) have been reported to date. The aim of this study was to characterize the sleep patterns and biochemical profile of oldest old individuals (N = 10, age 85–105 years old) and compare them to young adults (N = 15, age 20–30 years old) and older adults (N = 13, age 60–70 years old). All subjects underwent full-night polysomnography, 1-week of actigraphic recording and peripheral blood collection. Sleep electroencephalogram spectral analysis was also performed. The oldest old individuals showed lower sleep efficiency and REM sleep when compared to the older adults, while stage N3 percentage and delta power were similar across the groups. Oldest old individuals maintained strictly regular sleep-wake schedules and also presented higher HDL-cholesterol and lower triglyceride levels than older adults. The present study revealed novel data regarding specific sleep patterns and maintenance of slow wave sleep in the oldest old group. Taken together with the favorable lipid profile, these results contribute with evidence to the importance of sleep and lipid metabolism regulation in the maintenance of longevity in humans. PMID:25009494

  8. Children's Preference for Response Cost or Positive Reinforcement as Working Conditions.

    ERIC Educational Resources Information Center

    Sattler, Howard E.

    1978-01-01

    Significant results favor positive reinforcement and high win ratio in producing shorter average times to complete a response. The 80 first- and third-grade subjects exhibited a preference for continuing the task under the positive reinforcement condition. (RL)

  9. Heat transfer analysis in a two-side heated smooth square vertical channel with adverse and favorable mixed convection

    SciTech Connect

    Dutta, S.; Zhang, X.; Khan, J.A.; Bell, D.

    1997-07-01

    Experimental heat transfer measurements and analysis for mixed convection in a vertical square channel are presented. The flow direction is changed with respect to the earth's gravity field by selectively opening and closing the flow control valves. Desired flow directions are selected such that buoyancy assists or opposes the bulk flow direction pressure gradient. The heating condition is asymmetric. Most previous experiments used symmetrically heated circular tubes. Present configuration shows significant increase in the Nusselt number in both assisted and opposed flow conditions. In general, opposed flow shows higher heat transfer coefficients. Unlike symmetric heating conditions, Nusselt number ratio is observed to be increasing with increasing Gr/Re or Gr/Re{sup 2} ratios for both assisted and opposed flow conditions.

  10. Rainbow trout (Oncorhynchus mykiss) resistance to columnaris disease is heritable and favorably correlated with bacterial cold water disease resistance.

    PubMed

    Evenhuis, J P; Leeds, T D; Marancik, D P; LaPatra, S E; Wiens, G D

    2015-04-01

    Columnaris disease (CD), caused by Flavobacterium columnare, is an emerging disease affecting rainbow trout aquaculture. Objectives of this study were to 1) estimate heritability of CD resistance in a rainbow trout line (ARS-Fp-R) previously selected 4 generations for improved bacterial cold water disease (BCWD) resistance; 2) estimate genetic correlations among CD resistance, BCWD resistance, and growth to market BW; and 3) compare CD resistance among the ARS-Fp-R, ARS-Fp-S (selected 1 generation for increased BCWD susceptibility), and ARS-Fp-C (selection control) lines. Heritability of CD resistance was estimated using data from a waterborne challenge of 44 full-sib ARS-Fp-R families produced using a paternal half-sib mating design, and genetic correlations were estimated using these data and 5 generations of BCWD resistance, 9-mo BW (approximately 0.5 kg), and 12-mo BW (approximately 1.0 kg) data from 405 ARS-Fp-R full-sib families. The CD and BCWD challenges were initiated at approximately 52 and 84 d posthatch, or approximately 650 and 1,050 degree days (°C × d), respectively. Survival of ARS-Fp-R families ranged from 0 to 48% following CD challenge and heritability estimates were similar between CD (0.17 ± 0.09) and BCWD (0.18 ± 0.03) resistance, and the genetic correlation between these 2 traits was favorable (0.35 ± 0.25). Genetic correlations were small and antagonistic (-0.15 ± 0.08 to -0.19 ± 0.24) between the 2 resistance traits and 9- and 12-mo BW. Two challenges were conducted in consecutive years to compare CD resistance among ARS-Fp-R, ARS-Fp-C, and ARS-Fp-S families. In the first challenge, ARS-Fp-R families (83% survival) had greater CD resistance than ARS-Fp-C (73.5%; P = 0.02) and ARS-Fp-S (68%; P < 0.001) families, which did not differ (P = 0.16). In the second challenge, using an approximately 2.5-fold greater challenge dose, ARS-Fp-R families exhibited greater CD resistance (56% survival) than ARS-Fp-S (38% survival; P = 0.02) families

  11. On the pre-perihelion temporal activity of comet 9P/Tempel 1 during the favorable apparition of 2005

    NASA Astrophysics Data System (ADS)

    de Almeida, A.; Serrano, G.; Sanzovo, G.; Trevisan Sanzovo, D.

    2014-07-01

    The short-period (5.5 years) comet 9P/Tempel 1 was revisited by NASA's Stardust-NExT probe in 2011 February 15, in a flyby at a distance of only about 181 km. This is the first time a comet is visited twice by two different probes (the first visit in 2005 July 4, by NASA's Deep Impact probe). Tempel 1 is not a bright or very active comet. The brightest apparent magnitude in 25 appearances, since the discovery (1867), has been m=9.5, well below the limit of visibility to the naked eye. Here, we study the temporal activity, based on 495 apparent visual magnitude estimates (ICQ), obtained during the very favorable apparition of 2005 (the comet passed at 0.71 au from the Earth in 2005 May 3) by the Semi-Empirical Method of Visual Magnitudes (SEMVM, de Almeida, Singh&Huebner, 1997). We determine a model dependent activity at the time immediately before the Deep Impact (4 July 2005 at 5:52 UTC) in fairly good agreement with Schleicher et al. (2006), Feaga et al. (2007) and Gicquel et al. (2012) from the Spitzer spacecraft observations, and a day later, at the time of the perihelion passage (5 July 2005 at 5:31 UTC), also in good agreement with Biver et al. (2007) and Farnham et al. (2010), most likely powered by water-ice sublimation. Our results are consistent, for an active area of 10% and a minimum nuclear radius of 2.5 km , with the radio OH observations in 18-cm (Howell et al., 2007; Biver et al., 2007), and the H_2O observations by satellites SWAN (Mäkinen et al., 2007; Bensch et al., 2007) and Odin (Biver et al., 2007), in the pre-perihelion phase.

  12. DASH Eating Pattern Is Associated with Favorable Left Ventricular Function in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Nguyen, Ha T.; Bertoni, Alain G.; Nettleton, Jennifer A.; Bluemke, David A.; Levitan, Emily B.; Burke, Gregory L.

    2014-01-01

    Objective Potential associations between consistency with the Dietary Approaches to Stop Hypertension (DASH) diet and preclinical stages of heart failure (HF) in a large multiethnic cohort have not been evaluated. This study sought to determine the cross-sectional relationship between the DASH eating pattern and left ventricular (LV) function in the Multi-Ethnic Study of Atherosclerosis (MESA). Design A total of 4506 men and women from four ethnic groups (40% white, 24% African American, 22% Hispanic American, and 14% Chinese American) aged 45–84 years and free of clinical cardiovascular disease (CVD) were studied. Diet was assessed using a validated food-frequency questionnaire. LV functional parameters including end-diastolic volume, stroke volume, and LV ejection fraction were measured by magnetic resonance imaging. Multivariate analyses were conducted to examine the association between LV function and DASH eating pattern (including high consumption of fruits, vegetables, whole grains, poultry, fish, nuts, and low-fat dairy products and low consumption of red meat, sweets, and sugar-sweetened beverages). Results A 1-unit increase in DASH eating pattern score was associated with a 0.26 ml increase in end-diastolic volume and increases of 0.10 ml/m2 in stroke volume, adjusted for key confounders. A 1-unit increase in DASH eating pattern score was also associated with a 0.04% increase in ejection fraction, but the relationship was marginally significant (p = 0.08). Conclusions In this population, greater DASH diet consistency is associated with favorable LV function. DASH dietary patterns could be protective against HF. PMID:23756584

  13. Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.

    PubMed

    Tähtinen, Siri; Kaikkonen, Saija; Merisalo-Soikkeli, Maiju; Grönberg-Vähä-Koskela, Susanna; Kanerva, Anna; Parviainen, Suvi; Vähä-Koskela, Markus; Hemminki, Akseli

    2015-01-01

    Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I) therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience.

  14. Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state.

    PubMed

    Aharoni, Saar; Lati, Yoni; Aviram, Michael; Fuhrman, Bianca

    2015-01-01

    It was documented that pomegranate has anti-inflammatory effects. In this study, we investigated a direct effect of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype. In vitro, PJ and its major polyphenols dose-dependently attenuated macrophage response to M1 proinflammatory activation in J774.A1 macrophage-like cell line. This was evidenced by a significant decrease in TNFα and IL-6 secretion in response to stimulation by IFNγ and Lipopolysaccharide. In addition, PJ and punicalagin dose-dependently promoted the macrophages toward a M2 anti-inflammatory phenotype, as determined by a significant increase in the spontaneous secretion of IL-10. In mice, supplementation with dietary PJ substantially inhibited the M2 to M1 macrophage phenotypic shift associated with age, toward a favorable anti-inflammatory M2 phenotype. This effect was also reflected in the mice atherosclerotic plaques, as evaluated by the distinct expression of arginase isoforms. PJ consumption inhibited the increment of arginase II (Arg II, M1) mRNA expression during aging, and maintained the levels of Arg I (M2) expression similar to those in young mice aorta. This study demonstrates, for the first time, that pomegranate polyphenols directly suppress macrophage inflammatory responses and promote M1 to M2 switch in macrophage phenotype. Furthermore, this study indicates that PJ consumption may inhibit the progressive proinflammatory state in the aorta along atherosclerosis development with aging, due to a switch in macrophage phenotype from proinflammatory M1 to anti-inflammatory M2.

  15. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula.

    PubMed

    Lee, Woo Yong; Park, Kyu Joo; Cho, Yong Beom; Yoon, Sang Nam; Song, Kee Ho; Kim, Do Sun; Jung, Sang Hun; Kim, Mihyung; Yoo, Hee-Won; Kim, Inok; Ha, Hunjoo; Yu, Chang Sik

    2013-11-01

    Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence.

  16. Dechlorination of three tetrachlorobenzene isomers by contaminated harbor sludge-derived enrichment cultures follows thermodynamically favorable reactions.

    PubMed

    Lu, Yue; Ramiro-Garcia, Javier; Vandermeeren, Pieter; Herrmann, Steffi; Cichocka, Danuta; Springael, Dirk; Atashgahi, Siavash; Smidt, Hauke

    2017-03-01

    Dechlorination patterns of three tetrachlorobenzene isomers, 1,2,3,4-, 1,2,3,5-, and 1,2,4,5-TeCB, were studied in anoxic microcosms derived from contaminated harbor sludge. The removal of doubly, singly, and un-flanked chlorine atoms was noted in 1,2,3,4- and 1,2,3,5-TeCB fed microcosms, whereas only singly flanked chlorine was removed in 1,2,4,5-TeCB microcosms. The thermodynamically more favorable reactions were selectively followed by the enriched cultures with di- and/or mono-chlorobenzene as the main end products of the reductive dechlorination of all three isomers. Based on quantitative PCR analysis targeting 16S rRNA genes of known organohalide-respiring bacteria, the growth of Dehalococcoides was found to be associated with the reductive dechlorination of all three isomers, while growth of Dehalobacter, another known TeCB dechlorinator, was only observed in one 1,2,3,5-TeCB enriched microcosm among biological triplicates. Numbers of Desulfitobacterium and Geobacter as facultative dechlorinators were rather stable suggesting that they were not (directly) involved in the observed TeCB dechlorination. Bacterial community profiling suggested bacteria belonging to the phylum Bacteroidetes and the order Clostridiales as well as sulfate-reducing members of the class Deltaproteobacteria as putative stimulating guilds that provide electron donor and/or organic cofactors to fastidious dechlorinators. Our results provide a better understanding of thermodynamically preferred TeCB dechlorinating pathways in harbor environments and microbial guilds enriched and active in anoxic TeCB dechlorinating microcosms.

  17. Favorable effects of carotid endarterectomy on baroreflex sensitivity and cardiovascular neural modulation: a 4-month follow-up.

    PubMed

    Dalla Vecchia, Laura; Barbic, Franca; Galli, Andrea; Pisacreta, Massimo; Gornati, Rosella; Porretta, Tiziano; Porta, Alberto; Furlan, Raffaello

    2013-06-15

    Carotid surgery variably modifies carotid afferent innervation, thus affecting arterial baroreceptor sensitivity. Low arterial baroreflex sensitivity is a well-known independent risk factor for cardiovascular diseases. The aim of this study was to assess the 4-mo effects of carotid endarterectomy (CEA) on arterial baroreceptor sensitivity and cardiovascular autonomic profile in patients with unilateral carotid stenosis. We enrolled 20 patients (72 ± 8 yr) with unilateral >70% carotid stenosis. ECG, beat-by-beat blood pressure, and respiration were continuously recorded before and 126 ± 9 days after CEA, at rest and during a 75° head-up tilt. Both pharmacological (modified Oxford technique, BRS) and spontaneous (index α, spectral analysis) arterial baroreflex sensitivity were assessed. Cardiovascular autonomic profile was evaluated by plasma catecholamines and spectral indexes of cardiac sympathovagal modulation [low-frequency R-R interval (LFRR), low frequency-to high frequency ratio (LF/HF), high-frequency R-R interval (HFRR)] and sympathetic vasomotor control [low-frequency systolic arterial pressure (LFSAP)] obtained from heart rate and SAP variability. After CEA, both the index α and BRS were higher (P < 0.02) at rest. SAP variance decreased both at rest and during tilt (P < 0.02). Before surgery, tilt did not modify the autonomic profile compared with baseline. After CEA, tilt increased LF/HF and LFSAP and reduced HFRR compared with rest (P < 0.02). Four months after CEA was performed, arterial baroreflex sensitivity was enhanced. Accordingly, the patients' autonomic profile had shifted toward reduced cardiac and vascular sympathetic activation and enhanced cardiac vagal activity. The capability to increase cardiovascular sympathetic activation in response to orthostasis was restored. Baroreceptor sensitivity improvement might play an additional role in the more favorable outcome observed in patients after carotid surgery.

  18. The β-sheet core is the favored candidate of engineering SDR for enhancing thermostability but not for activity.

    PubMed

    Lou, Deshuai; Tan, Jun; Zhu, Liancai; Ji, Shunlin; Wang, Bochu

    2017-01-26

    7α-Hydroxysteroid dehydrogenases (7α-HSDHs) can stereoselectively catalyze steroids, aromatic α-ketoesters, and benzaldehyde analogues playing a critical role in the biotransformation and poor thermostability that hinders their biomedical and industrial applications. Based on the three-dimensional structure of 7α-HSDH from Clostridium absonum (CA 7α-HSDH), recently reported program MAESTRO was used to compute the ΔΔG and predict the single-point mutants that could enhance its thermostability. Four mutants were selected and verified experimentally. The results from the circular dichroism spectrum indicated that three of the mutants, N89L, N184I, and A185I, fitted a three-state model and the values for TmN→I and TmI→D increased with different ranges. In particular, the TmN→I for the N184I mutant increased maximally by 9.93°C. Meanwhile, the denaturation process of the G189I mutant fitted the two-state model and it was more stable than the wild type, judging from the denaturation curves. Nevertheless, the enzyme catalytic activity analysis suggested that only the N89L mutant held a 2.28% catalytic efficiency, compared to the wild type, CA 7α-HSDH, and the activities of the other three mutants could not be detected. Molecular dynamics (MD) simulations were performed to determine the structural changes that occurred in the mutations and the results indicated that β-sheet structures in the mutants without detectable activity had changed significantly. Judging from the locations of the mutated sites, residues in the β-sheet core were considered as the favored candidates for SDR engineering to enhance the thermostability but not for activity holding.

  19. Defects in the regulatory clearance mechanisms favor the breakdown of self-tolerance during spontaneous autoimmune orchitis.

    PubMed

    Pelletier, R-Marc; Yoon, Suk Ran; Akpovi, Casimir D; Silvas, Emil; Vitale, María Leiza

    2009-03-01

    We identified aberrations leading to spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and natural model for autoimmunity. This study provides evidence favoring the view that a malfunction of the clearance mechanisms for apoptotic cell debris arising from imbalances in phagocyte receptors or cytokines acting on Sertoli cells constitutes a major factor leading to breakdown of self-tolerance during spontaneous AIO. Serum anti-sperm antibody titers measured by ELISA reflected spermatogenic activity without causing immune inflammatory responses. Orchitic mink showed excess antibody production accompanied by spermatogenic arrest, testicular leukocyte infiltration, and infertility. AIO serum labeled the postacrosomal region, the mid and end piece of mink sperm, whereas normal mink serum did not. Normal serum labeled plasma membranes, whereas AIO serum reacted with germ cell nuclei. Western blot analyses revealed that AIO serum reacted specifically to a 23- and 50-kDa protein. The number of apostain-labeled apoptotic cells was significantly higher in orchitic compared with normal tubules. However, apoptosis levels measured by ELISA in seminiferous tubular fractions (STf) were not significantly different in normal and orchitic tubules. The levels of CD36, TNF-alpha, TNF-alpha RI, IL-6, and Fas but not Fas-ligand (L), and ATP-binding cassette transporter ABCA1 were changed in AIO STf. TNF-alpha and IL-6 serum levels were increased during AIO. Fas localized to germ cells, Sertoli cells, and the lamina propria of the tubules and Fas-L, to germ cells. Fas colocalized with Fas-L in residual bodies in normal testis and in giant cells and infiltrating leukocytes in orchitic tubules.

  20. Middle-aged rats orally supplemented with gel-encapsulated catechin favorably increases blood cytosolic NADPH levels.

    PubMed

    Cueno, Marni E; Tamura, Muneaki; Ochiai, Kuniyasu

    2015-04-15

    Green tea catechins are primarily known to function as free radical scavengers and have several beneficial uses. Orally supplemented catechin (OSC) was previously shown to increase mitochondrial heme and catalase levels in rat heart blood, however, its effect in the cytosol has not been elucidated. Here, we determined the effects of OSC in the rat heart blood cytosol. We used middle-aged (40 week-old) and young (4 week-old) rats throughout the study. We isolated blood cytosol, verified its purity, and determined heme, hydrogen peroxide (H2O2) levels, catalase (CAT) activities, gp91(phox) amounts, NADP and NAD pools, sirtuin 1 (SIRT1) and glutathione reductase (GR) activities, and free fatty acids (FFA). We established that OSC is associated with decreased heme-dependent H2O2 amounts while increasing heme-independent CAT activity. Moreover, we found that OSC-related decrease in NAD(+) amounts among middle-aged rats is associated to increased NADPH levels and SIRT1 activity. In contrast, we associated OSC-related decrease in NAD(+) amounts among young rats to decreased NADPH levels and increased SIRT1 activity. This highlights a major difference between catechin-treated middle-aged and young rats. Furthermore, we observed that cytosolic FFA and GR levels were significantly increased only among OSC-treated middle-aged rats which we hypothesize are related to increased NADPH levels. This insinuates that OSC treatment allows higher catechin amounts to enter the bloodstream of middle-aged rats. We propose that this would favorably increase NADPH amounts and lead to the simultaneous decrease in NADPH-related pro-oxidant activity and increase in NADPH-related biomolecules and anti-oxidant activities.

  1. Host modulation by a parasite: how Leishmania infantum modifies the intestinal environment of Lutzomyia longipalpis to favor its development.

    PubMed

    Santos, Vania Cristina; Vale, Vladimir Fazito; Silva, Sydnei Magno; Nascimento, Alexandre Alves Sousa; Saab, Natalia Alvim Araujo; Soares, Rodrigo Pedro Pinto; Michalick, Marilene Suzan Marques; Araujo, Ricardo Nascimento; Pereira, Marcos Horacio; Fujiwara, Ricardo Toshio; Gontijo, Nelder Figueiredo

    2014-01-01

    Some reports have described the interference of Leishmania on sand flies physiology, and such behavior most likely evolved to favor the development and transmission of the parasite. Most of these studies showed that Leishmania could modulate the level of proteases in the midgut after an infective blood meal, and decreased proteolytic activity is indeed beneficial for the development of promastigotes in the gut of sand flies. In the present study, we performed a detailed investigation of the intestinal pH in Lutzomyia longipalpis females naturally infected with Leishmania infantum and investigated the production of trypsin by these insects using different approaches. Our results allowed us to propose a mechanism by which these parasites interfere with the physiology of L. longipalpis to decrease the production of proteolytic enzymes. According to our hypothesis L. infantum promastigotes indirectly interfere with the production of trypsin by modulating the mechanism that controls the intestinal pH via the action of a yet non-identified substance released by promastigote forms inside the midgut. This substance is not an acid, whose action would be restrict on to release H+ to the medium, but is a substance that is able to interfere with midgut physiology through a mechanism involving pH control. According to our hypothesis, as the pH decreases, the proteolytic enzymes efficiency is also reduced, leading to a decline in the supply of amino acids to the enterocytes: this decline reduces the stimulus for protease production because it is regulated by the supply of amino acids, thus leading to a delay in digestion.

  2. Urethral stricture vaporization with the KTP laser provides evidence for a favorable impact of laser surgery on wound healing

    NASA Astrophysics Data System (ADS)

    Schmidlin, Franz R.; Venzi, Giordano; Jichlinski, Patrice; Oswald, Michael; Delacretaz, Guy P.; Gabbiani, Giulio; Leisinger, Hans-Juerg; Graber, Peter

    1997-12-01

    The objective of this study was to evaluate and compare the safety and efficacy of the KTP 532 laser to direct vision internal urethrotomy (DVIU) in the management of urethral strictures. A total of 32 patients were randomized prospectively in this study, 14 DVIU and 18 KTP 532 laser. Patients were evaluated postoperatively with flowmetry and in the case of recurrence with cystourethrography at 3, 12, 24 weeks. With the KTP 532 laser complete symptomatic and uredynamic success was achieved in 15 (83%) patients at 12 and 24 weeks. Success rate was lower in the DVIU group with 9 (64%) patients at 12 weeks and 8 (57%) patients at 24 weeks. Mean preoperative peak-flow was improved from 6 cc/s to 20 cc/s at 3, 12 and 24 weeks with the KTP laser. With DVIU mean preoperative peak-flow was improved from 5.5 cc/s to 20 cc/s at 3 weeks followed by a steady decrease to 13 cc/s at 12 weeks and to 12 cc/s 24 weeks. No complication was observed in either group of patients. Our results confirm that stricture vaporization with the KTP 532 laser is a safe and efficient procedure. The better results after laser surgery make it also a valuable alternative in the endoscopic treatment of urethral strictures. These findings suggest a favorable influence of laser surgery on wound healing with less wound contraction and scarring. The lack of contraction of laser wounds might be related to the absence and the lack of organization of myofibroblasts in laser induced lesions.

