WorldWideScience

Sample records for multiple dendrochronological responses

  1. Multiple dendrochronological responses to the eruption of Cinder Cone, Lassen Volcanic National Park, California

    Science.gov (United States)

    Sheppard, P.R.; Ort, M.H.; Anderson, K.C.; Clynne, M.A.; May, E.M.

    2009-01-01

    Two dendrochronological properties – ring width and ring chemistry – were investigated in trees near Cinder Cone in Lassen Volcanic National Park, northeastern California, for the purpose of re-evaluating the date of its eruption. Cinder Cone is thought to have erupted in AD 1666 based on ring-width evidence, but interpreting ring-width changes alone is not straightforward because many forest disturbances can cause changes in ring width. Old Jeffrey pines growing in Cinder Cone tephra and elsewhere for control comparison were sampled. Trees growing in tephra show synchronous ring-width changes at AD 1666, but this ring-width signal could be considered ambiguous for dating the eruption because changes in ring width can be caused by other events. Trees growing in tephra also show changes in ring phosphorus, sulfur, and sodium during the late 1660s, but inter-tree variability in dendrochemical signals makes dating the eruption from ring chemistry alone difficult. The combination of dendrochemistry and ring-width signals improves confidence in dating the eruption of Cinder Cone over the analysis of just one ring-growth property. These results are similar to another case study using dendrochronology of ring width and ring chemistry at Parícutin, Michoacán, Mexico, a cinder cone that erupted beginning in 1943. In both cases, combining analysis with ring width and ring chemistry improved confidence in the dendro-dating of the eruptions.

  2. Vulnerability of white spruce tree growth in interior Alaska in response to climate variability: dendrochronological, demographic, and experimental perspectives

    Science.gov (United States)

    A.D. McGuire; R.W. Ruess; A. Lloyd; J. Yarie; J.S. Clein; G.P. Juday

    2010-01-01

    This paper integrates dendrochronological, demographic, and experimental perspectives to improve understanding of the response of white spruce (Picea glauca (Moench) Voss) tree growth to climatic variability in interior Alaska. The dendrochronological analyses indicate that climate warming has led to widespread declines in white spruce growth...

  3. [Research advances in dendrochronology].

    Science.gov (United States)

    Fang, Ke-Yan; Chen, Qiu-Yan; Liu, Chang-Zhi; Cao, Chun-Fu; Chen, Ya-Jun; Zhou, Fei-Fei

    2014-07-01

    Tree-ring studies in China have achieved great advances since the 1990s, particularly for the dendroclimatological studies which have made some influence around the world. However, because of the uneven development, limited attention has been currently paid on the other branches of dendrochronology. We herein briefly compared the advances of dendrochronology in China and of the world and presented suggestions on future dendrochronological studies. Large-scale tree-ring based climate reconstructions in China are highly needed by employing mathematical methods and a high quality tree-ring network of the ring-width, density, stable isotope and wood anatomy. Tree-ring based field climate reconstructions provide potentials on explorations of climate forcings during the reconstructed periods via climate diagnosis and process simulation.

  4. An organismal view of dendrochronology

    Science.gov (United States)

    Kevin T. Smith

    2008-01-01

    An organism is the most basic unit of independent life. The tree-ring record is defined by organismal processes. Dendrochronology contributes to investigations far removed from organismal biology, e.g., archeology, climatology, disturbance ecology, etc. The increasing integration of dendrochronology into a diverse research community suggests an opportunity for a brief...

  5. Reconstructing Fire History: An Exercise in Dendrochronology

    Science.gov (United States)

    Lafon, Charles W.

    2005-01-01

    Dendrochronology is used widely to reconstruct the history of forest disturbances. I created an exercise that introduces the use of dendrochronology to investigate fire history and forest dynamics. The exercise also demonstrates how the dendrochronological technique of crossdating is employed to age dead trees and identify missing rings. I…

  6. Growth divergence: a challenging opportunity for dendrochronology

    Science.gov (United States)

    Buras, Allan; Sass-Klaassen, Ute; Wilmking, Martin

    2017-04-01

    Dendrochronology is an essential cornerstone of paleoclimatology and the evaluation of climate change impacts on forest ecosystems. However, a growing body of literature indicates that the standard dendrochronological approach may too rigorously neglect individualistic tree-growth (e.g. Wilmking et al., 2004, Buras et al., 2016). Amongst others, these studies showed convincing evidence that individual trees of the same species sampled at one site expressed different long-term growth patterns and therefore differing climate-growth relationships. This phenomenon is commonly termed growth divergence (GD) and possibly weakens our ability to correctly estimate past climate variability as discussed in the context of the so-called divergence phenomenon (D'Arrigo et al., 2008). In this context, climate change may naturally select for trees on the stand-level which are better adapted to future conditions. Although GD has been reported for several sites, the standard dendrochronological approach yet does not consider the existence of GD. A possible reason for this methodological persistence is the lack of detailed information on the frequency, magnitude, and impact of GD occurrence. To assess GD occurrence and related tree-individual variations in climate-growth response we conducted a global GD study by using 134 ring-width data representing 52 tree species and 16 genera distributed over 115 sites across 22 countries. Our analyses clearly reveal GD to be a common phenomenon as occurring in 85 % of all sites. GD was clearly related to the degree of tree-individual differences in climate-growth response. Respective transfer functions which appropriately accounted for GD by selection of tree-cohorts with a high share of long-term variance on average increased the precision and stability of tree-ring based climate reconstructions. Concluding, incorporation of GD assessments into the dendrochronological approach has a strong potential to improve the precision of our predictions

  7. Applications of PIXE in dendrochronology

    International Nuclear Information System (INIS)

    Revesz, P.; Mayer, J.W.; Vizkelethy, G.; Kuniholm, P.I.; Griggs, C.B.; Kuniholm, H.E.; Newton, M.W.; Tarter, S.L.

    1991-01-01

    The Bard Hall Ion Beam Facility has developed external proton beams at 1-3 MeV for ion-induced x-ray emission studies of artists' pigments and metallic printers inks. The authors have extended these PIXE measurements to analysis of Athenian Tetradrachms (5th and 6th centuries BC). In both pigment and coin studies they have compared PIXE analyses with those from XRF and electron micro probe for calibration purposes. The Aegean Dendrochronology Project has developed over 5500 years of tree-ring chronologies for the Aegean, Balkans, and Eastern Mediterranean. Included are forest sites adjacent to mining and smelting operations, also sites at the upper timberline where the annual growth-rings might be expected to have picked up fallout from volcanic activity around the world. A preliminary examination of selected rings by PIXE has shown remarkable differences from year to year in the deposition of various elements, notable Zn, Fe, and Cu. The authors propose to look at a number of selected annual ring sequences to see (1) whether one can chart the progress of known metallurgical activity; (2) whether one can find evidence for volcanic effects, both for absolutely-dated volcanoes such as Krakatoa, Tambora, and Sumbawa, and for problematic volcanoes such as Santorini/Thera

  8. DendroCT - Dendrochronology without damage

    DEFF Research Database (Denmark)

    Bill, Jan; Daly, Aoife; Johnsen, Øistein

    2012-01-01

    The paper describes an evaluation of the applicability of computer tomography in archaeological dendrochronology. Two different computer tomographs were tested, a . Siemens Somatom Emotion single slice scanner developed for medical use, and a . Nikon Metrology model . XT H 225 LC, which is an ind...

  9. Irregularities in the dendrochronological calibration curve

    International Nuclear Information System (INIS)

    Ottaway, J.H.; Ottaway, B.

    1975-01-01

    A discussion is presented on the reality or otherwise of short-term deviations from a linear or smooth curve relating conventional C-14 dates to dendrochronological measurements. The possibility of the effect of short-term changes in the earth's atmosphere and in the oceans, and particularly in their temperature, is considered. (U.K.)

  10. Dendrochronological Investigations of Valonia Oak Trees in Western Greece

    Directory of Open Access Journals (Sweden)

    Andreas Papadopoulos

    2016-06-01

    Full Text Available Background and Purpose: Valonia oak (Quercus ithaburensis subsp. macrolepis (Kotschy Hedge & Yalt. is an east Mediterranean endemic, xerothermic and deciduous tree of particular interest in forestry. There has been a growing demand lately to include the species in reforestations in Greece which also increased the interest to investigate its response to climate change. The main purpose of this research is to study valonia oak from a dendrochronological – dendroclimatological point of view within its Mediterranean distribution range. Materials and Methods: Sampling took place in characteristic valonia oak stands where cross sections or tree-cores were taken from 40 trees. The cross sections and the tree-cores were prepared and cross-dated using standard dendrochronological methods and tree-ring widths were measured to the nearest 0.001 mm using the Windendro software program. The ARSTAN program was used to standardize the tree-ring data and to calculate dendrochronological statistical parameters. The inter-annual variability of tree-ring width and the radial growth trend were examined. Finally, tree-ring widths to climate relationships were calculated by orthogonal regression in combination with the bootstrap procedure using master residual chronology and monthly precipitation, temperature data and scPDSI drought index, from October of the n-1 year up to November of the n year. Results: The master chronology of valonia oak trees in Western Greece reaches 365 years, with an average ring width of 0.89 mm and with mean sensitivity being 0.21. The variation of the tree-ring widths indicates the influence of climate and human intervention in the past. Tree-ring to climate relationships show that valonia oak growth is positively affected by precipitations in January and March and by drought reduction during June and July. Conclusions: Valonia oak in Western Greece is a species of great interest for dendrochronological and dendroclimatological studies

  11. Activation analysis and dendrochronology for estimating pollution histories

    International Nuclear Information System (INIS)

    Pillay, K.K.

    1976-01-01

    Neutron activation analysis of wood shavings from tree rings have shown that plant tissues grown through periods of varying environmental conditions keep permanent records of the trace elements they received though nutrients from their immediate surroundings. Detailed examination of several species of trees, along with dendrochronological data, suggest the possibilities of utilizing this technique for pollution monitoring as well as for developing valuable information for environmental modelling. The multielemental analyses of tree ring samples were done using multiple neutron irradiation and gamma-ray spectrometry using a high resolution Ge(Li) detector and a software orinted programmable multichannel analyzer. The neutron activation analysis consisted of two reactor irradiations and at least three countings at different decay periods. (T.G.)

  12. Dendrochronology of Utah Juniper (Juniperus osteosperma (Torr.) Little)

    Science.gov (United States)

    R. Justin Derose; Matthew F. Bekker; Roger Kjelgren; Brendan M. Buckley; James H. Speer; Eric B. Allen

    2016-01-01

    Utah juniper was a foundational species for the discipline of dendrochronology, having been used in the early 20th Century investigations of Mesa Verde, but has been largely ignored by dendrochronologists since. Here we present dendrochronological investigations of Utah juniper core and cross-sectional samples from four sites in northern Utah. We demonstrate that,...

  13. The Dendrochronological Dating of Timber Crossings in West Jutland, Denmark

    DEFF Research Database (Denmark)

    Daly, Aoife

    2006-01-01

    The dendrochronological analyses of a large number of timbers from two sites are described. Nybro causeway in west Jutland, Denmark, which was built in the 8th century AD, consists of numerous phases, identifiable due to the large number of dendrochronologically dated timbers, of which many had...

  14. Dendrochronology of Strain-Relaxed Islands

    International Nuclear Information System (INIS)

    Merdzhanova, T.; Kiravittaya, S.; Rastelli, A.; Stoffel, M.; Denker, U.; Schmidt, O.G.

    2006-01-01

    We report on the observation and study of tree-ring structures below dislocated SiGe islands (superdomes) grown on Si(001) substrates. Analogous to the study of tree rings (dendrochronology), these footprints enable us to gain unambiguous information on the growth and evolution of superdomes and their neighboring islands. The temperature dependence of the critical volume for dislocation introduction is measured and related to the composition of the islands. We show clearly that island coalescence is the dominant pathway towards dislocation nucleation at low temperatures, while at higher temperatures anomalous coarsening is effective and leads to the formation of a depletion region around superdomes

  15. Dendrochronology of strain-relaxed islands.

    Science.gov (United States)

    Merdzhanova, T; Kiravittaya, S; Rastelli, A; Stoffel, M; Denker, U; Schmidt, O G

    2006-06-09

    We report on the observation and study of tree-ring structures below dislocated SiGe islands (superdomes) grown on Si(001) substrates. Analogous to the study of tree rings (dendrochronology), these footprints enable us to gain unambiguous information on the growth and evolution of superdomes and their neighboring islands. The temperature dependence of the critical volume for dislocation introduction is measured and related to the composition of the islands. We show clearly that island coalescence is the dominant pathway towards dislocation nucleation at low temperatures, while at higher temperatures anomalous coarsening is effective and leads to the formation of a depletion region around superdomes.

  16. Dendrochronology of bristlecone pine, Pinus longaeva

    International Nuclear Information System (INIS)

    Ferguson, C.W.

    1979-01-01

    Since 1953 the Laboratory of Tree-Ring Research has conducted dendrochronological studies of bristlecone pine Pinus longaeva D.K. Bailey, sp. nov.) in the White Mountains of California. This research resulted in the establishment of a continuous tree-ring sequence of 8253 yr. The millennia-old pines have emerged as a unique source of chronological data and the precisely dated wood is essential to certain paleoenvironmental and geophysical investigations. Over 1000 dendrochronologically dated decade samples of bristlecone pine supplied to three C-14 laboratories have been used to calibrate the radiocarbon time scale for the past seven millennia, a development of far reaching consequences in the fields of archaeology and geology. In addition, recent advances in other methods of analyzing past climatic variability - techniques involving stable isotope ratios, amino acid racemization, remanent magnetism and trace element abundances - have greatly increased the demand for wood of known age and, hence, for chronology development. Spanning the past 7500 yr, 1138 prepared decade samples, with a total weight of nearly 16 kg are available for study. (author)

  17. Plant responses to multiple herbivory

    NARCIS (Netherlands)

    Li, Yehua

    2016-01-01

    This thesis explores whether aphid-infestation interferes with the plant response to chewing herbivores and whether this impacts performance and behaviour of individual chewing insect herbivores and their natural enemies, as well as the entire insect community. I investigated this using three

  18. TREE SELECTING AND TREE RING MEASURING IN DENDROCHRONOLOGICAL INVESTIGATIONS

    Directory of Open Access Journals (Sweden)

    Sefa Akbulut

    2004-04-01

    Full Text Available Dendrochronology is a method of dating which makes use of the annual nature of tree growth. Dendrochronology may be divided into a number of subfields, each of which covers one or more aspects of the use of tree ring data: dendroclimatology, dendrogeomorphology, dendrohydrology, dendroecology, dendroarchaelogy, and dendrogylaciology. Basic of all form the analysis of the tree rings. The wood or tree rings can aid to dating past events about climatology, ecology, geology, hydrology. Dendrochronological studies are conducted either on increment cores or on discs. It may be seen abnormalities on tree rings during the measurement like that false rings, missing rings, reaction wood. Like that situation, increment cores must be extracted from four different sides of each tree and be studied as more as on tree.

  19. A Dendrochronological Analysis of Red Oak Borer Abundance

    Science.gov (United States)

    Rose-Marie Muzika; Richard P. Guyette

    2004-01-01

    Unprecedented outbreaks of red oak borer (Enaphalodes rufulus Haldemann) have occurred in the lower Midwestern United States. Although generally not a mortality agent, red oak borer appears to contribute to general oak decline and mortality. The objective of this project was to explore dendrochronology as a means of determining the role of tree age,...

  20. The Tunguska event and Cheko Lake origin: dendrochronological analysis

    Czech Academy of Sciences Publication Activity Database

    Fantucci, R.; Serra, R.; Kletetschka, Günther; Di Martino, M.

    2015-01-01

    Roč. 14, č. 3 SI (2015), s. 345-357 ISSN 1473-5504 Institutional support: RVO:67985831 Keywords : cosmic body impact * collapse crater * dendrochronology * Tunguska * tree rings * Russia * Siberia Subject RIV: DB - Geology ; Mineralogy Impact factor: 1.184, year: 2015

  1. Dendrochronology in the dry tropics: the Ethiopian case

    NARCIS (Netherlands)

    Wils, T.; Sass-Klaassen, U.; Eshetu, Z.; Bräuning, A.; Gebrenirstos, A.; Couralet, C.; Robertson, I.; Touchan, R.; Koprowski, M.; Conway, D.; Briffa, K.R.; Beeckman, H.

    2011-01-01

    Dendrochronology is developing outside temperate and boreal regions. Over the past decade substantial progress has been made in Mediterranean and wet tropical regions. However, research in dry tropical regions, notably those of sub-Saharan Africa, has remained fragmentary. Here, we try to identify

  2. Dendrochronological potential of the alpine shrub Rhododendron nivale on the south-eastern Tibetan Plateau.

    Science.gov (United States)

    Liang, Eryuan; Eckstein, Dieter

    2009-09-01

    Shrubs and dwarf shrubs are wider spread on the Tibetan Plateau than trees and hence offer a unique opportunity to expand the present dendrochronological network into extreme environments beyond the survival limit of trees. Alpine shrublands on the Tibetan Plateau are characterized by rhododendron species. The dendrochronological potential of one alpine rhododendron species and its growth response to the extreme environment on the south-east Tibetan Plateau were investigated. Twenty stem discs of the alpine snowy rhododendron (Rhododendron nivale) were collected close to the tongue of the Zuoqiupu Glacier in south-east Tibet, China. The skeleton plot technique was used for inter-comparison between samples to detect the growth pattern of each stem section. The ring-width chronology was developed by fitting a negative exponential function or a straight line of any slope. Bootstrapping correlations were calculated between the standard chronology and monthly climate data. The wood of snowy rhododendron is diffuse-porous with evenly distributed small-diameter vessels. It has well-defined growth rings. Most stem sections can be visually and statistically cross-dated. The resulting 75-year-long standard ring-width chronology is highly correlated with a timberline fir chronology about 200 km apart, providing a high degree of confidence in the cross-dating. The climate/growth association of alpine snowy rhododendron and of this timberline fir is similar, reflecting an impact of monthly mean minimum temperatures in November of the previous year and in July during the year of ring formation. The alpine snowy rhododendron offers new research directions to investigate the environmental history of the Tibetan Plateau in those regions where up to now there was no chance of applying dendrochronology.

  3. The role of dendrochronology in natural resource management

    Science.gov (United States)

    Ramzi Touchan; Malcolm Hughes

    2000-01-01

    The discipline of dendrochronology, that is, development and use of time series of annual growth rings of trees, is a set of techniques by which the annual growth layers of trees may be assigned to definite calendar years. The history of changes in the trees’ environment may be reconstructed using various properties of tree rings. In this paper we will discuss how tree...

  4. Quality improvement through multiple response optimization

    International Nuclear Information System (INIS)

    Noorossana, R.; Alemzad, H.

    2003-01-01

    The performance of a product is often evaluated by several quality characteristics. Optimizing the manufacturing process with respect to only one quality characteristic will not always lead to the optimum values for other characteristics. Hence, it would be desirable to improve the overall quality of a product by improving quality characteristics, which are considered to be important. The problem consists of optimizing several responses using multiple objective decision making approach and design of experiments. A case study will be discussed to show the application of the proposal method

  5. Dendrochronological dating for the study of historical buildings

    Directory of Open Access Journals (Sweden)

    Mauro Bernabei

    2012-12-01

    Full Text Available This article addresses the discipline of dendrochronology and, especially, one of its most useful aspects for the study, restoration and appreciation of architectonic heritage: dating. In its pages it deals with the origin, foundations and principles of this technique, the requisites for its application, the different ways of obtaining samples, the use of statistics and the various difficulties, limitations and aspects of dating. Finally, it touches upon the ­field of dendroprovenance, that is, the technique used to discover the geographic origin of timber by means of concrete examples of works performed by the authors, such as the Church of the Nativity in Bethlehem, Palestine.

  6. Quantifications of dendrochronological information from contrasting microdensitometric measuring circumstances of experimental wood samples

    International Nuclear Information System (INIS)

    Helama, S.; Bégin, Y.; Vartiainen, M.; Peltola, H.; Kolström, T.; Meriläinen, J.

    2012-01-01

    We analyzed how the pretreatment method of Scots pine (Pinus sylvestris L.) wood specimens together with X-ray methodology applied for density analyses affect resulting tree-ring data and derived proxy-based climate information. We also evaluated whether these results from two contrasting laboratory circumstances could be homogenized by applying dendroclimatic statistical methods. For this study, we measured a pair of X-ray based microdensitometry datasets using double samples of subfossil and recent wood specimens. Dendrochronological information of earlywood and latewood series was examined to determine for alterations in the resulting data. We found that the level of overall density, its trend over cambial ages and the growth amplitude altered due to the sample pretreatment/density measuring exercise, which means that comparisons of heterogeneous datasets should be, in general, regarded cautiously. Dendrochronological standardization did, however, even out several potentially biasing influences from the differing overall densities and their trends. The two latewood (maximum) density chronologies yielded paleoclimatic reconstructions which both calibrated and verified satisfactorily with the instrumental warm-season (March–September) mean temperatures. The transfer functions were found to further equalize the differences between the two proxy records. We recommend (if no strictly homogenous data are available) reconciling similar data assemblages through transfer functions with multiple independent variables. - Highlights: ► We applied X-ray microdensitometry to treering analysis of modern and subfossil wood. ► We reveal the spectrum of methodology-dependent differences. ► We evaluate the climate change signals in X-ray based data of modern and subfossil tree-rings. ► Data homogenization was done using standardization and transfer function techniques. ► Methods allow careful utilization of tree-ring databases for climate change studies.

  7. Can dendrochronology procedures estimate historical Tree Water Footprint?

    Science.gov (United States)

    Fernandes, Tarcísio J. G.; Del Campo, Antonio D.; Molina, Antonio J.

    2013-04-01

    Whole estimates of tree water use are becoming increasingly important in forest science and forest scientists have long sought to develop reliable techniques to estimate tree water use. In this sense accurately determining or estimate the quantity of water transpired by trees and forests is important and can be used to determine "green" water footprint. The use of dendrochronology is relative common in the study of effects and interactions between growth and climatic variables, but few studies deal with the relationship with water footprint. The main objective of this study is determining the historical tree water-use in a planted stand by dendrochronological approaches. This study was performed in South-eastern Spain, in an area covered by 50-60 years old Pinus halepensis Mil. plantations with high tree density (ca.1288/ha) due to low forest management. The experimental set-up consisted of two plots (30x30m), one corresponding to a thinning treatment performed in 2008 (t10) and the other thinned in 1998 (t1) to assess the mid-term effects of thinning. After one year of thinning four representative trees were select in each plot to measure transpiration by heat pulse sensor (sapflow velocity, vs). The accumulated daily values of transpiration (L day-1) were estimated multiplying the values of vs by sapwood area of each selected tree. After transpiration measurements two cores per tree were taken for establishing the tree-rings chronologies. The cores were prepared, their ring-width were measured and standardised in basal area increment index (BAI-i) following usual dendrochronological methods. The dendrochronology analyses showed a general variability in ring width during the initial growth (15 years), while in the following years the width rings were very small, conditioned by climate. The year after thinning (1999 or 2009) all trees in the treatments showed significant increases in ring width. The average vs for t1 and t10 were 3.59 cm h-1 and 1.95 cm h-1, and

  8. Use of dendrochronology and dendrochemistry in environmental forensics: Does it meet the Daubert criteria?

    Science.gov (United States)

    Balouet, J.-C.; Smith, K.T.; Vroblesky, D.; Oudijk, G.

    2009-01-01

    Dendrochronological methods have been in use for more than 100 years, providing us a record of climate, human activities (archaeology), floods, fire, mudslides and other geological and biological events. More recently, dendrochemisty has been used to assess the time frames of the onset and existence of environmental contamination. This article assesses the scientific status of dendrochronology and dendrochemistry with respect to the admissibility of expert testimony and Daubert legal criteria. The purpose of this article is to identify the crucial scientific aspects of dendrochronology and dendrochemistry that address the Daubert criteria and Rule 702 as amended in 2000. To clarify terminology, dendrochronology is the precise and reliable assignment of the year of formation of tree rings. Dendroecology is the use of dendrochronology to understand ecological and environmental processes (Schweingruber, 1996). Dendrochemistry is a subdiscipline of dendrochronology that analyzes and interprets the wood chemistry of precisely dated tree rings. Forensic dendrochemistry applies dendrochemistry to resolve environmental disputes and generally deal with questions regarding the timing and/or the source of environmental incidents. One significant application of forensic dendrochemistry to expert testimony is to address issues of anthropogenic contamination. Forensic dendroecology is a similar term to forensic dendrochemistry, but forensic dendrochemistry will be used in this discussion as the latter term emphasizes the use of chemical detection methods. Because dendrochemistry is based on the foundation of dendrochronology, both the former specialty and the latter broader discipline will be discussed. ?? Taylor & Francis Group, LLC.

  9. Can multiple-choice questions simulate free-response questions?

    OpenAIRE

    Lin, Shih-Yin; Singh, Chandralekha

    2016-01-01

    We discuss a study to evaluate the extent to which free-response questions could be approximated by multiple-choice equivalents. Two carefully designed research-based multiple-choice questions were transformed into a free-response format and administered on the final exam in a calculus-based introductory physics course. The original multiple-choice questions were administered in another similar introductory physics course on final exam. Findings suggest that carefully designed multiple-choice...

  10. Using module analysis for multiple choice responses

    DEFF Research Database (Denmark)

    Brewe, Eric; Bruun, Jesper; Bearden, Ian

    2016-01-01

    We describe a methodology for carrying out a network analysis of Force Concept Inventory (FCI) responses that aims to identify communities of incorrect responses. This method first treats FCI responses as a bipartite, student X response, network. We then use Locally Adaptive Network Sparsificatio...