  3. A new scalar resonance at 750 GeV: towards a proof of concept in favor of strongly interacting theories

    NASA Astrophysics Data System (ADS)

    Son, Minho; Urbano, Alfredo

    2016-05-01

    We interpret the recently observed excess in the diphoton invariant mass as a new spin-0 resonant particle. On theoretical grounds, an interesting question is whether this new scalar resonance belongs to a strongly coupled sector or a well-defined weakly coupled theory. A possible UV-completion that has been widely considered in literature is based on the existence of new vector-like fermions whose loop contributions — Yukawa-coupled to the new resonance — explain the observed signal rate. The large total width preliminarily suggested by data seems to favor a large Yukawa coupling, at the border of a healthy perturbative definition. This potential problem can be fixed by introducing multiple vector-like fermions or large electric charges, bringing back the theory to a weakly coupled regime. However, this solution risks to be only a low-energy mirage: large multiplicity or electric charge can dangerously reintroduce the strong regime by modifying the renormalization group running of the dimensionless couplings. This issue is also tightly related to the (in)stability of the scalar potential. First, we study — in the theoretical setup described above — the parametric behavior of the diphoton signal rate, total width, and one-loop β functions. Then, we numerically solve the renormalization group equations, taking into account the observed diphoton signal rate and total width, to investigate the fate of the weakly coupled theory. We find that — with the only exception of few fine-tuned directions — weakly coupled interpretations of the excess are brought back to a strongly coupled regime if the running is taken into account.

  4. Fatigue favors in vitro Th1 and Th17-like cell expansion and reduces corticoid sensitivity in MS patients.

    PubMed

    Alvarenga-Filho, Hélcio; Salles, Marisa; Hygino, Joana; Ferreira, Thais B; Sacramento, Priscila M; Monteiro, Clarice; Vasconcelos, Claudia Cristina F; Alvarenga, Regina Maria Papais; Bento, Cleonice A M

    2017-02-15

    Fatigue is a common "ghost" symptom in patients with multiple sclerosis (MS), an autoimmune disease mediated by T cells that target myelin antigens of the central nervous system. As fatigue has been associated with inflammatory states, its occurrence may negatively impact MS progression. The aim of this study was to evaluate the impact of fatigue on the cytokine profile of patients with relapsing-remitting (RR) MS. For our study, blood were collected from MS patients in clinical remission phase with (n=15) and without (n=15) fatigue. Cytokines were detected by ELISA in the plasma and supernatant collected from anti-CD3/anti-CD28-activated T cells or LPS-stimulated monocytes. In some wells, different doses of hydrocortisone (HC) were added at the beginning of the culture. Here, peripheral levels of IL-6 and TNF-α, as well as in vitro production of cytokines related to Th17 (IL-6, IL-17, IL-22, and GM-CSF) or Th1 (IFN-γ) phenotypes, were elevated in fatigued patients and their levels were associated with fatigue severity. The same phenomenon was observed between the production of IL-6, TNF-α, IL-1β, and IL-23 by monocytes and fatigue. Moreover, HC was less efficient in inhibiting in vitro inflammatory cytokine production in patients with fatigue, mainly those produced by both CD8(+) T cells and monocytes. Our data, although preliminary, suggests that the occurrence of fatigue, by favoring the in vitro production of Th1/Th17-related cytokines and corticoid resistance, may negatively impact the course of MS.

  5. Subboiling Moist Heat Favors the Selection of Enteric Pathogen Clostridium difficile PCR Ribotype 078 Spores in Food

    PubMed Central

    Rodriguez-Palacios, Alexander; Ilic, Sanja; LeJeune, Jeffrey T.

    2016-01-01

    Emerging enteric pathogens could have not only more antibiotic resistance or virulence traits; they could also have increased resistance to heat. We quantified the effects of minimum recommended cooking and higher temperatures, individually on a collection of C. difficile isolates and on the survival probability of a mixture of emerging C. difficile strains. While minimum recommended cooking time/temperature combinations (63–71°C) allowed concurrently tested strains to survive, higher subboiling temperatures reproducibly favored the selection of newly emerging C. difficile PCR ribotype 078. Survival ratios for “ribotypes 078” :  “other ribotypes” (n = 49 : 45 isolates) from the mid-2000s increased from 1 : 1 and 0.7 : 1 at 85°C (for 5 and 10 minutes, resp.) to 2.3 : 1 and 3 : 1 with heating at 96°C (for 5 and 10 minutes, resp.) indicating an interaction effect between the heating temperature and survival of C. difficile genotypes. In multistrain heating experiments, with PCR ribotypes 027 and 078 from 2004 and reference type strain ATCC 9689 banked in the 1970s, multinomial logistic regression (P < 0.01) revealed PCR ribotype 078 was the most resistant to increasing lethal heat treatments. Thermal processes (during cooking or disinfection) may contribute to the selection of emergent specific virulent strains of C. difficile. Despite growing understanding of the role of cooking on human evolution, little is known about the role of cooking temperatures on the selection and evolution of enteric pathogens, especially spore-forming bacteria. PMID:27375748

  6. Metabolic Syndrome Triggered by High-Fructose Diet Favors Choroidal Neovascularization and Impairs Retinal Light Sensitivity in the Rat

    PubMed Central

    Thierry, Magalie; Pasquis, Bruno; Acar, Niyazi; Grégoire, Stéphane; Febvret, Valérie; Buteau, Bénédicte; Gambert-Nicot, Ségolène; Bron, Alain M.; Creuzot-Garcher, Catherine P.; Bretillon, Lionel

    2014-01-01

    Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model. PMID:25380250

  7. Causes of Death in Men With Prevalent Diabetes and Newly Diagnosed High- Versus Favorable-Risk Prostate Cancer

    SciTech Connect

    D'Amico, Anthony V.; Braccioforte, Michelle H.; Moran, Brian J.; Chen, Ming-Hui

    2010-08-01

    Purpose: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. Methods: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whether PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. Results: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p = .002) to present with high-grade PCa but were not treated less aggressively (p = .33) and did not have an increased risk of PCSM (p = .58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p = .035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p = .001), and all-cause mortality (AHR, 2.4; 95% CI, 1.2-4.7; p = .01) compared to favorable-risk PCa. Conclusion: Aggressive management of pDM is warranted in men with high-risk PCa.

  8. Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer.

    PubMed

    Li, Kai; Zhu, Zhengpeng; Luo, Jin; Fang, Jingyi; Zhou, Huanhuan; Hu, Min; Maskey, Ninu; Yang, Guifang

    2015-01-01

    Chemokine receptor CXCR3 has been proved to play an important role in tumorigenesis and tumor progression in many malignancies, but its precise efficacy on gastric cancer (GC) has not been evaluated yet. The present study was aimed to explore the correlation of chemokine receptor CXCR3 with tumor-infiltrating lymphocytes (TILs) and prognosis in advanced gastric cancer (GC). Expression of CXCR3 and CD4+, CD8+ TILs was conducted in 192 advanced GC specimens and 48 corresponding paracancerous tissues by immunohistochemical (IHC) analysis. CXCR3 expression in GC tissues was significantly higher than that in paracancerous tissues (P<0.001) and CD8+, CD4+ TILs infiltration increased with high CXCR3 expression (P=0.032 and P<0.001, respectively). Our study showed significantly lower CXCR3 expression in patients with greater tumor invasion depth and lymph node metastasis compared with patients with lesser tumor invasion depth and without lymph node metastasis (P=0.002 and P=0.001, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high CD8+ TILs infiltration had longer overall survival (OS) (log-rank test, P<0.001 and P=0.002, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (P=0.002). The present study suggested that CXCR3 expression was upregulated in advanced GC and was associated with increased CD4+, CD8+ TILs infiltration and improved OS. Therefore, CXCR3 overexpression is implicated as a favorable prognostic biomarker in human advanced GC.

  9. Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment

    PubMed Central

    Chen, You-ming; Zhang, Ting; Cai, Qing-xian; Zhang, Xiao-hong; Zhao, Zhi-xing

    2017-01-01

    Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, −1.33 versus 0.86, P < 0.001). The albumin levels and platelet counts significantly increased during the follow-up period after SVR (44.27 ± 4.09 versus 42.63 ± 4.37, P = 0.037 and 173.89 ± 87.36 versus 160.11 ± 77.97, P = 0.047). These data indicated that HCV-related cirrhotic patients with SVR after PegIFN + RBV may have a favorable clinical course and improvements in laboratory data. Moreover, HCC should be monitored. PMID:28232944

  10. Outcomes of Children With Favorable Histology Wilms Tumor and Peritoneal Implants Treated in National Wilms Tumor Studies-4 and -5

    SciTech Connect

    Kalapurakal, John A.; Green, Daniel M.; Haase, Gerald; Anderson, James R.; Dome, Jeffrey S.; Grundy, Paul E.

    2010-06-01

    Purpose: There are no published reports on the optimal management and survival rates of children with Wilms tumor (WT) and peritoneal implants (PIs). Methods and Materials: Among favorable histology WT patients enrolled in the National Wilms Tumor Study (NWTS)-4 and NWTS-5, 57 children had PIs at the time of nephrectomy. The median age was 3 years 5 months (range, 3 months to 14 years). The majority of children (42 of 57 [74%)] had Stage III tumors; 15 had Stage IV disease. All patients received multimodality therapy. Of 56 children who underwent primary surgery, 48 (84%) had gross total resection of all tumors. All patients received 3-drug chemotherapy with vincristine, dactinomycin, and doxorubicin. Whole-abdomen radiotherapy (RT) was used in 47 patients (82%), and in 50 patients (88%) the RT dose was 10.5 Gy. Results: After a median follow-up of 7.5 years, the overall abdominal and systemic tumor control rates were 97% and 93%, respectively. A comparative analysis between children with PIs and those without PIs showed no significant differences in the clinical characteristics between the two groups. The 5-year event-free survival rates with and without PIs were 90% (95% confidence interval, 78-96%) and 83% (95% confidence interval, 81-85%) respectively (p = 0.20). Conclusions: Multimodality therapy with surgery, whole-abdomen RT, and three-drug chemotherapy delivered according to the NWTS-4 and -5 protocols resulted in excellent abdominal and systemic tumor control rates. All children should be monitored in long-term surveillance programs for the early detection and management of therapy-related toxicities.

  11. Favorable Alteration of Tumor Microenvironment by Immunomodulatory Cytokines for Efficient T-Cell Therapy in Solid Tumors

    PubMed Central

    Tähtinen, Siri; Kaikkonen, Saija; Merisalo-Soikkeli, Maiju; Grönberg-Vähä-Koskela, Susanna; Kanerva, Anna; Parviainen, Suvi; Vähä-Koskela, Markus; Hemminki, Akseli

    2015-01-01

    Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I) therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience. PMID:26107883

  12. Effects of developmental conditions on growth, stress, and telomeres in black-legged kittiwake chicks.

    PubMed

    Young, Rebecca C; Welcker, Jorg; Barger, Christopher P; Hatch, Scott A; Merkling, Thomas; Kitaiskaia, Evgenia V; Haussmann, Mark F; Kitaysky, Alexander S

    2017-03-30

    Early-life conditions can drive ageing patterns and life history strategies throughout the lifespan. Certain social, genetic, and nutritional developmental conditions are more likely to produce high-quality offspring: those with good likelihood of recruitment and productivity. Here we call such conditions "favored states" and explore their relationship with physiological variables during development in a long-lived seabird, the black-legged kittiwake (Rissa tridactyla). Two favored states were experimentally generated by manipulation of food availability and brood size, while hatching order and sex were also explored as naturally generating favored states. Thus, the favored states we explored were high food availability, lower levels of sibling competition, hatching first, and male sex. We tested the effects of favored developmental conditions on growth, stress, telomere length (a molecular marker associated with lifespan), and nestling survival. Generation of favored states through manipulation of both the nutritional and social environments furthered our understanding of their relative contributions to development and phenotype: increased food availability led to larger body size, reduced stress, and higher antioxidant status, while lower sibling competition (social environment) led to lower telomere loss and longer telomere lengths in fledglings. Telomere length predicted nestling survival, and wing growth was also positively correlated with telomere length, supporting the idea that telomeres may indicate individual quality, mediated by favored states. This article is protected by copyright. All rights reserved.

  13. Social media for message testing: a multilevel approach to linking favorable viewer responses with message, producer, and viewer influence on YouTube.

    PubMed

    Paek, Hye-Jin; Hove, Thomas; Jeon, Jehoon

    2013-01-01

    To explore the feasibility of social media for message testing, this study connects favorable viewer responses to antismoking videos on YouTube with the videos' message characteristics (message sensation value [MSV] and appeals), producer types, and viewer influences (viewer rating and number of viewers). Through multilevel modeling, a content analysis of 7,561 viewer comments on antismoking videos is linked with a content analysis of 87 antismoking videos. Based on a cognitive response approach, viewer comments are classified and coded as message-oriented thought, video feature-relevant thought, and audience-generated thought. The three mixed logit models indicate that videos with a greater number of viewers consistently increased the odds of favorable viewer responses, while those presenting humor appeals decreased the odds of favorable message-oriented and audience-generated thoughts. Some significant interaction effects show that videos produced by laypeople may hinder favorable viewer responses, while a greater number of viewer comments can work jointly with videos presenting threat appeals to predict favorable viewer responses. Also, for a more accurate understanding of audience responses to the messages, nuance cues should be considered together with message features and viewer influences.

  14. Effects of favorable alleles for water-soluble carbohydrates at grain filling on grain weight under drought and heat stresses in wheat.

    PubMed

    Zhang, Bin; Li, Weiyu; Chang, Xiaoping; Li, Runzhi; Jing, Ruilian

    2014-01-01

    Drought, heat and other abiotic stresses during grain filling can result in reductions in grain weight. Conserved water-soluble carbohydrates (WSC) at early grain filling play an important role in partial compensation of reduced carbon supply. A diverse population of 262 historical winter wheat accessions was used in the present study. There were significant correlations between 1000-grain weight (TGW) and four types of WSC, viz. (1) total WSC at the mid-grain filling stage (14 days after flowering) produced by leaves and non-leaf organs; (2) WSC contributed by current leaf assimilation during the mid-grain filling; (3) WSC in non-leaf organs at the mid-grain filling, excluding the current leaf assimilation; and (4) WSC used for respiration and remobilization during the mid-grain filling. Association and favorable allele analyses of 209 genome-wide SSR markers and the four types of WSC were conducted using a mixed linear model. Seven novel favorable WSC alleles exhibited positive individual contributions to TGW, which were verified under 16 environments. Dosage effects of pyramided favorable WSC alleles and significantly linear correlations between the number of favorable WSC alleles and TGW were observed. Our results suggested that pyramiding more favorable WSC alleles was effective for improving both WSC and grain weight in future wheat breeding programs.

  15. Brand Cigarillos: Low Price but High Particulate Matter Levels—Is Their Favorable Taxation in the European Union Justified?

    PubMed Central

    Wasel, Julia; Boll, Michael; Schulze, Michaela; Mueller, Daniel; Bundschuh, Matthias; Groneberg, David A.; Gerber, Alexander

    2015-01-01

    emissions between cigarettes and cigarillos, we think that a favorable taxation of cigarillos is not justifiable. PMID:26258782

  16. Ugandan Women’s View of the IUD: Generally Favorable but Many Have Misperceptions About Health Risks

    PubMed Central

    Twesigye, Rogers; Buyungo, Peter; Kaula, Henry; Buwembo, Dennis

    2016-01-01

    ABSTRACT Background: Between 2001 and 2006, IUD use in Uganda stagnated at 0.2% among women of reproductive age (WRA) ages 15–49. By 2011, IUD use had increased slightly to 0.4%. Recent studies report a significant increase in IUD use to 3.8%, but it is still low. Because the IUD is a little-used method in Uganda, we assessed the acceptability of the IUD by surveying women about their perceptions, attitudes, and beliefs. Methods: In August and September 2014, we conducted a cross-sectional survey among 1,505 WRA exiting public and private health facilities in Uganda. We collected information on women’s attitudes, knowledge, and beliefs about the IUD, as well as their perceptions about its availability. We classified women’s responses according to a behavior change framework with 3 summary constructs: opportunity (structural factors that influence behavior), ability (skills to perform the behavior), and motivation (self-interest in adopting the behavior). As these 3 types of factors are more favorable to the desired behavior (in this case, use of the IUD), individuals are more likely to perform the behavior. Cross-tabulations compared the percentage results of perceptions and knowledge by key background characteristics. Results: Most (87.8%) of the surveyed women had heard of the IUD, and nearly two-thirds had a positive attitude toward the method. But a lower percentage (38.6%) had accurate information about the IUD and more than half (51.6%) did not think the method was available in a nearby facility. More than half of the women believed incorrectly that the IUD can damage the womb (57%), that it reduces sexual pleasure (54%), and that it can cause cancer (58%). Current use of family planning or of a modern method specifically was positively associated with awareness and accurate knowledge and beliefs about the IUD. Married women had significantly higher awareness of the IUD than single women, and they had better knowledge and belief scores. The type of

  17. Geothermal systems in volcanic arcs: Volcanic characteristics and surface manifestations as indicators of geothermal potential and favorability worldwide

    NASA Astrophysics Data System (ADS)

    Stelling, P.; Shevenell, L.; Hinz, N.; Coolbaugh, M.; Melosh, G.; Cumming, W.

    2016-09-01

    This paper brings a global perspective to volcanic arc geothermal assessments by evaluating trends and correlations of volcanic characteristic and surface manifestation data from world power production sites in subduction zone volcanic settings. The focus of the work was to evaluate volcanic centers individually and as a group in these arcs by correlating various geologic characteristics with known potential to host electricity grade geothermal systems at the volcanic centers. A database was developed that describes key geologic factors expected to be indicative of productive geothermal systems in a global training set, which includes all 74 subduction zone volcanic centers world-wide with current or proven power production capability. Importantly, this data set only contains data from subduction zone volcanoes and contains no negative cases, limiting the populations of any statistical groups. Regardless, this is the most robust geothermal benchmark training set for magmatic-heated systems to date that has been made public. The work reported here is part of a larger project that included data collection, evaluation, correlations and weightings, fairway and favorability modeling and mapping, prediction of blind systems, and uncertainty analysis to estimate errors associated with model predictions. This first paper describes volcano characteristics, compositions and eruption ages and trends along with surface manifestation observations and temperatures as they relate to known power producing systems. Our findings show a strong correlation between the presence and size of active flank fumarole areas and installed power production. Additionally, the majority of volcanic characteristics, including long-held anecdotal correlations related to magmatic composition or size, have limited to no correlation with power production potential. Notable exceptions are correlations between greater power yield from geothermal systems associated with older (Pleistocene) caldera systems

  18. A Structurally Unresolved Head Segment of Defined Length Favors Proper Measles Virus Hemagglutinin Tetramerization and Efficient Membrane Fusion Triggering

    PubMed Central

    Navaratnarajah, Chanakha K.; Rosemarie, Quincy

    2015-01-01

    ABSTRACT Paramyxoviruses include several insidious and ubiquitous pathogens of humans and animals, with measles virus (MeV) being a prominent one. The MeV membrane fusion apparatus consists of a receptor binding protein (hemagglutinin [H]) tetramer and a fusion (F) protein trimer. Four globular MeV H heads are connected to a tetrameric stalk through flexible linkers. We sought here to characterize the function of a 17-residue H-head segment proximal to the stalk that was unresolved in all five MeV H-head crystal or cocrystal structures. In particular, we assessed whether its primary sequence and length are critical for proper protein oligomerization and intracellular transport or for membrane fusion triggering. Extensive alanine substitutions had no effect on fusion triggering, suggesting that sequence identity is not critical for this function. Excessive shortening of this segment reduced or completely abrogated fusion trigger function, while length compensation restored it. We then characterized the mechanism of function loss. Mutated H proteins were efficiently transported to the cell surface, but certain alterations enhancing linker flexibility resulted in accumulation of high-molecular-weight H oligomers. Some oligomers had reduced fusion trigger capacity, while others retained this function. Thus, length and rigidity of the unresolved head segment favor proper H tetramerization and counteract interactions between subunits from different tetramers. The structurally unresolved H-head segment, together with the top of the stalk, may act as a leash to provide the right degree of freedom for the heads of individual tetramers to adopt a triggering-permissive conformation while avoiding improper contacts with heads of neighboring tetramers. IMPORTANCE Understanding the molecular mechanism of membrane fusion triggering may allow development of new antiviral strategies. The fusion apparatus of paramyxoviruses consists of a receptor binding tetramer and a fusion

  19. Oncogenic transformation of mesenchymal stem cells decreases Nrf2 expression favoring in vivo tumor growth and poorer survival

    PubMed Central

    2014-01-01

    Background The transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious. Methods We employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided. Results We found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers. Conclusions Our data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and

  20. Does Government Subsidy Guide Private Universities towards Favorable Directions?: A Preliminary Analysis on Financial Data of Private Universities

    ERIC Educational Resources Information Center

    Li, Jianmin

    2010-01-01

    With the decreasing college-aged population and the transforming policy environment in Japan, private universities are confronted with management crises, such as bankruptcy, mergers, etc. As the second largest source of funding, government subsidies for private universities is considered to have contributed to enhancing educational conditions and…

  1. Impact of pavement conditions on crash severity.

    PubMed

    Li, Yingfeng; Liu, Chunxiao; Ding, Liang

    2013-10-01

    Pavement condition has been known as a key factor related to ride quality, but it is less clear how exactly pavement conditions are related to traffic crashes. The researchers used Geographic Information System (GIS) to link Texas Department of Transportation (TxDOT) Crash Record Information System (CRIS) data and Pavement Management Information System (PMIS) data, which provided an opportunity to examine the impact of pavement conditions on traffic crashes in depth. The study analyzed the correlation between several key pavement condition ratings or scores and crash severity based on a large number of crashes in Texas between 2008 and 2009. The results in general suggested that poor pavement condition scores and ratings were associated with proportionally more severe crashes, but very poor pavement conditions were actually associated with less severe crashes. Very good pavement conditions might induce speeding behaviors and therefore could have caused more severe crashes, especially on non-freeway arterials and during favorable driving conditions. In addition, the results showed that the effects of pavement conditions on crash severity were more evident for passenger vehicles than for commercial vehicles. These results provide insights on how pavement conditions may have contributed to crashes, which may be valuable for safety improvement during pavement design and maintenance. Readers should notice that, although the study found statistically significant effects of pavement variables on crash severity, the effects were rather minor in reality as suggested by frequency analyses.

  2. Coagulase-negative Staphylococci favor conversion of arginine into ornithine despite a widespread genetic potential for nitric oxide synthase activity.

    PubMed

    Sánchez Mainar, María; Weckx, Stefan; Leroy, Frédéric

    2014-12-01

    Within ecosystems that are poor in carbohydrates, alternative substrates such as arginine may be of importance to coagulase-negative staphylococci (CNS). However, the versatility of arginine conversion in CNS remains largely uncharted. Therefore, a set of 86 strains belonging to 17 CNS species was screened for arginine deiminase (ADI), arginase, and nitric oxide synthase (NOS) activities, in view of their ecological relevance. In fermented meats, for instance, ADI could improve bacterial competitiveness, whereas NOS may serve as an alternative nitrosomyoglobin generator to nitrate and nitrite curing. About 80% of the strains were able to convert arginine, but considerable inter- and intraspecies heterogeneity regarding the extent and mechanism of conversion was found. Overall, ADI was the most commonly employed pathway, resulting in mixtures of ornithine and small amounts of citrulline. Under aerobic conditions, which are more relevant for skin-associated CNS communities, several strains shifted toward arginase activity, leading to the production of ornithine and urea. The obtained data indeed suggest that arginase occurs relatively more in CNS isolates from a dairy environment, whereas ADI seems to be more abundant in strains from a fermented meat background. With some exceptions, a reasonable match between phenotypic ADI and arginase activity and the presence of the encoding genes (arcA and arg) was found. With respect to the NOS pathway, however, only one strain (Staphylococcus haemolyticus G110) displayed phenotypic NOS-like activity under aerobic conditions, despite a wide prevalence of the NOS-encoding gene (nos) among CNS. Hence, the group of CNS displays a strain- and condition-dependent toolbox of arginine-converting mechanisms with potential implications for competitiveness and functionality.

  3. Coagulase-Negative Staphylococci Favor Conversion of Arginine into Ornithine despite a Widespread Genetic Potential for Nitric Oxide Synthase Activity

    PubMed Central

    Sánchez Mainar, María; Weckx, Stefan

    2014-01-01

    Within ecosystems that are poor in carbohydrates, alternative substrates such as arginine may be of importance to coagulase-negative staphylococci (CNS). However, the versatility of arginine conversion in CNS remains largely uncharted. Therefore, a set of 86 strains belonging to 17 CNS species was screened for arginine deiminase (ADI), arginase, and nitric oxide synthase (NOS) activities, in view of their ecological relevance. In fermented meats, for instance, ADI could improve bacterial competitiveness, whereas NOS may serve as an alternative nitrosomyoglobin generator to nitrate and nitrite curing. About 80% of the strains were able to convert arginine, but considerable inter- and intraspecies heterogeneity regarding the extent and mechanism of conversion was found. Overall, ADI was the most commonly employed pathway, resulting in mixtures of ornithine and small amounts of citrulline. Under aerobic conditions, which are more relevant for skin-associated CNS communities, several strains shifted toward arginase activity, leading to the production of ornithine and urea. The obtained data indeed suggest that arginase occurs relatively more in CNS isolates from a dairy environment, whereas ADI seems to be more abundant in strains from a fermented meat background. With some exceptions, a reasonable match between phenotypic ADI and arginase activity and the presence of the encoding genes (arcA and arg) was found. With respect to the NOS pathway, however, only one strain (Staphylococcus haemolyticus G110) displayed phenotypic NOS-like activity under aerobic conditions, despite a wide prevalence of the NOS-encoding gene (nos) among CNS. Hence, the group of CNS displays a strain- and condition-dependent toolbox of arginine-converting mechanisms with potential implications for competitiveness and functionality. PMID:25281381

  4. The Impact of Individual Ability, Favorable Team Member Scores, and Student Perception of Course Importance on Student Preference of Team-Based Learning and Grading Methods

    ERIC Educational Resources Information Center

    Su, Allan Yen-Lun

    2007-01-01

    This study explores the impact of individual ability and favorable team member scores on student preference of team-based learning and grading methods, and examines the moderating effects of student perception of course importance on student preference of team-based learning and grading methods. The author also investigates the relationship…

  5. Evaluating Subtest "g" Saturation Levels via the Single Trait-Correlated Uniqueness (STCU) SEM Approach: Evidence in Favor of Crystallized Subtests as the Best Indicators of "g"

    ERIC Educational Resources Information Center

    Gignac, Gilles E.

    2006-01-01

    Several published claims have asserted that the general factor of intelligence derived from conventional intelligence batteries such as the Wechsler scales are biased in favor of verbal intelligence subtests, resulting in the observation of excessively large "g" factor loadings from these subtests. Using the single trait-correlated…

  6. The impact of individual ability, favorable team member scores, and student perception of course importance on student preference of team-based learning and grading methods.

    PubMed

    Su, Allan Yen-Lun

    2007-01-01

    This study explores the impact of individual ability and favorable team member scores on student preference of team-based learning and grading methods, and examines the moderating effects of student perception of course importance on student preference of team-based learning and grading methods. The author also investigates the relationship between student perception of course importance and their responses to social loafing. Results indicate that individual ability on the preference of team-based learning was affected by the three levels of favorable team member scores. For students with a low level of individual ability, the preference for team-based learning was significant among students with each of three levels of favorable team member scores (p < .05). However, the team-based learning and grading methods was not significant (p > .05). The findings also reveal a negative correlation between student perception of course importance and their responses to social loafing (p < .05). Findings note the importance of teachers' grading methods, student perceptions of course importance as well as individual ability and favorable team member scores in the team selection process to promote student attitude toward team-based learning.

  7. Preliminary assessment of the geochemistry and mineral favorability of the postorogenic granites of the southeastern Arabian Shield, Kingdom of Saudi Arabia

    USGS Publications Warehouse

    Stuckless, John S.; VanTrump, G.; Christiansen, E.H.; Bush, C.A.; Bunker, C.M.; Bartel, A.J.

    1983-01-01

    Further quantitative analysis is recommended to verify and accurately delineate anomalous concentrations of trace elements. Trend surface analysis of all available data for postorogenic granites from the eastern Arabian Shield is suggested as a method for testing regional variations in the protolith that might control locations of highly favorable areas of ore deposition.

  8. P300-based Stroop study with low probability and target Stroop oddballs: the evidence still favors the response selection hypothesis.

    PubMed

    Rosenfeld, J Peter; Skogsberg, Katieann R

    2006-06-01

    This paper addresses the issue of the locus of action in cognitive processing during Stroop effects. It uses the P300 latency to assess stimulus processing effects, but, for the first time, under conditions in which Stroop stimuli are rare and target stimuli. The study was also concerned with demonstrating that apparent P300s during verbal responding are in fact uninterpretable due to contamination of EEG by speech-related artifact. Three studies were presented. In Study 1, there were 3 blocks, each containing 1 of 3 types of rare Stroop stimuli (p = .15), congruent, neutral, and incongruent. There were also 3 response modes: button press (BUTTON), speaking aloud (VERBAL), and speaking to self (SILENT). Three sessions were used, each for a different response style. The only task was to name the color on each trial. In the 2 non-verbal blocks, Reaction Time (RT) varied by stimulus type; congruent < neutral < incongruent. P300 latency was the same across blocks in these non-verbal conditions in which one saw the classic Pz > Cz > Fz distribution. The much larger, speech artifact-contaminated "P300s" in the VERBAL blocks did suggest a Stroop effect, especially at Fz and Cz, where "P300s" were larger than at Pz. In Study 2, there were 2 response modes, VERBAL and SILENT, and only two rare Stroop stimuli; neutral and incongruent, 1 per block. In each of these blocks, one word-color combination was a designated target requiring a unique response. The subject was to name the color followed by a yes or no to categorize the target or non-target. Again the RT for incongruents was greater than RT for neutrals, without a parallel effect in P300 latency. Again, the rostral ERPs appeared artifactual in the VERBAL condition. Study 3 was a replication of the second study, except that motivated subjects, versus Psychology pool recruits, were used. The latency-RT correlation still failed to obtain. Thus, using classic P300-eliciting antecedents-rare and target (Stroop) stimuli

  9. Predictive value of isolated epileptiform discharges for a favorable therapeutic response to antiepileptic drugs in nonepileptic psychiatric patients.

    PubMed

    Boutros, Nash N; Kirollos, Sandra B; Pogarell, Oliver; Gallinat, Jürgen

    2014-02-01

    The efficacy of antiepileptic drugs (AEDs) in treating behavioral symptoms in nonepileptic psychiatric patients with abnormal EEGs is currently unknown. Although isolated epileptiform discharges have been reported in many psychiatric conditions, they are most commonly observed in patients with aggression, panic, or autistic spectrum disorders. The literature search was guided by 3 criteria: (1) studies had patients who did not experience seizures, (2) patients had EEGs, and (3) an AED was administered. Most important finding is that the number of "controlled" studies was extremely small. Overall, most reports suggest that the use of an AED can be associated with clinical and, at times, improved EEG abnormalities. Additionally, six controlled studies were found for other psychiatric disorders, such as learning disabilities with similar results. Overall, the use of anticonvulsants to treat nonepileptic psychiatric patients needs further controlled studies to better define indications, adequate EEG work-up, best AED to be used, and optimal durations of treatment attempts.

  10. Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects

    PubMed Central

    Gammella, Elena; Recalcati, Stefania; Cairo, Gaetano

    2016-01-01

    Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings. PMID:27006749

  11. Two poplar-associated bacterial isolates induce additive favorable responses in a constructed plant-microbiome system

    SciTech Connect

    Jawdy, Sara S.; Gunter, Lee E.; Engle, Nancy L.; Yang, Zamin Koo; Lu, Tse-Yuan S.; Tschaplinski, Timothy J.; Tuskan, Gerald A.; Doktycz, Mitchel John; Pelletier, Dale A.; Weston, David J.; Timm, Colin M.; Henning, Jeremiah A.; Aufrecht, Jayde; Gee, Emily; Nookaew, Intawat

    2016-04-26

    Here, the biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. In this work we study the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Inoculation individually with either bacterial isolate increased root growth relative to uninoculated controls. Root area, photosynthetic efficiency, gene expression and metabolite expression data in individual and dual inoculated treatments indicate that the effects of these bacteria are unique and additive, suggesting that the function of a microbiome community may be predicted from the additive functions of the individual members.

  12. Two poplar-associated bacterial isolates induce additive favorable responses in a constructed plant-microbiome system

    DOE PAGES

    Jawdy, Sara S.; Gunter, Lee E.; Engle, Nancy L.; ...

    2016-04-26

    Here, the biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. In this work we study the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Inoculation individually with either bacterial isolate increased root growth relative to uninoculated controls. Root area, photosynthetic efficiency, gene expression and metabolite expression data in individual and dual inoculated treatments indicate that the effects of these bacteria are unique and additive, suggesting that the function of a microbiome communitymore » may be predicted from the additive functions of the individual members.« less

  13. Opioid receptor agonists may favorably affect bone mechanical properties in rats with estrogen deficiency-induced osteoporosis.

    PubMed

    Janas, Aleksandra; Folwarczna, Joanna

    2017-02-01

    The results of epidemiological, clinical, and in vivo and in vitro experimental studies on the effect of opioid analgesics on bone are inconsistent. The aim of the present study was to investigate the effect of morphine (an agonist of opioid receptors), buprenorphine (a partial μ opioid receptor agonist and κ opioid receptor antagonist), and naloxone (an antagonist of opioid receptors) on the skeletal system of female rats in vivo. The experiments were carried out on 3-month-old Wistar rats, divided into two groups: nonovariectomized (intact; NOVX) rats and ovariectomized (OVX) rats. The bilateral ovariectomy was performed 7 days before the start of drug administration. Morphine hydrochloride (20 mg/kg/day s.c.), buprenorphine (0.05 mg/kg/day s.c.), or naloxone hydrochloride dihydrate (2 mg/kg/day s.c.) were administered for 4 weeks to NOVX and OVX rats. In OVX rats, the use of morphine and buprenorphine counteracted the development of osteoporotic changes in the skeletal system induced by estrogen deficiency. Morphine and buprenorphine beneficially affected also the skeletal system of NOVX rats, but the effects were much weaker than those in OVX rats. Naloxone generally did not affect the rat skeletal system. The results confirmed the role of opioid receptors in the regulation of bone remodeling processes and demonstrated, in experimental conditions, that the use of opioid analgesics at moderate doses may exert beneficial effects on the skeletal system, especially in estrogen deficiency.

  14. Two Poplar-Associated Bacterial Isolates Induce Additive Favorable Responses in a Constructed Plant-Microbiome System

    PubMed Central

    Timm, Collin M.; Pelletier, Dale A.; Jawdy, Sara S.; Gunter, Lee E.; Henning, Jeremiah A.; Engle, Nancy; Aufrecht, Jayde; Gee, Emily; Nookaew, Intawat; Yang, Zamin; Lu, Tse-Yuan; Tschaplinski, Timothy J.; Doktycz, Mitchel J.; Tuskan, Gerald A.; Weston, David J.

    2016-01-01

    The biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. The Populus root microbiome is a diverse community that has high abundance of β- and γ-Proteobacteria, both classes which include multiple plant-growth promoting representatives. To understand the contribution of individual microbiome members in a community, we studied the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Both strains increased lateral root formation and root hair production in Arabidopsis plate assays and are predicted to encode for different functions related to growth and plant growth promotion in Populus hosts. Inoculation individually, with either bacterial isolate, increased root growth relative to uninoculated controls, and while root area was increased in mixed inoculation, the interaction term was insignificant indicating additive effects of root phenotype. Complementary data including photosynthetic efficiency, whole-transcriptome gene expression and GC-MS metabolite expression data in individual and mixed inoculated treatments indicate that the effects of these bacterial strains are unique and additive. These results suggest that the function of a microbiome community may be predicted from the additive functions of the individual members. PMID:27200001

  15. The effects of an intervention to increase liberal arts mathematics and science majors' knowledge of and attitudinal favorability toward the teaching profession

    NASA Astrophysics Data System (ADS)

    Klemballa, Carolyn

    In light of the persistent shortage of qualified mathematics and science teachers and the new teacher qualification provisions of the recently passed No Child Left Behind Act, This study tested the impact of an educational intervention designed to enhance interest in public school teaching careers among undergraduate students who were declared/intended majors in mathematics and/or natural science. Besides salary, research reveals content fear as the biggest roadblock to attracting mathematics and science teachers. Because of this, liberal arts majors in mathematics and science are a target pool of individuals to recruit into teaching. The researcher hypothesized that knowledge and attitudinal favorability would both increase after an intervention about teaching careers and that an increase in one variable would be associated with the other. Also, knowledge and attitudinal favorability would have a greater increase after a more intensive intervention than a less intensive intervention or no intervention. The researcher also hypothesized that if undergraduates were less decided in their career, lower classmen, and female, their attitudes toward the teaching profession would increase the most. One hundred eighty-nine college students, 73 males and 116 females, including 85 freshmen, 67 sophomores, 18 juniors and 19 seniors, at University A and University B were randomly assigned to a workshop, reading, or control group. The workshop group attended a workshop about the teaching profession. The reading group read articles with the same information presented in the workshop. The control group read unrelated articles. The findings from this study indicate that an intervention about teaching does significantly increase both knowledge and attitudinal favorability toward teaching (p < .01). A low significant correlation was found between knowledge and attitudinal favorability (p < .05). Findings also suggested that a more intensive intervention yields a higher increase in

  16. Fraction SX of maitake mushroom favorably influences blood glucose levels and blood pressure in streptozotocin-induced diabetic rats.

    PubMed

    Preuss, Harry G; Echard, Bobby; Fu, Jia; Perricone, Nicholas V; Bagchi, Debasis; Kaylor, Mark; Zhuang, Cun

    2012-10-01

    We assessed whether fraction SX derived from maitake mushroom could play a beneficial role in the treatment of a laboratory model of type-1 diabetes by decreasing circulating glucose levels and lowering blood pressure (BP). We injected 50 mg/kg body weight (BW) streptozotocin (STZ) intraperitoneally (i.p.) into 48 male Sprague-Dawley rats (SD) to produce a laboratory model of type-1 diabetes. SD were divided into four groups of 12 SD. A control group ate straight pulverized rat chow. To three treatment groups, we added into the pulverized rat chow: gliclazide (10 mg/kg), pioglitazone (10-30 mg/kg), or maitake SX (2.5 g/kg). In addition to measuring BW, circulating glucose level, and BP, the following procedures were also carried out: insulin challenge (insulin sensitivity), losartan challenge (renin-angiotensin system activity), Nw-nitro-L arginine-methyl ester hydrochloride (LNAME) challenge (nitric oxide [NO] system activity), and evaluation of serum angiotensin converting enzyme (ACE) activity. All treatments compared with control generally decreased circulating glucose levels, but only the maitake SX consistently enhanced measured insulin sensitivity. We found that maitake SX could significantly lower systolic blood pressure (SBP) in diabetic SD. In general, only SD receiving maitake SX, not the two drugs, showed decreased activity of the renin-angiotensin system and increased NO system activity compared with control under the conditions examined. Our results suggest that maitake SX may be useful for treating perturbations in glucose-insulin metabolism and elevated BP in type-1 diabetes.

  17. Principal Eigenvalue Minimization for an Elliptic Problem with Indefinite Weight and Robin Boundary Conditions

    SciTech Connect

    Hintermueller, M.; Kao, C.-Y.; Laurain, A.

    2012-02-15

    This paper focuses on the study of a linear eigenvalue problem with indefinite weight and Robin type boundary conditions. We investigate the minimization of the positive principal eigenvalue under the constraint that the absolute value of the weight is bounded and the total weight is a fixed negative constant. Biologically, this minimization problem is motivated by the question of determining the optimal spatial arrangement of favorable and unfavorable regions for a species to survive. For rectangular domains with Neumann boundary condition, it is known that there exists a threshold value such that if the total weight is below this threshold value then the optimal favorable region is like a section of a disk at one of the four corners; otherwise, the optimal favorable region is a strip attached to the shorter side of the rectangle. Here, we investigate the same problem with mixed Robin-Neumann type boundary conditions and study how this boundary condition affects the optimal spatial arrangement.

  18. PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

    PubMed Central

    Kim, Hye Ryun; Ha, Sang-Jun; Hong, Min Hee; Heo, Su Jin; Koh, Yoon Woo; Choi, Eun Chang; Kim, Eun Kyung; Pyo, Kyoung Ho; Jung, Inkyung; Seo, Daekwan; Choi, Jaewoo; Cho, Byoung Chul; Yoon, Sun Och

    2016-01-01

    To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3+ or CD8+ TILs, Foxp3+ Tregs, and PD-1+ TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1+ T cells and Foxp3+ Tregs are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC. PMID:27841362

  19. Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan.

    PubMed

    Hirokawa, Katsuiku; Utsuyama, Masanori; Kikuchi, Yuko

    2016-02-01

    High level of growth hormone (GH) is necessary for the activation of thymic function to promote T cell differentiation in the early stage of animal life. In the later stage of the life, administration of GH promotes the development of immune system and rejuvenates declined immune function of elderly people. By contraries, GH deficiency is favorable for the longer lifespan, as hypo-pituitary dwarf mice such as Ames and Snell dwarf mice exhibit longer lifespan than control. Furthermore over-expression of heterologous or homologous GH in transgenic mice shortens the lifespan. Ecuadorians carrying mutations of GH receptor gene are short in height, but exhibited low frequency of malignancy and no cases of diabetes. These data indicate that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH.

  20. Fracture Analysis of Vessels. Oak Ridge FAVOR, v06.1, Computer Code: Theory and Implementation of Algorithms, Methods, and Correlations

    SciTech Connect

    Williams, P. T.; Dickson, T. L.; Yin, S.

    2007-12-01

    The current regulations to insure that nuclear reactor pressure vessels (RPVs) maintain their structural integrity when subjected to transients such as pressurized thermal shock (PTS) events were derived from computational models developed in the early-to-mid 1980s. Since that time, advancements and refinements in relevant technologies that impact RPV integrity assessment have led to an effort by the NRC to re-evaluate its PTS regulations. Updated computational methodologies have been developed through interactions between experts in the relevant disciplines of thermal hydraulics, probabilistic risk assessment, materials embrittlement, fracture mechanics, and inspection (flaw characterization). Contributors to the development of these methodologies include the NRC staff, their contractors, and representatives from the nuclear industry. These updated methodologies have been integrated into the Fracture Analysis of Vessels -- Oak Ridge (FAVOR, v06.1) computer code developed for the NRC by the Heavy Section Steel Technology (HSST) program at Oak Ridge National Laboratory (ORNL). The FAVOR, v04.1, code represents the baseline NRC-selected applications tool for re-assessing the current PTS regulations. This report is intended to document the technical bases for the assumptions, algorithms, methods, and correlations employed in the development of the FAVOR, v06.1, code.

  1. Genetic Analysis in Maize Foundation Parents with Mapping Population and Testcross Population: Ye478 Carried More Favorable Alleles and Using QTL Information Could Improve Foundation Parents.

    PubMed

    Liu, Yinghong; Hou, Xianbin; Xiao, Qianlin; Yi, Qiang; Bian, Shaowei; Hu, Yufeng; Liu, Hanmei; Zhang, Junjie; Hao, Xiaoqin; Cheng, Weidong; Li, Yu; Huang, Yubi

    2016-01-01

    The development of maize foundation parents is an important part of genetics and breeding research, and applying new genetic information to produce foundation parents has been challenging. In this study, we focused on quantitative trait loci (QTLs) and general combining ability (GCA) of Ye478, a widely used foundation parent in China. We developed three sets of populations for QTL mapping and to analyze the GCA for some agronomic traits. The assessment of 15 traits resulted in the detection of 251 QTLs in six tested environments, with 119 QTLs identified through a joint analysis across all environments. Further, analyses revealed that most favorable alleles for plant type-related traits were from Ye478, and more than half of the favorable alleles for yield-related traits were from R08, another foundation parent used in southwestern China, suggesting that different types of foundation parents carried different favorable alleles. We observed that the GCA for most traits (e.g., plant height and 100-kernel weight) was maintained in the inbred lines descended from the foundation parents. Additionally, the continuous improvement in the GCA of the descendants of the foundation parents was consistent with the main trend in maize breeding programs. We identified three significant genomic regions that were highly conserved in three Ye478 descendants, including the stable QTL for plant height. The GCA for the traits in the F7 generation revealed that the QTLs for the given traits per se were affected by additive effects in the same way in different populations.

  2. Pedagogical Conditions of Ensuring Students' Readiness for Scientific Researches--Example of Technical University

    ERIC Educational Resources Information Center

    Slessarev, Yuri Vassilyevich; Moisseyev, Vassily Borisovich; Vostroknutov, Evgeniy Vladimirovich

    2015-01-01

    This article describes pedagogical conditions of ensuring students readiness for scientific researches on the basis of scientific literature and experience of Penza State Technological University students. Introduction of suggested conditions favors the process of training of highly skilled expert who is ready for generation of new ideas in fields…

  3. Skin Condition Finder

    MedlinePlus

    ... SKIN CONDITIONS HEALTH TOPICS FOR PROFESSIONALS Rash and Skin Condition Finder 1 Select Age Group Infant Child ... Toe Toe Webspace Toe Nail CLOSE About the Skin Condition Finder Have a health question or concern? ...

  4. Paralysis: Secondary Conditions

    MedlinePlus

    ... 5pm ET. 1-800-539-7309 ☰ Living with Paralysis Get Support Get Involved Research Events Blog & Forum About Us Donate Living with Paralysis > Health > Secondary conditions Secondary conditions Secondary conditions refer ...