  11. An Updated Review of Dendrochronological Investigations in Mexico, a Megadiverse Country with a High Potential for Tree-Ring Sciences

    Directory of Open Access Journals (Sweden)

    Andrea C. Acosta-Hernández

    2017-05-01

    Full Text Available Dendrochronology is a very useful science to reconstruct the long-term responses of trees and other woody plants forming annual rings in response to their environment. The present review considered Mexico, a megadiverse country with a high potential for tree-ring sciences given its high climatic and environmental variability. We reviewed papers considering Mexican tree species that were published from 2001 to 2016. Most of these studies examined tree species from temperate forests, mainly in the pine and fir species. The review included 31 tree species. The most intensively sampled family and species were the Pinaceae and Douglas fir (Pseudotsuga menziessi (Mirb. Franco, respectively. Some threatened tree species were also studied. Dendrochronological investigations were mainly conducted in northern and central Mexico, with Durango being the most sampled state. The reviewed studies were mostly developed for hydroclimatic reconstructions, which were mainly based on the tree-ring width as a proxy for the climate. Tree-ring studies were carried out in both national and foreign institutions. Our review identified relevant research gaps for dendrochronologists such as: (i biomes which are still scarcely studied (e.g., tropical dry forests and (ii approaches still rarely applied to Mexican forests as dendroecology.

  12. Observations on Listener Responses from Multiple Perspectives

    NARCIS (Netherlands)

    de Kok, I.A.; Heylen, Dirk K.J.

    In this paper we present three studies that investigate the individual differences in nonverbal listening behavior. Besides collecting a corpus of listener responses, we asked people to watch a video of a speaker and indicate where they would produce a listener response. Also we asked people to

  13. Optimization of multi-response dynamic systems integrating multiple ...

    African Journals Online (AJOL)

    It also results in better optimization performance than back-propagation neural network-based approach and data mining-based approach reported by the past researchers. Keywords: multiple responses, multiple regression, weighted dynamic signal-to-noise ratio, performance measure modelling, response function ...

  14. Maritime Coastlines: A New Ecosystem for Dendrochronological Analysis

    Science.gov (United States)

    Tucker, C. S.; Trepanier, J. C.; Harley, G. L.; DeLong, K. L.

    2017-12-01

    Research at the forefront of dendrochronology is investigating the usefulness of coastal tree-ring chronologies as climatic and environmental proxies. We hypothesize trees growing on the margin of freshwater-brackish environments are sensitive to climate variability similar to those in other climatically stressed regions (e.g., the arid Southwest U.S.) and can be used for dendrochronological analyses. This study explores rings from Pinus elliottii var. elliottii trees in the Grand Bay National Estuarine Research Reserve (GBNERR) growing less than 2 km from the Gulf of Mexico. Interseries correlations (r=0.68, p<0.01) and average mean sensitivities (r=0.57, p<0.01) for these trees are higher than most Southeast U.S. tree-ring studies. P. elliottii growth in this study is significantly correlated to Standardized Precipitation-Evapotranspiration Index (SPEI; r=0.5, p<0.05) during this species' growing season (May-October). Though precipitation and temperatures in the region are favorable for tree growth, coastal processes (e.g., saltwater intrusion, brackish groundwater, aerosolized salt) are substantial regulators of growth to the maritime trees at GBNERR, which makes individuals sensitive to climate variability. Significant correlations with pressure regimes during these trees' growing season suggest that as pressure decreases over the northern Gulf of Mexico coast, thus producing precipitation, pressure increases over the Caribbean. Previous research proposes that the Central U.S. receives important precipitation sources from the Caribbean through the `Maya Express', and our results show that this precipitation may also be important to northern Gulf of Mexico coastal ecosystems. P. elliottii growth in this study is significantly correlated to tropical cyclone storm surge and is not significantly correlated to tropical cyclone high winds, which supports other studies' hypotheses that Pinus spp. are susceptible to saltwater intrusion and not high winds. Additionally

  15. Advancing dendrochronological studies of fire in the United States

    Science.gov (United States)

    Harley, Grant L.; Baisan, Christopher H.; Brown, Peter M.; Falk, Donald A.; Flatley, William T.; Grissino-Mayer, Henri D.; Hessl, Amy; Heyerdahl, Emily K.; Kaye, Margot W.; Lafon, Charles W.; Margolis, Ellis; Maxwell, R. Stockton; Naito, Adam T.; Platt, William J.; Rother, Monica T.; Saladyga, Thomas; Sherriff, Rosemary L.; Stachowiak, Lauren A.; Stambaugh, Michael C.; Sutherland, Elaine Kennedy; Taylor, Alan H.

    2018-01-01

    Dendroecology is the science that dates tree rings to their exact calendar year of formation to study processes that influence forest ecology (e.g., Speer 2010, Amoroso et al., 2017). Reconstruction of past fire regimes is a core application of dendroecology, linking fire history to population dynamics and climate effects on tree growth and survivorship. Since the early 20th century when dendrochronologists recognized that tree rings retained fire scars (e.g., Figure 1), and hence a record of past fires, they have conducted studies worldwide to reconstruct the historical range and variability of fire regimes (e.g., frequency, severity, seasonality, spatial extent), the influence of fire regimes on forest structure and ecosystem dynamics, and the top-down (e.g., climate) and bottom-up (e.g., fuels, topography) drivers of fire that operate at a range of temporal and spatial scales. As in other scientific fields, continued application of dendrochronological techniques to study fires has shaped new trajectories for the science. Here we highlight some important current directions in the United States (US) and call on our international colleagues to continue the conversation with perspectives from other countries.

  16. High pressure multiple shock response of aluminum

    International Nuclear Information System (INIS)

    Lawrence, R.J.; Asay, J.R.

    1977-01-01

    It is well known that both dynamic yield strength and rate-dependent material response exert direct influence on the development of surface and interface instabilities under conditions of strong shock loading. A detailed understanding of these phenomena is therefore an important aspect of the analysis of dynamic inertial confinement techniques which are being used in such applications as the generation of controlled thermonuclear fusion. In these types of applications the surfaces and interfaces under consideration can be subjected to cyclic loading characterized by shock pressures on the order of 100 GPa or more. It thus becomes important to understand how rate effects and material strength differ from the values observed in the low pressure regime where they are usually measured, as well as how they are altered by the loading history

  17. Modeling Rabbit Responses to Single and Multiple Aerosol ...

    Science.gov (United States)

    Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

  18. Combined dendrochronological and radiocarbon dating of six Russian icons from the 15th-17th centuries

    Science.gov (United States)

    Dolgikh, A. V.; Matskovsky, V. V.; Voronin, K. V.; Solomina, O. N.

    2017-06-01

    The results of dendrochronological and radiocarbon dating by means of accelerator mass spectrometry (AMS) of six medieval icons, originating from northern European Russia and painted on wooden panels made from Scots pine, dated to the 15th to 17th centuries are presented. The panels of each icon were studied using dendrochronology. Five to six AMS dates were obtained for four icons. Although five icons were dendro-dated successfully, one failed to be reliably cross-dated with the existing master tree-ring chronologies and it was dated by radiocarbon wiggle-matching. Dendrochronological dating and wiggle-matching of radiocarbon dates allowed us to determine the narrow chronological intervals of icon creation.

  19. Multiple Response Regression for Gaussian Mixture Models with Known Labels.

    Science.gov (United States)

    Lee, Wonyul; Du, Ying; Sun, Wei; Hayes, D Neil; Liu, Yufeng

    2012-12-01

    Multiple response regression is a useful regression technique to model multiple response variables using the same set of predictor variables. Most existing methods for multiple response regression are designed for modeling homogeneous data. In many applications, however, one may have heterogeneous data where the samples are divided into multiple groups. Our motivating example is a cancer dataset where the samples belong to multiple cancer subtypes. In this paper, we consider modeling the data coming from a mixture of several Gaussian distributions with known group labels. A naive approach is to split the data into several groups according to the labels and model each group separately. Although it is simple, this approach ignores potential common structures across different groups. We propose new penalized methods to model all groups jointly in which the common and unique structures can be identified. The proposed methods estimate the regression coefficient matrix, as well as the conditional inverse covariance matrix of response variables. Asymptotic properties of the proposed methods are explored. Through numerical examples, we demonstrate that both estimation and prediction can be improved by modeling all groups jointly using the proposed methods. An application to a glioblastoma cancer dataset reveals some interesting common and unique gene relationships across different cancer subtypes.

  20. Dendrochronology of Atriplex portulacoides and Artemisia maritima in Wadden Sea salt marshes

    NARCIS (Netherlands)

    Decuyper, M.; Slim, P.A.; Loon-Steensma, van J.M.

    2014-01-01

    The study uses a rather unusual method, dendrochronology, to investigate the growth and survival of Atriplex portulacoides L. and Artemisia maritima L. on salt marshes at two field sites on the Dutch North Sea barrier islands of Terschelling and Ameland. By providing information on longevity of

  1. [Cedrela odorata (Meliaceae) potential for dendrochronological studies in the Selva Central of Perú].

    Science.gov (United States)

    Pereyra Espinoza, Manuel Jesús; Inga Guillen, Gaby Janet; Santos Morales, Mariano; Arisméndiz Rodríguez, Rodolfo

    2014-06-01

    Despite the progress made during the past 20 years, searching dendrochronological potential in tropical and subtropical tree species, tropical dendrochronology, is still in a development stage. The aim of this research was to determine the potential of C. odorata for dendrochronological studies in the Selva Central of Perú. The tree-ring anatomical characteristics were carefully examined and we were able to develop a 215 year (1795-2 009) tree-ring chronology and correlate it with precipitation records. The tree-ring chronology was developed based on 47 series of 27 trees. Tree rings are clearly delimited by large pore diameters in earlywood and small ones in latewood associated with marginal and paratracheal parenchyma. The tree-ring chronology was related to precipitation records from Satipo and significant correlations were found with the previous rainy season and late dry season of the current growth period. Moreover, we found close relationship between tree growth and total precipitations of the hydrological period (December to September) for the interval 1990-2009. These results demonstrate the influence of rainfall at different stages of C. odorata radial growth. The good discrimination of annual rings, strong relationship with precipitation, the wide range and longevity of trees (200 years) make C. odorata a very promising species for dendrochronological studies in tropical and subtropical forest of America.

  2. Combining dendrochronology and matrix modelling in demographic studies: An evaluation for Juniperus procera in Ethiopia

    NARCIS (Netherlands)

    Couralet, C.; Sass, U.G.W.; Sterck, F.J.; Zuidema, P.A.

    2005-01-01

    Tree demography was analysed by applying dendrochronological techniques and matrix modelling on a static data set of Juniperus procera populations of Ethiopian dry highland forests. Six permanent sample plots were established for an inventory of diameters and 11 stem discs were collected for

  3. C14-Crash. The C14-method and dendrochronology, unveiling the illusion. 2. rev. ed.

    International Nuclear Information System (INIS)

    Bloess, C.; Niemitz, H.U.

    2000-01-01

    In this second edition of the book, which was published almost three years after the first edition, the authors reiterate and substantiate their doubts as to the basic theories underlying the radiocarbon dating method and the applicability of dendrochronology. (orig/CB) [de

  4. A dendrochronological fire history of Opeongo lookout in Algonquin Park, Ontario

    Science.gov (United States)

    Richard P. Guyette; Daniel C. Dey

    1995-01-01

    Fire-scarred stumps and natural snags of red pine (Pinus resinosa Ait.) on a 70-m tall bluff along Costello Creek, 2 km south of Lake Opeongo, were dated using dendrochronological methods. A fire scar chronology was constructed from 18 of the red pine samples that contained 34 dated fire scars.

  5. An experimental evaluation of fire history reconstruction using dendrochronology in white oak (Quercus alba)

    Science.gov (United States)

    Ryan W. McEwan; Todd F. Hutchinson; Robert D. Ford; Brian C. McCarthy

    2007-01-01

    Dendrochronological analysis of fire scars on tree cross sections has been critically important for understanding historical fire regimes and has influenced forest management practices. Despite its value as a tool for understanding historical ecosystems, tree-ring-based fire history reconstruction has rarely been experimentally evaluated. To examine the efficacy of...

  6. Using simulations and data to evaluate mean sensitivity (ζ) as a useful statistic in dendrochronology

    Science.gov (United States)

    Andrew G. Bunn; Esther Jansma; Mikko Korpela; Robert D. Westfall; James Baldwin

    2013-01-01

    Mean sensitivity (ζ) continues to be used in dendrochronology despite a literature that shows it to be of questionable value in describing the properties of a time series. We simulate first-order autoregressive models with known parameters and show that ζ is a function of variance and autocorrelation of a time series. We then use 500 random tree-ring...

  7. Using simulations and data to evaluate mean sensitivity (ζ) as a useful statistic in dendrochronology

    NARCIS (Netherlands)

    Bunn, A.G.; Jansma, E.; Korpela, M.; Westfall, R.D.; Baldwin, J.

    2013-01-01

    Mean sensitivity (ζ) continues to be used in dendrochronology despite a literature that shows it to be of questionable value in describing the properties of a time series. We simulate first-order autoregressive models with known parameters and show that ζ is a function of variance and

  8. Editorial: Papers from the 7th International Conference on Dendrochronology - Cultural Diversity, Environmental Variability

    Science.gov (United States)

    Margaret S. Devall; Elaine K. Sutherland

    2008-01-01

    The 7th International Conference on Dendrochronology - Cultural Diversity, Environmental Variability was held in Beijing, China from 11 to 17 June 2006. The conference was organized and hosted by the Institute of Botany, Chinese Academy of Sciences (IB_CAS) in conjunction with the International Union of Forest Research Organizations (IUFRO) Working Group 5.01.07 (Tree-...

  9. Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.

    Science.gov (United States)

    Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H

    2017-01-01

    Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.

  10. Pavlovian conditioning of multiple opioid-like responses in mice.

    Science.gov (United States)

    Bryant, Camron D; Roberts, Kristofer W; Culbertson, Christopher S; Le, Alan; Evans, Christopher J; Fanselow, Michael S

    2009-07-01

    Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

  11. Reliability of psychophysiological responses across multiple motion sickness stimulation tests

    Science.gov (United States)

    Stout, C. S.; Toscano, W. B.; Cowings, P. S.

    1995-01-01

    Although there is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation, very little evidence exists that examines the reproducibility of autonomic responses within subjects during motion sickness stimulation. Our objectives were to examine the reliability of autonomic responses and symptom levels across five testing occasions using the (1) final minute of testing, (2) change in autonomic response and the change in symptom level, and (3) strength of the relationship between the change in symptom level and the change in autonomic responses across the entire motion sickness test. The results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and symptoms throughout the test duration are less stable across the tests. Finally, autonomic responses and symptom levels are significantly related across the entire motion sickness test.

  12. Ion Uptake Determination of Dendrochronologically-Dated Trees Using Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kenan Unlu; P.I. Kuniholm; D.K.H. Schwarz; N.O. Cetiner; J.J. Chiment

    2009-03-30

    Uptake of metal ions by plan roots is a function of the type and concentration of metal in the soil, the nutrient biochemistry of the plant, and the immediate environment of the root. Uptake of gold (Au) is known to be sensitive to soil pH for many species. Soil acidification due to acid precipitation following volcanic eruptions can dramatically increase Au uptake by trees. Identification of high Au content in tree rings in dendrochronologically-dated, overlapping sequences of trees allows the identification of temporally-conscribed, volcanically-influenced periods of environmental change. Ion uptake, specifically determination of trace amounts of gold, was performed for dendrochronologically-dated tree samples utilizing Neutron Activation Analysis (NAA) technique. The concentration of gold was correlated with known enviironmental changes, e.g. volcanic activities, during historic periods.

  13. Terahertz pulse imaging for tree-ring analysis: a preliminary study for dendrochronology applications

    International Nuclear Information System (INIS)

    Jackson, J B; Mourou, M; Whitaker, J F; Labaune, J; Mourou, G A; Duling, I N III; Williamson, S L; Lavier, C; Menu, M

    2009-01-01

    Time-domain terahertz reflection imaging is presented as a novel method of measuring otherwise inaccessible tree rings in wooden cultural heritage for the purpose of tree-ring crossdating. Axial and lateral two-dimensional terahertz images of obscured ring patterns are statistically validated with respect to their corresponding optical photographs via adapted dendrochronological methods. Results are compared to similar analysis of x-ray images of a wood specimen

  14. Visualization-based analysis of multiple response survey data

    Science.gov (United States)

    Timofeeva, Anastasiia

    2017-11-01

    During the survey, the respondents are often allowed to tick more than one answer option for a question. Analysis and visualization of such data have difficulties because of the need for processing multiple response variables. With standard representation such as pie and bar charts, information about the association between different answer options is lost. The author proposes a visualization approach for multiple response variables based on Venn diagrams. For a more informative representation with a large number of overlapping groups it is suggested to use similarity and association matrices. Some aggregate indicators of dissimilarity (similarity) are proposed based on the determinant of the similarity matrix and the maximum eigenvalue of association matrix. The application of the proposed approaches is well illustrated by the example of the analysis of advertising sources. Intersection of sets indicates that the same consumer audience is covered by several advertising sources. This information is very important for the allocation of the advertising budget. The differences between target groups in advertising sources are of interest. To identify such differences the hypothesis of homogeneity and independence are tested. Recent approach to the problem are briefly reviewed and compared. An alternative procedure is suggested. It is based on partition of a consumer audience into pairwise disjoint subsets and includes hypothesis testing of the difference between the population proportions. It turned out to be more suitable for the real problem being solved.

  15. Integrating Dendrochronology, Climate and Satellite Remote Sensing to Better Understand Savanna Landscape Dynamics in the Okavango Delta, Botswana

    Directory of Open Access Journals (Sweden)

    Jane Southworth

    2013-11-01

    Full Text Available This research examines the integration and potential uses of linkages between climate dynamics, savanna vegetation and landscape level processes within a highly vulnerable region, both in terms of climate variability and social systems. We explore the combined applications of two time-series methodologies: (1 climate signals detected in tree ring growth, from published literature, chronologies from the International Tree-Ring Data Bank, and minimal preliminary field data; and (2 new primary production (NPP data of vegetation cover over time derived from remotely sensed analyses. Both time-series are related to the regional patterns of precipitation, the principle driver of plant growth in the area. The approach is temporally and spatially multiscalar and examines the relationships between vegetation cover, type and amount, and precipitation shifts. We review literature linking dendrochronology, climate, and remotely sensed imagery, and, in addition, provide unique preliminary analyses from a dry study site located on the outer limit of the Okavango Delta. The work demonstrates integration across the different data sources, to provide a more holistic view of landscape level processes occurring in the last 30-50 years. These results corroborate the water-limited nature of the region and the dominance of precipitation in controlling vegetation growth. We present this integrative analysis of vegetation and climate change, as a prospective approach to facilitate the development of long-term climate/vegetation change records across multiple scales.

  16. Seismic structural response analysis for multiple support excitation

    International Nuclear Information System (INIS)

    Shaw, D.E.

    1975-01-01

    In the seismic analysis of nuclear power plant equipment such as piping systems situations often arise in which piping systems span between adjacent structures or between different elevations in the same structure. Owing to the differences in the seismic time history response of different structures or different elevations of the same structure, the input support motion will differ for different supports. The concept of a frequency dependent participation factor and rotational response spectra accounting for phase differences between support excitations is developed by using classical equations of motion to formulate the seismic response of a structure subjected to multiple support excitation. The essence of the method lies in describing the seismic excitation of a multiply excited structure in terms of translational and rotational spectra used at every support and a frequency dependent spatial distribution function derived from the phase relationships of the different support time histories. In this manner it is shown that frequency dependent participation factors can be derived from the frequency dependent distribution functions. Examples are shown and discussed relative to closed form solutions and the state-of-the-art techniques presently being used for the solution of problems of multiply excited structures

  17. Transient response of the 'multiple water-bag' plasma

    International Nuclear Information System (INIS)

    Lim Cheeseng

    1989-01-01

    A charge activates impulsively and then decays temporally within a MWB (multiple water-bag)-modelled warm plasma. The transient problem is formulated and asymptotically resolved for large time. The response potential comprises two characteristically distinct quantities W and W N : W is a superposition of spherically expanding, moderately attenuated Kelvin waves contributed by certain points on a subset of dispersion curves; W N is a superposition, associated with two other dispersion curves, of three spherical wavefunctions, one of which incorporates the Fresnel integrals. A transient state feature of the MWB discretization is the partitioning of the response field by growing (fast) fronts, (trailing) slow caustics and a j -surfaces, the fastest among these being an a N- surface (thermal front) which pushes back a quasi-static exterior. Contrary to expectations, there is no response jump across any of those growing partitions. Wavefunctions near the slow caustics possess Airy factors. A rest state ultimately develops behind the slowest slow caustic. An application is made to the fluid plasma. (author)

  18. Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Richard A Rudick

    Full Text Available BACKGROUND: Interferon-beta (IFNβ is used to inhibit disease activity in multiple sclerosis (MS, but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified. METHODS: The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70 or poor response (n = 15. Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs. RESULTS: The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual 'IFN response fingerprint'. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections. CONCLUSION: MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients.

  19. Prediction of response to interferon therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Søndergaard, Helle Bach; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5...... genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β. METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed...... prospectively after the initiation of their first treatment with IFN-β. RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk...

  20. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  1. Dynamic response of multiple nanobeam system under a moving nanoparticle

    Directory of Open Access Journals (Sweden)

    Shahrokh Hosseini Hashemi

    2018-03-01

    Full Text Available In this article, nonlocal continuum based model of multiple nanobeam system (MNBS under a moving nanoparticle is investigated using Eringen’s nonlocal theory. Beam layers are assumed to be coupled by winkler elastic medium and the nonlocal Euler-Bernoulli beam theory is used to model each layer of beam. The Hamilton’s principle, Eigen function technique and the Laplace transform method are employed to solve the governing equations. Analytical solutions of the transverse displacements for MNBs with simply supported boundary condition are presented for double layered and three layered MNBSs. For higher number of layers, the governing set of equations is solved numerically and the results are presented. This study shows that small-scale parameter has a significant effect on dynamic response of MNBS under a moving nanoparticle. Sensitivity of dynamical deflection to variation of nonlocal parameter, stiffness of Winkler elastic medium and number of nanobeams are presented in nondimensional form for each layer. Keywords: Dynamic response, Analytical solution, Moving particle, Nanobeam, Multi-layered nanobeam

  2. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Lidia De Riccardis

    2016-12-01

    Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  3. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.

    Science.gov (United States)

    De Riccardis, Lidia; Ferramosca, Alessandra; Danieli, Antonio; Trianni, Giorgio; Zara, Vincenzo; De Robertis, Francesca; Maffia, Michele

    2016-12-01

    Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  4. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    Science.gov (United States)

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  5. A diagnostic tree model for polytomous responses with multiple strategies.

    Science.gov (United States)

    Ma, Wenchao

    2018-04-23

    Constructed-response items have been shown to be appropriate for cognitively diagnostic assessments because students' problem-solving procedures can be observed, providing direct evidence for making inferences about their proficiency. However, multiple strategies used by students make item scoring and psychometric analyses challenging. This study introduces the so-called two-digit scoring scheme into diagnostic assessments to record both students' partial credits and their strategies. This study also proposes a diagnostic tree model (DTM) by integrating the cognitive diagnosis models with the tree model to analyse the items scored using the two-digit rubrics. Both convergent and divergent tree structures are considered to accommodate various scoring rules. The MMLE/EM algorithm is used for item parameter estimation of the DTM, and has been shown to provide good parameter recovery under varied conditions in a simulation study. A set of data from TIMSS 2007 mathematics assessment is analysed to illustrate the use of the two-digit scoring scheme and the DTM. © 2018 The British Psychological Society.

  6. Using Module Analysis for Multiple Choice Responses: A New Method Applied to Force Concept Inventory Data

    Science.gov (United States)

    Brewe, Eric; Bruun, Jesper; Bearden, Ian G.

    2016-01-01

    We describe "Module Analysis for Multiple Choice Responses" (MAMCR), a new methodology for carrying out network analysis on responses to multiple choice assessments. This method is used to identify modules of non-normative responses which can then be interpreted as an alternative to factor analysis. MAMCR allows us to identify conceptual…

  7. Can Free-Response Questions Be Approximated by Multiple-Choice Equivalents?

    OpenAIRE

    Lin, Shih-Yin; Singh, Chandralekha

    2016-01-01

    We discuss a study to evaluate the extent to which free-response questions can be approximated by multiple-choice equivalents. Two carefully designed research-based multiple-choice questions were transformed into a free-response format and administered on the final exam in a calculus-based introductory physics course. The original multiple-choice questions were administered in another, similar introductory physics course on the final exam. Our findings suggest that carefully designed multiple...

  8. Dating furniture and coopered vessels without waney edge - Reconstructing historical wood-working in Austria with the help of dendrochronology.

    Science.gov (United States)

    Klein, Andrea; Nemestothy, Sebastian; Kadnar, Julia; Grabner, Michael

    In the present study, 208 furniture and 168 coopered vessels from three Austrian museums were examined. Dendrochronology was used to date objects and to extract further information such as the necessary time for seasoning, wood loss through wood-working and methods of construction. In most cases sampling was done by sanding the cross section and making digital photographs using a picture frame and measuring digitally. The dendrochronological dates of the sampled furniture range between 1524 and 1937. The group of furniture includes cupboards, chests, tables, benches, commodes and beds. In many cases furniture was artfully painted and sometimes even shows a painted year. With the help of dendrochronology it was proved that some objects had been painted for some time after construction, or had been over-painted. Most furniture, however, was painted immediately after completion. In this case, the seasoning and storage time of the boards and the wood loss due to shaping can be verified. As an average value, 14 years have passed between the dendrochronological date of the outermost ring and the painting. The time span includes time of seasoning and storage and the rings lost by wood-working. This leads, on the one hand to a short storage time of less than 10 years and on the other hand to very little wood loss due to manufacturing. Those boards being less shaped turned out to be back panels of cupboards, therefore they are recommended to be sampled for dating. Coopered vessels were dated between 1612 and 1940. There was evidence that staves were split and not sawn in many cases. The staves were often split out of the outermost part of the tree and hardly any wood was worked away which was proved by the close dendrochronological dates of the single staves of a vessel. Since there is a short time of storage and only little wood loss through wood-working, dating of objects without a waney edge becomes reasonable.

  9. A novel dendrochronological approach reveals drivers of carbon sequestration in tree species of riparian forests across spatiotemporal scales.