  5. Chinese Conditionals and the Theory of Conditionals.

    ERIC Educational Resources Information Center

    Chierchia, Gennaro

    2000-01-01

    Summarizes the main features of discourse representation theory, situation-based approaches, and dynamic semantics, and discusses the role the novelty condition plays in each of them, providing the main theoretical coordinates against which to try an assessment of the role of the Chinese conditional and a proposal put forth by Chang and Huang…

  6. Competition between rhizobia under different environmental conditions affects the nodulation of a legume.

    PubMed

    Ji, Zhao Jun; Yan, Hui; Cui, Qing Guo; Wang, En Tao; Chen, Wen Feng; Chen, Wen Xin

    2017-03-01

    Mutualistic symbiosis and nitrogen fixation of legume rhizobia play a key role in ecological environments. Although many different rhizobial species can form nodules with a specific legume, there is often a dominant microsymbiont, which has the highest nodule occupancy rates, and they are often known as the "most favorable rhizobia". Shifts in the most favorable rhizobia for a legume in different geographical regions or soil types are not well understood. Therefore, in order to explore the shift model, an experiment was designed using successive inoculations of rhizobia on one legume. The plants were grown in either sterile vermiculite or a sandy soil. Results showed that, depending on the environment, a legume could select its preferential rhizobial partner in order to establish symbiosis. For perennial legumes, nodulation is a continuous and sequential process. In this study, when the most favorable rhizobial strain was available to infect the plant first, it was dominant in the nodules, regardless of the existence of other rhizobial strains in the rhizosphere. Other rhizobial strains had an opportunity to establish symbiosis with the plant when the most favorable rhizobial strain was not present in the rhizosphere. Nodule occupancy rates of the most favorable rhizobial strain depended on the competitiveness of other rhizobial strains in the rhizosphere and the environmental adaptability of the favorable rhizobial strain (in this case, to mild vermiculite or hostile sandy soil). To produce high nodulation and efficient nitrogen fixation, the most favorable rhizobial strain should be selected and inoculated into the rhizosphere of legume plants under optimum environmental conditions.

  7. Surprising coordination for plutonium in the first plutonium(III) borate.

    PubMed

    Wang, Shuao; Alekseev, Evgeny V; Depmeier, Wulf; Albrecht-Schmitt, Thomas E

    2011-03-21

    The first plutonium(III) borate, Pu(2)[B(12)O(18)(OH)(4)Br(2)(H(2)O)(3)]·0.5H(2)O, has been prepared by reacting plutonium(III) with molten boric acid under strictly anaerobic conditions. This compound contains a three-dimensional polyborate network with triangular holes that house the plutonium(III) sites. The plutonium sites in this compound are 9- and 10-coordinate and display atypical geometries.

  8. REACH. Air Conditioning Units.

    ERIC Educational Resources Information Center

    Garrison, Joe; And Others

    As a part of the REACH (Refrigeration, Electro-Mechanical, Air-Conditioning, Heating) electromechanical cluster, this student manual contains individualized instructional units in the area of air conditioning. The instructional units focus on air conditioning fundamentals, window air conditioning, system and installation, troubleshooting and…

  9. Genetic Analysis in Maize Foundation Parents with Mapping Population and Testcross Population: Ye478 Carried More Favorable Alleles and Using QTL Information Could Improve Foundation Parents

    PubMed Central

    Liu, Yinghong; Hou, Xianbin; Xiao, Qianlin; Yi, Qiang; Bian, Shaowei; Hu, Yufeng; Liu, Hanmei; Zhang, Junjie; Hao, Xiaoqin; Cheng, Weidong; Li, Yu; Huang, Yubi

    2016-01-01

    The development of maize foundation parents is an important part of genetics and breeding research, and applying new genetic information to produce foundation parents has been challenging. In this study, we focused on quantitative trait loci (QTLs) and general combining ability (GCA) of Ye478, a widely used foundation parent in China. We developed three sets of populations for QTL mapping and to analyze the GCA for some agronomic traits. The assessment of 15 traits resulted in the detection of 251 QTLs in six tested environments, with 119 QTLs identified through a joint analysis across all environments. Further, analyses revealed that most favorable alleles for plant type-related traits were from Ye478, and more than half of the favorable alleles for yield-related traits were from R08, another foundation parent used in southwestern China, suggesting that different types of foundation parents carried different favorable alleles. We observed that the GCA for most traits (e.g., plant height and 100-kernel weight) was maintained in the inbred lines descended from the foundation parents. Additionally, the continuous improvement in the GCA of the descendants of the foundation parents was consistent with the main trend in maize breeding programs. We identified three significant genomic regions that were highly conserved in three Ye478 descendants, including the stable QTL for plant height. The GCA for the traits in the F7 generation revealed that the QTLs for the given traits per se were affected by additive effects in the same way in different populations. PMID:27721817

  10. Cohorts based on Decade of Death: No Evidence for Secular Trends Favoring Later Cohorts in Cognitive Aging and Terminal Decline in the AHEAD Study

    PubMed Central

    Hülür, Gizem; Infurna, Frank J.; Ram, Nilam; Gerstorf, Denis

    2012-01-01

    Studies of birth-year cohorts examined over the same age range often report secular trends favoring later-born cohorts, who are cognitively fitter and show less steep cognitive declines than earlier-born cohorts. However, there is initial evidence that those advantages of later-born cohorts do not carry into the last years of life, suggesting that pervasive mortality-related processes minimize differences that were apparent earlier in life. Elaborating this work from an alternative perspective on cohort differences, we compared rates of cognitive aging and terminal decline in episodic memory between cohorts based on the year participants had died, earlier (between 1993 and 1999) or later in historical time (between 2000 and 2010). Specifically, we compared trajectories of cognitive decline in two death-year cohorts of participants in the Asset and Health Dynamics among the Oldest Old (AHEAD) Study that were matched on age at death and education and controlled for a variety of additional covariates. Results revealed little evidence of secular trends favoring later cohorts. To the contrary, the cohort that died in the 2000s showed a less favorable trajectory of age-related memory decline than the cohort who died in the 1990s. In examinations of change in relation to time-to-death, the cohort dying in the 2000s experienced even steeper terminal declines than the cohort dying in the 1990s. We suggest that secular increases in “manufacturing” survival may exacerbate age- and mortality-related cognitive declines among the oldest old. PMID:23046001

  11. “Covalent Hydration” Reactions in Model Monomeric Ru 2,2'-Bipyridine Complexes: Thermodynamic Favorability as a Function of Metal Oxidation and Overall Spin States

    SciTech Connect

    Ozkanlar, Abdullah; Cape, Jonathan L.; Hurst, James K.; Clark, Aurora E.

    2011-09-05

    Density functional theory (DFT) has been used to investigate the plausibility of water addition to the simple mononuclear ruthenium complexes, [(NH{sub 3}){sub 3}(bpy)Ru=O]{sup 2+}/{sup 3+} and [(NH{sub 3}){sub 3}(bpy)RuOH]{sup 3+}, in which the OH fragment adds to the 2,2{prime}-bipyridine (bpy) ligand. Activation of bpy toward water addition has frequently been postulated within the literature, although there exists little definitive experimental evidence for this type of 'covalent hydration'. In this study, we examine the energetic dependence of the reaction upon metal oxidation state, overall spin state of the complex, as well as selectivity for various positions on the bipyridine ring. The thermodynamic favorability is found to be highly dependent upon all three parameters, with free energies of reaction that span favorable and unfavorable regimes. Aqueous addition to [(NH{sub 3}){sub 3}(bpy)Ru=O]{sup 3+} was found to be highly favorable for the S = 1/2 state, while reduction of the formal oxidation state on the metal center makes the reaction highly unfavorable. Examination of both facial and meridional isomers reveals that when bipyridine occupies the position trans to the ruthenyl oxo atom, reactivity toward OH addition decreases and the site preferences are altered. The electronic structure and spectroscopic signatures (EPR parameters and simulated spectra) have been determined to aid in recognition of 'covalent hydration' in experimental systems. EPR parameters are found to uniquely characterize the position of the OH addition to the bpy as well as the overall spin state of the system.

  12. Species Selection Favors Dispersive Life Histories in Sea Slugs, but Higher Per-Offspring Investment Drives Shifts to Short-Lived Larvae

    PubMed Central

    Krug, Patrick J.; Vendetti, Jann E.; Ellingson, Ryan A.; Trowbridge, Cynthia D.; Hirano, Yayoi M.; Trathen, Danielle Y.; Rodriguez, Albert K.; Swennen, Cornelis; Wilson, Nerida G.; Valdés, Ángel A.

    2015-01-01

    For 40 years, paleontological studies of marine gastropods have suggested that species selection favors lineages with short-lived (lecithotrophic) larvae, which are less dispersive than long-lived (planktotrophic) larvae. Although lecithotrophs appeared to speciate more often and accumulate over time in some groups, lecithotrophy also increased extinction rates, and tests for state-dependent diversification were never performed. Molecular phylogenies of diverse groups instead suggested lecithotrophs accumulate without diversifying due to frequent, unidirectional character change. Although lecithotrophy has repeatedly originated in most phyla, no adult trait has been correlated with shifts in larval type. Thus, both the evolutionary origins of lecithotrophy and its consequences for patterns of species richness remain poorly understood. Here, we test hypothesized links between development mode and evolutionary rates using likelihood-based methods and a phylogeny of 202 species of gastropod molluscs in Sacoglossa, a clade of herbivorous sea slugs. Evolutionary quantitative genetics modeling and stochastic character mapping supported 27 origins of lecithotrophy. Tests for correlated evolution revealed lecithotrophy evolved more often in lineages investing in extra-embryonic yolk, the first adult trait associated with shifts in development mode across a group. However, contrary to predictions from paleontological studies, species selection actually favored planktotrophy; most extant lecithotrophs originated through recent character change, and did not subsequently diversify. Increased offspring provisioning in planktotrophs thus favored shifts to short-lived larvae, which led to short-lived lineages over macroevolutionary time scales. These findings challenge long-standing assumptions about the effects of alternative life histories in the sea. Species selection can explain the long-term persistence of planktotrophy, the ancestral state in most clades, despite frequent

  13. Early-Stage Hyperoxia Is Associated with Favorable Neurological Outcomes and Survival after Severe Traumatic Brain Injury: A Post-Hoc Analysis of the Brain Hypothermia Study.

    PubMed

    Fujita, Motoki; Oda, Yasutaka; Yamashita, Susumu; Kaneda, Kotaro; Kaneko, Tadashi; Suehiro, Eiichi; Dohi, Kenji; Kuroda, Yasuhiro; Kobata, Hitoshi; Tsuruta, Ryosuke; Maekawa, Tsuyoshi

    2017-01-19

    The effects of hyperoxia on the neurological outcomes of patients with severe traumatic brain injury (TBI) are still controversial. We examined whether the partial pressure of arterial oxygen (PaO2) and hyperoxia were associated with neurological outcomes and survival by conducting post-hoc analyses of the Brain Hypothermia (B-HYPO) study, a multi-center randomized controlled trial of mild therapeutic hypothermia for severe TBI. The differences in PaO2 and PaO2/fraction of inspiratory oxygen (P/F) ratio on the 1st day of admission were compared between patients with favorable (n = 64) and unfavorable (n = 65) neurological outcomes and between survivors (n = 90) and deceased patients (n = 39). PaO2 and the P/F ratio were significantly greater in patients with favorable outcomes than in patients with unfavorable neurological outcomes (PaO2: 252 ± 122 vs. 202 ± 87 mm Hg, respectively, p = 0.008; P/F ratio: 455 ± 171 vs. 389 ± 155, respectively, p = 0.022) and in survivors than in deceased patients (PaO2: 242 ± 117 vs. 193 ± 75 mm Hg, respectively, p = 0.005; P/F ratio: 445 ± 171 vs. 370 ± 141, respectively, p = 0.018). Similar tendencies were observed in subgroup analyses in patients with fever control and therapeutic hypothermia, and in patients with an evacuated mass or other lesions (unevacuated lesions). PaO2 was independently associated with survival (odds ratio 1.008, p = 0.037). These results suggested that early-stage hyperoxia might be associated with favorable neurological outcomes and survival following severe TBI.

  14. Defectors Can Create Conditions That Rescue Cooperation

    PubMed Central

    Waite, Adam James; Cannistra, Caroline; Shou, Wenying

    2015-01-01

    Cooperation based on the production of costly common goods is observed throughout nature. This is puzzling, as cooperation is vulnerable to exploitation by defectors which enjoy a fitness advantage by consuming the common good without contributing fairly. Depletion of the common good can lead to population collapse and the destruction of cooperation. However, population collapse implies small population size, which, in a structured population, is known to favor cooperation. This happens because small population size increases variability in cooperator frequency across different locations. Since individuals in cooperator-dominated locations (which are most likely cooperators) will grow more than those in defector-dominated locations (which are most likely defectors), cooperators can outgrow defectors globally despite defectors outgrowing cooperators in each location. This raises the possibility that defectors can lead to conditions that sometimes rescue cooperation from defector-induced destruction. We demonstrate multiple mechanisms through which this can occur, using an individual-based approach to model stochastic birth, death, migration, and mutation events. First, during defector-induced population collapse, defectors occasionally go extinct before cooperators by chance, which allows cooperators to grow. Second, empty locations, either preexisting or created by defector-induced population extinction, can favor cooperation because they allow cooperator but not defector migrants to grow. These factors lead to the counterintuitive result that the initial presence of defectors sometimes allows better survival of cooperation compared to when defectors are initially absent. Finally, we find that resource limitation, inducible by defectors, can select for mutations adaptive to resource limitation. When these mutations are initially present at low levels or continuously generated at a moderate rate, they can favor cooperation by further reducing local population size

  15. Defectors Can Create Conditions That Rescue Cooperation.

    PubMed

    Waite, Adam James; Cannistra, Caroline; Shou, Wenying

    2015-12-01

    Cooperation based on the production of costly common goods is observed throughout nature. This is puzzling, as cooperation is vulnerable to exploitation by defectors which enjoy a fitness advantage by consuming the common good without contributing fairly. Depletion of the common good can lead to population collapse and the destruction of cooperation. However, population collapse implies small population size, which, in a structured population, is known to favor cooperation. This happens because small population size increases variability in cooperator frequency across different locations. Since individuals in cooperator-dominated locations (which are most likely cooperators) will grow more than those in defector-dominated locations (which are most likely defectors), cooperators can outgrow defectors globally despite defectors outgrowing cooperators in each location. This raises the possibility that defectors can lead to conditions that sometimes rescue cooperation from defector-induced destruction. We demonstrate multiple mechanisms through which this can occur, using an individual-based approach to model stochastic birth, death, migration, and mutation events. First, during defector-induced population collapse, defectors occasionally go extinct before cooperators by chance, which allows cooperators to grow. Second, empty locations, either preexisting or created by defector-induced population extinction, can favor cooperation because they allow cooperator but not defector migrants to grow. These factors lead to the counterintuitive result that the initial presence of defectors sometimes allows better survival of cooperation compared to when defectors are initially absent. Finally, we find that resource limitation, inducible by defectors, can select for mutations adaptive to resource limitation. When these mutations are initially present at low levels or continuously generated at a moderate rate, they can favor cooperation by further reducing local population size

  16. TARGET Researchers Identify Mutations in SIX1/2 and microRNA Processing Genes in Favorable Histology Wilms Tumor | Office of Cancer Genomics

    Cancer.gov

    TARGET researchers molecularly characterized favorable histology Wilms tumor (FHWT), a pediatric renal cancer. Comprehensive genome and transcript analyses revealed single-nucleotide substitution/deletion mutations in microRNA processing genes (15% of FHWT patients) and Sine Oculis Homeobox Homolog 1/2 (SIX1/2) genes (7% of FHWT patients). SIX1/2 genes play a critical role in renal development and were not previously associated with FHWT, thus presenting a novel role for SIX1/2 pathway aberrations in this disease.

  17. Ojibwe lesbian visual AIDS: On the Red Road with Carole laFavor, Her Giveaway (1988), and Native LGBTQ2 film history.

    PubMed

    Estrada, Gabriel

    2016-01-01

    After a century of suppression across the Silent, Classic, and New Hollywood eras, Native Lesbian/Gay media began to proliferate in the post-AIDS 1980s and into the second millennium. Her Giveaway: A Spiritual Journey with AIDS (1988) is a key tribal health AIDS video that exemplified a new contemporary media combination of visual, erotic, and theological sovereignty. The video's central Red Road narrative by the lesbian, Ojibwe, and AIDS/HIV+ spokesperson Carole laFavor emphasizes Native American traditional healing methods involving the medicine wheel and a reclamation of Native lesbian/gay identity.

  18. L-leucine supplementation worsens the adiposity of already obese rats by promoting a hypothalamic pattern of gene expression that favors fat accumulation.

    PubMed

    Zampieri, Thais T; Torres-Leal, Francisco L; Campaña, Amanda B; Lima, Fabio B; Donato, Jose

    2014-04-02

    Several studies showed that l-leucine supplementation reduces adiposity when provided before the onset of obesity. We studied rats that were exposed to a high-fat diet (HFD) for 10 weeks before they started to receive l-leucine supplementation. Fat mass was increased in l-leucine-supplemented rats consuming the HFD. Accordingly, l-leucine produced a hypothalamic pattern of gene expression that favors fat accumulation. In conclusion, l-leucine supplementation worsened the adiposity of rats previously exposed to HFD possibly by central mechanisms.

  19. Role of Steel Object Surface Condition on Behavior During Deformation

    NASA Astrophysics Data System (ADS)

    D'yachenko, S. S.; Ponomarenko, I. V.; Dub, S. N.

    2015-09-01

    Comparative analysis is provided for specimen mechanical properties of steels 18KhGT and 20Kh with tensile testing in relation to surface treatment: grinding, polishing, nitriding, carburizing, and ion-plasma treatment. It is shown that surface condition has a considerable effect on specimen behavior during deformation. It is established that the most favorable effect applies to ion bombardment with low-energy ions recommended as an effective method for improving component structural strength.

  20. Decompressing Emulsion Droplets Favors Coalescence

    NASA Astrophysics Data System (ADS)

    Bremond, Nicolas; Thiam, Abdou R.; Bibette, Jérôme

    2008-01-01

    The destabilization process of an emulsion under flow is investigated in a microfluidic device. The experimental approach enables us to generate a periodic train of droplet pairs, and thus to isolate and analyze the basic step of the destabilization, namely, the coalescence of two droplets which collide. We demonstrate a counterintuitive phenomenon: coalescence occurs during the separation phase and not during the impact. Separation induces the formation of two facing nipples in the contact area that hastens the connection of the interfaces prior to fusion. Moreover, droplet pairs initially stabilized by surfactants can be destabilized by forcing the separation. Finally, we note that the fusion mechanism is responsible for a cascade of coalescence events in a compact system of droplets where the separation is driven by surface tension.

  1. Selecting Presuppositions in Conditional Clauses. Results from a Psycholinguistic Experiment

    PubMed Central

    Domaneschi, Filippo; Carrea, Elena; Penco, Carlo; Greco, Alberto

    2016-01-01

    In this paper, we propose an experiment concerning presupposition selection in conditional sentences containing a presupposition trigger in the consequent. Many theories claim that sentences like if p, qq'—where q is the presupposition of the assertive component q'—have unconditional presuppositions, namely, they simply project q. Other theories suggest that these kinds of conditional sentences project conditional presuppositions of the form if p, q. Data collected suggest two results: (i) in accordance with other experiments (by Romoli), dependence between the presupposition q and the antecedent p favors the selection of a conditional presupposition if p, q. (ii) presupposition selection in conditional sentences with a trigger in the consequent is affected by speakers' cognitive load: if speakers are highly cognitive loaded, then they are less disposed to select a conditional presupposition. We conclude by arguing that cognitive load represents a key factor for the analysis of linguistic and philosophical theories of context. PMID:26793146

  2. The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation

    SciTech Connect

    Hoppe, R.T.; Kushlan, P.; Kaplan, H.S.; Rosenberg, S.A.; Brown, B.W.

    1981-09-01

    Between 1975 and 1978, 51 patients with favorable histology non-Hodgkin's lymphomas, pathologic stage III-IV, were treated prospectively on a randomized treatment protocol. Treatment options were single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP), or fractionated whole body irradiation followed by low dose involved field irradiation. The median follow-up interval in this group of patients is not 41 mo. Actuarial survival is excellent, 84% at 4 yr for the entire group, with similar survival observed for each of the three treatment options. Initial complete remission rates (64%, 88%, and 71%) were not significantly different in the three treatment arms. Frequent relapse after initial remission induction was noted, however, with a freedom from relapse at 4 yr of only 25%. The toxicities of the three therapies were acceptable. Acute complications of therapy were most numerous in the group of patients treated with CVP; however, long-term hematologic depression was most commonly observed in patients treated with whole body irradiation. In general, hematologic complications were more frequent among patients who had marrow involvement and intact spleens at the time of initial therapy. The relationship of this study to other clinical trials in the management of patients with advanced stage favorable histology lymphomas and its implications for future clinical trials are discussed.

  3. Characteristics of the Middle Jurassic marine source rocks and prediction of favorable source rock kitchens in the Qiangtang Basin of Tibet

    NASA Astrophysics Data System (ADS)

    Ding, Wenlong; Wan, Huan; Zhang, Yeqian; Han, Guangzhi

    2013-04-01

    We have evaluated the hydrocarbon-bearing potential of Middle Jurassic marine source rocks in the Qiangtang Basin, Tibet, through a comprehensive study of samples from a large number of surface outcrops in different structural units, and from the Qiang-D2 Well in the southern Qiangtang Depression. Data that were acquired, including the depositional environment, thickness of sedimentary units, and organic geochemistry, are used to identify the principal controlling factors and predict the location of favorable hydrocarbon kitchens. The source rocks are mainly platform limestone of the Middle Jurassic Buqu Formation. This formation comprises a suite of intra-platform sag marls, micrites, and black shales that were deposited in a deep-water and restricted depositional environment. The marls form hydrocarbon-rich source rocks with organic matter that is mainly type II and in the mature to highly mature stage. In the Dongco-Hulu Lake and Tupoco-Baitan Lake deep sags, limestone also forms a medium-level source rock. In the Qiangtang Basin, limestone is the favorable source rock kitchen and is more significant in this regard than mudstone. The results provide important constraints on evaluating the hydrocarbon potential of Jurassic marine source rocks and for locating petroleum resources in the Qiangtang Basin.

  4. Favorable cardiovascular risk factor profile is associated with reduced prevalence of coronary artery calcification and inflammation in asymptomatic nondiabetic white men.