    Science.gov (United States)

    Rieger, Isaak; Kowarik, Ingo; Cherubini, Paolo; Cierjacks, Arne

    2017-01-01

    Aboveground carbon (C) sequestration in trees is important in global C dynamics, but reliable techniques for its modeling in highly productive and heterogeneous ecosystems are limited. We applied an extended dendrochronological approach to disentangle the functioning of drivers from the atmosphere (temperature, precipitation), the lithosphere (sedimentation rate), the hydrosphere (groundwater table, river water level fluctuation), the biosphere (tree characteristics), and the anthroposphere (dike construction). Carbon sequestration in aboveground biomass of riparian Quercus robur L. and Fraxinus excelsior L. was modeled (1) over time using boosted regression tree analysis (BRT) on cross-datable trees characterized by equal annual growth ring patterns and (2) across space using a subsequent classification and regression tree analysis (CART) on cross-datable and not cross-datable trees. While C sequestration of cross-datable Q. robur responded to precipitation and temperature, cross-datable F. excelsior also responded to a low Danube river water level. However, CART revealed that C sequestration over time is governed by tree height and parameters that vary over space (magnitude of fluctuation in the groundwater table, vertical distance to mean river water level, and longitudinal distance to upstream end of the study area). Thus, a uniform response to climatic drivers of aboveground C sequestration in Q. robur was only detectable in trees of an intermediate height class and in taller trees (>21.8m) on sites where the groundwater table fluctuated little (≤0.9m). The detection of climatic drivers and the river water level in F. excelsior depended on sites at lower altitudes above the mean river water level (≤2.7m) and along a less dynamic downstream section of the study area. Our approach indicates unexploited opportunities of understanding the interplay of different environmental drivers in aboveground C sequestration. Results may support species-specific and

  10. Dendrochronological analysis of the roof of the Nanebevzetí Panny Marie and Sv. Ondřeje church in Staré Hobzí

    Directory of Open Access Journals (Sweden)

    Michal Rybníček

    2004-01-01

    Full Text Available The work deals with dendrochronological analysis of the roof truss of parish church in the locality of Stare Hobzi. The dendrochronological analysis gave an integrated view on a complicated development of this building and it helped us to restore the succession of building adjustments performed on this building. The work is also to introduce the dendrochronology branch to people who participate on or direct perform building-historical research and to show them that it could be an essential helper in their work.

  11. Drought-adaptation potential in Fagus sylvatica: linking moisture availability with genetic diversity and dendrochronology.

    Directory of Open Access Journals (Sweden)

    Andrea R Pluess

    Full Text Available BACKGROUND: Microevolution is essential for species persistence especially under anticipated climate change scenarios. Species distribution projection models suggested that the dominant tree species of lowland forests in Switzerland, European beech (Fagus sylvatica L., might disappear from most areas due to expected longer dry periods. However, if genotypes at the moisture boundary of the species climatic envelope are adapted to lower moisture availability, they can serve as seed source for the continuation of beech forests under changing climates. METHODOLOGY/PRINCIPAL FINDINGS: With an AFLP genome scan approach, we studied neutral and potentially adaptive genetic variation in Fagus sylvatica in three regions containing a dry and a mesic site each (n(ind. = 241, n(markers = 517. We linked this dataset with dendrochronological growth measures and local moisture availabilities based on precipitation and soil characteristics. Genetic diversity decreased slightly at dry sites. Overall genetic differentiation was low (F(st = 0.028 and Bayesian cluster analysis grouped all populations together suggesting high (historical gene flow. The Bayesian outlier analyses indicated 13 markers with three markers differing between all dry and mesic sites and the others between the contrasting sites within individual regions. A total of 41 markers, including seven outlier loci, changed their frequency with local moisture availability. Tree height and median basal growth increments were reduced at dry sites, but marker presence/absence was not related to dendrochronological characteristics. CONCLUSION AND THEIR SIGNIFICANCE: The outlier alleles and the makers with changing frequencies in relation to moisture availability indicate microevolutionary processes occurring within short geographic distances. The general genetic similarity among sites suggests that 'preadaptive' genes can easily spread across the landscape. Yet, due to the long live span of

  12. Validating numerical simulations of snow avalanches using dendrochronology: the Cerro Ventana event in Northern Patagonia, Argentina

    Directory of Open Access Journals (Sweden)

    A. Casteller

    2008-05-01

    Full Text Available The damage caused by snow avalanches to property and human lives is underestimated in many regions around the world, especially where this natural hazard remains poorly documented. One such region is the Argentinean Andes, where numerous settlements are threatened almost every winter by large snow avalanches. On 1 September 2002, the largest tragedy in the history of Argentinean mountaineering took place at Cerro Ventana, Northern Patagonia: nine persons were killed and seven others injured by a snow avalanche. In this paper, we combine both numerical modeling and dendrochronological investigations to reconstruct this event. Using information released by local governmental authorities and compiled in the field, the avalanche event was numerically simulated using the avalanche dynamics programs AVAL-1D and RAMMS. Avalanche characteristics, such as extent and date were determined using dendrochronological techniques. Model simulation results were compared with documentary and tree-ring evidences for the 2002 event. Our results show a good agreement between the simulated projection of the avalanche and its reconstructed extent using tree-ring records. Differences between the observed and the simulated avalanche, principally related to the snow height deposition in the run-out zone, are mostly attributed to the low resolution of the digital elevation model used to represent the valley topography. The main contributions of this study are (1 to provide the first calibration of numerical avalanche models for the Patagonian Andes and (2 to highlight the potential of Nothofagus pumilio tree-ring records to reconstruct past snow-avalanche events in time and space. Future research should focus on testing this combined approach in other forested regions of the Andes.

  13. Drought-adaptation potential in Fagus sylvatica: linking moisture availability with genetic diversity and dendrochronology.

    Science.gov (United States)

    Pluess, Andrea R; Weber, Pascale

    2012-01-01

    Microevolution is essential for species persistence especially under anticipated climate change scenarios. Species distribution projection models suggested that the dominant tree species of lowland forests in Switzerland, European beech (Fagus sylvatica L.), might disappear from most areas due to expected longer dry periods. However, if genotypes at the moisture boundary of the species climatic envelope are adapted to lower moisture availability, they can serve as seed source for the continuation of beech forests under changing climates. With an AFLP genome scan approach, we studied neutral and potentially adaptive genetic variation in Fagus sylvatica in three regions containing a dry and a mesic site each (n(ind.) = 241, n(markers) = 517). We linked this dataset with dendrochronological growth measures and local moisture availabilities based on precipitation and soil characteristics. Genetic diversity decreased slightly at dry sites. Overall genetic differentiation was low (F(st) = 0.028) and Bayesian cluster analysis grouped all populations together suggesting high (historical) gene flow. The Bayesian outlier analyses indicated 13 markers with three markers differing between all dry and mesic sites and the others between the contrasting sites within individual regions. A total of 41 markers, including seven outlier loci, changed their frequency with local moisture availability. Tree height and median basal growth increments were reduced at dry sites, but marker presence/absence was not related to dendrochronological characteristics. CONCLUSION AND THEIR SIGNIFICANCE: The outlier alleles and the makers with changing frequencies in relation to moisture availability indicate microevolutionary processes occurring within short geographic distances. The general genetic similarity among sites suggests that 'preadaptive' genes can easily spread across the landscape. Yet, due to the long live span of trees, fostering saplings originating from dry sites and

  14. Seismic response analysis of structural system subjected to multiple support excitation

    International Nuclear Information System (INIS)

    Wu, R.W.; Hussain, F.A.; Liu, L.K.

    1978-01-01

    In the seismic analysis of a multiply supported structural system subjected to nonuniform excitations at each support point, the single response spectrum, the time history, and the multiple response spectrum are the three commonly employed methods. In the present paper the three methods are developed, evaluated, and the limitations and advantages of each method assessed. A numerical example has been carried out for a typical piping system. Considerably smaller responses have been predicted by the time history method than that by the single response spectrum method. This is mainly due to the fact that the phase and amplitude relations between the support excitations are faithfully retained in the time history method. The multiple response spectrum prediction has been observed to compare favourably with the time history method prediction. Based on the present evaluation, the multiple response spectrum method is the most efficient method for seismic response analysis of structural systems subjected to multiple support excitation. (Auth.)

  15. Multiple-Choice versus Constructed-Response Tests in the Assessment of Mathematics Computation Skills.

    Science.gov (United States)

    Gadalla, Tahany M.

    The equivalence of multiple-choice (MC) and constructed response (discrete) (CR-D) response formats as applied to mathematics computation at grade levels two to six was tested. The difference between total scores from the two response formats was tested for statistical significance, and the factor structure of items in both response formats was…

  16. Pavlovian conditioning of multiple opioid-like responses in mice

    OpenAIRE

    Bryant, Camron D.; Roberts, Kristofer W.; Culbertson, Christopher S.; Le, Alan; Evans, Christopher J.; Fanselow, Michael S.

    2009-01-01

    Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2 mg/kg, i.p.) in a novel context and subsequently g...

  17. Optimization of multi-response dynamic systems integrating multiple ...

    African Journals Online (AJOL)

    regression and Taguchi's dynamic signal-to-noise ratio concept ..... algorithm for dynamic multi-response optimization based on goal programming approach. .... problem-solving confirmation, if no grave infringement of model suppositions is ...

  18. Bisensory stimulation increases gamma-responses over multiple cortical regions.

    Science.gov (United States)

    Sakowitz, O W; Quiroga, R Q; Schürmann, M; Başar, E

    2001-04-01

    In the framework of the discussion about gamma (approx. 40 Hz) oscillations as information carriers in the brain, we investigated the relationship between gamma responses in the EEG and intersensory association. Auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) were compared with bisensory evoked potentials (BEPs; simultaneous auditory and visual stimulation) in 15 subjects. Gamma responses in AEPs, VEPs and BEPs were assessed by means of wavelet decomposition. Overall maximum gamma-components post-stimulus were highest in BEPs (P < 0.01). Bisensory evoked gamma-responses also showed significant central, parietal and occipital amplitude-increases (P < 0.001, P < 0.01, P < 0.05, respectively; prestimulus interval as baseline). These were of greater magnitude when compared with the unisensory responses. As a correlate of the marked gamma responses to bimodal stimulation we suggest a process of 'intersensory association', i.e. one of the steps between sensory transmission and perception. Our data may be interpreted as a further example of function-related gamma responses in the EEG.

  19. Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

    Science.gov (United States)

    Li, Zebin; Li, Ting

    2018-02-01

    Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

  20. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged...

  1. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    OpenAIRE

    Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

  2. Hydrologic modelling and dendrochronology as tool of site-species adequation assessment in a changing climate context

    OpenAIRE

    Sohier, Catherine; Debruxelles, Jérôme; Brusten, Thomas; Bauwens, Alexandra; Claessens, Hugues; Degre, Aurore

    2010-01-01

    A hydrologic model is related to dendrochronological measurements performed in a 52 years old Spruce stand. The site is situated on a hillside with shallow and acid brown soil in the ecoregion of Ardenne (Wallonia, Southern Belgium). Hydrologic modelling The hydrologic simulation runs from 1971 to 2005 at daily time step. The model is based on an EPIC code, adapted to the site concerning soil reservoirs depth, characteristic water contents, root profile and water uptake. Weather data c...

  3. Introducing wood anatomical and dendrochronological aspects of herbaceous plants: applications of the Xylem Database to vegetation science

    Czech Academy of Sciences Publication Activity Database

    Büntgen, Ulf; Psomas, A.; Schweingruber, F. H.

    2014-01-01

    Roč. 25, č. 4 (2014), s. 967-977 ISSN 1100-9233 R&D Projects: GA MŠk(CZ) EE2.3.20.0248 Institutional support: RVO:67179843 Keywords : dendrochronology * dicotyledon * environmental change * functional traits * herbs * life form * non-forest vegetation * secondary growth * shrub * vegetation cover * wood anatomy * Xylem formation Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 3.709, year: 2014

  4. Responses of an isolation system with distinct multiple frequencies

    International Nuclear Information System (INIS)

    Wu, Ting-shu; Seidensticker, R.W.

    1991-01-01

    Base isolation systems are generally designed with a single natural frequency. A major concern for these isolation systems is that, if the dominant frequency of a future earthquake is equal or close to the system's natural frequency, the ground motion will be greatly amplified because of resonance,and the superstructure would suffer severe damages. This paper present an isolation system designed with two distinct frequencies. Its responses to different ground motions, including a harmonic motion, show that no excessive amplification will occur. Adoption of this isolation system would greatly enhance the safety of an isolated superstructure against future strong earthquakes. 3 refs., 4 figs., 2 tabs

  5. DMXAA: An antivascular agent with multiple host responses

    International Nuclear Information System (INIS)

    Baguley, Bruce C.; Ching, L.-M.

    2002-01-01

    Purpose: To measure host responses to the antivascular agent DMXAA (5,6-dimethylxanthenone-4-acetic acid) and to compare them with those of other antivascular agents. Methods: Induction of tumor necrosis was measured in s.c. murine Colon 38 carcinomas growing in normal or tumor necrosis factor (TNF) receptor-1 knockout mice. Plasma and tumor tissue TNF concentrations were measured by ELISA. Plasma concentrations of 5-hydroxyindoleacetic acid (as a measure of serotonin release) and nitrite (as a measure of nitric oxide release) were measured by high-performance liquid chromatography. Results: Administration of DMXAA to tumor-bearing mice increased plasma and tumor tissue-associated TNF, in addition to increasing plasma nitric oxide, distinguishing its action from that of mitotic poisons that had an antivascular action. Results from TNF receptor-1 knockout mice showed that TNF played an important role in both its antitumor action and its host toxicity. Release of serotonin occurred in response to mitotic poisons, as well as to DMXAA. Conclusions: The antivascular action of DMXAA involves in situ production in tumor tissue of a cascade of vasoactive events, including a direct effect on vascular endothelial cells and indirect vascular effects involving TNF, other cytokines, serotonin, and nitric oxide. Now that Phase I clinical trials of DMXAA are completed, the optimization of this cascade in cancer patients is a major challenge. Plasma 5-hydroxyindoleacetic acid concentrations may provide a useful surrogate marker for the antivascular effects of DMXAA and other antivascular agents

  6. Multiple Resource Host Architecture (MRHA) for the Mobile Detection Assessment Response System (MDARS) Revision A

    National Research Council Canada - National Science Library

    Everett, H

    2000-01-01

    The Mobile Detection Assessment and Response System (MDARS) program employs multiple robotic security platforms operating under the high level control of a remote host, with the direct supervision of a human operator...

  7. Coupled multiple-response versus free-response conceptual assessment: An example from upper-division physics

    Directory of Open Access Journals (Sweden)

    Bethany R. Wilcox

    2014-10-01

    Full Text Available Free-response research-based assessments, like the Colorado Upper-division Electrostatics Diagnostic (CUE, provide rich, fine-grained information about students’ reasoning. However, because of the difficulties inherent in scoring these assessments, the majority of the large-scale conceptual assessments in physics are multiple choice. To increase the scalability and usability of the CUE, we set out to create a new version of the assessment that preserves the insights afforded by a free-response format while exploiting the logistical advantages of a multiple-choice assessment. We used our extensive database of responses to the free-response CUE to construct distractors for a new version where students can select multiple responses and receive partial credit based on the accuracy and consistency of their selections. Here, we describe the development of this modified CUE format, which we call coupled multiple response (CMR, and present data from direct comparisons of both versions. We find that the two formats have the same average score and perform similarly on multiple measures of validity and reliability, suggesting that the new version is a potentially viable alternative to the original CUE for the purpose of large-scale research-based assessment. We also compare the details of student responses on each of the two versions. While the CMR version does not capture the full scope of potential student responses, nearly three-quarters of our students’ responses to the free-response version contained one or more elements that matched options provided on the CMR version.

  8. On the Equivalence of Constructed-Response and Multiple-Choice Tests.

    Science.gov (United States)

    Traub, Ross E.; Fisher, Charles W.

    Two sets of mathematical reasoning and two sets of verbal comprehension items were cast into each of three formats--constructed response, standard multiple-choice, and Coombs multiple-choice--in order to assess whether tests with indentical content but different formats measure the same attribute, except for possible differences in error variance…

  9. Applications of dendrochronology and sediment geochronology to establish reference episodes for evaluations of environmental radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Waugh, W.J.; Carroll, J.; Abraham, J.D.; Landeen, D.S. [Roy F. Weston, Inc., U.S. Department of Energy, Grand Junction Office, 2597 B 3/4 Road, Grand Junction, CO 81503 (United States)

    1998-12-01

    Dendrochronology and sediment geochronology have been used to demonstrate retrospective monitoring of environmental radioactivity at United States Department of Energy (DOE) sites. {sup 14}C in annual growth rings of sagebrush preserved the temporal and spatial patterns of {sup 14}C resulting from dispersion downwind of a nuclear fuel processing facility at the Hanford Site in Washington State. As far as 10 km downwind of the facility, {sup 14}C concentrations were significantly higher in growth rings formed during a fuel processing episode than in rings produced during preoperational or postoperational episodes. An episode of uranium mill tailings deposition in pond sediments at the Grand Junction Office in Colorado was reconstructed using {sup 210}Pb geochronology constrained by a marker of peak {sup 137}Cs fallout. Uranium concentrations in ponds sediments deposited after the processing episode provide a reasonable cleanup standard. These reference episodes of environmental radioactivity reconstructed from measurements taken within contaminated environments can improve or replace reference area data as baseline information for dose reconstructions, risk assessments, and the establishment of cleanup standards. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  10. Applications of dendrochronology and sediment geochronology to establish reference episodes for evaluations of environmental radioactivity

    International Nuclear Information System (INIS)

    Waugh, W.J.; Carroll, J.; Abraham, J.D.; Landeen, D.S.

    1998-01-01

    Dendrochronology and sediment geochronology have been used to demonstrate retrospective monitoring of environmental radioactivity at United States Department of Energy (DOE) sites. 14 C in annual growth rings of sagebrush preserved the temporal and spatial patterns of 14 C resulting from dispersion downwind of a nuclear fuel processing facility at the Hanford Site in Washington State. As far as 10 km downwind of the facility, 14 C concentrations were significantly higher in growth rings formed during a fuel processing episode than in rings produced during preoperational or postoperational episodes. An episode of uranium mill tailings deposition in pond sediments at the Grand Junction Office in Colorado was reconstructed using 210 Pb geochronology constrained by a marker of peak 137 Cs fallout. Uranium concentrations in ponds sediments deposited after the processing episode provide a reasonable cleanup standard. These reference episodes of environmental radioactivity reconstructed from measurements taken within contaminated environments can improve or replace reference area data as baseline information for dose reconstructions, risk assessments, and the establishment of cleanup standards. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  11. Dendrochronological evaluation of historic changes in Lake Stirniai (Lithuania) water level

    International Nuclear Information System (INIS)

    Stasytyte, I.; Pakalnis, R.

    2005-01-01

    Full text: Dendrochronological research was carried out on Pinus sylvestris L. timber extracted from Lake Stirniai (55 o 15'04'' latitude (N) and 25 o 38'49'' longitude (E)). As a result, the tree ring width floating chronology spanning 213 years was compiled. Radiocarbon dating of the samples indicated that pines grew from 1103 ± 80 AD to 1315 ± 80 AD. Fragments of stems and roots of pines were found waterlogged in 1 m water layer. It means that in the Medieval Warm Period, the ground water level in the habitat of archaeological pines was below the nowadays lake level for at least by 1 m. The growth conditions became unfavourable in ∼ 1270 ± 80 AD. At the end of the 13 th century the climate became damper, lake transgression started, the trees of Scots pine became dry. The basic cause of transgression seems to be the bogged bed of the rivulet Stirna flowing out of the lake. This phenomenon was caused by the changed climate conditions. The formant analysis of the radial increase of the stems of archaeological Scots pine in Lake Stirniai revealed 52.9; 30.3; 21.1; 17.5; 15.0; 11.2 year long-term fluctuation cycles. Comparison of the obtained data with the present cycles is foreseen. (author)

  12. Radiocarbon dating and Dendrochronology for Statigraphic Units near Tebano, Senio Northern Apennines - Time frame of Climatic Fluctuation at the onset of the Younger Dryas

    Science.gov (United States)

    Eggenschwiler, Loren; Hajdas, Irka; Cherubini, Paolo; Picotti, Vincenzo; Saurer, Matthias

    2017-04-01

    The presence of Pinus [sylvestris] provides an insight into dramatic events due to climatic changes. Several major and minor climatic fluctuations have had a strong impact on terrestrial and marine environments since the last glacial period to present day (Ravazzi et al. 2006). This study aims to describe the response of a fluvial environment through the use of dendrochronology and stratigraphy. Here, we intend to get a better understanding of how these climatic fluctuations affect the behavior of the Senio River (Lotter et al. 1992). In Tebano, Italy, several Pinus sylvestris subfossil trunks were discovered during excavation for an irrigation pool. Subfossil samples were collected to analyze the climate during the Younger Dryas (11,000 years BP) in detail. Charcoal samples from the Bubano clay quarry extend our research to further to 35,500 cal. years BP. The combination of dendrochronology along with stratigraphy allowed us to examine the climate at a detailed local and apply it to a broader spectrum. Tree-ring measurements and cross dating provided a better understanding and verification of extreme events that occurred during the lifespans of the trees. The use of stable isotopes indicates the extreme conditions that occurred. Radiocarbon dating validates the age of the samples and what geological period they come from. Along with stratigraphy, we were able to compile depth data to create a sediment curve. Using various methods throughout this study, we discovered the climatic situation of Pinus 11,000 years BP and are able to compare them with samples from today. These present day samples mark two of the southernmost extents of the Pinus population. We were then able to comprehend the magnitude of sediment supply and precipitation. Through this collection of methods and data, we are able to understand the influence of climate change in the past and the potential changes of the future. REFERENCES Lotter, A. F.; Eicher, U.; Siegenthaler, U.; Birks, H. J. B

  13. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies

    DEFF Research Database (Denmark)

    Lohse, Louise; Nielsen, Jens; Kamstrup, Søren

    2005-01-01

    In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present. study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a...

  14. Coupled Multiple-Response versus Free-Response Conceptual Assessment: An Example from Upper-Division Physics

    Science.gov (United States)

    Wilcox, Bethany R.; Pollock, Steven J.

    2014-01-01

    Free-response research-based assessments, like the Colorado Upper-division Electrostatics Diagnostic (CUE), provide rich, fine-grained information about students' reasoning. However, because of the difficulties inherent in scoring these assessments, the majority of the large-scale conceptual assessments in physics are multiple choice. To increase…

  15. Experimental design and multiple response optimization. Using the desirability function in analytical methods development.

    Science.gov (United States)

    Candioti, Luciana Vera; De Zan, María M; Cámara, María S; Goicoechea, Héctor C

    2014-06-01

    A review about the application of response surface methodology (RSM) when several responses have to be simultaneously optimized in the field of analytical methods development is presented. Several critical issues like response transformation, multiple response optimization and modeling with least squares and artificial neural networks are discussed. Most recent analytical applications are presented in the context of analytLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, ArgentinaLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, Argentinaical methods development, especially in multiple response optimization procedures using the desirability function. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Dendrochronological evidence of cockchafer (Melolontha sp.) outbreaks in subfossil tree-trunks from Tovačov (CZ Moravia)

    Czech Academy of Sciences Publication Activity Database

    Kolář, Tomáš; Rybníček, M.; Tegel, W.

    2013-01-01

    Roč. 31, č. 1 (2013), s. 29-33 ISSN 1125-7865 R&D Projects: GA MŽP(CZ) SP/2D1/93/07; GA MŠk(CZ) ED1.1.00/02.0073; GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : Cockchafer * Oak * Tree-ring * Dendrochronology * Subfossil trunk Subject RIV: EH - Ecology, Behaviour Impact factor: 1.697, year: 2013 http://www.sciencedirect.com/science/article/pii/S1125786512000574

  17. Making assessments while taking repeated risks: a pattern of multiple response pathways.

    Science.gov (United States)

    Pleskac, Timothy J; Wershbale, Avishai

    2014-02-01

    Beyond simply a decision process, repeated risky decisions also require a number of cognitive processes including learning, search and exploration, and attention. In this article, we examine how multiple response pathways develop over repeated risky decisions. Using the Balloon Analogue Risk Task (BART) as a case study, we show that 2 different response pathways emerge over the course of the task. The assessment pathway is a slower, more controlled pathway where participants deliberate over taking a risk. The 2nd pathway is a faster, more automatic process where no deliberation occurs. Results imply the slower assessment pathway is taken as choice conflict increases and that the faster automatic response is a learned response. Based on these results, we modify an existing formal cognitive model of decision making during the BART to account for these dual response pathways. The slower more deliberative response process is modeled with a sequential sampling process where evidence is accumulated to a threshold, while the other response is given automatically. We show that adolescents with conduct disorder and substance use disorder symptoms not only evaluate risks differently during the BART but also differ in the rate at which they develop the more automatic response. More broadly, our results suggest cognitive models of judgment decision making need to transition from treating observed decisions as the result of a single response pathway to the result of multiple response pathways that change and develop over time.

  18. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

    Directory of Open Access Journals (Sweden)

    Sunmi Song

    2015-06-01

    Full Text Available The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  19. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor.

    Science.gov (United States)

    Song, Sunmi; Graham-Engeland, Jennifer E; Corwin, Elizabeth J; Ceballos, Rachel M; Taylor, Shelley E; Seeman, Teresa; Klein, Laura Cousino

    2015-01-01

    The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  20. Responses of stream microbes to multiple anthropogenic stressors in a mesocosm study.

    Science.gov (United States)

    Nuy, Julia K; Lange, Anja; Beermann, Arne J; Jensen, Manfred; Elbrecht, Vasco; Röhl, Oliver; Peršoh, Derek; Begerow, Dominik; Leese, Florian; Boenigk, Jens

    2018-08-15

    Stream ecosystems are affected by multiple anthropogenic stressors worldwide. Even though effects of many single stressors are comparatively well studied, the effects of multiple stressors are difficult to predict. In particular bacteria and protists, which are responsible for the majority of ecosystem respiration and element flows, are infrequently studied with respect to multiple stressors responses. We conducted a stream mesocosm experiment to characterize the responses of single and multiple stressors on microbiota. Two functionally important stream habitats, leaf litter and benthic phototrophic rock biofilms, were exposed to three stressors in a full factorial design: fine sediment deposition, increased chloride concentration (salinization) and reduced flow velocity. We analyzed the microbial composition in the two habitat types of the mesocosms using an amplicon sequencing approach. Community analysis on different taxonomic levels as well as principle component analyses (PCoAs) based on realtive abundances of operational taxonomic units (OTUs) showed treatment specific shifts in the eukaryotic biofilm community. Analysis of variance (ANOVA) revealed that Bacillariophyta responded positively salinity and sediment increase, while the relative read abundance of chlorophyte taxa decreased. The combined effects of multiple stressors were mainly antagonistic. Therefore, the community composition in multiply stressed environments resembled the composition of the unstressed control community in terms of OTU occurrence and relative abundances. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Use of dendrochronological method in Pinus halepensis to estimate the soil erosion in the South East of Madrid (Spain).