    PubMed

    Michos, Erin D; Santos, Raul D; Narla, Venkata; Pandey, Shivda; Meneghelo, Romeu; Carvalho, Jose A; Budoff, Matthew J; Blumenthal, Roger S; Nasir, Khurram

    2008-01-01

    Middle-aged individuals with favorable levels of all major cardiovascular risk factors (CVRFs) have much lower age-specific risks for incident cardiovascular disease (CVD). However, the relationship of the absence of CVRFs with subclinical CVD and inflammation is not well described. We classified 440 asymptomatic Brazilian men (aged 46+/-7 years) based on the number of CVRFs (smoking, systolic blood pressure > or =130 mm Hg, low-density lipoprotein cholesterol > or =130 mg/dL, high-density lipoprotein cholesterol <40 mg/dL, triglycerides > or =150 mg/dL, fasting glucose > or =100 mg/dL, and waist circumference >102 cm). Only 7% had no CVRFs, whereas 1, 2, 3, and > or =4 CVRFs were observed in 18%, 24%, 21%, and 29%, respectively. In age-adjusted analysis, each lower CVRF profile was associated with lower odds of prevalent coronary artery calcium (odds ratio, 0.75; P=.002) and elevated white blood cell count (odds ratio, 0.70; P<.001). Our study supports the notion that a favorable CVD profile is associated with less underlying atherosclerosis and inflammation and further highlights the importance of primary prevention of CVRFs.

  5. Diseases and Conditions

    MedlinePlus

    ... Home 4 Ways to Find Exposures Related Health Concerns Wars & Operations Exposure Categories A-Z Index Agent ... Conditions Diseases & Conditions Index Military Exposure Related Health Concerns Gulf War Veterans' Illnesses Influenza (Flu) Influenza (Flu) ...

  6. Mean Atmospheric Conditions - Australian Tropical Operating Conditions.

    DTIC Science & Technology

    1981-10-01

    The ARDU mean tropical atmosphere differs significantly from the ICAO standard atmosphere and is based upon data gathered prior to 1965. More recent...atmosphere and the ICAO atmosphere to describe mean conditions in their respective regions of application. It is recommended, however, that where extreme

  7. Inflation of Conditional Predictions

    ERIC Educational Resources Information Center

    Koriat, Asher; Fiedler, Klaus; Bjork, Robert A.

    2006-01-01

    The authors report 7 experiments indicating that conditional predictions--the assessed probability that a certain outcome will occur given a certain condition--tend to be markedly inflated. The results suggest that this inflation derives in part from backward activation in which the target outcome highlights aspects of the condition that are…

  8. [Conditioning mechanisms and psychoneuroimmunology].

    PubMed

    Stockhorst, Ursula; Klosterhalfen, Sibylle

    2005-01-01

    This chapter deals with the role of conditioning principles in psychoneuroimmunology (PNI). We will first describe the paradigms of classical and instrumental conditioning and classify immune parameters that are subject to conditioning (chapter 1). So far, PNI research mainly uses classical (or Pavlovian) conditioning. We will summarize some of the paradigmatic studies, mainly animal studies (chapter 2) and also describe studies that support the clinical relevance of classical conditioning, i. e., in the pharmacological treatment of autoimmune diseases, transplantation and tumor chemotherapy (chapter 3). A study of our group on anticipatory immunomodulation in pediatric cancer patients is reported. Mechanisms mediating conditioned immunomodulation are summarized (chapter 4). We also describe studies that analyze the impact of instrumental conditioning contingencies on immune functioning (chapter 5). Finally, research perspectives are summarized (chapter 6).

  9. A review of trazodone use in psychiatric and medical conditions.

    PubMed

    Khouzam, Hani Raoul

    2017-01-01

    Trazodone is an antidepressant that is FDA-approved for the treatment of depression. It has been used by mental health and primary care providers for the treatment of multiple psychiatric and medical conditions .This review describes trazodone mechanism of action, formulation, dosage and adverse effects and then summarizes the beneficial effects of trazodone in the treatment of various psychiatric and medical conditions such as major depression, as well non-approved FDA indications such as insomnia,anxiety disorders, posttraumatic stress disorder, obsessive compulsive disorder, feeding and eating disorders, substance use disorders, behavioral disturbances associated with cognitive dysfunction, sexual dysfunction, certain pain conditions, and rehabilitation after acute ischemic stroke. Despite trazodone's favorable effects in the treatment of FDA-unapproved psychiatric and medical conditions, large, randomized controlled clinical trials are still needed to confirm its efficacy in the treatment of the multiple conditions for which it is often used in clinical practice.

  10. IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-β1 to induce bronchial epithelial-mesenchymal transition (EMT)

    PubMed Central

    Ji, Xiaoying; Li, Jinxiu; Xu, Li; Wang, Wenjing; Luo, Ming; Luo, Shuangling; Ma, Libing; Li, Keng; Gong, Subo; He, Long; Zhang, Zhijun; Yang, Ping; Zhou, Zhiguang; Xiang, Xudong; Wang, Cong-Yi

    2013-01-01

    Severe asthma is a chronic airway disease characterized by the Th2/Th17-polarized inflammation along with permanent airway remodeling. Despite past extensive studies, the exact role for Th2 and Th17 cytokines in asthmatic pathoetiology, particularly in the pathogenesis of bronchial epithelial-mesenchymal transition (EMT), is yet to be fully addressed. We herein conducted studies in 16-HBE cells and demonstrated that Th2-derived IL-4 and Th17-derived IL-17A provide a chronic inflammatory milieu that favors TGF-β1 to induce bronchial EMT. A synergic action was noted between TGF-β1, IL-4 and IL-17A in terms of induction of EMT. IL-4 and IL-17A synergized with TGF-β1 to induce epithelial cells re-entering cell cycle, and to promote epithelial to mesenchymal morphological transistion, and by which they enhanced the capacity of TGF-β1 to suppress E-cadherin expression, and to induce a-SMA expression in epithelial cells. Mechanistic studies revealed that this synergic action is coordinated by the regulation of ERK1/2 activity. Our results not only provide a novel insight into the understanding of the mechanisms underlying airway remodeling in asthmatic condition, but also have the potential for developing more effective therapeutic strategies against severe asthmatics in clinical settings. PMID:23923066

  11. Long-term survival after a favorable response to anti-EGFR antibody plus chemotherapy to treat bone marrow metastasis: a case report of KRAS-wildtype rectal cancer

    PubMed Central

    Nakamura, Sho; Fukui, Tadahisa; Suzuki, Shuhei; Takeda, Hiroyuki; Watanabe, Kaname; Yoshioka, Takashi

    2017-01-01

    Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient’s medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy. PMID:28260928

  12. How to increase treatment effectiveness and efficiency in psychiatry: creative psychopharmacotherapy - part 2: creating favorable treatment context and fostering patients' creativity.

    PubMed

    Jakovljević, Miro

    2013-09-01

    Any medical or psychosocial treatment has two components, one associated with the specific effects of the treatment itself, and the other related to the treatment context, individual perception, imagination, subjective meaning and psychobiological response. Psychopharmacotherapy is a context dependent practice because different contexts affect the meaning of biological variables in different ways. Creation of favorable treatment context as well as creative collaboration with patients and their families may significantly improve treatment outcome. Positive therapeutic context is fundamental for treatment success in psychiatry because it may significantly increase placebo and decrease nocebo responses. Creative approach to psychopharmacotherapy reflects a creative synergism between clinical pharmacology and positive psychology of creativity in the frame of transdisciplinary holistic, integrative and person-centered psychiatry.

  13. Favored use of anti-predator netting (APN) applied for the farming of clams leads to little benefits to industry while increasing nearshore impacts and plastics pollution.

    PubMed

    Bendell, L I

    2015-02-15

    An overview of the efficacy of anti-predator netting (APN) used by the shellfish industry is presented. There is little support that the currently favored APN effectively protects farmed clams from predators. Evidence does suggest that APN leads to impacts and pollution. APN is an attractant for predators, e.g., crabs, by providing a refuge within Ulva sp. which attaches onto the surface of APN. APN entrains silt and organic matter and increases sediment temperatures degrading habitat underneath the APN. APN present hazards to fish and wildlife and is a source of plastics to the marine environment. The continued use of ineffective APN does not serve either the environment or industry well, and many of these issues could be addressed through the alternate use of "ancient" technology used by aboriginal people to maintain clam gardens; building of rock walls optimizing the amount of clam habitat thereby increasing numbers without the use of APN.

  14. Communication: Phase behavior of materials with isotropic interactions designed by inverse strategies to favor diamond and simple cubic lattice ground states.

    PubMed

    Jain, Avni; Errington, Jeffrey R; Truskett, Thomas M

    2013-10-14

    We use molecular simulation to construct equilibrium phase diagrams for two recently introduced model materials with isotropic, soft-repulsive pair interactions designed to favor diamond and simple cubic lattice ground states, respectively, over a wide range of densities [Jain et al., Soft Matter 9, 3866 (2013)]. We employ free energy based Monte Carlo simulation techniques to precisely trace the inter-crystal and fluid-crystal coexistence curves. We find that both model materials display rich polymorphic phase behavior featuring stable crystals corresponding to the target ground-state structures, as well as a variety of other crystalline (e.g., hexagonal and body-centered cubic) phases and multiple reentrant melting transitions.

  15. Acylglucuronide in alkaline conditions: migration vs. hydrolysis.

    PubMed

    Di Meo, Florent; Steel, Michele; Nicolas, Picard; Marquet, Pierre; Duroux, Jean-Luc; Trouillas, Patrick

    2013-06-01

    This work rationalizes the glucuronidation process (one of the reactions of the phase II metabolism) for drugs having a carboxylic acid moiety. At this stage, acylglucuronides (AG) metabolites are produced, that have largely been reported in the literature for various drugs (e.g., mycophenolic acid (MPA), diclofenac, ibuprofen, phenylacetic acids). The competition between migration and hydrolysis is rationalized by adequate quantum calculations, combing MP2 and density functional theory (DFT) methods. At the molecular scale, the former process is a real rotation of the drug around the glucuconic acid. This chemical-engine provides four different metabolites with various toxicities. Migration definitely appears feasible under alkaline conditions, making proton release from the OH groups. The latter reaction (hydrolysis) releases the free drug, so the competition is of crucial importance to tackle drug action and elimination. From the theoretical data, both migration and hydrolysis appear kinetically and thermodynamically favored, respectively.

  16. Concentrative nucleoside transporter 3 as a prognostic indicator for favorable outcome of t(8;21)-positive acute myeloid leukemia patients after cytarabine-based chemotherapy.

    PubMed

    Song, Ju Han; Cho, Kyung-Min; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Kim, Nan Young; Kim, Hee-Je; Lee, Tae-Hyang; Hwang, Seung Yong; Kim, Tae Sung

    2015-07-01

    Although acute myeloid leukemia (AML) exhibits diverse responses to chemotherapy, patients harboring the t(8;21) translocation are part of a favorable risk group. However, the reason why this subgroup is more responsive to cytarabine-based therapy has not been elucidated. In the present study, we analyzed expression levels of cytarabine metabolism-related genes in patients diagnosed with AML with or without t(8;21) and investigated their correlation with clinical outcomes after cytarabine-based therapy. Among the 8 genes studied, expression of the concentrative nucleoside transporter 3 (CNT3) gene was significantly higher in t(8;21)-positive patients compared to the others in the test population and the validation cohort (P<0.001 in Mann-Whitney U test; P<0.002 in Pearson's correlation analysis). Additionally, in both multivariate and univariate analyses, t(8;21)-positive patients categorized in a higher CNT3 expression tertile had longer disease-free survival [hazard ratio (HR), 0.117; 95% confidence interval (CI), 0.025-0.557; P=0.008] and overall survival (HR, 0.062; 95% CI, 0.007-0.521; P=0.010) compared to t(8;21)-positive patients in a lower CNT3 expression tertile. Notably, these trends did not occur in t(8;21)-negative patients. Our results demonstrate that CNT3 expression is associated with overall favorable outcomes and is predictive of clinical outcomes in AML patients with t(8;21). This suggests that CNT3 expression can be used to optimize treatment strategies for AML patients.

  17. Effect of Polymer Gate Dielectrics on Charge Transport in Carbon Nanotube Network Transistors: Low-k Insulator for Favorable Active Interface.

    PubMed

    Lee, Seung-Hoon; Xu, Yong; Khim, Dongyoon; Park, Won-Tae; Kim, Dong-Yu; Noh, Yong-Young

    2016-11-30

    Charge transport in carbon nanotube network transistors strongly depends on the properties of the gate dielectric that is in direct contact with the semiconducting carbon nanotubes. In this work, we investigate the dielectric effects on charge transport in polymer-sorted semiconducting single-walled carbon nanotube field-effect transistors (s-SWNT-FETs) by using three different polymer insulators: A low-permittivity (εr) fluoropolymer (CYTOP, εr = 1.8), poly(methyl methacrylate) (PMMA, εr = 3.3), and a high-εr ferroelectric relaxor [P(VDF-TrFE-CTFE), εr = 14.2]. The s-SWNT-FETs with polymer dielectrics show typical ambipolar charge transport with high ON/OFF ratios (up to ∼10(5)) and mobilities (hole mobility up to 6.77 cm(2) V(-1) s(-1) for CYTOP). The s-SWNT-FET with the lowest-k dielectric, CYTOP, exhibits the highest mobility owing to formation of a favorable interface for charge transport, which is confirmed by the lowest activation energies, evaluated by the fluctuation-induced tunneling model (FIT) and the traditional Arrhenius model (EaFIT = 60.2 meV and EaArr = 10 meV). The operational stability of the devices showed a good agreement with the activation energies trend (drain current decay ∼14%, threshold voltage shift ∼0.26 V in p-type regime of CYTOP devices). The poor performance in high-εr devices is accounted for by a large energetic disorder caused by the randomly oriented dipoles in high-k dielectrics. In conclusion, the low-k dielectric forms a favorable interface with s-SWNTs for efficient charge transport in s-SWNT-FETs.

  18. Favorable outcomes of hydroxychloroquine in insulin resistance may be accomplished by adjustment of the endothelial dysfunction as well as the skewed balance of adipokines.

    PubMed

    Abdel-Hamid, Ahmed A M; Firgany, Alaa El-Din L

    2016-07-01

    Hydroxychloroquine (HCQ) has been demonstrated to reduce the risk to develop diabetes mellitus (DM). However no previous experimental study had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in insulin resistance (IR). In addition, the mechanism by which HCQ can prevent DM is not well understood. In this study, we hypothesized that the possible favorable outcome of HCQ may be partly achieved by its molecular effect on the endothelial stress markers as well as on the imparied balance of the adipokines that usually accompanies IR. A total of 54 rats were divided equally into; control, high fat diet (HFD) and HFD+HCQ groups (received standard chow, HFD and HFD+HCQ respectively). After 12 weeks, samples from pancreas as well as visceral adipose tissue (VAT) were histologically studied for the consequent changes. In the HFD group, there were mild degenerative changes and expansion of the IOL accompanied with a significantly increased (p<0.05) β-cell area%, mass, proliferation and neogenesis as well as a significantly decreased (p<0.05) α-cell area% compared with the other groups. On combining HCQ with HFD, reversal of these changes along with correction of the impaired adipokines levels (leptin, adiponectin, resistin, visfatin and lipocalin-2) and significant decrease (p<0.05) of the vascular endothelial stress markers (sE-selectin, sICAM and sVICAM) were manifested compared with the HFD group. Therefore, HCQ favorable effects in IR may be attributed to relieving of the endothelial stress as well as normalization of the skewed balance of adipokines.

  19. TET2 exon 2 skipping is an independent favorable prognostic factor for cytogenetically normal acute myelogenous leukemia (AML): TET2 exon 2 skipping in AML.

    PubMed

    Mohamed, Aminetou Mint; Balsat, Marie; Koering, Catherine; Maucort-Boulch, Delphine; Boissel, Nicolas; Payen-Gay, Lea; Cheok, Meyling; Mortada, Hussein; Auboeuf, Didier; Pinatel, Christiane; El-Hamri, Mohamed; Tigaud, Isabelle; Hayette, Sandrine; Dumontet, Charles; Cros, Emeline; Flandrin-Gresta, Pascale; Nibourel, Olivier; Preudhomme, Claude; Thomas, Xavier; Nicolini, Franck-Emmanuel; Solly, Françoise; Guyotat, Denis; Campos, Lydia; Michallet, Mauricette; Ceraulo, Antony; Mortreux, Franck; Wattel, Eric

    2017-01-16

    In AML, approximately one-third of expressed genes are abnormally spliced, including aberrant TET2 exon 2 expression. In a discovery cohort (n=99), TET2 exon 2 skipping (TET2E2S) was found positively associated with a significant reduction in the cumulative incidence of relapse (CIR). Age, cytogenetics, and TET2E2S were independent prognostic factors for disease-free survival (DFS), and favorable effects on outcomes predominated in cytogenetic normal (CN)-AML and younger patients. Using the same cutoff in a validation cohort of 86 CN-AML patients, TET2E2S(high) patients were found to be younger than TET2(low) patients without a difference in the rate of complete remission. However, TET2E2S(high) patients exhibited a significantly lower CIR (p<10(-4)). TET2E2S and FLT3-ITD, but not age or NPM1 mutation status were independent prognostic factors for DFS and event-free survival (EFS), while TET2E2S was the sole prognostic factor that we identified for overall survival (OS). In both the intermediate-1 and favorable ELN genetic categories, TET2E2S remained significantly associated with prolonged survival. There was no correlation between TET2E2S status and outcomes in 34 additional AML patients who were unfit for IC. Therefore our results suggest that assessments of TET2 exon 2 splicing status might improve risk stratification in CN-AML patients treated with IC.

  20. Closure of mitochondrial potassium channels favors opening of the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.

    PubMed

    Korotkov, Sergey M; Brailovskaya, Irina V; Shumakov, Anton R; Emelyanova, Larisa V

    2015-06-01

    It is known that a closure of ATP sensitive (mitoKATP) or BK-type Ca(2+) activated (mitoKCa) potassium channels triggers opening of the mitochondrial permeability transition pore (MPTP) in cells and isolated mitochondria. We found earlier that the Tl(+)-induced MPTP opening in Ca(2+)-loaded rat liver mitochondria was accompanied by a decrease of 2,4-dinitrophenol-uncoupled respiration and increase of mitochondrial swelling and ΔΨmito dissipation in the medium containing TlNO3 and KNO3. On the other hand, our study showed that the mitoKATP inhibitor, 5-hydroxydecanoate favored the Tl(+)-induced MPTP opening in the inner membrane of Ca(2+)-loaded rat heart mitochondria (Korotkov et al. 2013). Here we showed that 5-hydroxydecanoate increased the Tl(+)-induced MPTP opening in the membrane of rat liver mitochondria regardless of the presence of mitoKATP modulators (diazoxide and pinacidil). This manifested in more pronounced decrease in the uncoupled respiration and acceleration of both the swelling and the ΔΨmito dissipation in isolated rat liver mitochondria, incubated in the medium containing TlNO3, KNO3, and Ca(2+). A slight delay in Ca(2+)-induced swelling of the mitochondria exposed to diazoxide could be result of an inhibition of succinate oxidation by the mitoKATP modulator. Mitochondrial calcium retention capacity (CRC) was markedly decreased in the presence of the mitoKATP inhibitor (5-hydroxydecanoate) or the mitoKCa inhibitor (paxilline). We suggest that the closure of mitoKATP or mitoKCa in calcium loaded mitochondria favors opening of the Tl(+)-induced MPTP in the inner mitochondrial membrane.

  1. Intracerebral and Intravenous Transplantation Represents a Favorable Approach for Application of Human Umbilical Cord Mesenchymal Stromal Cells in Intracerebral Hemorrhage Rats

    PubMed Central

    Xie, Jiang; Wang, Bin; Wang, Lian; Dong, Fang; Bai, Gang; Liu, Yongjun

    2016-01-01

    Background Intracerebral hemorrhage (ICH) is one severe subtype of stroke, with a very complex pathology. Stem cell-based therapy holds promising potential in the treatment of neurological disorders. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have a therapeutic effect in recovery from brain damage following ICH. The aim of this study was to identify an effective and convenient way of using UC-MSCs in the ICH rat model. Material/Methods CM-DiI-labeled human UC-MSCs were transplanted intracerebrally or intravenously into collagenase VII-induced ICH rat models. Neurological function was evaluated before ICH and at 0, 7, 14, 21, and 28 days after treatment. ICH rats were sacrificed to evaluate the injury volume. Neurogenesis and angiogenesis and vascular areas were investigated using microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and 4′,6-diamidino-2-phenylindole (DAPI) immunohistochemistry at two weeks after transplantation. Results The intracerebral and intravenous administration of UC-MSCs both resulted in significant improvement in neurological function and decrease in injury volume of ICH rats. Transplanted UC-MSCs were chemotactic in vivo and showed a predominant distribution around the ICH region. In addition, UC-MSCs could integrate into the cerebral vasculature in both groups. Conclusions Both intracerebral and intravenous administration of UC-MSCs could have a favorable effect on recovery of neurological function in ICH rats, although the fundamental mechanisms may be different between the two groups. Our data suggest that intravenous implantation of UC-MSCs could serve as a favorable approach for cell-based therapy in central nervous system (CNS) diseases according to clinical needs. PMID:27703134

  2. TWEAK favors phosphate-induced calcification of vascular smooth muscle cells through canonical and non-canonical activation of NFκB

    PubMed Central

    Hénaut, L; Sanz, A B; Martin-Sanchez, D; Carrasco, S; Villa-Bellosta, R; Aldamiz-Echevarria, G; Massy, Z A; Sanchez-Nino, M D; Ortiz, A

    2016-01-01

    Vascular calcification (VC) is associated with increased cardiovascular mortality in aging, chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM) and atherosclerosis. TNF-like weak inducer of apoptosis (TWEAK) recently emerged as a new biomarker for the diagnosis and prognosis of cardiovascular diseases. TWEAK binding to its functional receptor Fn14 was reported to promote several steps of atherosclerotic plaque progression. However, no information is currently available on the role of TWEAK/Fn14 on the development of medial calcification, which is highly prevalent in aging, CKD and T2DM. This study explored the involvement of TWEAK in human vascular smooth muscle cells (h-VSMCs) calcification in vitro. We report that TWEAK binding to Fn14 promotes inorganic phosphate-induced h-VSMCs calcification, favors h-VSMCs osteogenic transition, decreasing acta2 and myh11 and increasing bmp2 mRNA and tissue non-specific alkaline phosphatase (TNAP), and increases MMP9 activity. Blockade of the canonical NFκB pathway reduced by 80% TWEAK pro-calcific properties and decreased osteogenic transition, TNAP and MMP9 activity. Blockade of non-canonical NFκB signaling by a siRNA targeting RelB reduced by 20% TWEAK pro-calcific effects and decreased TWEAK-induced loss of h-VSMCs contractile phenotype and MMP9 activity, without modulating bmp2 mRNA or TNAP activity. Inhibition of ERK1/2 activation by a MAPK kinase inhibitor did not influence TWEAK pro-calcific properties. Our results suggest that TWEAK/Fn14 directly favors inorganic phosphate-induced h-VSMCs calcification by activation of both canonical and non-canonical NFκB pathways. Given the availability of neutralizing anti-TWEAK strategies, our study sheds light on the TWEAK/Fn14 axis as a novel therapeutic target in the prevention of VC. PMID:27441657

  3. Intraoperative Spillage of Favorable Histology Wilms Tumor Cells: Influence of Irradiation and Chemotherapy Regimens on Abdominal Recurrence. A Report From the National Wilms Tumor Study Group

    SciTech Connect

    Kalapurakal, John A.; Li, Sierra M.; Breslow, Norman E.; Beckwith, J. Bruce; Ritchey, Michael L.; Shamberger, Robert C.; Haase, Gerald M.; Thomas, Patrick R.M.; Grundy, Paul; Green, Daniel M.; D'Angio, Giulio J.