    Science.gov (United States)

    Pérez-Rodríguez, Raquel; Marques, Maria Jose; Bienes, Ramón

    2007-05-25

    The rate of soil erosion in pine forests (Pinus halepensis) located in the Southeast of Madrid has been estimated using dendrochronological analysis based on the change in ring-growth pattern from concentric to eccentric when the root is exposed. Using 49 roots spread across five inclined areas, it has been found that the length and direction of the hillsides, as well as their vegetation cover affect the rate of erosion, while the slope itself does not. The erosion rates found for the different areas studied vary between 3.5 and 8.8 mm year(-1), that is between 40 and 101 t ha(-1) year(-1) respectively. These values are between 2 and 3 times greater than those predicted by USLE, for which this equation underestimates soil loss for Central Spain's Mediterranean conditions. Nonetheless, both methods (using dendrochronology to determine actual soil loss and theoretical prediction with USLE) are able to establish the same significant differences among the areas studied, allowing for the comparative estimate of the severity of the area's erosion problem.

  2. Dendrochronology and radiocarbon dating of conifer trees and buried logs from the Stanley River, Tasmania

    Energy Technology Data Exchange (ETDEWEB)

    Cook, E. [Columbia Univ., Palisades, NY (United States). Tree-Ring Lab; Barbetti, M.; Taylor, G.; Yu, Z.; Thompson, B.; Weeks, L. [Sydney Univ., Sydney, NSW (Australia). The NWG Macintosh Centre for Quaternary Dating; Buckley, B. [Tasmania Univ., Sandy Bay, TAS (Australia). Inst of Antarctic and Southern Ocean Studies

    1997-12-31

    Full text: Dendrochronological studies are being carried out on two endemic conifer species in the Stanley River area of western Tasmania. Living trees are growing along the river banks, adjacent floodplain areas, and occasionally on the lower hill-slopes. Many ancient logs are exposed in the bed and banks of the river, and several major excavations have been carried out in floodplain sediments up to a hundred metres distant from the present river channel. A tree-ring chronology for Huon pine (Lagarostrobos franklinii) now extends from the present back to 571 BC. This chronology has been constructed using cores from living trees (up to 1400 years old), sections from trees felled during logging operations in the early 1980s, and sections from subfossil logs in the river banks and floodplain sediments. Living celery-top pine (Phyllocladus aspleniifolius) trees are up to 500 years old, and a short chronology is being developed for this species as well. Large excavations have been carried out over several years in floodplain sediments, and sections have now been taken from a total of 350 subfossil logs. Both Huon and celery-top pine are represented in the collection. They range in age from >38 ka to modern, with good coverage for the periods 9-3.5 ka and from 2.5 ka to the present. A floating tree-ring chronology for Huon pine has been established for the period ca. 7200-3500 cal BP, and is gradually being augmented. In the collection of about 350 ancient conifer logs from the Stanley River, about 150 currently have known ages while the remaining 200 have yet to be studied. Most of them have ages less than 9000 cal BP, but about 10% of them are older. Four of them are more than 30,000 years old, and may be Last Interglacial in age. Nine of them are known to be between 18,000 and 10,000 years old, and six are between 10,000 and 9,000 years old. Our augmented collection has become an increasingly important archive for further tree-ring and carbon isotope studies. Paper

  3. Dendrochronology and radiocarbon dating of conifer trees and buried logs from the Stanley River, Tasmania

    International Nuclear Information System (INIS)

    Cook, E.; Barbetti, M.; Taylor, G.; Yu, Z.; Thompson, B.; Weeks, L.; Buckley, B.

    1997-01-01

    Full text: Dendrochronological studies are being carried out on two endemic conifer species in the Stanley River area of western Tasmania. Living trees are growing along the river banks, adjacent floodplain areas, and occasionally on the lower hill-slopes. Many ancient logs are exposed in the bed and banks of the river, and several major excavations have been carried out in floodplain sediments up to a hundred metres distant from the present river channel. A tree-ring chronology for Huon pine (Lagarostrobos franklinii) now extends from the present back to 571 BC. This chronology has been constructed using cores from living trees (up to 1400 years old), sections from trees felled during logging operations in the early 1980s, and sections from subfossil logs in the river banks and floodplain sediments. Living celery-top pine (Phyllocladus aspleniifolius) trees are up to 500 years old, and a short chronology is being developed for this species as well. Large excavations have been carried out over several years in floodplain sediments, and sections have now been taken from a total of 350 subfossil logs. Both Huon and celery-top pine are represented in the collection. They range in age from >38 ka to modern, with good coverage for the periods 9-3.5 ka and from 2.5 ka to the present. A floating tree-ring chronology for Huon pine has been established for the period ca. 7200-3500 cal BP, and is gradually being augmented. In the collection of about 350 ancient conifer logs from the Stanley River, about 150 currently have known ages while the remaining 200 have yet to be studied. Most of them have ages less than 9000 cal BP, but about 10% of them are older. Four of them are more than 30,000 years old, and may be Last Interglacial in age. Nine of them are known to be between 18,000 and 10,000 years old, and six are between 10,000 and 9,000 years old. Our augmented collection has become an increasingly important archive for further tree-ring and carbon isotope studies

  4. Electromagnetic velocity gauge: use of multiple gauges, time response, and flow perturbations

    International Nuclear Information System (INIS)

    Erickson, L.M.; Johnson, C.B.; Parker, N.L.; Vantine, H.C.; Weingart, R.C.; Lee, R.S.

    1981-01-01

    We have developed an in-situ electromagnetic velocity (EMV) gauge system for use in multiple-gauge studies of initiating and detonating explosives. We have also investigated the risetime of the gauge and the manner in which it perturbs a reactive flow. We report on the special precautions that are necessary in multiple gauge experiments to reduce lead spreading, simplify target fabrication problems and minimize cross talk through the conducting explosive. Agreement between measured stress records and calculations from multiple velocity gauge data give us confidence that our velocity gauges are recording properly. We have used laser velocity interferometry to measure the gauge risetime in polymethyl methacrylate (PMMA). To resolve the difference in the two methods, we have examined hydrodynamic and material rate effects. In addition, we considered the effects of shock tilt, electronic response and magntic diffusion on the gauge's response time

  5. Increased multiaxial lumbar motion responses during multiple-impulse mechanical force manually assisted spinal manipulation

    Directory of Open Access Journals (Sweden)

    Gunzburg Robert

    2006-04-01

    Full Text Available Abstract Background Spinal manipulation has been found to create demonstrable segmental and intersegmental spinal motions thought to be biomechanically related to its mechanisms. In the case of impulsive-type instrument device comparisons, significant differences in the force-time characteristics and concomitant motion responses of spinal manipulative instruments have been reported, but studies investigating the response to multiple thrusts (multiple impulse trains have not been conducted. The purpose of this study was to determine multi-axial segmental and intersegmental motion responses of ovine lumbar vertebrae to single impulse and multiple impulse spinal manipulative thrusts (SMTs. Methods Fifteen adolescent Merino sheep were examined. Tri-axial accelerometers were attached to intraosseous pins rigidly fixed to the L1 and L2 lumbar spinous processes under fluoroscopic guidance while the animals were anesthetized. A hand-held electromechanical chiropractic adjusting instrument (Impulse was used to apply single and repeated force impulses (13 total over a 2.5 second time interval at three different force settings (low, medium, and high along the posteroanterior axis of the T12 spinous process. Axial (AX, posteroanterior (PA, and medial-lateral (ML acceleration responses in adjacent segments (L1, L2 were recorded at a rate of 5000 samples per second. Peak-peak segmental accelerations (L1, L2 and intersegmental acceleration transfer (L1–L2 for each axis and each force setting were computed from the acceleration-time recordings. The initial acceleration response for a single thrust and the maximum acceleration response observed during the 12 multiple impulse trains were compared using a paired observations t-test (POTT, alpha = .05. Results Segmental and intersegmental acceleration responses mirrored the peak force magnitude produced by the Impulse Adjusting Instrument. Accelerations were greatest for AX and PA measurement axes. Compared to

  6. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    Science.gov (United States)

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  7. Testing effect of a drug using multiple nested models for the dose–response

    DEFF Research Database (Denmark)

    Baayen, C.; Hougaard, P.; Pipper, C. B.

    2015-01-01

    of the assumed dose–response model. Bretz et al. (2005, Biometrics 61, 738–748) suggested a combined approach, which selects one or more suitable models from a set of candidate models using a multiple comparison procedure. The method initially requires a priori estimates of any non-linear parameters...

  8. Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis.

    NARCIS (Netherlands)

    Novakovic, A.M.; Krekels, E.H.; Munafo, A.; Ueckert, S.; Karlsson, M.O.

    2016-01-01

    In this study, we report the development of the first item response theory (IRT) model within a pharmacometrics framework to characterize the disease progression in multiple sclerosis (MS), as measured by Expanded Disability Status Score (EDSS). Data were collected quarterly from a 96-week phase III

  9. IsoGeneGUI : Multiple approaches for dose-response analysis of microarray data using R

    NARCIS (Netherlands)

    Otava, Martin; Sengupta, Rudradev; Shkedy, Ziv; Lin, Dan; Pramana, Setia; Verbeke, Tobias; Haldermans, Philippe; Hothorn, Ludwig A.; Gerhard, Daniel; Kuiper, Rebecca M.; Klinglmueller, Florian; Kasim, Adetayo

    2017-01-01

    The analysis of transcriptomic experiments with ordered covariates, such as dose-response data, has become a central topic in bioinformatics, in particular in omics studies. Consequently, multiple R packages on CRAN and Bioconductor are designed to analyse microarray data from various perspectives

  10. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis

    DEFF Research Database (Denmark)

    Kjølhede, Tue; Dalgas, Ulrik; Brolin Gade, Anne

    2016-01-01

    Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying...

  11. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Science.gov (United States)

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  12. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    Science.gov (United States)

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

  13. Time since death and decay rate constants of Norway spruce and European larch deadwood in subalpine forests determined using dendrochronology and radiocarbon dating

    Science.gov (United States)

    Petrillo, M.; Cherubini, P.; Fravolini, G.; Ascher, J.; Schärer, M.; Synal, H.-A.; Bertoldi, D.; Camin, F.; Larcher, R.; Egli, M.

    2015-09-01

    Due to the large size and highly heterogeneous spatial distribution of deadwood, the time scales involved in the coarse woody debris (CWD) decay of Picea abies (L.) Karst. and Larix decidua Mill. in Alpine forests have been poorly investigated and are largely unknown. We investigated the CWD decay dynamics in an Alpine valley in Italy using the five-decay class system commonly employed for forest surveys, based on a macromorphological and visual assessment. For the decay classes 1 to 3, most of the dendrochronological samples were cross-dated to assess the time that had elapsed since tree death, but for decay classes 4 and 5 (poorly preserved tree rings) and some others not having enough tree rings, radiocarbon dating was used. In addition, density, cellulose and lignin data were measured for the dated CWD. The decay rate constants for spruce and larch were estimated on the basis of the density loss using a single negative exponential model. In the decay classes 1 to 3, the ages of the CWD were similar varying between 1 and 54 years for spruce and 3 and 40 years for larch with no significant differences between the classes; classes 1-3 are therefore not indicative for deadwood age. We found, however, distinct tree species-specific differences in decay classes 4 and 5, with larch CWD reaching an average age of 210 years in class 5 and spruce only 77 years. The mean CWD rate constants were 0.012 to 0.018 yr-1 for spruce and 0.005 to 0.012 yr-1 for larch. Cellulose and lignin time trends half-lives (using a multiple-exponential model) could be derived on the basis of the ages of the CWD. The half-lives for cellulose were 21 yr for spruce and 50 yr for larch. The half-life of lignin is considerably higher and may be more than 100 years in larch CWD.

  14. Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes.

    Science.gov (United States)

    Sanchez-Alberola, Neus; Campoy, Susana; Barbé, Jordi; Erill, Ivan

    2012-02-03

    The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an essential role in these organisms and sheds light into the

  15. To core, or not to core: the impact of coring on tree health and a best-practice framework for collecting dendrochronological information from living trees.

    Science.gov (United States)

    Tsen, Edward W J; Sitzia, Tommaso; Webber, Bruce L

    2016-11-01

    Trees are natural repositories of valuable environmental information that is preserved in the growth and structure of their stems, branches and roots. Dendrochronological analyses, based on the counting, crossdating and characterisation of incrementally formed wood rings, offer powerful insights for diverse fields including ecology, climatology and archaeology. The application of this toolset is likely to increase in popularity over coming decades due to advances in the field and a reduction in the cost of analyses. In research settings where the continued value of living trees subject to dendrochronological investigation is important, the use of an increment bore corer to extract trunk tissue is considered the best option to minimise negative impacts on tree health (e.g. stress and fitness). A small and fragmented body of literature, however, reports significant after-effects, and in some cases fatal outcomes, from this sampling technique. As it stands, the literature documenting increment bore coring (IBC) impacts lacks experimental consistency and is poorly replicated, making it difficult for prospective users of the method to assess likely tree responses to coring. This paucity of information has the potential to lead to destructive misuse of the method and also limits its safe implementation in circumstances where the risk of impacts may be appropriate. If IBC is to fulfil its potential as a method of choice across research fields, then we must first address our limited understanding of IBC impacts and provide a framework for its appropriate future use. Firstly, we review the historical context of studies examining the impacts of IBC on trees to identify known patterns, focal issues and biases in existing knowledge. IBC wound responses, particularly those that impact on lumber quality, have been the primary focus of prior studies. No universal treatment was identified that conclusively improved wound healing and few studies have linked wound responses to tree

  16. Variable dead time counters. 1 - theoretical responses and the effects of neutron multiplication

    International Nuclear Information System (INIS)

    Lees, E.W.; Hooton, B.W.

    1978-10-01

    A theoretical expression is derived for calculating the response of any variable dead time counter (VDC) used in the passive assay of plutonium by neutron counting of the natural spontaneous fission activity. The effects of neutron multiplication in the sample arising from interactions of the original spontaneous fission neutrons is shown to modify the linear relationship between VDC signal and Pu mass. Numerical examples are shown for the Euratom VDC and a systematic investigation of the various factors affecting neutron multiplication is reported. Limited comparisons between the calculations and experimental data indicate provisional validity of the calculations. (author)

  17. A likelihood-based time series modeling approach for application in dendrochronology to examine the growth-climate relations and forest disturbance history

    Science.gov (United States)

    A time series intervention analysis (TSIA) of dendrochronological data to infer the tree growth-climate-disturbance relations and forest disturbance history is described. Maximum likelihood is used to estimate the parameters of a structural time series model with components for ...

  18. Extinction produces context inhibition and multiple-context extinction reduces response recovery in human predictive learning.

    Science.gov (United States)

    Glautier, Steven; Elgueta, Tito; Nelson, James Byron

    2013-12-01

    Two experiments with human participants were used to investigate recovery of an extinguished learned response after a context change using ABC designs. In an ABC design, the context changes over the three successive stages of acquisition (context A), extinction (context B), and test (context C). In both experiments, we found reduced recovery in groups that had extinction in multiple contexts, and that the extinction contexts acquired inhibitory strength. These results confirm those of previous investigations, that multiple-context extinction can produce less response recovery than single-context extinction, and they also provide new evidence for the involvement of contextual inhibitory processes in extinction in humans. The foregoing results are broadly in line with a protection-from-extinction account of response recovery. Yet, despite the fact that we detected contextual inhibition, predictions based on protection-from-extinction were not fully reliable for the single- and multiple-context group differences that we observed in (1) rates of extinction and (2) the strength of context inhibition. Thus, although evidence was obtained for a protection-from-extinction account of response recovery, this account can not explain all of the data.

  19. Effects of extinction in multiple contexts on renewal of instrumental responses.

    Science.gov (United States)

    Bernal-Gamboa, Rodolfo; Nieto, Javier; Uengoer, Metin

    2017-09-01

    In two experiments with rats, we investigated the effects of using multiple contexts during extinction on renewal of lever-pressing behavior. During the first phase of both experiments, rats were reinforced to press a lever for food in Context A. Then, responses underwent extinction. For half of the animals, extinction sessions were conducted in a single context, whereas the other half received extinction in three different contexts. In Experiment 1, we observed that extinction in multiple contexts eliminated ABC renewal, but had no detectable impact on ABA renewal. Experiment 2 revealed that conducting extended extinction training in multiple contexts attenuated ABA renewal. Theoretical and clinical implications of the present findings are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Probing of multiple magnetic responses in magnetic inductors using atomic force microscopy.

    Science.gov (United States)

    Park, Seongjae; Seo, Hosung; Seol, Daehee; Yoon, Young-Hwan; Kim, Mi Yang; Kim, Yunseok

    2016-02-08

    Even though nanoscale analysis of magnetic properties is of significant interest, probing methods are relatively less developed compared to the significance of the technique, which has multiple potential applications. Here, we demonstrate an approach for probing various magnetic properties associated with eddy current, coil current and magnetic domains in magnetic inductors using multidimensional magnetic force microscopy (MMFM). The MMFM images provide combined magnetic responses from the three different origins, however, each contribution to the MMFM response can be differentiated through analysis based on the bias dependence of the response. In particular, the bias dependent MMFM images show locally different eddy current behavior with values dependent on the type of materials that comprise the MI. This approach for probing magnetic responses can be further extended to the analysis of local physical features.

  1. Generation of synthetic time histories compatible with multiple-damping design response spectra

    International Nuclear Information System (INIS)

    Lilhanand, K.; Tseng, W.S.

    1987-01-01

    Seismic design of nuclear power plants as currently practiced requires time history analyses be performed to generate floor response spectra for seismic qualification of piping, equipment, and components. Since design response spectra are normally prescribed in the form of smooth spectra, the generation of synthetic time histories whose response spectra closely match the ''target'' design spectra of multiple damping values, is often required for the seismic time history analysis purpose. Various methods of generation of synthetic time histories compatible with target response spectra have been proposed in the literature. Since the mathematical problem of determining a time history from a given set of response spectral values is not unique, an exact solution is not possible, and all the proposed methods resort to some forms of approximate solutions. In this paper, a new iteration scheme, is described which effectively removes the difficulties encountered by the existing methods. This new iteration scheme can not only improve the accuracy of spectrum matching for a single-damping target spectrum, but also automate the spectrum matching for multiple-damping target spectra. The applicability and limitations as well as the method adopted to improve the numerical stability of this new iteration scheme are presented. The effectiveness of this new iteration scheme is illustrated by two example applications

  2. All of the above: When multiple correct response options enhance the testing effect.

    Science.gov (United States)

    Bishara, Anthony J; Lanzo, Lauren A

    2015-01-01

    Previous research has shown that multiple choice tests often improve memory retention. However, the presence of incorrect lures often attenuates this memory benefit. The current research examined the effects of "all of the above" (AOTA) options. When such options are correct, no incorrect lures are present. In the first three experiments, a correct AOTA option on an initial test led to a larger memory benefit than no test and standard multiple choice test conditions. The benefits of a correct AOTA option occurred even without feedback on the initial test; for both 5-minute and 48-hour retention delays; and for both cued recall and multiple choice final test formats. In the final experiment, an AOTA question led to better memory retention than did a control condition that had identical timing and exposure to response options. However, the benefits relative to this control condition were similar regardless of the type of multiple choice test (AOTA or not). Results suggest that retrieval contributes to multiple choice testing effects. However, the extra testing effect from a correct AOTA option, rather than being due to more retrieval, might be due simply to more exposure to correct information.

  3. Validation and analysis of the coupled multiple response Colorado upper-division electrostatics diagnostic

    Directory of Open Access Journals (Sweden)

    Bethany R. Wilcox

    2015-11-01

    Full Text Available Standardized conceptual assessment represents a widely used tool for educational researchers interested in student learning within the standard undergraduate physics curriculum. For example, these assessments are often used to measure student learning across educational contexts and instructional strategies. However, to support the large-scale implementation often required for cross-institutional testing, it is necessary for these instruments to have question formats that facilitate easy grading. Previously, we created a multiple-response version of an existing, validated, upper-division electrostatics diagnostic with the goal of increasing the instrument’s potential for large-scale implementation. Here, we report on the validity and reliability of this new version as an independent instrument. These findings establish the validity of the multiple-response version as measured by multiple test statistics including item difficulty, item discrimination, and internal consistency. Moreover, we demonstrate that the majority of student responses to the new version are internally consistent even when they are incorrect and provide an example of how the new format can be used to gain insight into student difficulties with specific content in electrostatics.

  4. Charcoal from a prehistoric copper mine in the Austrian Alps: dendrochronological and dendrological data, demand for wood and forest utilisation.

    Science.gov (United States)

    Pichler, Thomas; Nicolussi, Kurt; Goldenberg, Gert; Hanke, Klaus; Kovács, Kristóf; Thurner, Andrea

    2013-02-01

    During prehistory fire-setting was the most appropriate technique for exploiting ore deposits. Charcoal fragments found in the course of archaeological excavations in a small mine called Mauk E in the area of Schwaz/Brixlegg (Tyrol, Austria) are argued to be evidence for the use of this technology. Dendrochronological analyses of the charcoal samples yielded calendar dates for the mining activities showing that the exploitation of the Mauk E mine lasted approximately one decade in the late 8th century BC. Dendrological studies show that the miners utilised stem wood of spruce and fir from forests with high stand density for fire-setting and that the exploitation of the Mauk E mine had only a limited impact on the local forests.

  5. Reliability of Autonomic Responses and Malaise Across Multiple Motion Sickness Stimulation Tests

    Science.gov (United States)

    Stout, Cynthia S.; Toscano, William B.; Cowings, Patricia S.

    1993-01-01

    There is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation. Additionally, a paucity of data exists that examines the variability within an individual across repeated motion sickness tests. Investigators have also examined the relationship of autonomic responses to motion sickness development. These investigations have used analyses at discrete points in time to describe this relationship. This approach fails to address the time course of autonomic responses and malaise development throughout the motion sickness test. Our objectives were to examine the reliability of autonomic responses and malaise using the final minute of the motion sickness test across five testing occasions, to examine the reliability of the change in autonomic responses and the change in malaise across five testing occasions, and to examine the relationship between changes in autonomic responses and changes in malaise level across the entire motion sickness test. Our results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and malaise throughout the test duration were less stable across the tests. We attribute this instability to variations in individual susceptibility and the error associated with estimating a measure of autonomic gain.

  6. An experimental study of the response of the multiple support piping systems

    International Nuclear Information System (INIS)

    Chiba, T.; Koyanagi, R.

    1987-01-01

    From the test results, following remarks have been obtained. 1. Since the effect of internal pressure was not so small on the stress response, its effect should be considered in the design of piping systems. 2. The effect of the phase of excitations was fairly dominant to the response of piping systems. From this fact, the adopting of the support structures which have different dynamic characteristics may be one of the more realistic approaches to reduce the response of piping systems. 3. The acceleration responses near the support points are always underestimated because the natural modes of the analysis are zero at these support points. 4. If the pseudo-static response is dominant, the stress responses near the support points are always overestimated by the ABS method to support groups. In such case the SRSS method is recommended. 5. The 10% method to the closely spaced modes is conservative for the flexible piping. The closely spaced mode methods to these flexible piping systems should be used carefully. 6. The SRSS combination method is offered the reasonable results to the space, modes and support groups in the multiple response spectra method. (orig.)

  7. Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes

    Directory of Open Access Journals (Sweden)

    Sanchez-Alberola Neus

    2012-02-01

    Full Text Available Abstract Background The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Results Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Conclusions Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an

  8. Adaptive responses to salinity stress across multiple life stages in anuran amphibians.

    Science.gov (United States)

    Albecker, Molly A; McCoy, Michael W

    2017-01-01

    In many regions, freshwater wetlands are increasing in salinity at rates exceeding historic levels. Some freshwater organisms, like amphibians, may be able to adapt and persist in salt-contaminated wetlands by developing salt tolerance. Yet adaptive responses may be more challenging for organisms with complex life histories, because the same environmental stressor can require responses across different ontogenetic stages. Here we investigated responses to salinity in anuran amphibians: a common, freshwater taxon with a complex life cycle. We conducted a meta-analysis to define how the lethality of saltwater exposure changes across multiple life stages, surveyed wetlands in a coastal region experiencing progressive salinization for the presence of anurans, and used common garden experiments to investigate whether chronic salt exposure alters responses in three sequential life stages (reproductive, egg, and tadpole life stages) in Hyla cinerea , a species repeatedly observed in saline wetlands. Meta-analysis revealed differential vulnerability to salt stress across life stages with the egg stage as the most salt-sensitive. Field surveys revealed that 25% of the species known to occur in the focal region were detected in salt-intruded habitats. Remarkably, Hyla cinerea was found in large abundances in multiple wetlands with salinity concentrations 450% higher than the tadpole-stage LC 50 . Common garden experiments showed that coastal (chronically salt exposed) populations of H. cinerea lay more eggs, have higher hatching success, and greater tadpole survival in higher salinities compared to inland (salt naïve) populations. Collectively, our data suggest that some species of anuran amphibians have divergent and adaptive responses to salt exposure across populations and across different life stages. We propose that anuran amphibians may be a novel and amenable natural model system for empirical explorations of adaptive responses to environmental change.