    2010-01-15

    Purpose: We undertook this study to determine (1) the frequency with which spilled tumor cells of favorable histology produced intra-abdominal disease in patients treated with differing chemotherapy regimens and abdominal radiation therapy (RT) and (2) the patterns of relapse and outcomes in such patients. Methods and Materials: The influence of RT dose (0, 10, and 20 Gy), RT fields (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2 drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence rates was analyzed by logistic regression in 450 patients. Each patient was considered at risk for two types of failure: flank and subdiaphragmatic beyond-flank recurrence, with the correlation between the two outcomes accounted for in the analyses. Results: The crude odds ratio for the risk of recurrence relative to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates with and without spillage, respectively, were 79% and 87% for relapse-free survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04). Conclusions: Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor spillage. Tumor spillage in Stage II patients reduced relapse-free survival and overall survival, but only the latter was of statistical significance. These data provide a basis for assessing the risks vs. benefits when considering treatment for children with favorable histology Wilms tumor and surgical spillage.

  4. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    SciTech Connect

    Breslow, Norman E. . E-mail: norm@u.washington.edu; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-05-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes.

  5. Upfront Systemic Chemotherapy and Short-Course Radiotherapy with Delayed Surgery for Locally Advanced Rectal Cancer with Distant Metastases: Outcomes, Compliance, and Favorable Prognostic Factors

    PubMed Central

    Kim, Tae Hyung; Ahn, Joong Bae; Jung, Minkyu; Kim, Tae Il; Kim, Hoguen; Shin, Sang Joon; Kim, Nam Kyu

    2016-01-01

    Purpose/Objective(s) Optimal treatment for locally advanced rectal cancer (LARC) with distant metastasis remains elusive. We aimed to evaluate upfront systemic chemotherapy and short-course radiotherapy (RT) followed by delayed surgery for such patients, and to identify favorable prognostic factors. Materials/Methods We retrospectively reviewed 50 LARC patients (cT4 or cT3, <2 mm from the mesorectal fascia) with synchronous metastatic disease. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival, treatment-related toxicity, and compliance. We considered P values <0.05 significant. Results At 22 months median follow-up, the median PFS time was 16 months and the 2-year PFS rate was 34.8%. Thirty-five patients who received radical surgery for primary and metastatic tumors were designated the curable group. Six patients with clinical complete response (ypCR) of metastases who underwent radical surgery for only the primary tumor were classified as potentially curable. Nine patients who received no radical surgery (3 received palliative surgery) were deemed the palliative group. The ypCR rate among surgery patients was 13.6%. PFS rates for the curable or potentially curable groups were significantly longer than that of the palliative group (P<0.001). On multivariate analysis, solitary organ metastasis and R0 status were independent prognostic factors for PFS. Conclusions These findings demonstrated that a strong possibility that upfront chemotherapy and short-course RT with delayed surgery are an effective alternative treatment for LARC with potentially resectable distant metastasis, owing to achievement of pathologic down-staging, R0 resection, and favorable compliance and toxicity, despite the long treatment duration. PMID:27536871

  6. Conditional Belief Types

    DTIC Science & Technology

    2016-04-19

    hypothetical knowledge , conditional probability, counterfactuals REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 10. SPONSOR/MONITOR’S...spaces are closely related to the sphere models of counterfactual conditionals and to models of hypothetical knowledge . 3 Approved for public release...hypothetical knowledge . Keywords: Conditional probability; Type spaces; Hypothetical knowledge ; Counterfactuals JEL Classification: C70; C72; D80; D82

  7. Context and Pavlovian conditioning.

    PubMed

    Landeira-Fernandez, J

    1996-02-01

    Procedurally, learning has to occur in a context. Several lines of evidence suggest that contextual stimuli actively affect learning and expression of the conditional response. The experimental context can become associated with the unconditional stimulus (US), especially when the US is presented in a context in the absence of a discrete conditional stimulus (CS). Moreover, context can modulate CS-US associations. Finally, it appears that context can become associated with the CS when it is presented before the CS-US training. The purpose of the present paper is to review some of the relevant literature that considers the context as an important feature of Pavlovian conditioning and to discuss some of the main learning theories that incorporate the context into their theoretical framework. The paper starts by mentioning historical positions that considered context an important variable in conditioning and then describes how the approach to contextual conditioning changed with the modern study of Pavlovian conditioning. Various forms of measurement of context conditioning are presented and the associative strength attached to context in several experimental paradigms is examined. The possible functions that context may acquire during conditioning are pointed out and related to major learning theories. Moreover, the effect of certain neurological manipulations on context conditioning is presented and these results are discussed in terms of possible functions that the context might acquire during Pavlovian conditioning. It is concluded that contextual stimuli acquire different functions during normal conditioning. A procedure in which animals are exposed to an aversive US immediately after they are placed in the experimental context is suggested as a useful control for the study of context conditioning.

  8. Nonparametric conditional estimation

    SciTech Connect

    Owen, A.B.

    1987-01-01

    Many nonparametric regression techniques (such as kernels, nearest neighbors, and smoothing splines) estimate the conditional mean of Y given X = chi by a weighted sum of observed Y values, where observations with X values near chi tend to have larger weights. In this report the weights are taken to represent a finite signed measure on the space of Y values. This measure is studied as an estimate of the conditional distribution of Y given X = chi. From estimates of the conditional distribution, estimates of conditional means, standard deviations, quantiles and other statistical functionals may be computed. Chapter 1 illustrates the computation of conditional quantiles and conditional survival probabilities on the Stanford Heart Transplant data. Chapter 2 contains a survey of nonparametric regression methods and introduces statistical metrics and von Mises' method for later use. Chapter 3 proves some consistency results. Chapter 4 provides conditions under which the suitably normalized errors in estimating the conditional distribution of Y have a Brownian limit. Using von Mises' method, asymptotic normality is obtained for nonparametric conditional estimates of compactly differentiable statistical functionals.

  9. NATIONAL COASTAL CONDITION REPORT

    EPA Science Inventory

    The National Coastal Condition report compiles several available data sets from different agencies and areas of the country and summarizes them to present a broad baseline picture of the condition of coastal waters. Although data sets presented in this report do not cover all coa...

  10. CONDITIONAL DISTANCE CORRELATION

    PubMed Central

    Wang, Xueqin; Pan, Wenliang; Hu, Wenhao; Tian, Yuan; Zhang, Heping

    2015-01-01

    Statistical inference on conditional dependence is essential in many fields including genetic association studies and graphical models. The classic measures focus on linear conditional correlations, and are incapable of characterizing non-linear conditional relationship including non-monotonic relationship. To overcome this limitation, we introduces a nonparametric measure of conditional dependence for multivariate random variables with arbitrary dimensions. Our measure possesses the necessary and intuitive properties as a correlation index. Briefly, it is zero almost surely if and only if two multivariate random variables are conditionally independent given a third random variable. More importantly, the sample version of this measure can be expressed elegantly as the root of a V or U-process with random kernels and has desirable theoretical properties. Based on the sample version, we propose a test for conditional independence, which is proven to be more powerful than some recently developed tests through our numerical simulations. The advantage of our test is even greater when the relationship between the multivariate random variables given the third random variable cannot be expressed in a linear or monotonic function of one random variable versus the other. We also show that the sample measure is consistent and weakly convergent, and the test statistic is asymptotically normal. By applying our test in a real data analysis, we are able to identify two conditionally associated gene expressions, which otherwise cannot be revealed. Thus, our measure of conditional dependence is not only an ideal concept, but also has important practical utility. PMID:26877569

  11. Monitoring of Working Conditions and the Nature of Their Influence on Health of Students and Academic Staff

    ERIC Educational Resources Information Center

    Vinichenko, Mikhail V.; Kirillov, Andrey V.; Frolova, Elena V.; Kaurova, Olga V.; Makushkin, Sergey A.

    2016-01-01

    The relevance of the research is conditioned by the need to win the competition struggle by certain organizations and area in general. Education has recently become very popular for the training of highly professional staff. However, achieving this goal is possible by means of creation of favorable working and learning conditions, maintaining…

  12. Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women.

    PubMed

    Karl, J Philip; Meydani, Mohsen; Barnett, Junaidah B; Vanegas, Sally M; Goldin, Barry; Kane, Anne; Rasmussen, Helen; Saltzman, Edward; Vangay, Pajau; Knights, Dan; Chen, C-Y Oliver; Das, Sai Krupa; Jonnalagadda, Satya S; Meydani, Simin N; Roberts, Susan B

    2017-03-01

    Background: The effect of whole grains on the regulation of energy balance remains controversial.Objective: We aimed to determine the effects of substituting whole grains for refined grains, independent of body weight changes, on energy-metabolism metrics and glycemic control.Design: The study was a randomized, controlled, parallel-arm controlled-feeding trial that was conducted in 81 men and postmenopausal women [49 men and 32 women; age range: 40-65 y; body mass index (in kg/m(2)): <35.0]. After a 2-wk run-in period, participants were randomly assigned to consume 1 of 2 weight-maintenance diets for 6 wk. Diets differed in whole-grain and fiber contents [mean ± SDs: whole grain-rich diet: 207 ± 39 g whole grains plus 40 ± 5 g dietary fiber/d; refined grain-based diet: 0 g whole grains plus 21 ± 3 g dietary fiber/d] but were otherwise similar. Energy metabolism and body-composition metrics, appetite, markers of glycemic control, and gut microbiota were measured at 2 and 8 wk.Results: By design, body weight was maintained in both groups. Plasma alkylresorcinols, which are biomarkers of whole-grain intake, increased in the whole grain-rich diet group (WG) but not in the refined grain-based diet group (RG) (P-diet-by-time interaction < 0.0001). Beta ± SE changes (ΔWG compared with ΔRG) in the resting metabolic rate (RMR) (43 ± 25 kcal/d; P = 0.04), stool weight (76 ± 12 g/d; P < 0.0001), and stool energy content (57 ± 17 kcal/d; P = 0.003), but not in stool energy density, were higher in the WG. When combined, the favorable energetic effects in the WG translated into a 92-kcal/d (95% CI: 28, 156-kcal/d) higher net daily energy loss compared with that of the RG (P = 0.005). Prospective consumption (P = 0.07) and glycemia after an oral-glucose-tolerance test (P = 0.10) trended toward being lower in the WG than in the RG. When nonadherent participants were excluded, between-group differences in stool energy content and glucose tolerance increased, and between

  13. The role of marriage in the causal pathway from economic conditions early in life to mortality.

    PubMed

    van den Berg, Gerard J; Gupta, Sumedha

    2015-03-01

    This paper analyzes the interplay between early-life conditions and marital status, as determinants of adult mortality. We use individual data from Dutch registers (years 1815-2000), combined with business cycle conditions in childhood as indicators of early-life conditions. The empirical analysis estimates bivariate duration models of marriage and mortality, allowing for unobserved heterogeneity. Results show that conditions around birth and school going ages are important for marriage and mortality. Men typically enjoy a protective effect of marriage, whereas women suffer during childbearing ages. However, having been born under favorable economic conditions reduces female mortality during childbearing ages.

  14. Systematizing semishortening conditions

    NASA Astrophysics Data System (ADS)

    Ju, C.-Y.; Siegel, W.

    2014-12-01

    We rederive semishortening conditions for four-dimensional superconformal field theory with a different approach. These conditions have similar patterns that can be generalized to weaker constraints, including all those of Dolan and Osborn [Ann. Phys. (Amsterdam) 307, 41 (2003)]. In particular, for the case of N =4 super-Yang-Mills theory formulated in projective superspace, we find constraints for all Bogomol'nyi-Prasad-Sommerfield operators. We also give an example how constraints can be found from known ones. These constraints are a subset of our maximal set of semishortening conditions.

  15. Application of 670 nm InGaP laser and microcurrent favors the healing of second-degree burns in Wistar rats

    NASA Astrophysics Data System (ADS)

    Belli, M.; Fernandes, C. R.; Neves, L. M. G.; Mourão, V.; Barbieri, R.; Esquisatto, M. A. M.; Amaral, M. E. C.; Santos, G. M. T.; Mendonça, F. A. S.

    2015-02-01

    The treatment of burn wounds has been a challenge due to their severity and associated multiple complications, and represents a major public health problem. This study investigated the effects of 670 nm InGaP laser irradiation and microcurrent (10 µA) stimulation on the healing of second-degree burns inflicted on the back of Wistar rats. Seventy-two animals were divided into four groups: no treatment (C); animals irradiated with a 670 nm InGaP laser (L); animals receiving microcurrent stimulation (10 µA/3 min) (MC); animals receiving 670 nm InGaP laser therapy and microcurrent stimulation (10 µA/3 min) on alternate days (MCL). Wound samples were collected on days 7, 14 and 21 of treatment for structural and morphometric analysis and for Western blotting to quantify the expression of TGF-β1 and VEGF. The applied alone and alternate of laser and microcurrent reduced the number of inflammatory cells and increased the number of newly formed vessels and fibroblasts, collagen fiber content and fiber reorganization. The two treatments also favorably modified the expression of VEGF and TGF-β1, inducing angiogenesis and decreasing the inflammation time.

  16. Highly favorable outcome in BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

    PubMed

    Boudin, L; Gonçalves, A; Sabatier, R; Moretta, J; Sfumato, P; Asseeva, P; Livon, D; Bertucci, F; Extra, J-M; Tarpin, C; Houvenaegel, G; Lambaudie, E; Tallet, A; Resbeut, M; Sobol, H; Charafe-Jauffret, E; Calmels, B; Lemarie, C; Boher, J-M; Viens, P; Eisinger, F; Chabannon, C

    2016-08-01

    Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

  17. Expression of KISS1 and KISS1R (GPR54) may be used as favorable prognostic markers for patients with non-small cell lung cancer.

    PubMed

    Sun, Yan-Bin; Xu, Shun

    2013-08-01

    Lung cancer is the most commonly diagnosed cancer worldwide. Loss of KISS1 expression has been associated with progression and poor prognosis of various cancers, however, the precise role of KISS1 expression in non-small cell lung cancer (NSCLC) is not well defined. KISS1 receptor (KISS1R, also named GPR54) coupled to KISS1, has been shown to play a pivotal role in suppressing cancer metastasis. In this study, 56 NSCLC specimens were divided into stage IIIB (locally advanced) and stage IV (metastatic). The mRNA and protein levels of KISS1 and KISS1R in cancer tissues were found to be lower compared to that in normal tissues using RT-PCR and western blot analysis, respectively. In addition, the expression of both KISS1 and KISS1R in stage IV NSCLC was lower compared to that in stage IIIB stage NSCLC. The cumulative survival rate of the patients with KISS1 or KISS1R expression was significantly higher compared to that without expression. KISS1 or KISS1R expression in NSCLC can be used to indicate favorable prognosis for disease outcome. Metastin, the product of the KISS1 gene, was lower in the serum of patients with stage IV NSCLC compared to that in stage IIIB NSCLC.

  18. Low ABCB1 and high OCT1 levels play a favorable role in the molecular response to imatinib in CML patients in the community clinical practice.

    PubMed

    da Cunha Vasconcelos, Flavia; Mauricio Scheiner, Marcos Antonio; Moellman-Coelho, Arthur; Mencalha, André Luiz; Renault, Ilana Zalcberg; Rumjanek, Vivian Mary; Maia, Raquel Ciuvalschi

    2016-12-01

    Despite the favorable clinical evolution of patients with chronic myeloid leukemia (CML), resistance or intolerance to imatinib is present in approximately 35% of patients. Sokal score is a widely used risk factor, however efflux and influx transporters are provisional risk factors implicated in imatinib resistance. This study analyzed Sokal score, ABCB1, ABCG2 and OCT1 mRNA transporter expression levels as well as P-glycoprotein expression and efflux transporters activity to seek a possible correlation between these factors and the molecular response at 12 months from imatinib start as well as 8-year overall survival (OS). Low plus intermediate Sokal score correlated to optimal imatinib responses, as well as OS at 8-years, thus confirming the established role of Sokal score as a prognostic factor in CML patients. Low ABCB1 and high OCT1 mRNA levels were associated with an optimal molecular response, while the inverse levels were associated with non-responders (warning and failure) patients. Our results suggest that ABCB1 and OCT1 mRNA expressions may present biological relevance to identify responder and non-responder patients to imatinib treatment.

  19. Taenia taeniaeformis in Rat Favors Protracted Skin Lesions Caused by Sporothrix schenckii Infection: Dectin-1 and IL-17 Are Dispensable for Clearance of This Fungus

    PubMed Central

    Huang, Huaiqiu; Xue, Ruzeng; Hu, Xuchu; Li, Meirong; Zhong, Yi; Yuan, Liyan

    2012-01-01

    We occasionally found that cestode Taenia taeniaeformis in rats favored Sporothrix schenckii infection and survival, causing protracted cutaneous lesions. In this study, we compared the pathology and cytokines profile of rats co-infected with the two pathogens and infected with S. schenckii alone to explore underlying mechanisms. In the co-infection group, there was high expression of β-glucan receptor Dectin-1 in the cutaneous lesions and no multinucleated giant cells, but in the S. schenckii infection group the opposite was observed. Cytokines profiles demonstrated an expected finding that IL-4, commonly expressed in helminth and fungus infection, is undetectable in the two infection groups. In the single fungal infection group, cytokines IFN-γ, IL-10 and IL-17 kept increasing in the first few weeks of infection to a peak which was followed by gradual decrease. This study showed that Dectin-1 and IL-17, which were believed to be the major anti-fungus mechanisms, are Th2 independent and dispensable for clearance of S. schenckii infection, suggesting that S. schenckii has a different molecular recognition pattern and evokes anti-infection mechanisms other than Dectin-1 and IL-17. PMID:23285072

  20. Taenia taeniaeformis in rat favors protracted skin lesions caused by Sporothrix schenckii infection: Dectin-1 and IL-17 are dispensable for clearance of this fungus.

    PubMed

    Zhang, Xiaohui; Zhang, Jing; Huang, Huaiqiu; Xue, Ruzeng; Hu, Xuchu; Li, Meirong; Zhong, Yi; Yuan, Liyan

    2012-01-01

    We occasionally found that cestode Taenia taeniaeformis in rats favored Sporothrix schenckii infection and survival, causing protracted cutaneous lesions. In this study, we compared the pathology and cytokines profile of rats co-infected with the two pathogens and infected with S. schenckii alone to explore underlying mechanisms. In the co-infection group, there was high expression of β-glucan receptor Dectin-1 in the cutaneous lesions and no multinucleated giant cells, but in the S. schenckii infection group the opposite was observed. Cytokines profiles demonstrated an expected finding that IL-4, commonly expressed in helminth and fungus infection, is undetectable in the two infection groups. In the single fungal infection group, cytokines IFN-γ, IL-10 and IL-17 kept increasing in the first few weeks of infection to a peak which was followed by gradual decrease. This study showed that Dectin-1 and IL-17, which were believed to be the major anti-fungus mechanisms, are Th2 independent and dispensable for clearance of S. schenckii infection, suggesting that S. schenckii has a different molecular recognition pattern and evokes anti-infection mechanisms other than Dectin-1 and IL-17.

  1. Infrared spectroscopy of matrix-isolated polycyclic aromatic hydrocarbon cations. 2. The members of the thermodynamically most favorable series through coronene

    NASA Technical Reports Server (NTRS)

    Hudgins, D. M.; Allamandola, L. J.

    1995-01-01

    Gaseous, ionized polycyclic aromatic hydrocarbons (PAHs) are thought to be responsible for a very common family of interstellar infrared emission bands. Here the near- and mid-infrared spectra of the cations of the five most thermodynamically favored PAHs up to coronene:phenanthrene, pyrene, benzo[e]pyrene, benzo[ghi]perylene, and coronene, are presented to test this hypothesis. For those molecules that have been studied previously (pyrene, pyrene-d10, and coronene), band positions and relative intensities are in agreement. In all of these cases we report additional features. Absolute integrated absorbance values are given for the phenanthrene, perdeuteriophenanthrene, pyrene, benzo[ghi]perylene, and coronene cations. With the exception of coronene, the cation bands corresponding to the CC modes are typically 2-5 times more intense than those of the CH out-of-plane bending vibrations. For the cations, the CC stretching and CH in-plane bending modes give rise to bands that are an order of magnitude stronger than those of the neutral species, and the CH out-of-plane bends produce bands that are 5-20 times weaker than those of the neutral species. This behavior is similar to that found in most other PAH cations studied to date. The astronomical implications of these PAH cation spectra are also discussed.

  2. A network-based analysis of colon cancer splicing changes reveals a tumorigenesis-favoring regulatory pathway emanating from ELK1

    PubMed Central

    Hollander, Dror; Donyo, Maya; Atias, Nir; Mekahel, Keren; Melamed, Zeev; Yannai, Sivan; Lev-Maor, Galit; Shilo, Asaf; Schwartz, Schraga; Barshack, Iris; Sharan, Roded; Ast, Gil

    2016-01-01

    Splicing aberrations are prominent drivers of cancer, yet the regulatory pathways controlling them are mostly unknown. Here we develop a method that integrates physical interaction, gene expression, and alternative splicing data to construct the largest map of transcriptomic and proteomic interactions leading to cancerous splicing aberrations defined to date, and identify driver pathways therein. We apply our method to colon adenocarcinoma and non-small-cell lung carcinoma. By focusing on colon cancer, we reveal a novel tumor-favoring regulatory pathway involving the induction of the transcription factor MYC by the transcription factor ELK1, as well as the subsequent induction of the alternative splicing factor PTBP1 by both. We show that PTBP1 promotes specific RAC1, NUMB, and PKM splicing isoforms that are major triggers of colon tumorigenesis. By testing the pathway's activity in patient tumor samples, we find ELK1, MYC, and PTBP1 to be overexpressed in conjunction with oncogenic KRAS mutations, and show that these mutations increase ELK1 levels via the RAS-MAPK pathway. We thus illuminate, for the first time, a full regulatory pathway connecting prevalent cancerous mutations to functional tumor-inducing splicing aberrations. Our results demonstrate our method is applicable to different cancers to reveal regulatory pathways promoting splicing aberrations. PMID:26860615

  3. Infrared Spectroscopy of Matrix-Isolated Polycyclic Aromatic Hydrocarbon Cations. Part 2; The Members of the Thermodynamically Most Favorable Series through Coronene

    NASA Technical Reports Server (NTRS)

    Hudgins, D. M.; Allamandola, L. J.

    1995-01-01

    Gaseous, ionized polycyclic aromatic hydrocarbons (PAHS) are thought to be responsible for a very common family of interstellar infrared emission bands. Here the near- and mid-infrared spectra of the cations of the five most thermodynamically favored PAHs up to coronene: phenanthrene, pyrene, benzo[e]pyrene, benzo-[ghi]perylene, and coronene, are presented to test this hypothesis. For those molecules that have been studied previously (pyrene, pyrene-d(sub 10), and coronene), band positions and relative intensities are in agreement. In all of these cases we report additional features. Absolute integrated absorbance values are given for the phenanthrene, perdeuteriophenanthrene, pyrene, benzo[ghi]perylene, and coronene cations. With the exception of coronene, the cation bands corresponding to the CC modes are typically 2-5 times more intense than those of the CH out-of-plane bending vibrations. For the cations, the CC stretching and CH in-plane bending modes give rise to bands that are an order of magnitude stronger than those of the neutral species, and the CH out-of-plane bends produce bands that are 5-20 times weaker than those of the neutral species. This behavior is similar to that found in most other PAH cations studied to date. The astronomical implications of these PAH cation spectra are also discussed.

  4. How light-harvesting semiconductors can alter the bias of reversible electrocatalysts in favor of H2 production and CO2 reduction.

    PubMed

    Bachmeier, Andreas; Wang, Vincent C C; Woolerton, Thomas W; Bell, Sophie; Fontecilla-Camps, Juan C; Can, Mehmet; Ragsdale, Stephen W; Chaudhary, Yatendra S; Armstrong, Fraser A

    2013-10-09

    The most efficient catalysts for solar fuel production should operate close to reversible potentials, yet possess a bias for the fuel-forming direction. Protein film electrochemical studies of Ni-containing carbon monoxide dehydrogenase and [NiFeSe]-hydrogenase, each a reversible electrocatalyst, show that the electronic state of the electrode strongly biases the direction of electrocatalysis of CO2/CO and H(+)/H2 interconversions. Attached to graphite electrodes, these enzymes show high activities for both oxidation and reduction, but there is a marked shift in bias, in favor of CO2 or H(+) reduction, when the respective enzymes are attached instead to n-type semiconductor electrodes constructed from CdS and TiO2 nanoparticles. This catalytic rectification effect can arise for a reversible electrocatalyst attached to a semiconductor electrode if the electrode transforms between semiconductor- and metallic-like behavior across the same narrow potential range (<0.25 V) that the electrocatalytic current switches between oxidation and reduction.

  5. CD117 expression in gammopathies is associated with an altered maturation of the myeloid and lymphoid hematopoietic cell compartments and favorable disease features

    PubMed Central

    Schmidt-Hieber, Martin; Pérez-Andrés, Martin; Paiva, Bruno; Flores-Montero, Juan; Perez, Jose J.; Gutierrez, Norma C.; Vidriales, Maria-Belen; Matarraz, Sergio; San Miguel, Jesus F.; Orfao, Alberto

    2011-01-01

    Aberrant CD117 expression is associated with a favorable outcome in multiple myeloma. We analyzed 106 patients with symptomatic multiple myeloma (n=50), smoldering multiple myeloma (n=38) and monoclonal gammopathy of undetermined significance (n=18) to elucidate biological features of CD117+ versus CD117− monoclonal gammopathies. CD117+ (mono)clonal plasma cells were detected in 30% symptomatic multiple myeloma, 45% smoldering multiple myeloma and 72% monoclonal gammopathy of undetermined significance patients. CD117 expression was associated with higher percentages of normal bone marrow plasma cells, CD117+ myeloid precursors and CD38+ B lymphocytes in all monoclonal gammopathies. Conversely, the number of bone marrow CD34+ myeloid cells and peripheral blood neutrophils was reduced among CD117+ multiple myeloma but not monoclonal gammopathy of undetermined significance patients. CD117 expression by (mono)clonal plasma cells is associated with uniquely altered patterns of production of hematopoietic bone marrow cells with decreased peripheral blood neutrophil counts and persistence of normal residual bone marrow plasma cells. PMID:20971816

  6. Low oxygen tension favored expansion and hematopoietic reconstitution of CD34(+) CD38(-) cells expanded from human cord blood-derived CD34(+) Cells.

    PubMed

    Wang, Ziyan; Du, Zheng; Cai, Haibo; Ye, Zhaoyang; Fan, Jinli; Tan, Wen-Song

    2016-07-01

    Oxygen tension is an important factor that regulates hematopoietic stem cells (HSCs) in both in vivo hematopoietic microenvironment and ex vivo culture system. Although the effect of oxygen tension on ex vivo expansion of HSCs was extensively studied, there were no clear descriptions on physiological function and gene expression analysis of HSCs under different oxygen tensions. In this study, the effects of oxygen tension on ex vivo expansion characteristics of human umbilical cord blood (UCB)-derived CD34(+) cells are evaluated. Moreover, the physiological function of expanded CD34(+) cells was assessed by secondary expansion ability ex vivo and hematopoietic reconstitution ability in vivo. Also, genetic profiling was applied to analyze the expression of genes related to cell function. It was found that low oxygen tension favored expansion of CD34(+) CD38(-) cells. Additionally, CD34(+) cells expanded under low oxygen tension showed better secondary expansion ability and reconstitution ability than those under atmospheric oxygen concentration. Finally, the genetic profiling of CD34(+) CD38(-) cells cultured under low oxygen tension was more akin to freshly isolated cells. These results collectively demonstrate that low oxygen tension was able to better maintain both self-renewal and hematopoietic reconstitution potential and may lay an experimental basis for clinical transplantation of HSCs.

  7. The functional response of bioactive titania-modified three-dimensional Ti-6Al-4V mesh structure toward providing a favorable pathway for intercellular communication and osteoincorporation.

    PubMed

    Nune, K C; Misra, R D K; Li, S J; Hao, Y L; Zhang, W

    2016-10-01

    The objective of the study is to fundamentally elucidate the biological response of 3D printed mesh structures subjected to plasma electrolytic oxidation process through the study of osteoblast functions. The cellular activity of plasma electrolytic-oxidized mesh structure was explored in terms of cell-to-cell communication involving proliferation, synthesis of extracellular and intracellular proteins, and mineralization. Upon plasma electrolytic oxidation of the mesh structure, a thin layer of bioactive titania with pore size 1-3 µm was nucleated on the surface. The combination of microporous bioactive titania and interconnected porous architecture provided the desired pathway for supply of nutrients and oxygen to cells and tissue and a favorable osteogenic microenvironment for tissue on-growth and in-growth, in relation to the unmodified mesh structure. The formation of a confluent layer as envisaged via electron microscopy and quantitative assessment of the expression level of proteins (actin, vinculin, and fibronectin) point toward the determining role of surface-modified mesh structure in modulating osteoblasts functions. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2488-2501, 2016.

  8. How Light-Harvesting Semiconductors Can Alter the Bias of Reversible Electrocatalysts in Favor of H2 Production and CO2 Reduction

    PubMed Central

    2013-01-01

    The most efficient catalysts for solar fuel production should operate close to reversible potentials, yet possess a bias for the fuel-forming direction. Protein film electrochemical studies of Ni-containing carbon monoxide dehydrogenase and [NiFeSe]-hydrogenase, each a reversible electrocatalyst, show that the electronic state of the electrode strongly biases the direction of electrocatalysis of CO2/CO and H+/H2 interconversions. Attached to graphite electrodes, these enzymes show high activities for both oxidation and reduction, but there is a marked shift in bias, in favor of CO2 or H+ reduction, when the respective enzymes are attached instead to n-type semiconductor electrodes constructed from CdS and TiO2 nanoparticles. This catalytic rectification effect can arise for a reversible electrocatalyst attached to a semiconductor electrode if the electrode transforms between semiconductor- and metallic-like behavior across the same narrow potential range (<0.25 V) that the electrocatalytic current switches between oxidation and reduction. PMID:24070184

  9. Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas

    PubMed Central

    Zhang, Wensheng; Edwards, Andrea; Fang, Zhide; Flemington, Erik K.; Zhang, Kun

    2016-01-01

    Patients with HPV-positive head neck squamous cell carcinomas (HNSCC) usually have a better prognosis than the HPV-negative cases while the underlying mechanism remains far from being well understood. We investigated this issue by an integrative analysis of clinically-annotated multi-omics HNSCC data released by the Cancer Genome Atlas. As confirmatory results, we found: (1) Co-occurrence of mutant TP53 and HPV infection was rare; (2) Regardless of HPV status, HNSCCs of wild-type TP53 implied a good survival chance for patients and had fewer genome-wide somatic mutations than those with a mutation burden on the gene. Our analysis further led to some novel observations. They included: (1) The genes involved in “DNA mismatch repair” pathway were up-regulated in HPV-positive tumors compared to normal tissue samples and HPV-negative cases, and thus constituted a strong predictive signature for the identification of HPV infection; (2) HPV infection could disrupt some regulatory miRNA-mRNA correlations operational in the HPV-negative tumors. In light of these results, we proposed a hypothesis for the favorable clinical outcomes of HPV-positive HNSCC patients. That is, the replication of HPV genome and/or its invasion into the genomes of cancer cells may enhance DNA repair mechanisms, which in turn limit the accumulation of lethal somatic mutations. PMID:27108969

  10. Conflict over condition-dependent sex allocation can lead to mixed sex-determination systems.

    PubMed

    Kuijper, Bram; Pen, Ido

    2014-11-01

    Theory suggests that genetic conflicts drive turnovers between sex-determining mechanisms, yet these studies only apply to cases where sex allocation is independent of environment or condition. Here, we model parent-offspring conflict in the presence of condition-dependent sex allocation, where the environment has sex-specific fitness consequences. Additionally, one sex is assumed to be more costly to produce than the other, which leads offspring to favor a sex ratio less biased toward the cheaper sex in comparison to the sex ratio favored by mothers. The scope for parent-offspring conflict depends on the relative frequency of both environments: when one environment is less common than the other, parent-offspring conflict can be reduced or even entirely absent, despite a biased population sex ratio. The model shows that conflict-driven invasions of condition-independent sex factors (e.g., sex chromosomes) result either in the loss of condition-dependent sex allocation, or, interestingly, lead to stable mixtures of condition-dependent and condition-independent sex factors. The latter outcome corresponds to empirical observations in which sex chromosomes are present in organisms with environment-dependent sex determination. Finally, conflict can also favor errors in environmental perception, potentially resulting in the loss of condition-dependent sex allocation without genetic changes to sex-determining loci.

  11. Alteration of media composition and light conditions change morphology, metabolic profile, and beauvericin biosynthesis in Cordyceps bassiana mycelium.

    PubMed

    Hyun, Sun-Hee; Lee, Seok-Young; Park, Shin Jung; Kim, Da Yeon; Chun, Young-Jin; Sung, Gi-Ho; Kim, Seong Hwan; Choi, Hyung-Kyoon

    2013-01-01

    Metabolic alterations of Cordyceps bassiana mycelium were investigated under the following culture medium and light conditions: dextrose agar supplemented with 0.5% yeast extract (SDAY) medium with light (SL), SDAY medium without light (SD), nut medium without light (ND), and iron-supplemented SDAY medium without light (FD). The levels of asparagine, aspartic acid, glutamic acid, glutamine, histidine, lysine, ornithine, and proline were significantly higher under SD and SL conditions. The levels of most of the alcohols, saturated fatty acids, unsaturated fatty acids, fatty acid esters, sterols, and terpenes were higher under the ND condition than in the other conditions, but beauvericin was not detectable under the ND condition. The FD condition was favorable for the enhanced production of aminomalonic acid, malic acid, mannonic acid, and erythritol. Thus, the metabolic characteristics of C. bassiana can be manipulated by varying the cultivation conditions, rendering this fungus potentially favorable as a nutraceutical and medicinal resource.

  12. National Wetland Condition Assessment

    EPA Pesticide Factsheets

    The NWCA is a collaborative, statistical survey of the nation's wetlands. It is one of four national surveys that EPA and its partners conduct to assess the condition and health of the nation's water resources.

  13. Pavement condition data analysis

    SciTech Connect

    Zaniewski, J.P.; Hudson, S.W.; Hudson, W.R.

    1987-07-01

    This paper describes a computer methodology for analyzing pavement condition data to define inputs for pavement management systems. This system of programs was developed during a Federal Highway Administration research project. In the project, eight state highway departments were studied to determine the types of pavement condition data collected, procedures used for collecting data, the inputs to the states' pavement management systems, and computer programs used by the states to analyze raw pavement condition data. Several of the programs were assembled into the Method for Analyzing Pavement Condition, MAPCON, during a project performed at Pennsylvania State University. These and other existing or new programs (a total of 18) were identified, tested, modified, and incorporated onto a MS/DOS microcomputer system. MAPCON guides the user through selection of analysis method, raw data entry, and data analysis.

  14. Common Childhood Orthopedic Conditions

    MedlinePlus

    ... might be linked to other conditions, such as cerebral palsy, muscle weakness disorders, autism, or other nervous system ... be related to existing medical problems such as cerebral palsy. Doctors rarely have to treat pigeon-toed feet. ...

  15. National Coastal Condition Assessment

    EPA Pesticide Factsheets

    The NCCA is a collaborative, statistical survey of the nation's coastal waters and the Great Lakes. It is one of four national surveys that EPA and its partners conduct to assess the condition and health of the nation's water resources.

  16. Pituitary Tumors: Condition Information

    MedlinePlus

    ... FOIA Jobs at NICHD Meetings, Conferences & Events Partnering & Donating to the NICHD Staff Directory Overview Condition Information ... gland causes the release of hormones in the body that control growth, metabolism, response to stress, and ...

  17. Power supply conditioning circuit

    NASA Technical Reports Server (NTRS)

    Primas, Lori E. (Inventor); Loveland, Rohan C. (Inventor)

    1988-01-01

    A conditioning circuit is provided with a constant current diode in series with a zener diode, the former having a high dynamic impedance and the latter a low dynamic impedance. The constant current diode can receive an input voltage with PARD. In conjunction with the zener diode fixed to a ground, a voltage divider is provided which can give an output voltage whose PARD was significantly reduced. The conditioning circuit is effective down to dc.

  18. Conditions affecting the foreskin.

    PubMed

    Hunter, David

    This article aims to provide an update on the anatomy of, and some of the conditions affecting, the foreskin. The cultural and religious significance of the foreskin will be explored, as well as nursing care and health promotion needs of men. The possible link between circumcision status and human immunodeficiency virus will be briefly discussed. Maintaining cleanliness of the genitals is advocated to reduce the incidence of inflammatory conditions.

  19. Air regenerating and conditioning

    NASA Technical Reports Server (NTRS)

    Grishayenkov, B. G.

    1975-01-01

    Various physicochemical methods of regenerating and conditioning air for spacecraft are described with emphasis on conditions which affect efficiency of the system. Life support systems used in closed, hermetically sealed environments are discussed with references to actual application in the Soviet Soyuz and Voskhod manned spacecraft. Temperature and humidity control, removal of carbon dioxide, oxygen regeneration, and removal of bacteria and viruses are among the factors considered.

  20. Conditional data watchpoint management

    DOEpatents

    Burdick, Dean Joseph; Vaidyanathan, Basu

    2010-08-24

    A method, system and computer program product for managing a conditional data watchpoint in a set of instructions being traced is shown in accordance with illustrative embodiments. In one particular embodiment, the method comprises initializing a conditional data watchpoint and determining the watchpoint has been encountered. Upon that determination, examining a current instruction context associated with the encountered watchpoint prior to completion of the current instruction execution, further determining a first action responsive to a positive context examination; otherwise, determining a second action.

  1. Conditions of Children in California

    ERIC Educational Resources Information Center

    Policy Analysis for California Education, Berkeley, CA.

    Although many California children are growing up in circumstances favoring school performance, many others are inhibited by poor health, poverty, low-quality child care, and other factors external to schools. This report assembles a set of indicators depicting California children's quality of life. Data are included on physical and mental health,…

  2. Causal conditionals and counterfactuals

    PubMed Central

    Frosch, Caren A.; Byrne, Ruth M.J.

    2012-01-01

    Causal counterfactuals e.g., ‘if the ignition key had been turned then the car would have started’ and causal conditionals e.g., ‘if the ignition key was turned then the car started’ are understood by thinking about multiple possibilities of different sorts, as shown in six experiments using converging evidence from three different types of measures. Experiments 1a and 1b showed that conditionals that comprise enabling causes, e.g., ‘if the ignition key was turned then the car started’ primed people to read quickly conjunctions referring to the possibility of the enabler occurring without the outcome, e.g., ‘the ignition key was turned and the car did not start’. Experiments 2a and 2b showed that people paraphrased causal conditionals by using causal or temporal connectives (because, when), whereas they paraphrased causal counterfactuals by using subjunctive constructions (had…would have). Experiments 3a and 3b showed that people made different inferences from counterfactuals presented with enabling conditions compared to none. The implications of the results for alternative theories of conditionals are discussed. PMID:22858874

  3. Choice and conditioned reinforcement.

    PubMed Central

    Fantino, E; Freed, D; Preston, R A; Williams, W A

    1991-01-01

    A potential weakness of one formulation of delay-reduction theory is its failure to include a term for rate of conditioned reinforcement, that is, the rate at which the terminal-link stimuli occur in concurrent-chains schedules. The present studies assessed whether or not rate of conditioned reinforcement has an independent effect upon choice. Pigeons responded on either modified concurrent-chains schedules or on comparable concurrent-tandem schedules. The initial link was shortened on only one of two concurrent-chains schedules and on only one of two corresponding concurrent-tandem schedules. This manipulation increased rate of conditioned reinforcement sharply in the chain but not in the tandem schedule. According to a formulation of delay-reduction theory, when the outcomes chosen (the terminal links) are equal, as in Experiment 1, choice should depend only on rate of primary reinforcement; thus, choice should be equivalent for the tandem and chain schedules despite a large difference in rate of conditioned reinforcement. When the outcomes chosen are unequal, however, as in Experiment 2, choice should depend upon both rate of primary reinforcement and relative signaled delay reduction; thus, larger preferences should occur in the chain than in the tandem schedules. These predictions were confirmed, suggesting that increasing the rate of conditioned reinforcement on concurrent-chains schedules may have no independent effect on choice. PMID:2037826

  4. Education, but not occupation or household income, is positively related to favorable dietary intake patterns in pregnant Japanese women: the Osaka Maternal and Child Health Study.

    PubMed

    Murakami, Kentaro; Miyake, Yoshihiro; Sasaki, Satoshi; Tanaka, Keiko; Ohya, Yukihiro; Hirota, Yoshio

    2009-03-01

    Although a large body of epidemiologic data accumulated in Western countries show that individuals with a higher socioeconomic position consume higher quality diets, information on such socioeconomic differences in the diets of non-Western populations, including Japanese, is absolutely lacking. This cross-sectional study examined the association of socioeconomic position with dietary intake in a group of pregnant Japanese women. Subjects were 1002 Japanese women during pregnancy. Socioeconomic position was assessed by education, occupation, and household income. Dietary intake was estimated using a validated, self-administered, comprehensive diet history questionnaire. Education was associated positively with intake of protein; total n-3 and marine-origin n-3 polyunsaturated fatty acids; dietary fiber; cholesterol; potassium; calcium; magnesium; iron; vitamins A, D, E, and C; and folate 9 and inversely with that of carbohydrate. No associations were seen between education and intake of total fat; saturated, monounsaturated, and total and n-6 polyunsaturated fatty acids; alcohol; or sodium. Regarding food, higher education was associated with a higher intake of vegetables, fish and shellfish, and potatoes and lower intake of rice. Education was not associated with intake of bread, noodles, confectioneries and sugars, fats and oils, pulses and nuts, meat, eggs, dairy products, or fruit. For occupation, housewives had a higher intake of dietary fiber, magnesium, iron, vitamin A, folate, and pulses and nuts than working women. Household income was not associated with any nutrient or food examined. In conclusion, education, but not occupation or household income, was positively associated with favorable dietary intake patterns in a group of pregnant Japanese women.

  5. The ratio of fish to meat in the diet is positively associated with favorable intake of food groups and nutrients among young Japanese women.

    PubMed

    Okubo, Hitomi; Sasaki, Satoshi; Murakami, Kentaro; Takahashi, Yoshiko

    2011-03-01

    Although fish and meat may exert opposing influences on chronic disease, information on the balance of intake between fish and meat to overall diet quality is limited, particularly in Japanese, who have a much higher fish intake than Western populations. The objective of this cross-sectional study was to test the hypothesis that intake balance between fish and meat is associated with food and nutrient intakes in young Japanese women. The subjects were 3716 Japanese dietetic students aged 18 to 20 years. Diet was assessed by a validated, self-administered diet history questionnaire. The dietary ratio of fish to meat was calculated from fish and meat intakes as a temporal indicator of overall intake balance. The ratio of fish to meat intake was associated positively with intakes of vegetables, fruits, pulses, dairy products, and alcohol, and negatively with those of energy-containing beverages and fat and oils. At the nutrient level, the ratio of fish to meat intake was associated negatively with intakes of energy, total fat, saturated fatty acids, n-6 polyunsaturated fatty acids, vitamin B(1), and zinc, and positively with those of protein, n-3 polyunsaturated fatty acids, dietary fiber, and key vitamins and minerals. After limiting analysis to nutrients derived from foods other than fish and meat, the ratio of fish to meat intake was positively associated with intakes of almost all vitamins and minerals examined. In conclusion, women who consumed more fish than meat (ratio >1) tended to choose more favorable food groups that included higher amounts of vegetables and fruits, resulting in a better profile of nutrient intake patterns.

  6. Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection

    PubMed Central

    Eing, Bodo R.; Müller, Marcus; King, Nicholas J. C.; Klupp, Barbara; Mettenleiter, Thomas C.; Kühn, Joachim E.

    2012-01-01

    Following productive, lytic infection in epithelia, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons that is interrupted by episodes of reactivation. In order to better understand what triggers this lytic/latent decision in neurons, we set up an organotypic model based on chicken embryonic trigeminal ganglia explants (TGEs) in a double chamber system. Adding HSV-1 to the ganglion compartment (GC) resulted in a productive infection in the explants. By contrast, selective application of the virus to distal axons led to a largely nonproductive infection that was characterized by the poor expression of lytic genes and the presence of high levels of the 2.0-kb major latency-associated transcript (LAT) RNA. Treatment of the explants with the immediate-early (IE) gene transcriptional inducer hexamethylene bisacetamide, and simultaneous co-infection of the GC with HSV-1, herpes simplex virus type 2 (HSV-2) or pseudorabies virus (PrV) helper virus significantly enhanced the ability of HSV-1 to productively infect sensory neurons upon axonal entry. Helper-virus-induced transactivation of HSV-1 IE gene expression in axonally-infected TGEs in the absence of de novo protein synthesis was dependent on the presence of functional tegument protein VP16 in HSV-1 helper virus particles. After the establishment of a LAT-positive silent infection in TGEs, HSV-1 was refractory to transactivation by superinfection of the GC with HSV-1 but not with HSV-2 and PrV helper virus. In conclusion, the site of entry appears to be a critical determinant in the lytic/latent decision in sensory neurons. HSV-1 entry into distal axons results in an insufficient transactivation of IE gene expression and favors the establishment of a nonproductive, silent infection in trigeminal neurons. PMID:22589716

  7. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency

    PubMed Central

    Fallahi, Ali Asghar; Shekarfroush, Shahnaz; Rahimi, Mostafa; Jalali, Amirhossain; Khoshbaten, Ali

    2016-01-01

    Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Materials and Methods: Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. Results: UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. Conclusion: This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance. PMID:27114795

  8. Impaired IFN-α production by plasmacytoid dendritic cells favors regulatory T-cell expansion that may contribute to breast cancer progression.