  9. The e-MSWS-12: improving the multiple sclerosis walking scale using item response theory.

    Science.gov (United States)

    Engelhard, Matthew M; Schmidt, Karen M; Engel, Casey E; Brenton, J Nicholas; Patek, Stephen D; Goldman, Myla D

    2016-12-01

    The Multiple Sclerosis Walking Scale (MSWS-12) is the predominant patient-reported measure of multiple sclerosis (MS) -elated walking ability, yet it had not been analyzed using item response theory (IRT), the emerging standard for patient-reported outcome (PRO) validation. This study aims to reduce MSWS-12 measurement error and facilitate computerized adaptive testing by creating an IRT model of the MSWS-12 and distributing it online. MSWS-12 responses from 284 subjects with MS were collected by mail and used to fit and compare several IRT models. Following model selection and assessment, subpopulations based on age and sex were tested for differential item functioning (DIF). Model comparison favored a one-dimensional graded response model (GRM). This model met fit criteria and explained 87 % of response variance. The performance of each MSWS-12 item was characterized using category response curves (CRCs) and item information. IRT-based MSWS-12 scores correlated with traditional MSWS-12 scores (r = 0.99) and timed 25-foot walk (T25FW) speed (r =  -0.70). Item 2 showed DIF based on age (χ 2  = 19.02, df = 5, p Item 11 showed DIF based on sex (χ 2  = 13.76, df = 5, p = 0.02). MSWS-12 measurement error depends on walking ability, but could be lowered by improving or replacing items with low information or DIF. The e-MSWS-12 includes IRT-based scoring, error checking, and an estimated T25FW derived from MSWS-12 responses. It is available at https://ms-irt.shinyapps.io/e-MSWS-12 .

  10. Predicting hearing thresholds and occupational hearing loss with multiple-frequency auditory steady-state responses.

    Science.gov (United States)

    Hsu, Ruey-Fen; Ho, Chi-Kung; Lu, Sheng-Nan; Chen, Shun-Sheng

    2010-10-01

    An objective investigation is needed to verify the existence and severity of hearing impairments resulting from work-related, noise-induced hearing loss in arbitration of medicolegal aspects. We investigated the accuracy of multiple-frequency auditory steady-state responses (Mf-ASSRs) between subjects with sensorineural hearing loss (SNHL) with and without occupational noise exposure. Cross-sectional study. Tertiary referral medical centre. Pure-tone audiometry and Mf-ASSRs were recorded in 88 subjects (34 patients had occupational noise-induced hearing loss [NIHL], 36 patients had SNHL without noise exposure, and 18 volunteers were normal controls). Inter- and intragroup comparisons were made. A predicting equation was derived using multiple linear regression analysis. ASSRs and pure-tone thresholds (PTTs) showed a strong correlation for all subjects (r = .77 ≈ .94). The relationship is demonstrated by the equationThe differences between the ASSR and PTT were significantly higher for the NIHL group than for the subjects with non-noise-induced SNHL (p tool for objectively evaluating hearing thresholds. Predictive value may be lower in subjects with occupational hearing loss. Regardless of carrier frequencies, the severity of hearing loss affects the steady-state response. Moreover, the ASSR may assist in detecting noise-induced injury of the auditory pathway. A multiple linear regression equation to accurately predict thresholds was shown that takes into consideration all effect factors.

  11. Density dependence governs when population responses to multiple stressors are magnified or mitigated.

    Science.gov (United States)

    Hodgson, Emma E; Essington, Timothy E; Halpern, Benjamin S

    2017-10-01

    Population endangerment typically arises from multiple, potentially interacting anthropogenic stressors. Extensive research has investigated the consequences of multiple stressors on organisms, frequently focusing on individual life stages. Less is known about population-level consequences of exposure to multiple stressors, especially when exposure varies through life. We provide the first theoretical basis for identifying species at risk of magnified effects from multiple stressors across life history. By applying a population modeling framework, we reveal conditions under which population responses from stressors applied to distinct life stages are either magnified (synergistic) or mitigated. We find that magnification or mitigation critically depends on the shape of density dependence, but not the life stage in which it occurs. Stressors are always magnified when density dependence is linear or concave, and magnified or mitigated when it is convex. Using Bayesian numerical methods, we estimated the shape of density dependence for eight species across diverse taxa, finding support for all three shapes. © 2017 by the Ecological Society of America.

  12. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

    Science.gov (United States)

    Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

    2017-09-01

    Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

  13. Exogenous ascorbic acid improves defence responses of sunflower (Helianthus annuus) exposed to multiple stresses.

    Science.gov (United States)

    Kaya, Armagan

    2017-09-01

    Ascorbic acid is an important antioxidant that plays role both on growth and development and also stress response of the plant. The purpose of this study was to determine the effect of ascorbate on physiological and biochemical changes of sunflower that was exposed to multiple stresses. Chlorophyll and carotenoid contents decreased and glutathione, ascorbate and malondialdehyde contents as well as antioxidant enzyme activities increased for sunflower plant that was exposed to 50 mM NaCl and pendimethalin at different concentrations. These changes were found to be more significant in groups simultaneously exposed to both stress factors. While malondialdehyde content decreased, chlorophyll, carotenoid, ascorbate, glutathione contents and antioxidant enzyme activities increased in plants treated exogenously with ascorbate, compared to the untreated samples. According to the findings of our study; compared to individual stress, the effect of stress is more pronounced in sunflower exposed to multiple stresses, and treatment with exogenous ascorbate reduces the negative effects of stress.

  14. A frequency domain global parameter estimation method for multiple reference frequency response measurements

    Science.gov (United States)

    Shih, C. Y.; Tsuei, Y. G.; Allemang, R. J.; Brown, D. L.

    1988-10-01

    A method of using the matrix Auto-Regressive Moving Average (ARMA) model in the Laplace domain for multiple-reference global parameter identification is presented. This method is particularly applicable to the area of modal analysis where high modal density exists. The method is also applicable when multiple reference frequency response functions are used to characterise linear systems. In order to facilitate the mathematical solution, the Forsythe orthogonal polynomial is used to reduce the ill-conditioning of the formulated equations and to decouple the normal matrix into two reduced matrix blocks. A Complex Mode Indicator Function (CMIF) is introduced, which can be used to determine the proper order of the rational polynomials.

  15. Integration of multiple cues allows threat-sensitive anti-intraguild predator responses in predatory mites

    Science.gov (United States)

    Walzer, Andreas; Schausberger, Peter

    2013-01-01

    Intraguild (IG) prey is commonly confronted with multiple IG predator species. However, the IG predation (IGP) risk for prey is not only dependent on the predator species, but also on inherent (intraspecific) characteristics of a given IG predator such as its life-stage, sex or gravidity and the associated prey needs. Thus, IG prey should have evolved the ability to integrate multiple IG predator cues, which should allow both inter- and intraspecific threat-sensitive anti-predator responses. Using a guild of plant-inhabiting predatory mites sharing spider mites as prey, we evaluated the effects of single and combined cues (eggs and/or chemical traces left by a predator female on the substrate) of the low risk IG predator Neoseiulus californicus and the high risk IG predator Amblyseius andersoni on time, distance and path shape parameters of the larval IG prey Phytoseiulus persimilis. IG prey discriminated between traces of the low and high risk IG predator, with and without additional presence of their eggs, indicating interspecific threat-sensitivity. The behavioural changes were manifest in distance moved, activity and path shape of IG prey. The cue combination of traces and eggs of the IG predators conveyed other information than each cue alone, allowing intraspecific threat-sensitive responses by IG prey apparent in changed velocities and distances moved. We argue that graded responses to single and combined IG predator cues are adaptive due to minimization of acceptance errors in IG prey decision making. PMID:23750040

  16. Optimization of Multiple Responses of Ultrasonic Machining (USM Process: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Rina Chakravorty

    2013-04-01

    Full Text Available Ultrasonic machining (USM process has multiple performance measures, e.g. material removal rate (MRR, tool wear rate (TWR, surface roughness (SR etc., which are affected by several process parameters. The researchers commonly attempted to optimize USM process with respect to individual responses, separately. In the recent past, several systematic procedures for dealing with the multi-response optimization problems have been proposed in the literature. Although most of these methods use complex mathematics or statistics, there are some simple methods, which can be comprehended and implemented by the engineers to optimize the multiple responses of USM processes. However, the relative optimization performance of these approaches is unknown because the effectiveness of different methods has been demonstrated using different sets of process data. In this paper, the computational requirements for four simple methods are presented, and two sets of past experimental data on USM processes are analysed using these methods. The relative performances of these methods are then compared. The results show that weighted signal-to-noise (WSN ratio method and utility theory (UT method usually give better overall optimisation performance for the USM process than the other approaches.

  17. New aspects of the ionospheric response to the October 2003 superstorms from multiple-satellite observations

    Science.gov (United States)

    Lei, Jiuhou; Wang, Wenbin; Burns, Alan G.; Yue, Xinan; Dou, Xiankang; Luan, Xiaoli; Solomon, Stanley C.; Liu, Yong C.-M.

    2014-03-01

    The total electron content (TEC) data measured by the Jason, CHAMP, GRACE, and SAC-C satellites, the in situ electron densities from CHAMP and GRACE, and the vertical E × B drifts from the ROCSAT, have been utilized to examine the ionospheric response to the October 2003 superstorms. The combination of observations from multiple satellites provides a unique global view of ionospheric storm effects, especially over the Pacific Ocean and American regions, which were under sunlit conditions during the main phases of the October 2003 superstorms. The main results of this study are as follows: (1) There were substantial increases in TEC in the daytime at low and middle latitudes during both superstorms. (2) The enhancements were greater during the 30 October superstorm and occurred over a wider range of local times. (3) They also tended to peak at earlier local times during this second event. (4) These TEC enhancement events occurred at the local times when there were enhancements in the upward vertical drift. (5) The strong upward vertical drifts are attributed to penetration electric fields, suggesting that these penetration electric fields played a significant role in the electron density enhancements during these superstorms. Overall, the main contribution of this study is the simultaneous view of the storm time ionospheric response from multiple satellites, and the association of local time differences in ionospheric plasma response with measured vertical drift variations.

  18. Community functional responses to soil and climate at multiple spatial scales: when does intraspecific variation matter?

    Directory of Open Access Journals (Sweden)

    Andrew Siefert

    Full Text Available Despite increasing evidence of the importance of intraspecific trait variation in plant communities, its role in community trait responses to environmental variation, particularly along broad-scale climatic gradients, is poorly understood. We analyzed functional trait variation among early-successional herbaceous plant communities (old fields across a 1200-km latitudinal extent in eastern North America, focusing on four traits: vegetative height, leaf area, specific leaf area (SLA, and leaf dry matter content (LDMC. We determined the contributions of species turnover and intraspecific variation to between-site functional dissimilarity at multiple spatial scales and community trait responses to edaphic and climatic factors. Among-site variation in community mean trait values and community trait responses to the environment were generated by a combination of species turnover and intraspecific variation, with species turnover making a greater contribution for all traits. The relative importance of intraspecific variation decreased with increasing geographic and environmental distance between sites for SLA and leaf area. Intraspecific variation was most important for responses of vegetative height and responses to edaphic compared to climatic factors. Individual species displayed strong trait responses to environmental factors in many cases, but these responses were highly variable among species and did not usually scale up to the community level. These findings provide new insights into the role of intraspecific trait variation in plant communities and the factors controlling its relative importance. The contribution of intraspecific variation to community trait responses was greatest at fine spatial scales and along edaphic gradients, while species turnover dominated at broad spatial scales and along climatic gradients.

  19. Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

    Science.gov (United States)

    Tarkun, Pinar; Atalay, Figen; Atesoglu, Elif Birtas; Mehtap, Ozgur; Simsek, Melih; Terzi, Esra; Geduk, Ayfer; Balli, Fatih; Batman, Adnan; Baydemir, Canan; Hacihanefioglu, Abdullah

    2015-05-01

    Two-thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high-dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment-related toxicities in patients treated with conventional and novel protocols. The records of 138 elderly (≥65 yr) patients with MM were retrospectively evaluated. The median overall survival(OS) of the patients was 46 months. The median progression-free survival (PFS) was 18 months. The OS and PFS of the patients treated with the conventional protocols did not differ significantly from those treated with the novel protocols. The statistical analysis of the quality of the response to the treatment with the conventional and novel therapies showed that complete remission (CR), combined with a very good partial response (VGPR), was significantly higher in the latter. However, the toxicities were higher in the novel treatment group. The novel drug protocols significantly increased the quality of the responses of elderly patients with MM to therapy, but they did not increase the patients' tolerability. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. MR Imaging in Monitoring and Predicting Treatment Response in Multiple Sclerosis.

    Science.gov (United States)

    Río, Jordi; Auger, Cristina; Rovira, Àlex

    2017-05-01

    MR imaging is the most sensitive tool for identifying lesions in patients with multiple sclerosis (MS). MR imaging has also acquired an essential role in the detection of complications arising from these treatments and in the assessment and prediction of efficacy. In the future, other radiological measures that have shown prognostic value may be incorporated within the models for predicting treatment response. This article examines the role of MR imaging as a prognostic tool in patients with MS and the recommendations that have been proposed in recent years to monitor patients who are treated with disease-modifying drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Nonlinear response to the multiple sine wave excitation of a softening--hardening system

    International Nuclear Information System (INIS)

    Koplik, B.; Subudhi, M.; Curreri, J.

    1979-01-01

    In studying the earthquake response of the HTGR core, it was observed that the system can display softening--hardening characteristics. This is of great consequence in evaluating the structural safety aspects of the core. In order to obtain a better understanding of the governing parameters, an investigation was undertaken with a single-degree-of-freedom system having a softening--hardening spring characteristic and excited by multiple sine waves. A parametric study varying the input amplitudes and the spring characteristic was performed. Transients were introduced into the system, and the jump phenomena between the lower softening characteristics to the higher hardening curve was studied

  2. Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Hegen, Harald; Adrianto, Indra; Lessard, Christopher J

    2016-01-01

    OBJECTIVE: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)-β treatment in patients with multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment...... were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays...

  3. Multiple Access Interference Reduction Using Received Response Code Sequence for DS-CDMA UWB System

    Science.gov (United States)

    Toh, Keat Beng; Tachikawa, Shin'ichi

    This paper proposes a combination of novel Received Response (RR) sequence at the transmitter and a Matched Filter-RAKE (MF-RAKE) combining scheme receiver system for the Direct Sequence-Code Division Multiple Access Ultra Wideband (DS-CDMA UWB) multipath channel model. This paper also demonstrates the effectiveness of the RR sequence in Multiple Access Interference (MAI) reduction for the DS-CDMA UWB system. It suggests that by using conventional binary code sequence such as the M sequence or the Gold sequence, there is a possibility of generating extra MAI in the UWB system. Therefore, it is quite difficult to collect the energy efficiently although the RAKE reception method is applied at the receiver. The main purpose of the proposed system is to overcome the performance degradation for UWB transmission due to the occurrence of MAI during multiple accessing in the DS-CDMA UWB system. The proposed system improves the system performance by improving the RAKE reception performance using the RR sequence which can reduce the MAI effect significantly. Simulation results verify that significant improvement can be obtained by the proposed system in the UWB multipath channel models.

  4. Impulsive response of an automatic transmission system with multiple clearances: Formulation, simulation and experiment

    Science.gov (United States)

    Crowther, Ashley R.; Singh, Rajendra; Zhang, Nong; Chapman, Chris

    2007-10-01

    Impulsive responses in geared systems with multiple clearances are studied when the mean torque excitation and system load change abruptly, with application to a vehicle driveline with an automatic transmission. First, torsional lumped-mass models of the planetary and differential gear sets are formulated using matrix elements. The model is then reduced to address tractable nonlinear problems while successfully retaining the main modes of interest. Second, numerical simulations for the nonlinear model are performed for transient conditions and a typical driving situation that induces an impulsive behaviour simulated. However, initial conditions and excitation and load profiles have to be carefully defined before the model can be numerically solved. It is shown that the impacts within the planetary or differential gears may occur under combinations of engine, braking and vehicle load transients. Our analysis shows that the shaping of the engine transient by the torque converter before reaching the clearance locations is more critical. Third, a free vibration experiment is developed for an analogous driveline with multiple clearances and three experiments that excite different response regimes have been carried out. Good correlations validate the proposed methodology.

  5. The Climate Response to Stratospheric Aerosol Geoengineering Can Be Tailored Using Multiple Injection Locations

    Energy Technology Data Exchange (ETDEWEB)

    MacMartin, Douglas G. [Mechanical and Aerospace Engineering, Cornell University, Ithaca NY USA; Department of Computing and Mathematical Sciences, California Institute of Technology, Pasadena CA USA; Kravitz, Ben [Atmospheric Sciences and Global Change Division, Pacific Northwest National Laboratory, Richland WA USA; Tilmes, Simone [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA; Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Richter, Jadwiga H. [Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Mills, Michael J. [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA; Lamarque, Jean-Francois [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA; Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Tribbia, Joseph J. [Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Vitt, Francis [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA

    2017-12-07

    The climate response to geoengineering with stratospheric aerosols has the potential to be designed to achieve some chosen objectives. By injecting different amounts of SO2 at multiple different latitudes, the spatial pattern of aerosol optical depth (AOD) can be partially controlled. We use simulations from the fully-coupled whole-atmosphere chemistry-climate model CESM1(WACCM), to demonstrate that three spatial degrees of freedom of AOD can be achieved by appropriately combining injection at different locations: an approximately spatially-uniform AOD distribution, the relative difference in AOD between Northern and Southern hemispheres, and the relative AOD in high versus low latitudes. For forcing levels that yield 1–2°C cooling, the AOD and surface temperature response are sufficiently linear in this model so that many climate effects can be predicted from single-latitude injection simulations. Optimized injection at multiple locations is predicted to improve compensation of CO2-forced climate change, relative to a case using only equatorial aerosol injection. The additional degrees of freedom can be used, for example, to balance interhemispheric temperature differences and the equator to pole temperature difference in addition to the global mean temperature; this is projected in this model to reduce the mean-square error in temperature compensation by 30%.

  6. Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

    Science.gov (United States)

    Paccagnella, A; Chiarion-Sileni, V; Soesan, M; Baggio, G; Bolzonella, S; De Besi, P; Casara, D; Frizzarin, M; Salvagno, L; Favaretto, A

    1991-09-01

    From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

  7. Analyzing Multiple-Choice Questions by Model Analysis and Item Response Curves

    Science.gov (United States)

    Wattanakasiwich, P.; Ananta, S.

    2010-07-01

    In physics education research, the main goal is to improve physics teaching so that most students understand physics conceptually and be able to apply concepts in solving problems. Therefore many multiple-choice instruments were developed to probe students' conceptual understanding in various topics. Two techniques including model analysis and item response curves were used to analyze students' responses from Force and Motion Conceptual Evaluation (FMCE). For this study FMCE data from more than 1000 students at Chiang Mai University were collected over the past three years. With model analysis, we can obtain students' alternative knowledge and the probabilities for students to use such knowledge in a range of equivalent contexts. The model analysis consists of two algorithms—concentration factor and model estimation. This paper only presents results from using the model estimation algorithm to obtain a model plot. The plot helps to identify a class model state whether it is in the misconception region or not. Item response curve (IRC) derived from item response theory is a plot between percentages of students selecting a particular choice versus their total score. Pros and cons of both techniques are compared and discussed.

  8. Cross-species multiple environmental stress responses: An integrated approach to identify candidate genes for multiple stress tolerance in sorghum (Sorghum bicolor (L. Moench and related model species.

    Directory of Open Access Journals (Sweden)

    Adugna Abdi Woldesemayat

    Full Text Available Crop response to the changing climate and unpredictable effects of global warming with adverse conditions such as drought stress has brought concerns about food security to the fore; crop yield loss is a major cause of concern in this regard. Identification of genes with multiple responses across environmental stresses is the genetic foundation that leads to crop adaptation to environmental perturbations.In this paper, we introduce an integrated approach to assess candidate genes for multiple stress responses across-species. The approach combines ontology based semantic data integration with expression profiling, comparative genomics, phylogenomics, functional gene enrichment and gene enrichment network analysis to identify genes associated with plant stress phenotypes. Five different ontologies, viz., Gene Ontology (GO, Trait Ontology (TO, Plant Ontology (PO, Growth Ontology (GRO and Environment Ontology (EO were used to semantically integrate drought related information.Target genes linked to Quantitative Trait Loci (QTLs controlling yield and stress tolerance in sorghum (Sorghum bicolor (L. Moench and closely related species were identified. Based on the enriched GO terms of the biological processes, 1116 sorghum genes with potential responses to 5 different stresses, such as drought (18%, salt (32%, cold (20%, heat (8% and oxidative stress (25% were identified to be over-expressed. Out of 169 sorghum drought responsive QTLs associated genes that were identified based on expression datasets, 56% were shown to have multiple stress responses. On the other hand, out of 168 additional genes that have been evaluated for orthologous pairs, 90% were conserved across species for drought tolerance. Over 50% of identified maize and rice genes were responsive to drought and salt stresses and were co-located within multifunctional QTLs. Among the total identified multi-stress responsive genes, 272 targets were shown to be co-localized within QTLs

  9. Additive effects prevail: The response of biota to multiple stressors in an intensively monitored watershed.

    Science.gov (United States)

    Gieswein, Alexander; Hering, Daniel; Feld, Christian K

    2017-09-01

    Freshwater ecosystems are impacted by a range of stressors arising from diverse human-caused land and water uses. Identifying the relative importance of single stressors and understanding how multiple stressors interact and jointly affect biology is crucial for River Basin Management. This study addressed multiple human-induced stressors and their effects on the aquatic flora and fauna based on data from standard WFD monitoring schemes. For altogether 1095 sites within a mountainous catchment, we used 12 stressor variables covering three different stressor groups: riparian land use, physical habitat quality and nutrient enrichment. Twenty-one biological metrics calculated from taxa lists of three organism groups (fish, benthic invertebrates and aquatic macrophytes) served as response variables. Stressor and response variables were subjected to Boosted Regression Tree (BRT) analysis to identify stressor hierarchy and stressor interactions and subsequently to Generalised Linear Regression Modelling (GLM) to quantify the stressors standardised effect size. Our results show that riverine habitat degradation was the dominant stressor group for the river fauna, notably the bed physical habitat structure. Overall, the explained variation in benthic invertebrate metrics was higher than it was in fish and macrophyte metrics. In particular, general integrative (aggregate) metrics such as % Ephemeroptera, Plecoptera and Trichoptera (EPT) taxa performed better than ecological traits (e.g. % feeding types). Overall, additive stressor effects dominated, while significant and meaningful stressor interactions were generally rare and weak. We concluded that given the type of stressor and ecological response variables addressed in this study, river basin managers do not need to bother much about complex stressor interactions, but can focus on the prevailing stressors according to the hierarchy identified. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Multiple Rapid Swallow Responses During Esophageal High-Resolution Manometry Reflect Esophageal Body Peristaltic Reserve

    Science.gov (United States)

    Shaker, Anisa; Stoikes, Nathaniel; Drapekin, Jesse; Kushnir, Vladimir; Brunt, L. Michael; Gyawali, C. Prakash

    2014-01-01

    OBJECTIVES Dysphagia may develop following antireflux surgery as a consequence of poor esophageal peristaltic reserve. We hypothesized that suboptimal contraction response following multiple rapid swallows (MRS) could be associated with chronic transit symptoms following antireflux surgery. METHODS Wet swallow and MRS responses on esophageal high-resolution manometry (HRM) were characterized collectively in the esophageal body (distal contractile integral (DCI)), and individually in each smooth muscle contraction segment (S2 and S3 amplitudes) in 63 patients undergoing antireflux surgery and in 18 healthy controls. Dysphagia was assessed using symptom questionnaires. The MRS/wet swallow ratios were calculated for S2 and S3 peak amplitudes and DCI. MRS responses were compared in patients with and without late postoperative dysphagia following antireflux surgery. RESULTS Augmentation of smooth muscle contraction (MRS/wet swallow ratios > 1.0) as measured collectively by DCI was seen in only 11.1% with late postoperative dysphagia, compared with 63.6% in those with no dysphagia and 78.1% in controls (P≤0.02 for each comparison). Similar results were seen with S3 but not S2 peak amplitude ratios. Receiver operating characteristics identified a DCI MRS/wet swallow ratio threshold of 0.85 in segregating patients with late postoperative dysphagia from those with no postoperative dysphagia with a sensitivity of 0.67 and specificity of 0.64. CONCLUSIONS Lack of augmentation of smooth muscle contraction following MRS is associated with late postoperative dysphagia following antireflux surgery, suggesting that MRS responses could assess esophageal smooth muscle peristaltic reserve. Further research is warranted to determine if antireflux surgery needs to be tailored to the MRS response. PMID:24019081

  11. Properties of a novel linear sulfur response mode in a multiple flame photometric detector.

    Science.gov (United States)

    Clark, Adrian G; Thurbide, Kevin B

    2014-01-24

    A new linear sulfur response mode was established in the multiple flame photometric detector (mFPD) by monitoring HSO* emission in the red spectral region above 600nm. Optimal conditions for this mode were found by using a 750nm interference filter and oxygen flows to the worker flames of this device that were about 10mL/min larger than those used for monitoring quadratic S2* emission. By employing these parameters, this mode provided a linear response over about 4 orders of magnitude, with a detection limit near 5.8×10(-11)gS/s and a selectivity of sulfur over carbon of about 3.5×10(3). Specifically, the minimum detectable masses for 10 different sulfur analytes investigated ranged from 0.4 to 3.6ng for peak half-widths spanning 4-6s. The response toward ten different sulfur compounds was examined and produced an average reproducibility of 1.7% RSD (n=10) and an average equimolarity value of 1.0±0.1. In contrast to this, a conventional single flame S2* mode comparatively yielded respective values of 6.7% RSD (n=10) and 1.1±0.4. HSO* emission in the mFPD was also found to be relatively much less affected by response quenching due to hydrocarbons compared to a conventional single flame S2* emission mode. Results indicate that this new alternative linear mFPD response mode could be beneficial for sulfur monitoring applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

    Science.gov (United States)

    Amor, Sandra; van der Star, Baukje J; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; Watchorn, Jonathan; Kuhle, Jens; Giovannoni, Gavin; Baker, David; Malaspina, Andrea; Puentes, Fabiola

    2014-09-01

    Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (ptreatment compared with baseline measurements (p=0.001). Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS. © The Author(s) 2014.

  13. Genetic and demographic responses of mosquitofish (Gambusia holbrooki) populations exposed to mercury for multiple generations

    Energy Technology Data Exchange (ETDEWEB)

    Tatara, C.P.; Mulvey, M.; Newman, M.C.

    1999-12-01

    Genetic and demographic responses of mosquitofish were examined after multiple generations of exposure to mercury. Previous studies of acute lethal exposures of mosquitofish to either mercury or arsenic demonstrated a consistent correlation between time to death and genotype at the glucosephosphate isomerase-2 (Gpi-2) locus. A mesocosm study involving mosquitofish populations exposed to mercury for 111 d showed significant female sexual selection and fecundity selection at the Gpi-2 locus. Here the mesocosm study was extended to populations exposed to mercury for several (approx. four) generations. After 2 years, control and mercury-exposed populations met Hardy-Weinberg expectations and showed no evidence of genetic bottlenecks. The mean number of heterozygous loci did not differ significantly between the mercury-exposed and control populations. Significant differences in allele frequencies at the Gpi-2 locus were observed between the mercury-exposed and control populations. Relative to the initial and control allele frequencies, the GPI-2{sup 100} allele frequency was lower, the Gpi-2{sup 66} allele frequency increased, but the Gpi-2{sup 38} allele frequency did not change in mercury-exposed populations. No significant differences were found in standard length, weight, sex ratio, or age class ratio between the control and mercury-exposed populations. Allele frequency changes at the Gpi-2 locus suggest population-level response to chronic mercury exposure. Changes in allele frequency may be useful as indicators of population response to contaminants, provided that the population in question is well understood.

  14. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

    Directory of Open Access Journals (Sweden)

    Scott Cukras

    Full Text Available Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  15. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

    Science.gov (United States)

    Cukras, Scott; Morffy, Nicholas; Ohn, Takbum; Kee, Younghoon

    2014-01-01

    Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  16. Non-invasive dendrochronology of late-medieval objects in Oslo: refinement of a technique and discoveries

    Science.gov (United States)

    Daly, Aoife; Streeton, Noëlle L. W.

    2017-06-01

    A technique for non-invasive dendrochronological analysis of oak was developed for archaeological material, using an industrial CT scanner. Since 2013, this experience has been extended within the scope of the research project `After the Black Death: Painting and Polychrome Sculpture in Norway'. The source material for the project is a collection of late-medieval winged altarpieces, shrines, polychrome sculpture, and fragments from Norwegian churches, which are owned by the Museum of Cultural History, University of Oslo. The majority cannot be sampled, and many are too large to fit into the CT scanner. For these reasons, a combined approach was adopted, utilizing CT scanning where possible, but preceded by an `exposed-wood' imaging technique. Both non-invasive techniques have yielded reliable results, and CT scanning has confirmed the reliability of the imaging technique alone. This paper presents the analytical methods, along with results from two of the 13 objects under investigation. Results for reliable dates and provenances provide new foundations for historical interpretations.

  17. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  18. Time dependent response of low velocity impact induced composite conical shells under multiple delamination

    Science.gov (United States)

    Dey, Sudip; Karmakar, Amit

    2014-02-01

    This paper presents the time dependent response of multiple delaminated angle-ply composite pretwisted conical shells subjected to low velocity normal impact. The finite element formulation is based on Mindlin's theory incorporating rotary inertia and effects of transverse shear deformation. An eight-noded isoparametric plate bending element is employed to satisfy the compatibility of deformation and equilibrium of resultant forces and moments at the delamination crack front. A multipoint constraint algorithm is incorporated which leads to asymmetric stiffness matrices. The modified Hertzian contact law which accounts for permanent indentation is utilized to compute the contact force, and the time dependent equations are solved by Newmark's time integration algorithm. Parametric studies are conducted with respect to triggering parameters like laminate configuration, location of delamination, angle of twist, velocity of impactor, and impactor's displacement for centrally impacted shells.

  19. Magnetospheric Response Associated With Multiple Atmospheric Reflections of Precipitated Electrons in Aurora.

    Science.gov (United States)

    Khazanov, G. V.; Merkin, V. G.; Zesta, E.; Sibeck, D. G.; Grubbs, G. A., II; Chu, M.; Wiltberger, M. J.

    2017-12-01

    The magnetosphere and ionosphere are strongly coupled by precipitating electrons during storm times. Therefore, first principle simulations of precipitating electron fluxes are required to understand storm time variations of ionospheric conductances and related electric fields. As has been discussed by Khazanov et al. [2015 - 2017], the first step in such simulations is initiation of electron precipitation from the Earth's plasma sheet via wave particle interaction processes into both magnetically conjugate points, and the step 2 is the follow up of multiple atmospheric reflections of electron fluxes formed at the boundary between the ionosphere and magnetosphere of two magnetically conjugate points. To demonstrate this effect on the global magnetospheric response the Lyon-Fedder-Mobarry global magnetosphere model coupled with the Rice Convection Model of the inner magnetosphere has been used and run for the geomagnetic storm of 17 March 2013.

  20. Multiple system responses program: Identification of concerns related to a number of specific regulatory issues

    International Nuclear Information System (INIS)

    Murphy, G.A.; Casada, M.L.; Palko, L.E.; Roberts, M.W.

    1989-10-01

    This document describes the activities and results of the Multiple System Responses (MSR) program conducted by the Nuclear Operations Analysis Center (NOAC) at Oak Ridge National Laboratory (ORNL). The objective of the MSR program was to gather and review documentation for several unresolved safety issues and related programs of interest, and from that documentation, describe any additional potential safety concerns. The MSR program provides information that will aid the NRC staff in making an assessment of the relative safety significance of the concerns through the established prioritization process. Judgments were not made regarding the validity of the concerns expressed by others. Rather, the concerns were documented and potential safety issues were developed and defined as specifically as possible. Twenty-one potential safety issues were developed from the documented concerns. Additional information was gathered to support the NRC efforts in reviewing these issues for prioritization. 73 refs., 2 tabs

  1. Gender effects on treatment response to interferon-beta in multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, M; Koch-Henriksen, N; Laursen, B

    2014-01-01

    BACKGROUND: Gender appears to play a role in incidence and disease course of multiple sclerosis (MS). OBJECTIVE: The objective was to determine whether male and female patients with MS respond differently to interferon-beta treatment in terms of reduction in relapse rates. METHODS: We included all....... Patients served as their own controls, and relapse rates were compared between NAb-negative and NAb-positive periods. RESULTS: NAbs significantly abrogated the interferon-beta treatment efficacy in both genders. The all-over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.......28-1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women...

  2. Global temperature response to the major volcanic eruptions in multiple reanalysis data sets

    Directory of Open Access Journals (Sweden)

    M. Fujiwara

    2015-12-01

    Full Text Available The global temperature responses to the eruptions of Mount Agung in 1963, El Chichón in 1982, and Mount Pinatubo in 1991 are investigated using nine currently available reanalysis data sets (JRA-55, MERRA, ERA-Interim, NCEP-CFSR, JRA-25, ERA-40, NCEP-1, NCEP-2, and 20CR. Multiple linear regression is applied to the zonal and monthly mean time series of temperature for two periods, 1979–2009 (for eight reanalysis data sets and 1958–2001 (for four reanalysis data sets, by considering explanatory factors of seasonal harmonics, linear trends, Quasi-Biennial Oscillation, solar cycle, and El Niño Southern Oscillation. The residuals are used to define the volcanic signals for the three eruptions separately, and common and different responses among the older and newer reanalysis data sets are highlighted for each eruption. In response to the Mount Pinatubo eruption, most reanalysis data sets show strong warming signals (up to 2–3 K for 1-year average in the tropical lower stratosphere and weak cooling signals (down to −1 K in the subtropical upper troposphere. For the El Chichón eruption, warming signals in the tropical lower stratosphere are somewhat smaller than those for the Mount Pinatubo eruption. The response to the Mount Agung eruption is asymmetric about the equator with strong warming in the Southern Hemisphere midlatitude upper troposphere to lower stratosphere. Comparison of the results from several different reanalysis data sets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis data sets. The consistencies and differences among different reanalysis data sets provide a measure of the confidence and uncertainty in our current understanding of the volcanic response. The results of this intercomparison study may be useful for validation of climate model responses to volcanic forcing and for assessing proposed

  3. Multiple Sclerosis Patients with Markedly Low Intrathecal Antibody Response in Sri Lanka

    Directory of Open Access Journals (Sweden)

    S. M. K. Gamage

    2018-01-01

    Full Text Available Multiple sclerosis (MS is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response. Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis. Sixty-nine MS patients were recruited to the study adhering to McDonald 2010 criteria. Their clinical presentation, characteristics of central nervous system lesions in magnetic resonance imaging, visual evoked potential (VEP results, oligoclonal bands (OCB, and AQP4 antibody status were studied. Of 69 MS patients, 54%, 6%, and 1% were relapsing remitting, secondary progressive, and primary progressive, respectively, and 39% were patients with clinically isolated syndrome. The commonest clinical presentations were cerebral motor followed by cerebral sensory and optic neuritis. Majority had typical periventricular and infratentorial lesions in MRI. Though not clinically apparent, bilateral delay of P100 wave latency was present in 52%. OCB positivity was 42% and AQP4 antibody was positive in only one patient. In conclusion, this group of Sri Lankan MS patients shares most of the clinical and radiological features of Caucasian MS patients. However, the OCB positivity is lower in this group, when compared to the Caucasian MS populations.

  4. Analysis of Brassica oleracea early stage abiotic stress responses reveals tolerance in multiple crop types and for multiple sources of stress.

    Science.gov (United States)

    Beacham, Andrew M; Hand, Paul; Pink, David Ac; Monaghan, James M

    2017-12-01

    Brassica oleracea includes a number of important crop types such as cabbage, cauliflower, broccoli and kale. Current climate conditions and weather patterns are causing significant losses in these crops, meaning that new cultivars with improved tolerance of one or more abiotic stress types must be sought. In this study, genetically fixed B. oleracea lines belonging to a Diversity Fixed Foundation Set (DFFS) were assayed for their response to seedling stage-imposed drought, flood, salinity, heat and cold stress. Significant (P ≤ 0.05) variation in stress tolerance response was found for each stress, for each of four measured variables (relative fresh weight, relative dry weight, relative leaf number and relative plant height). Lines tolerant to multiple stresses were found to belong to several different crop types. There was no overall correlation between the responses to the different stresses. Abiotic stress tolerance was identified in multiple B. oleracea crop types, with some lines exhibiting resistance to multiple stresses. For each stress, no one crop type appeared significantly more or less tolerant than others. The results are promising for the development of more environmentally robust lines of different B. oleracea crops by identifying tolerant material and highlighting the relationship between responses to different stresses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  5. Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions.

    Science.gov (United States)

    Ammann, Claudia; Lindquist, Martin A; Celnik, Pablo A

    It is well known that transcranial direct current stimulation (tDCS) is capable of modulating corticomotor excitability. However, a source of growing concern has been the observed inter- and intra-individual variability of tDCS-responses. Recent studies have assessed whether individuals respond in a predictable manner across repeated sessions of anodal tDCS (atDCS). The findings of these investigations have been inconsistent, and their methods have some limitations (i.e. lack of sham condition or testing only one tDCS intensity). To study inter- and intra-individual variability of atDCS effects at two different intensities on primary motor cortex (M1) excitability. Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in three separate conditions (2 mA, 1 mA, sham) each repeated three times separated by 48 h. Motor evoked potentials were recorded before and after stimulation (up to 30min). Time of testing was maintained consistent within participants. To estimate the reliability of tDCS effects across sessions, we calculated the Intra-class Correlation Coefficient (ICC). AtDCS at 2 mA, but not 1 mA, significantly increased cortical excitability at the group level in all sessions. The overall ICC revealed fair to high reliability of tDCS effects for multiple sessions. Given that the distribution of responses showed important variability in the sham condition, we established a Sham Variability-Based Threshold to classify responses and to track individual changes across sessions. Using this threshold an intra-individual consistent response pattern was then observed only for the 2 mA condition. 2 mA anodal tDCS results in consistent intra- and inter-individual increases of M1 excitability. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Leaf movement, photosynthesis and resource use efficiency responses to multiple environmental stress in Glycine max (soybean)

    International Nuclear Information System (INIS)

    Rosa, L.M.G.

    1993-01-01

    Increases in the concentration of greenhouse gases in the atmosphere, may cause a significant increase in temperature, with implications for general wind patterns and precipitation. Reductions in stratospheric ozone will result in increased levels of UV-B reaching earth's surface. During their lifetime plants must deal with a variety of co-occurring environmental stresses. Accordingly, studies into plant responses to multiple environmental factors is important to our understanding of limits to their growth, productivity, and distribution. Heliotropic leaf movements are a generalized plant response to environmental stresses, and the pattern of these movements can be altered by resource availability (e.g., water, and nitrogen). Previous greenhouse and field studies have demonstrated damaging effects of UV-B radiation in crop species, including soybean. Documented in this paper are Leaf movement and gas exchange responses of four soybean cultivars with different sensitivity to UV-B radiation to enhanced levels of UV-B, and modifications of these responses caused by water stress and nitrogen fertilization. UV-B radiation had no effect on the patterns of leaf orientation in soybean; however, a ranking of the cultivars based on midday leaf angles was the same as the ranking of these cultivars based on their sensitivity to UV-B radiation. Water and nitrogen altered the leaf movement patterns of soybeans. Gas exchange parameters in all four cultivars responded in a similar fashion to changes in leaf water potential. Reductions in water availability resulted in lower discrimination. Nitrogen fertilization in cv Forrest, also resulted in lower discrimination, especially under low water regimes, indicating a higher water use efficiency for fertilized plants. UV-B radiation resulted in lower discrimination in the UV-B sensitive CNS cultivar, indicating a stronger stomatal limitation to photosynthesis under increased UV-B levels

  7. Detailed assessment of gene activation levels by multiple hypoxia-responsive elements under various hypoxic conditions.

    Science.gov (United States)

    Takeuchi, Yasuto; Inubushi, Masayuki; Jin, Yong-Nan; Murai, Chika; Tsuji, Atsushi B; Hata, Hironobu; Kitagawa, Yoshimasa; Saga, Tsuneo

    2014-12-01

    HIF-1/HRE pathway is a promising target for the imaging and the treatment of intractable malignancy (HIF-1; hypoxia-inducible factor 1, HRE; hypoxia-responsive element). The purposes of our study are: (1) to assess the gene activation levels resulting from various numbers of HREs under various hypoxic conditions, (2) to evaluate the bidirectional activity of multiple HREs, and (3) to confirm whether multiple HREs can induce gene expression in vivo. Human colon carcinoma HCT116 cells were transiently transfected by the constructs containing a firefly luciferase reporter gene and various numbers (2, 4, 6, 8, 10, and 12) of HREs (nHRE+, nHRE-). The relative luciferase activities were measured under various durations of hypoxia (6, 12, 18, and 24 h), O2 concentrations (1, 2, 4, 8, and 16 %), and various concentrations of deferoxamine mesylate (20, 40, 80, 160, and 320 µg/mL growth medium). The bidirectional gene activation levels by HREs were examined in the constructs (dual-luc-nHREs) containing firefly and Renilla luciferase reporter genes at each side of nHREs. Finally, to test whether the construct containing 12HRE and the NIS reporter gene (12HRE-NIS) can induce gene expression in vivo, SPECT imaging was performed in a mouse xenograft model. (1) gene activation levels by HREs tended to increase with increasing HRE copy number, but a saturation effect was observed in constructs with more than 6 or 8 copies of an HRE, (2) gene activation levels by HREs increased remarkably during 6-12 h of hypoxia, but not beyond 12 h, (3) gene activation levels by HREs decreased with increasing O2 concentrations, but could be detected even under mild hypoxia at 16 % O2, (4) the bidirectionally proportional activity of the HRE was confirmed regardless of the hypoxic severity, and (5) NIS expression driven by 12 tandem copies of an HRE in response to hypoxia could be visualized on in vivo SPECT imaging. The results of this study will help in the understanding and assessment of

  8. Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Hesse, D; Limborg, S

    2012-01-01

    , monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA. Methods: Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25high and CD26high cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS......Background: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. Objective: To study the activation of CD4+ T cells...... (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05–1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers...

  9. [Response and prognosis of patients with multiple myeloma induced by PAD/TAD].

    Science.gov (United States)

    Zeng, Tianmei; He, Haiyan; Shi, Haotian; Xi, Hao; Du, Juan; Zhang, Chunyang; Jiang, Hua; Fu, Weijun; Zhou, Fan; Hou, Jian

    2015-03-17

    To evaluate the impact of cytogenetic grouping and autologous stem cell transplantation on the prognosis of patients with multiple myeloma (MM) induced by PAD (velcade+epirubicin+dexamethasone) and TAD (thalidomide+epirubicin+dexamethasone). A total of 191 patients with a definite diagnosis of MM were enrolled from May 2008 to December 2013 into this prospective study. They were non-randomly induced by PAD (n = 132) or TAD (n = 59) plus autologous stem cell transplantation or chemotherapy. Response and survival rates were also analyzed between two groups. The overall response rates of PAD and TAD groups were 84.4% (108/128) and 69.5% (41/59) (P = 0.011) respectively. The very good partial remission (VGPR) rates were 70.3% (90/128) and 32.2% (19/59) (P TAD. After PAD induction, cytogenetic grouping may further distinguish the prognosis of MM patients. For FISH high-risk patients, their PFS is prolonged by autologous stem cell transplantation.

  10. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

    Science.gov (United States)

    Lahuerta, Juan-Jose; Paiva, Bruno; Vidriales, Maria-Belen; Cordón, Lourdes; Cedena, Maria-Teresa; Puig, Noemi; Martinez-Lopez, Joaquin; Rosiñol, Laura; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Oriol, Albert; Teruel, Ana-Isabel; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Hernandez, Miguel T; Palomera, Luis; Martinez, Rafael; Martin, Alejandro; Alegre, Adrian; De la Rubia, Javier; Orfao, Alberto; Mateos, María-Victoria; Blade, Joan; San-Miguel, Jesus F

    2017-09-01

    Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients

  11. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

    OpenAIRE

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

    1993-01-01

    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene d...

  12. Analysis of the Multiple-Solution Response of a Flexible Rotor Supported on Non-Linear Squeeze Film Dampers

    Science.gov (United States)

    ZHU, C. S.; ROBB, D. A.; EWINS, D. J.

    2002-05-01

    The multiple-solution response of rotors supported on squeeze film dampers is a typical non-linear phenomenon. The behaviour of the multiple-solution response in a flexible rotor supported on two identical squeeze film dampers with centralizing springs is studied by three methods: synchronous circular centred-orbit motion solution, numerical integration method and slow acceleration method using the assumption of a short bearing and cavitated oil film; the differences of computational results obtained by the three different methods are compared in this paper. It is shown that there are three basic forms for the multiple-solution response in the flexible rotor system supported on the squeeze film dampers, which are the resonant, isolated bifurcation and swallowtail bifurcation multiple solutions. In the multiple-solution speed regions, the rotor motion may be subsynchronous, super-subsynchronous, almost-periodic and even chaotic, besides synchronous circular centred, even if the gravity effect is not considered. The assumption of synchronous circular centred-orbit motion for the journal and rotor around the static deflection line can be used only in some special cases; the steady state numerical integration method is very useful, but time consuming. Using the slow acceleration method, not only can the multiple-solution speed regions be detected, but also the non-synchronous response regions.

  13. USE OF MULTIPLE RESPONSE QUESTIONS (MRQS DURING LECTURE SESSIONS AS A TOOL TO ENHANCE LEARNING

    Directory of Open Access Journals (Sweden)

    Rosh

    2015-12-01

    Full Text Available INTRODUCTION Lecture classes are time tested solid method of teaching and have lot of advantages and few disadvantages. The main drawback is its unidirectional monotonous nature and many a time students fail to concentrate and understand especially when the sessions are long, and from the students’ point of view, many are boring too. Lecture sessions are still continued because of its various advantages. There are many methods tried to improve efficacy and effectiveness of lecture sessions including reinforcement, questions and discussions. There are many studies incorporating multiple choice questions (MCQs in lecture sessions for this purpose, with positive results. These sessions evoke creative thinking and enhance learning. For this purpose MCQs are to be prepared with care considering the areas to be covered. In order to make lecture classes more impressive, interesting and effective, we tried introducing a short multiple response session in between, along with some rewards for correct responses in terms of study materials. AIMS AND OBJECTIVES To study the impact of incorporation of MRQs during theory sessions to enhance the efficacy of teaching- learning process MATERIAL AND METHODS Study was conducted in a private medical college in Calicut. We surveyed 169 MBBS students initially with questionnaire covering various aspects of a lecture classes in general. For the next 6 months we incorporated MRQs in routine theory classes. Survey was then conducted again on the same group using same questionnaire and the results were compared. Scores were given according to performance, a maximum of 5 per question. RESULTS After 6 months the data showed substantial improvement in the understanding pattern of students. The average score regarding the usefulness increased from 3.57 to 3.91. After the intervention a substantial number agreed that the sessions have become more interesting, the score changed from 2.99 to 3.87. This also increased the

  14. Response of secondary production and its components to multiple stressors in nematode field populations.

    NARCIS (Netherlands)

    Doroszuk, A.; Brake, te E.; Crespo-Gonzalez, D.; Kammenga, J.E.

    2007-01-01

    Realistic measures of the impact of individual or multiple stressors are important for ecological risk assessment. Although multiple anthropogenic stressors are common in human-dominated environments, knowledge of their influence on functional population parameters such as secondary production (P)

  15. Dendrochronological study of the endangered shrub Vella pseudocytisus subsp. paui (Brassicaceae: implications for its recovery and conservation

    Directory of Open Access Journals (Sweden)

    Génova, Mar

    2013-12-01

    Full Text Available Dendrochronology is useful to determine plant longevity, to provide insights into the structure and dynamics of plant populations and to study the relationships between growth and environmental determinants. The dendrochronology of endangered shrubs is unexplored, although their use represents an opportunity to produce better conservation guidelines. We collected for this study 63 samples from already dead specimens of Vella pseudocytisus subsp. paui (Brassicaceae, an endangered Spanish endemism from three localities. We analyzed the relationship between ring data and plant size to determine the accuracy of using size as a proxy for plant age. We also explored the relationships between ring data and environmental variables to detect growth determinants. This shrub showed a high longevity as older individuals presented nearly 50 growth rings. The relationship between age and size is weak although it could be established based on the logarithmic function of plant biovolume. Significant relationships were found between rainfall and ring widths, showing that water limited annual growth. Finally, age structure characterized differences among populations, highlighting the effects of disturbance and land use. These results provided new opportunities for management within the ongoing recovery plan for the species.La dendrocronología es útil para determinar la longevidad de la planta, proporcionar información sobre la estructura y dinámica de las poblaciones vegetales y estudiar las relaciones entre el crecimiento y las variables ambientales. Hasta ahora no se había hecho uso de la dendrocronología en arbustos en peligro de extinción, aunque su empleo puede mejorar las directrices de conservación. En este estudio se han recolectado 63 especímenes ya muertos de tres localidades de Vella pseudocytisus subsp. paui (Brassicaceae, un endemismo español en peligro de extinción. Se han analizado las relaciones entre los grosores del anillo de

  16. Coaching Ourselves to Perform Multiplicity and Advocacy: A Response to Stephens and Mills

    Science.gov (United States)

    Cahnmann-Taylor, Melisa

    2014-01-01

    Cahnmann-Taylor draws on Boalian Theatre of the Oppressed to offer a practice for literacy teachers and coaches that can open up multiple perspectives and multiple levels of intentions and motivations for a teacher's decision making. She challenges coaches and teachers to engage in artistic examinations of multiplicity to move toward performing…

  17. New camera-based microswitch technology to monitor small head and mouth responses of children with multiple disabilities.

    Science.gov (United States)

    Lancioni, Giulio E; Bellini, Domenico; Oliva, Doretta; Singh, Nirbhay N; O'Reilly, Mark F; Green, Vanessa A; Furniss, Fred

    2014-06-01

    Assessing a new camera-based microswitch technology, which did not require the use of color marks on the participants' face. Two children with extensive multiple disabilities participated. The responses selected for them consisted of small, lateral head movements and mouth closing or opening. The intervention was carried out according to a multiple probe design across responses. The technology involved a computer with a CPU using a 2-GHz clock, a USB video camera with a 16-mm lens, a USB cable connecting the camera and the computer, and a special software program written in ISO C++ language. The new technology was satisfactorily used with both children. Large increases in their responding were observed during the intervention periods (i.e. when the responses were followed by preferred stimulation). The new technology may be an important resource for persons with multiple disabilities and minimal motor behavior.

  18. Recent climate warming forces contrasting growth responses of white spruce at treeline in Alaska through temperature thresholds

    Science.gov (United States)

    Martin Wilmking; Glenn P. Juday; Valerie A. Barber; Harold S.J. Zald

    2004-01-01

    Northern and high-latitude alpine treelines are generally thought to be limited by available warmth. Most studies of tree-growth-climate interaction at treeline as well as climate reconstructions using dendrochronology report positive growth response of treeline trees to warmer temperatures. However, population-wide responses of treeline trees to climate remain largely...

  19. Coding response to a case-mix measurement system based on multiple diagnoses.

    Science.gov (United States)

    Preyra, Colin

    2004-08-01

    To examine the hospital coding response to a payment model using a case-mix measurement system based on multiple diagnoses and the resulting impact on a hospital cost model. Financial, clinical, and supplementary data for all Ontario short stay hospitals from years 1997 to 2002. Disaggregated trends in hospital case-mix growth are examined for five years following the adoption of an inpatient classification system making extensive use of combinations of secondary diagnoses. Hospital case mix is decomposed into base and complexity components. The longitudinal effects of coding variation on a standard hospital payment model are examined in terms of payment accuracy and impact on adjustment factors. Introduction of the refined case-mix system provided incentives for hospitals to increase reporting of secondary diagnoses and resulted in growth in highest complexity cases that were not matched by increased resource use over time. Despite a pronounced coding response on the part of hospitals, the increase in measured complexity and case mix did not reduce the unexplained variation in hospital unit cost nor did it reduce the reliance on the teaching adjustment factor, a potential proxy for case mix. The main implication was changes in the size and distribution of predicted hospital operating costs. Jurisdictions introducing extensive refinements to standard diagnostic related group (DRG)-type payment systems should consider the effects of induced changes to hospital coding practices. Assessing model performance should include analysis of the robustness of classification systems to hospital-level variation in coding practices. Unanticipated coding effects imply that case-mix models hypothesized to perform well ex ante may not meet expectations ex post.