    PubMed

    Sisirak, Vanja; Faget, Julien; Gobert, Michael; Goutagny, Nadège; Vey, Nelly; Treilleux, Isabelle; Renaudineau, Sarah; Poyet, Gaelle; Labidi-Galy, Sana Intidhar; Goddard-Leon, Sophie; Durand, Isabelle; Le Mercier, Isabelle; Bajard, Agathe; Bachelot, Thomas; Puisieux, Alain; Puisieux, Isabelle; Blay, Jean-Yves; Ménétrier-Caux, Christine; Caux, Christophe; Bendriss-Vermare, Nathalie

    2012-10-15

    Infiltration and dysfunction of immune cells have been documented in many types of cancers. We previously reported that plasmacytoid dendritic cells (pDC) within primary breast tumors correlate with an unfavorable prognosis for patients. The role of pDC in cancer remains unclear but they have been shown to mediate immune tolerance in other pathophysiologic contexts. We postulated that pDC may interfere with antitumor immune response and favor tolerance in breast cancer. The present study was designed to decipher the mechanistic basis for the deleterious impact of pDC on the clinical outcome. Using fresh human breast tumor biopsies (N = 60 patients), we observed through multiparametric flow cytometry increased tumor-associated (TA) pDC (TApDC) rates in aggressive breast tumors, i.e., those with high mitotic index and the so-called triple-negative breast tumors (TNBT). Furthermore, TApDC expressed a partially activated phenotype and produced very low amounts of IFN-α following toll-like receptor activation in vitro compared with patients' blood pDC. Within breast tumors, TApDC colocalized and strongly correlated with TA regulatory T cells (TATreg), especially in TNBT. Of most importance, the selective suppression of IFN-α production endowed TApDC with the unique capacity to sustain FoxP3(+) Treg expansion, a capacity that was reverted by the addition of exogenous IFN-α. These findings indicate that IFN-α-deficient TApDC accumulating in aggressive tumors are involved in the expansion of TATreg in vivo, contributing to tumor immune tolerance and poor clinical outcome. Thus, targeting pDC to restore their IFN-α production may represent an attractive therapeutic strategy to overcome immune tolerance in breast cancer.

  9. A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum lipid profile of healthy men and women.

    PubMed

    Rajaram, S; Burke, K; Connell, B; Myint, T; Sabaté, J

    2001-09-01

    Frequent consumption of nuts is associated with decreased risk of cardiovascular disease. We investigated the effect of pecans rich in monounsaturated fat as an alternative to the Step 1 diet in modifying serum lipids and lipoproteins in men and women with normal to moderately high serum cholesterol. In a single-blind, randomized, controlled, crossover feeding study, we assigned 23 subjects (mean age: 38 y; 9 women, 14 men) to follow two diets, each for 4 wk: a Step I diet and a pecan-enriched diet (accomplished by proportionately reducing all food items in a Step I diet by one fifth for a 20% isoenergetic replacement with pecans). The percentage of energy from fat in the two diets was 28.3 and 39.6%, respectively. Both diets improved the lipid profile; however, the pecan-enriched diet decreased both serum total and LDL cholesterol by 0.32 mmol/L (6.7 and 10.4%, respectively) and triglyceride by 0.14 mmol/L (11.1%) beyond the Step I diet, while increasing HDL cholesterol by 0.06 mmol/L (2.5 mg/dL). Serum apolipoprotein B and lipoprotein(a) decreased by 11.6 and 11.1%, respectively, and apolipoprotein A1 increased by 2.2% when subjects consumed the pecan compared with the Step I diet. These differences were all significant (P < 0.05). A 20% isoenergetic replacement of a Step I diet with pecans favorably altered the serum lipid profile beyond the Step I diet, without increasing body weight. Nuts such as pecans that are rich in monounsaturated fat may therefore be recommended as part of prescribed cholesterol-lowering diet of patients or habitual diet of healthy individuals.

  10. Less Favorable Body Composition and Adipokines in South Asians Compared to Other U.S. Ethnic Groups: Results from the MASALA and MESA Studies

    PubMed Central

    Shah, Arti D.; Kandula, Namratha R.; Lin, Feng; Allison, Matthew A.; Carr, Jeffrey; Herrington, David; Liu, Kiang; Kanaya, Alka M.

    2015-01-01

    Background Small studies have shown that South Asians (SAs) have more total body, subcutaneous, visceral and hepatic fat and abnormal adipokine levels compared to Whites. However, comprehensive studies of body composition and adipokines in SAs compared to other ethnic groups are lacking. Methods Using harmonized data, we performed a cross-sectional analysis of two community-based cohorts: Mediators of Atherosclerosis of South Asians Living in America (MASALA, n=906) and Multi-Ethnic Study of Atherosclerosis (MESA which included 2,622 Whites; 803 Chinese Americans; 1,893 African Americans; and 1,496 Latinos). General linear models were developed to assess ethnic differences in ectopic fat (visceral, intermuscular, and pericardial fat; and hepatic attenuation), lean muscle mass, and adipokines (adiponectin and resistin). Models were adjusted for age, sex, site, alcohol use, smoking, exercise, education, household income and BMI. Ectopic fat models were additionally adjusted for hypertension, diabetes, HDL, and triglycerides. Adipokine models were adjusted for subcutaneous, visceral, intermuscular, and pericardial fat; and hepatic attenuation. Results Compared to all ethnic groups in MESA (Whites, Chinese Americans, African Americans, and Latinos), SAs had greater intermuscular fat (pairwise comparisons to each MESA group, p < 0.01), lower hepatic attenuation (p < 0.001), and less lean mass (p < 0.001). SAs had greater visceral fat compared to Chinese Americans, African Americans and Latinos (p < 0.05) and greater pericardial fat compared to African Americans (p < 0.001). SAs had lower adiponectin levels compared to other ethnic groups (p < 0.01; except Chinese Americans) and higher resistin levels than all groups (p < 0.001), even after adjusting for differences in body composition. Conclusion There are significant ethnic differences in ectopic fat, lean mass, and adipokines. A less favorable body composition and adipokine profile in South Asians may partially

  11. In Vitro Characterization of GS-8374, a Novel Phosphonate-Containing Inhibitor of HIV-1 Protease with a Favorable Resistance Profile ▿ †

    PubMed Central

    Callebaut, Christian; Stray, Kirsten; Tsai, Luong; Williams, Matt; Yang, Zheng-Yu; Cannizzaro, Carina; Leavitt, Stephanie A.; Liu, Xiaohong; Wang, Kelly; Murray, Bernard P.; Mulato, Andrew; Hatada, Marcos; Priskich, Tina; Parkin, Neil; Swaminathan, Swami; Lee, William; He, Gong-Xin; Xu, Lianhong; Cihlar, Tomas

    2011-01-01

    GS-8374 is a novel bis-tetrahydrofuran HIV-1 protease (PR) inhibitor (PI) with a unique diethylphosphonate moiety. It was selected from a series of analogs containing various di(alkyl)phosphonate substitutions connected via a linker to the para position of a P-1 phenyl ring. GS-8374 inhibits HIV-1 PR with high potency (Ki = 8.1 pM) and with no known effect on host proteases. Kinetic and thermodynamic analysis of GS-8374 binding to PR demonstrated an extremely slow off rate for the inhibitor and favorable contributions of both the enthalpic and entropic components to the total free binding energy. GS-8374 showed potent antiretroviral activity in T-cell lines, primary CD4+ T cells (50% effective concentration [EC50] = 3.4 to 11.5 nM), and macrophages (EC50 = 25.5 nM) and exhibited low cytotoxicity in multiple human cell types. The antiviral potency of GS-8374 was only moderately affected by human serum protein binding, and its combination with multiple approved antiretrovirals showed synergistic effects. When it was tested in a PhenoSense assay against a panel of 24 patient-derived viruses with high-level PI resistance, GS-8374 showed lower mean EC50s and lower fold resistance than any of the clinically approved PIs. Similar to other PIs, in vitro hepatic microsomal metabolism of GS-8374 was efficiently blocked by ritonavir, suggesting a potential for effective pharmacokinetic boosting in vivo. In summary, results from this broad in vitro pharmacological profiling indicate that GS-8374 is a promising candidate to be further assessed as a new antiretroviral agent with potential for clinical efficacy in both treatment-naïve and -experienced patients. PMID:21245449

  12. Screening Complex Biological Samples with Peptide Microarrays: The Favorable Impact of Probe Orientation via Chemoselective Immobilization Strategies on Clickable Polymeric Coatings.

    PubMed

    Gori, Alessandro; Sola, Laura; Gagni, Paola; Bruni, Giulia; Liprino, Marta; Peri, Claudio; Colombo, Giorgio; Cretich, Marina; Chiari, Marcella

    2016-11-16

    The generation of robust analytical data using microarray platforms strictly relies on optimal ligand-target interaction at the sensor surface, which, in turn, is inherently bound to the correct immobilization scheme of the interrogated bioprobes. In the present work, we performed a rigorous comparative analysis of the impact of peptide ligands immobilization strategy in the screening of Burkholderia cepacia complex (BCC) infections in patients affected by cystic fibrosis (CF). We generated arrays of previously validated Burkholderia derived peptide probes that were selectively oriented on polymeric coatings by means of different click-type reactions including thiol maleimide, copper-catalyzed azide-alkyne cycloaddition (CuAAC), and strain-promoted azide-alkyne cycloaddition (SPAAC). We compared immobilization efficiency among the different chemoselective reactions, and we evaluated diagnostic performances at a statistically significant level, also in contrast to random immobilization strategies. Our findings clearly support the favorable role of correct bioprobe orientation in discriminating seronegative from infected individuals and, in the last analysis, in generating more-reliable and more-reproducible data. Spacing biomolecules from the sensor surface by means of small hydrophilic linkers also positively affects the analytical performance and leads to increased statistical significance of data. Overall, all of the click immobilization strategies that were considered displayed a good efficiency. Interestingly, SPAAC-mediated conjugation using DBCO cyclooctyne for some peptides resulted in sequence-dependent autofluorescence in the Cy5 emission range wavelength, which could be circumvented by using a different fluorescence detection channel. On the basis of our results, we critically discuss the immobilization parameters that need to be carefully considered for peptide ligand immobilization purposes.

  13. The presence of CXCR4+ CD1a+ cells at onset of Langerhans cell histiocytosis is associated with a less favorable outcome

    PubMed Central

    Quispel, Willemijn T.; Stegehuis-Kamp, Janine A.; Blijleven, Laura; Santos, Susy J.; Lourda, Magda; van den Bos, Cor; van Halteren, Astrid G.S.; Egeler, R. Maarten

    2016-01-01

    abstract Purpose: Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder characterized by tissue accumulating CD1a+ histiocytes which frequently carry somatic mutations. Irrespective of mutation status, these LCH-cells display constitutively active kinases belonging to the MAPK pathway. We evaluated, in retrospect, the contribution of individual components of the MAPK-activating and chemotaxis-promoting TNF-CXCR4-CXCL12 axis to LCH manifestation and outcome. Experimental design: CXCR4, CXCL12 and TNF protein expression was immunohistochemically analyzed in 70 LCH-affected biopsies. The presence of CXCR4+CD1a+ cells in peripheral blood (PB) and/or bone marrow (BM) samples was evaluated by flowcytometry in 13 therapy-naive LCH-patients. Results: CXCL12 was detected in 68/70 (97%) biopsies. CXCR4+LCH-cells were present in 50/70 (71%) biopsies; their presence was associated with higher levels of intralesional TNF. Circulating CD1a+CXCR4+ cells were detected in 4/13 (31%) therapy-naïve LCH-patients which displayed BRAFV600E (2/4), MAP2K1 (1/4) or no (1/4) mutations in their tissues. These CD11c co-expressing CD1a+CXCR4+cells migrated to CXCL12 in chemotaxis assays. Lesional CXCR4+LCH-cells were detected in 18/20 cases who presented with LCH manifestation at multiple sites and in 5/23 (22%) patients who developed additional lesions after initially presenting with a single lesion. The CXCR4 status at onset proved to be an independent risk factor for LCH reactivation in multivariate analysis (odds ratio 10.4, p = 0.034). Conclusions: This study provides the first evidence that CXCR4 is involved in the homing and retention of LCH-cells in CXCL12-expressing tissues and qualifies CXCR4 as a candidate prognostic marker for less favorable disease outcome.

  14. Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.

    PubMed

    Tomizawa, Daisuke; Kato, Motohiro; Takahashi, Hiroyuki; Fujimura, Junya; Inukai, Takeshi; Fukushima, Takashi; Kiyokawa, Nobutaka; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira

    2015-11-01

    Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

  15. A CpG island methylator phenotype in acute myeloid leukemia independent of IDH mutations and associated with a favorable outcome.

    PubMed

    Kelly, A D; Kroeger, H; Yamazaki, J; Taby, R; Neumann, F; Yu, S; Lee, J T; Patel, B; Li, Y; He, R; Liang, S; Lu, Y; Cesaroni, M; Pierce, S A; Kornblau, S M; Bueso-Ramos, C E; Ravandi, F; Kantarjian, H M; Jelinek, J; Issa, J-Pj

    2017-01-31

    Genetic changes are infrequent in acute myeloid leukemia (AML) compared with other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CGI methylator phenotype (CIMP) (A-CIMP(+)). A-CIMP was associated with longer overall survival (OS) in this data set (median OS, years: A-CIMP(+)=not reached, CIMP(-)=1.17; P=0.08). For validation we used 194 samples from The Cancer Genome Atlas interrogated with Illumina 450k methylation arrays where we confirmed longer OS in A-CIMP (median OS, years: A-CIMP(+)=2.34, A-CIMP(-)=1.00; P=0.01). Hypermethylation in A-CIMP(+) favored CGIs (OR: CGI/non-CGI=5.21), and while A-CIMP(+) was enriched in CEBPA (P=0.002) and WT1 mutations (P=0.02), 70% of cases lacked either mutation. Hypermethylated genes in A-CIMP(+) function in pluripotency maintenance, and a gene expression signature of A-CIMP was associated with outcomes in multiple data sets. We conclude that CIMP in AML cannot be explained solely by gene mutations (for example, IDH1/2, TET2), and that curability in A-CIMP(+) AML should be validated prospectively.Leukemia advance online publication, 31 January 2017; doi:10.1038/leu.2017.12.

  16. Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy.

    PubMed

    Matsumoto, Kazumasa; Mochizuki, Kohei; Hirayama, Takahiro; Ikeda, Masaomi; Nishi, Morihiro; Tabata, Ken-ichi; Okazaki, Miyoko; Fujita, Tetsuo; Taoka, Yoshinori; Iwamura, Masatsugu

    2015-01-01

    This study was conducted to evaluate the effectiveness of a combination of gemcitabine and nedaplatin therapy among patients with metastatic urothelial carcinoma previously treated with two lines of chemotherapy. Between February 2009 and August 2013, 30 patients were treated with gemcitabine and paclitaxel as a second-line chemotherapy. All had received a first-line chemotherapy consisting of methotrexate, vinblastine, doxorubicin and cisplatin. Ten patients who had measurable histologically proven advanced or metastatic urothelial carcinoma of the urinary bladder and upper urinary tract received gemcitabine 1,000 mg/m2 on days 1, 8 and 15 and nedaplatin 70 mg/m2 on day 2 as a third-line chemotherapy. Tumors were assessed by imaging every two cycles. The median number of treatment cycles was 3.5. One patient had partial response and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. Among disease-controlled patients (n=4), median overall survival was 14.2 months. Myelosuppression was the most common toxicity. There were no therapy-related deaths. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted given the implications of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma.

  17. CD8+ T cells undergo activation and programmed death-1 repression in the liver of aged Ae2a,b−/− mice favoring autoimmune cholangitis

    PubMed Central

    Concepcion, Axel R.; Salas, January T.; Sáez, Elena; Sarvide, Sarai; Ferrer, Alex; Portu, Ainhoa; Uriarte, Iker; Hervás-Stubbs, Sandra; Oude Elferink, Ronald P.J.; Prieto, Jesús; Medina, Juan F.

    2015-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of unknown etiopathogenesis showing progressive autoimmune-mediated cholangitis. In PBC patients, the liver and lymphocytes exhibit diminished expression of AE2/SLC4A2, a Cl−/HCO3− anion exchanger involved in biliary bicarbonate secretion and intracellular pH regulation. Decreased AE2 expression may be pathogenic as Ae2a,b−/− mice reproduce hepatobiliary and immunological features resembling PBC. To understand the role of AE2 deficiency for autoimmunity predisposition we focused on the phenotypic changes of T cells that occur over the life-span of Ae2a,b−/− mice. At early ages (1-9 months), knockout mice had reduced numbers of intrahepatic T cells, which exhibited increased activation, programmed-cell-death (PD)-1 expression, and apoptosis. Moreover, young knockouts had upregulated PD-1 ligand (PD-L1) on bile-duct cells, and administration of neutralizing anti-PD-L1 antibodies prevented their intrahepatic T-cell deletion. Older (≥10 months) knockouts, however, showed intrahepatic accumulation of cytotoxic CD8+ T cells with downregulated PD-1 and diminished apoptosis. In-vitro DNA demethylation with 5-aza-2′-deoxycytidine partially reverted PD-1 downregulation of intrahepatic CD8+ T cells from aged knockouts. Conclusion: Early in life, AE2 deficiency results in intrahepatic T-cell activation and PD-1/PD-L1 mediated deletion. With aging, intrahepatic CD8+ T cells epigenetically suppress PD-1, and their consequential expansion and further activation favor autoimmune cholangitis. PMID:26396175

  18. Human epidermal growth factor receptor 4 (HER4) is a favorable prognostic marker of breast cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Jue; Yin, Jun; Yang, Qing; Ding, Feng; Chen, Xiao; Li, Bingjie; Tian, Xingsong

    2016-01-01

    Based on a large cohort of clinical studies involving a total of 8024 patients and reporting the effects of HER4 on breast cancer prognosis, we conducted the first meta-analysis and review of this type. We identified 26 studies published between 1985 and 2016 and assessed the prognostic value of HER4 in breast cancer by either real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR, for mRNA levels) or immunohistochemistry (IHC, for protein levels). Elevated expression of HER4 was significantly associated with longer relapse-free survival (RFS) (HR = 0.63; CI: 0.48−0.83; P = 0.001, random effects). Further subgroup analysis showed that our results were stable irrespective of subtype [Luminal: HR = 0.40, CI: 0.30−0.53, P < 0.001, fixed effects; triple negative breast cancer (TNBC): HR = 0.49, CI: 0.26−0.90, P = 0.02, fixed effects; and HER2-positive: HR = 0.53, CI: 0.40−0.71, P < 0.001, fixed effects]. Cytoplasmic HER4 was more effective than nuclear HER4 (HR = 0.74, CI: 0.60−0.92, P = 0.007, fixed effects) for predicting RFS. HER4 was also found to be a favorable prognostic marker for overall survival (OS) among patients with non-TNBC in the subgroup analysis (Luminal: HR = 0.71, CI: 0.52−0.95, P = 0.023, fixed effects; HER2-positive: HR = 0.48, CI: 0.26−0.89, P = 0.020, fixed effects). PMID:27736797

  19. Computer-Aided Design of Orally Bioavailable Pyrrolidine Carboxamide Inhibitors of Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis with Favorable Pharmacokinetic Profiles

    PubMed Central

    Kouassi, Affiba Florance; Kone, Mawa; Keita, Melalie; Esmel, Akori; Megnassan, Eugene; N’Guessan, Yao Thomas; Frecer, Vladimir; Miertus, Stanislav

    2015-01-01

    We have carried out a computational structure-based design of new potent pyrrolidine carboxamide (PCAMs) inhibitors of enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (MTb). Three-dimensional (3D) models of InhA-PCAMx complexes were prepared by in situ modification of the crystal structure of InhA-PCAM1 (Protein Data Bank (PDB) entry code: 4U0J), the reference compound of a training set of 20 PCAMs with known experimental inhibitory potencies (IC50exp). First, we built a gas phase quantitative structure-activity relationships (QSAR) model, linearly correlating the computed enthalpy of the InhA-PCAM complex formation and the IC50exp. Further, taking into account the solvent effect and loss of inhibitor entropy upon enzyme binding led to a QSAR model with a superior linear correlation between computed Gibbs free energies (ΔΔGcom) of InhA-PCAM complex formation and IC50exp (pIC50exp = −0.1552·ΔΔGcom + 5.0448, R2 = 0.94), which was further validated with a 3D-QSAR pharmacophore model generation (PH4). Structural information from the models guided us in designing of a virtual combinatorial library (VL) of more than 17 million PCAMs. The VL was adsorption, distribution, metabolism and excretion (ADME) focused and reduced down to 1.6 million drug like orally bioavailable analogues and PH4 in silico screened to identify new potent PCAMs with predicted IC50pre reaching up to 5 nM. Combining molecular modeling and PH4 in silico screening of the VL resulted in the proposed novel potent antituberculotic agent candidates with favorable pharmacokinetic profiles. PMID:26703572

  20. Detection of PrPSc in lung and mammary gland is favored by the presence of Visna/maedi virus lesions in naturally coinfected sheep

    PubMed Central

    Salazar, Eider; Monleón, Eva; Bolea, Rosa; Acín, Cristina; Pérez, Marta; Álvarez, Neila; Leginagoikoa, Iratxe; Juste, Ramón; Minguijón, Esmeralda; Reina, Ramsés; Glaria, Idoia; Berriatua, Eduardo; de Andrés, Damián; Badiola, Juan José; Amorena, Beatriz; Luján, Lluís

    2010-01-01

    There are few reports on the pathogenesis of scrapie (Sc) and Visna/maedi virus (VMV) coinfections. The aim of this work was to study in vivo as well as post mortem both diseases in 91 sheep. Diagnosis of Sc and VMV infections allowed the distribution of animals into five groups according to the presence (+) or absence (−) of infection by Sc and VMV: Sc−/VMV−, Sc−/VMV+, Sc+/VMV− and Sc+/VMV+. The latter was divided into two subgroups, with and without VMV-induced lymphoid follicle hyperplasia (LFH), respectively. In both the lung and mammary gland, PrPSc deposits were found in the germinal center of hyperplasic lymphoid follicles in the subgroup of Sc+/VMV+ having VMV-induced LFH. This detection was always associated with (and likely preceded by) PrPSc observation in the corresponding lymph nodes. No PrPSc was found in other VMV-associated lesions. Animals suffering from scrapie had a statistically significantly lower mean age than the scrapie free animals at the time of death, with no apparent VMV influence. ARQ/ARQ genotype was the most abundant among the 91 ewes and the most frequent in scrapie-affected sheep. VMV infection does not seem to influence the scrapie risk group distribution among animals from the five groups established in this work. Altogether, these data indicate that certain VMV-induced lesions can favor PrPSc deposits in Sc non-target organs such as the lung and the mammary gland, making this coinfection an interesting field that warrants further research for a better comprehension of the pathogenesis of both diseases. PMID:20423698