  20. Coding Response to a Case-Mix Measurement System Based on Multiple Diagnoses

    Science.gov (United States)

    Preyra, Colin

    2004-01-01

    Objective To examine the hospital coding response to a payment model using a case-mix measurement system based on multiple diagnoses and the resulting impact on a hospital cost model. Data Sources Financial, clinical, and supplementary data for all Ontario short stay hospitals from years 1997 to 2002. Study Design Disaggregated trends in hospital case-mix growth are examined for five years following the adoption of an inpatient classification system making extensive use of combinations of secondary diagnoses. Hospital case mix is decomposed into base and complexity components. The longitudinal effects of coding variation on a standard hospital payment model are examined in terms of payment accuracy and impact on adjustment factors. Principal Findings Introduction of the refined case-mix system provided incentives for hospitals to increase reporting of secondary diagnoses and resulted in growth in highest complexity cases that were not matched by increased resource use over time. Despite a pronounced coding response on the part of hospitals, the increase in measured complexity and case mix did not reduce the unexplained variation in hospital unit cost nor did it reduce the reliance on the teaching adjustment factor, a potential proxy for case mix. The main implication was changes in the size and distribution of predicted hospital operating costs. Conclusions Jurisdictions introducing extensive refinements to standard diagnostic related group (DRG)-type payment systems should consider the effects of induced changes to hospital coding practices. Assessing model performance should include analysis of the robustness of classification systems to hospital-level variation in coding practices. Unanticipated coding effects imply that case-mix models hypothesized to perform well ex ante may not meet expectations ex post. PMID:15230940

  1. The response of mouse skin to multiple small doses of radiation

    International Nuclear Information System (INIS)

    Denekamp, J.; Harris, S.R.

    1975-01-01

    The response of mouse skin has been tested by irradiating the foot of albino mice and scoring erythema and desquamation during the following month. Multiple small doses of 150, 250 and 350 rad have been given 'daily', and the test dose necessary to achieve a given reaction has been determined one day after the last small fraction. This test dose has been compared with the single dose necessary to produce the same reaction level in previously untreated mice, in order to determine the ratio of the slopes of the dose-response curve at low and high doses: Slope ratio = (single dose - test dose)/total fractionated priming dose. In three separate experiments the slope ratio decreased as the dose per fraction was reduced from 350 to 150 rad. This conflicts with the data of Dutreix et al, who found a constant slope ratio over this dose range. The present data are compared with those obtained by Denekamp using 4, 9 and 14 fractions of 300 rad and by Douglas et al, using the same experimental technique, over the dose range 45 to 200 rad/fraction. In addition, the results from multifraction experiments in which equal dose increments were administered until the requisite skin reaction was achieved are also analysed in terms of their slope ratio (Fowler et al. Douglas et al). When all these results are plotted it is impossible to be sure whether the slope ratio is decreasing over the range 300 to 45 rad per fraction, although it seems likely. Most of the values at low doses lie in the range 0.15 to 0.25, indicating that at low doses the radiation is only 15 to 25% as effective per rad in causing cell death as at higher doses. (author)

  2. Nonlinear dynamic response of whole pool multiple spent fuel racks subject to three-dimensional excitations

    International Nuclear Information System (INIS)

    Zhao, Y.; Wilson, P.R.; Stevenson, J.D.

    1995-01-01

    The seismic evaluation of submerged free standing spent fuel storage racks is more complicated than most other nuclear structural systems. When subjected to three dimensional (3-D) floor seismic excitations the dynamic responses of racks in a pool are hydro dynamically coupled with each other, with the fuel assemblies water in gaps. The motion behavior of the racks is significantly different from that observed using a 3D single rack mode. Few seismic analyses using 3-D whole pool multiple rack models are available in the literature. I this paper an analysis was performed for twelve racks using potential theory for the fluid-structure interaction, and using a 3-D whole pool multi-rack finite element model developed herein. The analysis includes the potential nonlinear dynamic behavior of the impact of fuel-rack, rack-rack and rack-pool wall, the tilting or uplift and the frictional sliding of rack supports, and the impact of the rack supports to the pool floor. (author). 12 refs., 7 figs., 1 tab

  3. mEBT: multiple-matching Evidence-based Translator of Murine Genomic Responses for Human Immunity Studies.

    Science.gov (United States)

    Tae, Donghyun; Seok, Junhee

    2018-05-29

    In this paper, we introduce multiple-matching Evidence-based Translator (mEBT) to discover genomic responses from murine expression data for human immune studies, which are significant in the given condition of mice and likely have similar responses in the corresponding condition of human. mEBT is evaluated over multiple data sets and shows improved inter-species agreement. mEBT is expected to be useful for research groups who use murine models to study human immunity. http://cdal.korea.ac.kr/mebt/. jseok14@korea.ac.kr. Supplementary data are available at Bioinformatics online.

  4. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

    International Nuclear Information System (INIS)

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-01-01

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues

  5. Response to dexamethasone is glucose-sensitive in multiple myeloma cell lines

    Directory of Open Access Journals (Sweden)

    Turturro Francesco

    2011-09-01

    Full Text Available Abstract Background Hyperglycemia is among the major side effects of dexamethasone (DEX. Glucose or glucocorticoid (GC regulates the expression of thioredoxin-interacting protein (TXNIP that controls the production of reactive oxygen species (ROS through the modulation of thioredoxin (TRX activity. Methods Multiple myeloma (MM cells were grown in 5 or 20 mM/L glucose with or without 25 μM DEX. Semiquantitative reverse transcription-PCR (RT-PCR was used to assess TXNIP RNA expression in response to glucose and DEX. ROS were detected by 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA. TRX activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorbtion and used to calculate the DEX IC50 in 20 mM/L glucose using the Chou's dose effect equation. Results TXNIP RNA level responded to glucose or DEX with the same order of magnitude ARH77 > NCIH929 > U266B1 in these cells. MC/CAR cells were resistant to the regulation. ROS level increased concurrently with reduced TRX activity. Surprisingly glucose increased TRX activity in MC/CAR cells keeping ROS level low. DEX and glucose were lacking the expected additive effect on TXNIP RNA regulation when used concurrently in sensitive cells. ROS level was significantly lower when DEX was used in conditions of hyperglycemia in ARH77/NCIH9292 cells but not in U266B1 cells. Dex-IC50 increased 10-fold when the dose response effect of DEX was evaluated with glucose in ARH && and MC/Car cells Conclusions Our study shows for the first time that glucose or DEX regulates important components of ROS production through TXNIP modulation or direct interference with TRX activity in MM cells. We show that glucose modulates the activity of DEX through ROS regualtion in MM cells. A better understanding of these pathways may help in improving the efficacy and reducing the toxicity of DEX, a drug still highly used in the treatment of

  6. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

    Science.gov (United States)

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-02-24

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

  7. Community Response to Multiple Sound Sources: Integrating Acoustic and Contextual Approaches in the Analysis

    Directory of Open Access Journals (Sweden)

    Peter Lercher

    2017-06-01

    Full Text Available Sufficient data refer to the relevant prevalence of sound exposure by mixed traffic sources in many nations. Furthermore, consideration of the potential effects of combined sound exposure is required in legal procedures such as environmental health impact assessments. Nevertheless, current practice still uses single exposure response functions. It is silently assumed that those standard exposure-response curves accommodate also for mixed exposures—although some evidence from experimental and field studies casts doubt on this practice. The ALPNAP-study population (N = 1641 shows sufficient subgroups with combinations of rail-highway, highway-main road and rail-highway-main road sound exposure. In this paper we apply a few suggested approaches of the literature to investigate exposure-response curves and its major determinants in the case of exposure to multiple traffic sources. Highly/moderate annoyance and full scale mean annoyance served as outcome. The results show several limitations of the current approaches. Even facing the inherent methodological limitations (energy equivalent summation of sound, rating of overall annoyance the consideration of main contextual factors jointly occurring with the sources (such as vibration, air pollution or coping activities and judgments of the wider area soundscape increases the variance explanation from up to 8% (bivariate, up to 15% (base adjustments up to 55% (full contextual model. The added predictors vary significantly, depending on the source combination. (e.g., significant vibration effects with main road/railway, not highway. Although no significant interactions were found, the observed additive effects are of public health importance. Especially in the case of a three source exposure situation the overall annoyance is already high at lower levels and the contribution of the acoustic indicators is small compared with the non-acoustic and contextual predictors. Noise mapping needs to go down to

  8. Multiple linear B-cell epitopes of classical swine fever virus glycoprotein E2 expressed in E.coli as multiple epitope vaccine induces a protective immune response

    Directory of Open Access Journals (Sweden)

    Wei Jian-Chao

    2011-07-01

    Full Text Available Abstract Classical swine fever is a highly contagious disease of swine caused by classical swine fever virus, an OIE list A pathogen. Epitope-based vaccines is one of the current focuses in the development of new vaccines against classical swine fever virus (CSFV. Two B-cell linear epitopes rE2-ba from the E2 glycoprotein of CSFV, rE2-a (CFRREKPFPHRMDCVTTTVENED, aa844-865 and rE2-b (CKEDYRYAISSTNEIGLLGAGGLT, aa693-716, were constructed and heterologously expressed in Escherichia coli as multiple epitope vaccine. Fifteen 6-week-old specified-pathogen-free (SPF piglets were intramuscularly immunized with epitopes twice at 2-week intervals. All epitope-vaccinated pigs could mount an anamnestic response after booster vaccination with neutralizing antibody titers ranging from 1:16 to 1:256. At this time, the pigs were subjected to challenge infection with a dose of 1 × 106 TCID50 virulent CSFV strain. After challenge infection, all of the rE2-ba-immunized pigs were alive and without symptoms or signs of CSF. In contrast, the control pigs continuously exhibited signs of CSF and had to be euthanized because of severe clinical symptoms at 5 days post challenge infection. The data from in vivo experiments shown that the multiple epitope rE2-ba shown a greater protection (similar to that of HCLV vaccine than that of mono-epitope peptide(rE2-a or rE2-b. Therefore, The results demonstrated that this multiple epitope peptide expressed in a prokaryotic system can be used as a potential DIVA (differentiating infected from vaccinated animals vaccine. The E.coli-expressed E2 multiple B-cell linear epitopes retains correct immunogenicity and is able to induce a protective immune response against CSFV infection.

  9. Role of inflammation gene polymorphisms on pain and response to radiotherapy in multiple myeloma patients with painful bone destructions

    OpenAIRE

    Rudžianskienė, Milda; Inčiūra, Arturas; Gerbutavičius, Rolandas; Dambrauskienė, Rūta; Rudžianskas, Viktoras; Juozaitytė, Elona

    2016-01-01

    Background: Previous researches have demonstrated, that the severity of pain perception and it’s response to analgesia is highly dependent on gene polymorphism encoding for cytokines. We evaluated 12 single nucleotide polymorphisms (SNP) in 6 genes encoding for cytokines in multiple myeloma patients (n = 81) and assessed their influence on pain severity and response to palliative radiotherapy. Methods: Pain intensity was assessed by Visual Analogue Scale. The total dose of opioids was convert...

  10. Reducing the number of options on multiple-choice questions: response time, psychometrics and standard setting.

    Science.gov (United States)

    Schneid, Stephen D; Armour, Chris; Park, Yoon Soo; Yudkowsky, Rachel; Bordage, Georges

    2014-10-01

    Despite significant evidence supporting the use of three-option multiple-choice questions (MCQs), these are rarely used in written examinations for health professions students. The purpose of this study was to examine the effects of reducing four- and five-option MCQs to three-option MCQs on response times, psychometric characteristics, and absolute standard setting judgements in a pharmacology examination administered to health professions students. We administered two versions of a computerised examination containing 98 MCQs to 38 Year 2 medical students and 39 Year 3 pharmacy students. Four- and five-option MCQs were converted into three-option MCQs to create two versions of the examination. Differences in response time, item difficulty and discrimination, and reliability were evaluated. Medical and pharmacy faculty judges provided three-level Angoff (TLA) ratings for all MCQs for both versions of the examination to allow the assessment of differences in cut scores. Students answered three-option MCQs an average of 5 seconds faster than they answered four- and five-option MCQs (36 seconds versus 41 seconds; p = 0.008). There were no significant differences in item difficulty and discrimination, or test reliability. Overall, the cut scores generated for three-option MCQs using the TLA ratings were 8 percentage points higher (p = 0.04). The use of three-option MCQs in a health professions examination resulted in a time saving equivalent to the completion of 16% more MCQs per 1-hour testing period, which may increase content validity and test score reliability, and minimise construct under-representation. The higher cut scores may result in higher failure rates if an absolute standard setting method, such as the TLA method, is used. The results from this study provide a cautious indication to health professions educators that using three-option MCQs does not threaten validity and may strengthen it by allowing additional MCQs to be tested in a fixed amount

  11. Sympathetic skin response in multiple sclerosis: a meta-analysis of case-control studies.

    Science.gov (United States)

    Margaritella, Nicolò; Mendozzi, Laura; Garegnani, Massimo; Gilardi, Elisabetta; Nemni, Raffaello; Pugnetti, Luigi

    2018-01-01

    The usefulness of sympathetic skin responses (SSR) in multiple sclerosis (MS) has been advocated by several studies in the last 20 years; however, due to a great heterogeneity of findings, a comprehensive meta-analysis of case-control studies is in order to pinpoint consistencies and investigate the causes of discrepancies. We searched MEDLINE, EMBASE and Cochrane databases for case-control studies comparing SSR absence frequency and latency between patients with MS and healthy controls. Thirteen eligible studies including 415 MS patients and 331 healthy controls were identified. The pooled analysis showed that SSR can be always obtained in healthy controls while 34% of patients had absent SSRs in at least one limb (95% CI 22-47%; p studies (I 2  = 90.3%). Patients' age explained 22% of the overall variability and positive correlations were found with Expanded Disability Status Scale and disease duration. The pooled mean difference of SSR latency showed a significant increase in patients on both upper (193 ms; 95% CI 120-270 ms) and lower (350 ms; 95% CI 190-510 ms) extremities. We tested the discriminatory value of SSR latency thresholds defined as the 95% confidence interval (CI) upper bound of the healthy controls, and validated the results on a new dataset. The lower limb threshold of 1.964 s produces the best results in terms of sensitivity 0.86, specificity 0.67, positive predicted value 0.75 and negative predicted value 0.80. Despite a considerable heterogeneity of findings, there is evidence that SSR is a useful tool in MS.

  12. Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis.

    Science.gov (United States)

    Novakovic, A M; Krekels, E H J; Munafo, A; Ueckert, S; Karlsson, M O

    2017-01-01

    In this study, we report the development of the first item response theory (IRT) model within a pharmacometrics framework to characterize the disease progression in multiple sclerosis (MS), as measured by Expanded Disability Status Score (EDSS). Data were collected quarterly from a 96-week phase III clinical study by a blinder rater, involving 104,206 item-level observations from 1319 patients with relapsing-remitting MS (RRMS), treated with placebo or cladribine. Observed scores for each EDSS item were modeled describing the probability of a given score as a function of patients' (unobserved) disability using a logistic model. Longitudinal data from placebo arms were used to describe the disease progression over time, and the model was then extended to cladribine arms to characterize the drug effect. Sensitivity with respect to patient disability was calculated as Fisher information for each EDSS item, which were ranked according to the amount of information they contained. The IRT model was able to describe baseline and longitudinal EDSS data on item and total level. The final model suggested that cladribine treatment significantly slows disease-progression rate, with a 20% decrease in disease-progression rate compared to placebo, irrespective of exposure, and effects an additional exposure-dependent reduction in disability progression. Four out of eight items contained 80% of information for the given range of disabilities. This study has illustrated that IRT modeling is specifically suitable for accurate quantification of disease status and description and prediction of disease progression in phase 3 studies on RRMS, by integrating EDSS item-level data in a meaningful manner.

  13. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls.

    Science.gov (United States)

    Bhargava, Pavan; Steele, Sonya U; Waubant, Emmanuelle; Revirajan, Nisha R; Marcus, Jacqueline; Dembele, Marieme; Cassard, Sandra D; Hollis, Bruce W; Crainiceanu, Ciprian; Mowry, Ellen M

    2016-05-01

    Vitamin D insufficiency is a risk factor for multiple sclerosis (MS), and patients do not always show the expected response to vitamin D supplementation. We aimed to determine if vitamin D supplementation leads to a similar increase in serum 25-hydroxyvitamin-D (25(OH)D) levels in patients with MS and healthy controls (HCs). Participants in this open-label study were female, white, aged 18-60 years, had 25(OH)D levels ⩽ 75 nmol/l at screening, and had relapsing-remitting MS (RRMS) or were HCs. Participants received 5000 IU/day of vitamin D3 for 90 days. Utilizing generalized estimating equations we examined the relationship between the primary outcome (serum 25(OH)D level) and the primary (MS versus HC status) and secondary predictors. For this study 27 MS patients and 30 HCs were enrolled. There was no significant difference in baseline 25(OH)D level or demographics except for higher body mass index (BMI) in the MS group (25.3 vs. 23.6 kg/m(2), p=0.035). In total, 24 MS subjects and 29 HCs completed the study. In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l (95%CI: 4.2, 29.2, p=0.008) lower increase in 25(OH)D levels compared with HCs. Patients with MS had a lower increase in 25(OH)D levels with supplementation, even after accounting for putative confounders. © The Author(s), 2015.

  14. Camera-based microswitch technology to monitor mouth, eyebrow, and eyelid responses of children with profound multiple disabilities

    NARCIS (Netherlands)

    Lancioni, G.E.; Bellini, D.; Oliva, D.; Singh, N.N.; O'Reilly, M.F.; Sigafoos, J.; Lang, R.B.; Didden, H.C.M.

    2011-01-01

    A camera-based microswitch technology was recently used to successfully monitor small eyelid and mouth responses of two adults with profound multiple disabilities (Lancioni et al., Res Dev Disab 31:1509-1514, 2010a). This technology, in contrast with the traditional optic microswitches used for

  15. Using a Fine-Grained Multiple-Choice Response Format in Educational Drill-and-Practice Video Games

    Science.gov (United States)

    Beserra, Vagner; Nussbaum, Miguel; Grass, Antonio

    2017-01-01

    When using educational video games, particularly drill-and-practice video games, there are several ways of providing an answer to a quiz. The majority of paper-based options can be classified as being either multiple-choice or constructed-response. Therefore, in the process of creating an educational drill-and-practice video game, one fundamental…

  16. Modeling hydrologic responses to deforestation/forestation and climate change at multiple scales in the Southern US and China

    Science.gov (United States)

    Ge Sun; Steven McNulty; Jianbiao Lu; James Vose; Devendra Amayta; Guoyi Zhou; Zhiqiang Zhang

    2006-01-01

    Watershed management and restoration practices require a clear understanding of the basic eco-hydrologic processes and ecosystem responses to disturbances at multiple scales (Bruijnzeel, 2004; Scott et al., 2005). Worldwide century-long forest hydrologic research has documented that deforestation and forestation (i.e. reforestation and afforestation) can have variable...

  17. Reconstructing mass balance of Garabashi Glacier (1800–2005 using dendrochronological data

    Directory of Open Access Journals (Sweden)

    E. A. Dolgova

    2013-01-01

    Full Text Available The exploration whether tree-ring data can be effectually applied for the mass balance reconstruction in Caucasus was the main goal of this research. Tree-ring width and maximum density chronologies of pine (Pinus sylvestris L. at seven high-elevation sites in Northern Caucasus were explored for this purpose. As well as in other places of the temperate zone tree- ring width has complex climate signal controlled both temperature and precipitation. Instrumental mass balance records of Garabashi Gglacier started at 1983s. It is well known that Caucasus glaciers intensively retreat in the last decades and according to instrumental data mass balance variations are mostly controlled by the ablation, i.e. summer temperature variations. Maximum density chronology has statistically significant correlation with mass balance due to summer temperature sensitivity and great input of ablation to total mass balance variations. To include in our reconstruction different climatically sensitive parameters, stepwise multiple regression model was used. The strongest relation (r = 0.88; r2 = 0.78; p < 0.05 between two ring-width and one maximum density chronologies was identified. Cross-validation test (r = 0.79; r2 = 0.62; p < 0.05 confirmed model adequacy and it allowed to reconstruct Garabashi Glacier mass balance for 1800–2005ss. Reconstructed and instrumental mass balance values coincide well except the most recent period in 2000s, when the reconstructed mass balance slightly underestimated the real values. However even in this period it remained negative as well as the instrumental records. The bias can be explained by the weak sensitivity of the chronologies to winter precipitation (i.e. accumulation. The tree-ring based mass balance reconstruction was compared with one based on meteorological data (since 1905s. Both reconstructions have good interannual agreement (r = 0.53; p < 0.05 particularly for the period between 1975 and 2005. According to the

  18. RECONSTRUCTION AND PREDICTION OF WATER BALANCE COMPONENTS FROM DENDROCHRONOLOGICAL DATA FOR THE NARYN RIVER BASIN (KYRGYZSTAN

    Directory of Open Access Journals (Sweden)

    V. G. Konovalov

    2012-01-01

    Full Text Available Suggested new method for reconstruction of runoff includes: 1. Search informative points based weather observations for dependence runoff = f(climate index. Climate index consists of normalized anomalies of annual precipitation and air temperature, together with water vapor pressure and total cloud amount in the June–September. 2. The selection of sites that represent local relationship between the index of climate and tree rings. 3. Getting the multivariate linear regression equation between the runoff V and tree rings D. Basic climatic period 1961–1990 is used as a calibration interval of time. Verification of the equations for 1940–1960 identified the need to use other arguments in addition to the width of tree rings. For this purpose, two climate index: PDSI and SPEI were tested. It is established that the empirical formulae V = f(D, PDSI and V = f(D, SPEI are suitable for assessing the annual flow of the Naryn in 1901–2006. In the report is described a process of  reconstruction of flow for the years 1700–2005 based on the data of the width of the tree rings, and taking into account the temporal variability of parameters of regression equations.Chronologies of the width and density of tree rings in the thirty-two tree ring sites were used to reconstruct long-term series of average summer air temperature Ts at meteorological stations of the Pamir and Tien Shan. The calibration interval of time was 1961–1990 to find equations Ts = f(D of third-order multiple regression, and independent control of their quality, done in 1932–1960. Combined correlation coefficient in 10 cases out of 15 was more than 0.80, a relative error of calculation Ts in 19611990 ranged from 0.13 to 4.73%, and in 1932–1960 from 0.23 to 8.10%. Duration of the reconstructed series Ts ranged from 100 to 278 years. Positive results were received for predicting a common and glacial runoff of Naryn river, a long-term range of density of tree rings. 

  19. Using a Classroom Response System to Improve Multiple-Choice Performance in AP[R] Physics

    Science.gov (United States)

    Bertrand, Peggy

    2009-01-01

    Participation in rigorous high school courses such as Advanced Placement (AP[R]) Physics increases the likelihood of college success, especially for students who are traditionally underserved. Tackling difficult multiple-choice exams should be part of any AP program because well-constructed multiple-choice questions, such as those on AP exams and…

  20. Multiple stress response of lowland stream benthic macroinvertebrates is dependent on habitat type

    DEFF Research Database (Denmark)

    Graeber, Daniel; Jensen, Tinna M.; Rasmussen, Jes

    2017-01-01

    Worldwide, lowland stream ecosystems are exposed to multiple anthropogenic stress due to the combination of water scarcity, eutrophication and fine sedimentation. The understanding of the effects of such multiple stress on stream benthic macroinvertebrates has been growing in the recent years...

  1. Dendrochronology as a source of data for landslide activity maps – an example from Beskid Żywiecki Mountains (Western Carpathians, Poland

    Directory of Open Access Journals (Sweden)

    Łuszczyńska Katarzyna

    2017-09-01

    Full Text Available We applied dendrochronological methods for dating landslide activity in the study area (3.75 km2, on the slopes of Sucha Mountain (1040 m a.s.l., in the Beskid Żywiecki Mountains, in the Western Carpathians. 46 sampling sites were distributed throughout the study area. At each site we sampled 1-3 coniferous trees: Norway spruces (Picea abies Karst. and/or silver firs (Abies alba Mill.. From each tree 2 cores were sampled: one from the upslope and the other from the downslope side of the stem. Based on tree-ring widths measured for opposite sides of stems we have calculated eccentricity index values and dated past landslide events. Mean frequency of landslides was obtained for each sampling site. Finally, the data was interpolated into a map of landslide activity. Inverse Distance Weighting (IDW interpolation has been applied. For most of the study area we found medium (19 sites and low (23 sites levels of landslide activity. The highest level of activity was recorded for the largest landslide slope and for the one small landslide. The study conducted on Sucha Mountain has shown that dendrochronology can be an effective method for analysing landslide activity and may be useful in further studies, including those for landslide hazard and risk assessments.

  2. Comparison of Cottonwood Dendrochronology and Optically Stimulated Luminescence Geochronometers Along a High Plains Meandering River, Powder River, Montana, USA

    Science.gov (United States)

    Hasse, T. R.; Schook, D. M.

    2017-12-01

    significant inherited ages due to partial bleaching during sediment transport in this high plains river with high suspended sediment loads. The dendrochronology of the adjacent cottonwood trees then offers an independent measurement of the inherited age of the OSL samples.

  3. Multiple linear regression to estimate time-frequency electrophysiological responses in single trials.

    Science.gov (United States)

    Hu, L; Zhang, Z G; Mouraux, A; Iannetti, G D

    2015-05-01

    Transient sensory, motor or cognitive event elicit not only phase-locked event-related potentials (ERPs) in the ongoing electroencephalogram (EEG), but also induce non-phase-locked modulations of ongoing EEG oscillations. These modulations can be detected when single-trial waveforms are analysed in the time-frequency domain, and consist in stimulus-induced decreases (event-related desynchronization, ERD) or increases (event-related synchronization, ERS) of synchrony in the activity of the underlying neuronal populations. ERD and ERS reflect changes in the parameters that control oscillations in neuronal networks and, depending on the frequency at which they occur, represent neuronal mechanisms involved in cortical activation, inhibition and binding. ERD and ERS are commonly estimated by averaging the time-frequency decomposition of single trials. However, their trial-to-trial variability that can reflect physiologically-important information is lost by across-trial averaging. Here, we aim to (1) develop novel approaches to explore single-trial parameters (including latency, frequency and magnitude) of ERP/ERD/ERS; (2) disclose the relationship between estimated single-trial parameters and other experimental factors (e.g., perceived intensity). We found that (1) stimulus-elicited ERP/ERD/ERS can be correctly separated using principal component analysis (PCA) decomposition with Varimax rotation on the single-trial time-frequency distributions; (2) time-frequency multiple linear regression with dispersion term (TF-MLRd) enhances the signal-to-noise ratio of ERP/ERD/ERS in single trials, and provides an unbiased estimation of their latency, frequency, and magnitude at single-trial level; (3) these estimates can be meaningfully correlated with each other and with other experimental factors at single-trial level (e.g., perceived stimulus intensity and ERP magnitude). The methods described in this article allow exploring fully non-phase-locked stimulus-induced cortical

  4. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

    Science.gov (United States)

    Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

    2012-08-07

    The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

  5. Responsive Neurostimulation System (RNS in setting of cranioplasty and history of multiple craniotomies

    Directory of Open Access Journals (Sweden)

    Jason Ledesma

    2016-09-01

    Conclusion: The case illustrates a possible limitation of SEEG placement, particularly in patients with a history of cranioplasty and multiple prior craniotomies. We also describe the first placement of an RNS generator and system in the setting of prior cranioplasty.

  6. Predicting multi-level drug response with gene expression profile in multiple myeloma using hierarchical ordinal regression.

    Science.gov (United States)

    Zhang, Xinyan; Li, Bingzong; Han, Huiying; Song, Sha; Xu, Hongxia; Hong, Yating; Yi, Nengjun; Zhuang, Wenzhuo

    2018-05-10

    Multiple myeloma (MM), like other cancers, is caused by the accumulation of genetic abnormalities. Heterogeneity exists in the patients' response to treatments, for example, bortezomib. This urges efforts to identify biomarkers from numerous molecular features and build predictive models for identifying patients that can benefit from a certain treatment scheme. However, previous studies treated the multi-level ordinal drug response as a binary response where only responsive and non-responsive groups are considered. It is desirable to directly analyze the multi-level drug response, rather than combining the response to two groups. In this study, we present a novel method to identify significantly associated biomarkers and then develop ordinal genomic classifier using the hierarchical ordinal logistic model. The proposed hierarchical ordinal logistic model employs the heavy-tailed Cauchy prior on the coefficients and is fitted by an efficient quasi-Newton algorithm. We apply our hierarchical ordinal regression approach to analyze two publicly available datasets for MM with five-level drug response and numerous gene expression measures. Our results show that our method is able to identify genes associated with the multi-level drug response and to generate powerful predictive models for predicting the multi-level response. The proposed method allows us to jointly fit numerous correlated predictors and thus build efficient models for predicting the multi-level drug response. The predictive model for the multi-level drug response can be more informative than the previous approaches. Thus, the proposed approach provides a powerful tool for predicting multi-level drug response and has important impact on cancer studies.

  7. Existence, Multiplicity, and Stability of Positive Solutions of a Predator-Prey Model with Dinosaur Functional Response

    Directory of Open Access Journals (Sweden)

    Xiaozhou Feng

    2017-01-01

    Full Text Available We investigate the property of positive solutions of a predator-prey model with Dinosaur functional response under Dirichlet boundary conditions. Firstly, using the comparison principle and fixed point index theory, the sufficient conditions and necessary conditions on coexistence of positive solutions of a predator-prey model with Dinosaur functional response are established. Secondly, by virtue of bifurcation theory, perturbation theory of eigenvalues, and the fixed point index theory, we establish the bifurcation of positive solutions of the model and obtain the stability and multiplicity of the positive solution under certain conditions. Furthermore, the local uniqueness result is studied when b and d are small enough. Finally, we investigate the multiplicity, uniqueness, and stability of positive solutions when k>0 is sufficiently large.

  8. Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

    Science.gov (United States)

    Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

    2015-01-01

    We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

  9. Evaluation of the serum free light chain (sFLC) analysis in prediction of response in symptomatic multiple myeloma patients

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T; Nielsen, Lars C

    2014-01-01

    BACKGROUND: Observational data from clinical studies indicate that the goal of first-line therapy in newly diagnosed patients with symptomatic multiple myeloma (MM) should be very good partial response (VGPR) or better, preferably before high-dose treatment. We evaluated the value of early...... patients with no response to treatment. The mean per cent reduction in iFLC 3 d after start of treatment was 52.3% and 23.6% (P = 0.021) in patients achieving ≥VGPR and PR, respectively. The mean per cent reduction in M-protein in patients achieving ≥VGPR and PR was not significantly different in the 6-wk...

  10. New hybrid multivariate analysis approach to optimize multiple response surfaces considering correlations in both inputs and outputs

    OpenAIRE

    Hejazi, Taha Hossein; Amirkabir University of Technology - Iran; Seyyed-Esfahani, Mirmehdi; Amirkabir University of Technology - Iran; Ramezani, Majid; Amirkabir University of Technology - Iran

    2014-01-01

    Quality control in industrial and service systems requires the correct setting of input factors by which the outputs result at minimum cost with desirable characteristics. There are often more than one input and output in such systems. Response surface methodology in its multiple variable forms is one of the most applied methods to estimate and improve the quality characteristics of products with respect to control factors. When there is some degree of correlation among the variables, the exi...

  11. Multiplicative Genotype-Environment Interaction as a Cause of Reversed Response to Directional Selection

    OpenAIRE

    Gimelfarb, A.

    1986-01-01

    In experiments with directional selection on a quantitative character a "reversed response" to selection is occasionally observed, when selection of individuals for a higher (lower) value of the character results in a lower (higher) value of the character among their offspring. A sudden change in environments or random drift is often assumed to be responsible for this. It is demonstrated in this paper that these two causes cannot account for the reversed response at least in some of the exper...

  12. Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

    Science.gov (United States)

    Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

    2017-10-01

    The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Immune responses of B. malayi thioredoxin (TRX) and venom allergen homologue (VAH) chimeric multiple antigen for lymphatic filariasis.

    Science.gov (United States)

    Anugraha, Gandhirajan; Jeyaprita, Parasurama Jawaharlal; Madhumathi, Jayaprakasam; Sheeba, Tamilvanan; Kaliraj, Perumal

    2013-12-01

    Although multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.

  14. Patient-reported questionnaires in MS rehabilitation: responsiveness and minimal important difference of the multiple sclerosis questionnaire for physiotherapists (MSQPT).

    Science.gov (United States)

    van der Maas, Nico Arie

    2017-03-16

    The Multiple Sclerosis Questionnaire for Physical Therapists (MSQPT) is a patient-rated outcome questionnaire for evaluating the rehabilitation of persons with multiple sclerosis (MS). Responsiveness was evaluated, and minimal important difference (MID) estimates were calculated to provide thresholds for clinical change for four items, three sections and the total score of the MSQPT. This multicentre study used a combined distribution- and anchor-based approach with multiple anchors and multiple rating of change questions. Responsiveness was evaluated using effect size, standardized response mean (SRM), modified SRM and relative efficiency. For distribution-based MID estimates, 0.2 and 0.33 standard deviations (SD), standard error of measurement (SEM) and minimal detectable change were used . Triangulation of anchor- and distribution-based MID estimates provided a range of MID values for each of the four items, the three sections and the total score of the MSQPT. The MID values were tested for their sensitivity and specificity for amelioration and deterioration for each of the four items, the three sections and the total score of the MSQPT. The MID values of each item and section and of the total score with the best sensitivity and specificity were selected as thresholds for clinical change. The outcome measures were the MSQPT, Hamburg Quality of Life Questionnaire for Multiple Sclerosis (HAQUAMS), rating of change questionnaires, Expanded Disability Status Scale, 6-metre timed walking test, Berg Balance Scale and 6-minute walking test. The effect size ranged from 0.46 to 1.49. The SRM data showed comparable results. The modified SRM ranged from 0.00 to 0.60. Anchor-based MID estimates were very low and were comparable with SD- and SEM-based estimates. The MSQPT was more responsive than the HAQUAMS in detecting improvement but less responsive in finding deterioration. The best MID estimates of the items, sections and total score, expressed in percentage of their

  15. Retrospektive evaluation of the response of montane forest ecosystem to multiple stress

    Czech Academy of Sciences Publication Activity Database

    Cudlín, Pavel; Novotný, Radek; Moravec, Ivo; Chmelíková, Ewa

    2001-01-01

    Roč. 20, č. 1 (2001), s. 108-124 ISSN 1335-342X R&D Projects: GA ČR GA526/98/1147 Institutional research plan: CEZ:AV0Z6087904 Keywords : norway spruce * multiple stress * crown structure Subject RIV: EH - Ecology, Behaviour Impact factor: 0.192, year: 2001

  16. Cellular response of pulp fibroblast to single or multiple photobiomodulation applications

    Science.gov (United States)

    Fernandes, Amanda; Lourenço Neto, Natalino; Teixeira Marques, Nadia Carolina; Lourenço Ribeiro Vitor, Luciana; Tavares Oliveira Prado, Mariel; Cardoso Oliveira, Rodrigo; Moreira Machado, Maria Aparecida Andrade; Marchini Oliveira, Thais

    2018-06-01

    This study aimed to evaluate in vitro the effects of single or multiple photobiomodulation (PBM) applications on the viability and proliferation of pulp fibroblasts. Pulp fibroblasts from human deciduous teeth were obtained from a biorepository, plated into 96-well plates, and irradiated according to the experimental groups. At 24 h, 48 h, and 72 h after irradiation, cell viability and proliferation were assessed through MTT and Crystal Violet assays, respectively. The intragroup comparison revealed statistically significant differences for 2.5 J cm‑2 (3×) with increasing viability at 72 h over 48 h (p  =  0.027). The intergroup analysis showed a greater viability of the multiple PBM applications 2.5 J cm‑2 (3×) over the single application 7.5 J cm‑2 (1×) at 72 h. The application of 5 J cm‑2 (1×) exhibited greater proliferation than the application of 7.5 J cm‑2 (1×), 2.5 J cm‑2 (2×) and 2.5 J cm‑2 (3×). Single or multiple PBM applications demonstration different stimulatory effects on pulp fibroblast. The results show that the group submitted to multiple irradiation presented significantly higher cell viability than the groups with single irradiation at 72 h. However, the photobiomodulation therapy with single irradiations was more effective on cell proliferation at 24 h.

  17. The biological clock modulates the human cortisol response in a multiplicative fashion

    NARCIS (Netherlands)

    van de Werken, Maan; Booij, Sanne H.; van der Zwan, J Esi; Simons, Mirre J. P.; Gordijn, Marijke C. M.; Beersma, Domien G. M.

    Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol

  18. Influence of Number Size, Problem Structure and Response Mode on Children's Solutions of Multiplication Word Problems.

    Science.gov (United States)

    De Corte, E.; And Others

    One important finding from recent research on multiplication word problems is that children's performances are strongly affected by the nature of the multiplier (whether it is an integer, decimal larger than 1 or a decimal smaller than 1). On the other hand, the size of the multiplicand has little or no effect on problem difficulty. The aim of the…

  19. Taking Teacher Responsibility into Account(ability): Explicating Its Multiple Components and Theoretical Status

    Science.gov (United States)

    Lauermann, Fani; Karabenick, Stuart A.

    2011-01-01

    Accountability systems have important implications for schooling. Missing from discussions about their implementation, however, are ways they affect teacher responsibility. Responsibility has been insufficiently explicated in the education literature, including its impact on teacher motivation, emotion, and behavior. We propose that a…

  20. Broadband Structural Dynamics: Understanding the Impulse-Response of Structures Across Multiple Length and Time Scales

    Science.gov (United States)

    2010-08-18

    Spectral domain response calculated • Time domain response obtained through inverse transform Approach 4: WASABI Wavelet Analysis of Structural Anomalies...differences at unity scale! Time Function Transform Apply Spectral Domain Transfer Function Time Function Inverse Transform Transform Transform  mtP

  1. Stochastic order in dichotomous item response models for fixed tests, research adaptive tests, or multiple abilities

    NARCIS (Netherlands)

    van der Linden, Willem J.

    1995-01-01

    Dichotomous item response theory (IRT) models can be viewed as families of stochastically ordered distributions of responses to test items. This paper explores several properties of such distributiom. The focus is on the conditions under which stochastic order in families of conditional

  2. Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

    Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

  3. Pooling Data from Multiple Longitudinal Studies: The Role of Item Response Theory in Integrative Data Analysis

    Science.gov (United States)

    Curran, Patrick J.; Hussong, Andrea M.; Cai, Li; Huang, Wenjing; Chassin, Laurie; Sher, Kenneth J.; Zucker, Robert A.

    2010-01-01

    There are a number of significant challenges encountered when studying development over an extended period of time including subject attrition, changing measurement structures across group and developmental period, and the need to invest substantial time and money. Integrative data analysis is an emerging set of methodologies that overcomes many of the challenges of single sample designs through the pooling of data drawn from multiple existing developmental studies. This approach is characterized by a host of advantages, but this also introduces several new complexities that must be addressed prior to broad adoption by developmental researchers. In this paper we focus on methods for fitting measurement models and creating scale scores using data drawn from multiple longitudinal studies. We present findings from the analysis of repeated measures of internalizing symptomatology that were pooled from three existing developmental studies. We describe and demonstrate each step in the analysis and we conclude with a discussion of potential limitations and directions for future research. PMID:18331129

  4. Endoplasmic reticulum stress response as a potential therapeutic target in multiple sclerosis

    OpenAIRE

    Getts, Meghann Teague; Getts, Daniel R.; Kohm, Adam P.; Miller, Stephen D

    2008-01-01

    Multiple Sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Since current treatments are aimed at nonspecifically down-regulating inflammation and natural mechanisms of repair and remyelination within the CNS are inadequate for recovery of function, MS patients presently only have available treatments that delay symptom progression. The complex nature of this disease means that only multifaceted treatments hold the promise of a cure. Recent studies i...

  5. Hemodynamic responses during and after multiple sets of stretching exercises performed with and without the Valsalva maneuver.

    Science.gov (United States)

    Lima, Tainah P; Farinatti, Paulo T V; Rubini, Ercole C; Silva, Elirez B; Monteiro, Walace D

    2015-05-01

    This study investigated the acute hemodynamic responses to multiple sets of passive stretching exercises performed with and without the Valsalva maneuver. Fifteen healthy men aged 21 to 29 years with poor flexibility performed stretching protocols comprising 10 sets of maximal passive unilateral hip flexion, sustained for 30 seconds with equal intervals between sets. Protocols without and with the Valsalva maneuver were applied in a random counterbalanced order, separated by 48-hour intervals. Hemodynamic responses were measured by photoplethysmography pre-exercise, during the stretching sets, and post-exercise. The effects of stretching sets on systolic and diastolic blood pressure were cumulative until the fourth set in protocols performed with and without the Valsalva maneuver. The heart rate and rate pressure product increased in both protocols, but no additive effect was observed due to the number of sets. Hemodynamic responses were always higher when stretching was performed with the Valsalva maneuver, causing an additional elevation in the rate pressure product. Multiple sets of unilateral hip flexion stretching significantly increased blood pressure, heart rate, and rate pressure product values. A cumulative effect of the number of sets occurred only for systolic and diastolic blood pressure, at least in the initial sets of the stretching protocols. The performance of the Valsalva maneuver intensified all hemodynamic responses, which resulted in significant increases in cardiac work during stretching exercises.

  6. Human cortical responses to slow and fast binaural beats reveal multiple mechanisms of binaural hearing.

    Science.gov (United States)

    Ross, Bernhard; Miyazaki, Takahiro; Thompson, Jessica; Jamali, Shahab; Fujioka, Takako

    2014-10-15

    When two tones with slightly different frequencies are presented to both ears, they interact in the central auditory system and induce the sensation of a beating sound. At low difference frequencies, we perceive a single sound, which is moving across the head between the left and right ears. The percept changes to loudness fluctuation, roughness, and pitch with increasing beat rate. To examine the neural representations underlying these different perceptions, we recorded neuromagnetic cortical responses while participants listened to binaural beats at a continuously varying rate between 3 Hz and 60 Hz. Binaural beat responses were analyzed as neuromagnetic oscillations following the trajectory of the stimulus rate. Responses were largest in the 40-Hz gamma range and at low frequencies. Binaural beat responses at 3 Hz showed opposite polarity in the left and right auditory cortices. We suggest that this difference in polarity reflects the opponent neural population code for representing sound location. Binaural beats at any rate induced gamma oscillations. However, the responses were largest at 40-Hz stimulation. We propose that the neuromagnetic gamma oscillations reflect postsynaptic modulation that allows for precise timing of cortical neural firing. Systematic phase differences between bilateral responses suggest that separate sound representations of a sound object exist in the left and right auditory cortices. We conclude that binaural processing at the cortical level occurs with the same temporal acuity as monaural processing whereas the identification of sound location requires further interpretation and is limited by the rate of object representations. Copyright © 2014 the American Physiological Society.

  7. Multiple bony metastases of breast cancer. Role of CA 15.3 and response to hormone therapy

    International Nuclear Information System (INIS)

    Lopez C, Nayara; Ramon G, Natividad; Sanchez M, Jose Ignacio; De Santiago G, Javier

    2012-01-01

    Bone metastases are involved in a 65-75% of advanced metastatic breast cancer cases. Tumoral markers (CEA, CA 15.3) are useful in the follow-up and evaluation of response to treatment. Hormonal therapy is the optimal treatment option in low grade metastatic breast cancer due to low toxicity and general long term good response. We present a breast cancer case treated with surgery, chemotherapy and radiotherapy. The patient was asymptomatic during the follow-up and multiple bone metastases were diagnosed as a result of an increased CA 15.3 marker found. Hormone therapy was the recommended initial treatment with good response and tolerance. Bone lesions remained stabilized for 7 years but after treatment suspension new bone lesions appeared. CA 15.3 marker had increased again. Reintroduction of hormonal therapy achieved again the stabilization of the lesions

  8. Heterogeneity of response to antipsychotics from multiple disorders in the schizophrenia spectrum.

    Science.gov (United States)

    Garver, D L; Holcomb, J A; Christensen, J D

    2000-12-01

    Antipsychotic response after the initiation of neuroleptic treatment shows wide variation in schizophrenic patient populations. In this overview, the authors suggest that the variance in antipsychotic drug response within schizophrenia can be reduced by resolving the schizophrenias into several discrete "endophenotypes," each with different etiologic underpinnings. Studies relating differences in the relative speed or completeness of antipsychotic response to differences in distribution of 2 biological markers with possible etiologic significance are reviewed. Such studies had assessed recently hospitalized, neuroleptic-free patients undergoing exacerbation of nonaffective psychotic disorders. Prior to initiation of neuroleptic, the cohort of patients had been assessed for the quantity of the dopamine metabolite homovanillic acid in plasma (pHVA) and had undergone the first of 2 magnetic resonance imaging (MRI) studies for analyses of ventricle volumes. A second MRI was subsequently performed during a period of (partial) remission to determine within-patient stability of ventricular volumes. These selected studies assessed the distribution of pHVA and distribution of rates of ventricular change, with non-normal distributions resolved by K-means clustering. The speed and completeness of neuroleptic-induced antipsychotic response were related to 3 clusters of patients delineated by modal distributions of pHVA and of apparent rates of ventricular change. At least 3 unique "endophenotypes" of the "group of the schizophrenias" can be defined with respect to speed and completeness of antipsychotic response. Each endophenotype appears to show at least one unique biological feature that differentiates it from a normal comparison group. A rapidly responsive psychosis was associated with excessive production of dopamine, as identifiable by elevation of pHVA and a "good-prognosis" course. A delayed-response psychosis had low-to-normal pHVA, clinically demonstrated persistent

  9. Dendrochronological dating of large woody debris on the example of Morávka River and Černá Opava River

    Directory of Open Access Journals (Sweden)

    Michal Rybníček

    2010-01-01

    Full Text Available Woody debris is an inseparable part of natural river channels. In a river ecosystem it affects the hydraulic, hydrological and morphological properties of the channel, and it is also of a biological significance. However, besides the positive effects, the woody debris can also have a negative impact, e.g. the reduction of the flow profile capacity or the destruction of waterside buildings. With the de­ve­lop­ment of log floating and timber trade, the woody debris started to be removed from the channels. Currently, within the process of stream revitalization, woody debris is being artificially placed into ri­vers. This paper deals with the possible dendrochronological dating of large woody debris (LWD and wood jams in the river channel and the riparian zone. Two sites have been chosen for the research, the Morávka River and the Černá Opava River. These sites have been chosen because of two dif­fe­rent types of riparian stands. The banks of the Morávka River are a soft wood floodplain forest (350 m ASL; the Černá Opava River has stands with nearly a hundred percent proportion of spruce (600 m ASL. The results of the research show that the species with diffuse-porous wood structure are very hard to date on the basis of Pressler borer cores. On the other hand, the sites with softwood species are easi­ly datable, especially if the trunks contain more than 40 tree-rings. At these sites it is possible to use the dendrochronological dating for the establishment of the temporal dynamics of the woody debris input in the river ecosystem.

  10. Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

    Directory of Open Access Journals (Sweden)

    Peter C Cook

    2011-03-01

    Full Text Available Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S products. Here, we show that multiple (4x exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4(+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x, dermal cells from multiply infected mice (4x, were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80(+MHC-II(-, but they did not impact the ability of antigen presenting cells (APC to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1(+, Ym-1(+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-II(hi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.

  11. L-Amino Acids Elicit Diverse Response Patterns in Taste Sensory Cells: A Role for Multiple Receptors

    Science.gov (United States)

    Pal Choudhuri, Shreoshi; Delay, Rona J.; Delay, Eugene R.

    2015-01-01

    Umami, the fifth basic taste, is elicited by the L-amino acid, glutamate. A unique characteristic of umami taste is the response potentiation by 5’ ribonucleotide monophosphates, which are also capable of eliciting an umami taste. Initial reports using human embryonic kidney (HEK) cells suggested that there is one broadly tuned receptor heterodimer, T1r1+T1r3, which detects L-glutamate and all other L-amino acids. However, there is growing evidence that multiple receptors detect glutamate in the oral cavity. While much is understood about glutamate transduction, the mechanisms for detecting the tastes of other L-amino acids are less well understood. We used calcium imaging of isolated taste sensory cells and taste cell clusters from the circumvallate and foliate papillae of C57BL/6J and T1r3 knockout mice to determine if other receptors might also be involved in detection of L-amino acids. Ratiometric imaging with Fura-2 was used to study calcium responses to monopotassium L-glutamate, L-serine, L-arginine, and L-glutamine, with and without inosine 5’ monophosphate (IMP). The results of these experiments showed that the response patterns elicited by L-amino acids varied significantly across taste sensory cells. L-amino acids other than glutamate also elicited synergistic responses in a subset of taste sensory cells. Along with its role in synergism, IMP alone elicited a response in a large number of taste sensory cells. Our data indicate that synergistic and non-synergistic responses to L-amino acids and IMP are mediated by multiple receptors or possibly a receptor complex. PMID:26110622

  12. Microstructural response and grain refinement mechanism of commercially pure titanium subjected to multiple laser shock peening impacts

    International Nuclear Information System (INIS)

    Lu, J.Z.; Wu, L.J.; Sun, G.F.; Luo, K.Y.; Zhang, Y.K.; Cai, J.; Cui, C.Y.; Luo, X.M.

    2017-01-01

    The microstructural response and grain subdivision process in commercially pure (CP) titanium subjected to multiple laser shock peening (LSP) impacts were investigated by means of optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. The micro-hardness curves as a function of the impact time were also determined. The deformation-induced grain refinement mechanism of the close-packed hexagonal (hcp) material by laser shock wave was subsequently analyzed. Experimental results showed that uniform equiaxed grains with an average size of less than 50 nm were generated due to the ultra-high plastic strain induced by multiple LSP impacts. Special attention was paid to four types of novel deformation-induced microstructural features, including a layered slip band in the tension deformation zone, and inverse-transformation martensite, micro-twin grating and micro-twin collision in the compression deformation zone. Furthermore, the grain refinement mechanism in the near-surface layer of CP titanium subjected to multiple LSP impacts contains two types of simultaneous subdivision modes: multi-directional mechanical twin (MT)-MT intersections at (sub)micrometer scale, and the intersection between longitudinal secondary MTs and transverse dislocation walls at nanometer scale. In addition, both grain refinement (nanocrystallization) and the existence of a small amount of inverse-transformation martensite induced by multiple LSP impacts contribute to an increase in the micro-hardness of the near-surface layer.

  13. Acute Responses of a Physical Training Session with a Nintendo Wii on Hemodynamic Variables of an Individual with Multiple Sclerosis.

    Science.gov (United States)

    Monteiro Junior, Renato Sobral; Dantas, Aretha; de Souza, Cíntia Pereira; da Silva, Elirez Bezerra

    2012-12-01

    Multiple sclerosis is a neurological illness that decreases motor functions. This disease can cause weakness of cardiorespiratory muscles and impaired functional capacity and quality of life. Therefore it requires preventive treatments. This study investigated the acute responses of a virtual physical training session with the Nintendo(®) (Kyoto, Japan) Wii™ on hemodynamic variables of an individual with multiple sclerosis (relapsing-remitting). A 34-year-old man with multiple sclerosis with previous experience in aerobic, strength, and functional training (2 years) was tested. His Expanded Disability Status Scale was 2.5. We compared the heart rate, blood pressure, and double product obtained at rest and during (heart rate) and after the Nintendo Wii games "Boxing" and "Sword Play." In rest, the variables were measured in the supine position. Our results showed positive hemodynamic alterations after execution of both games. The peak of heart rate was 121 beats per minute (65% of maximal heart rate) and 104 beats per minute (56% of maximal heart rate) for "Boxing" and "Sword Play," respectively. The training session with "Boxing" was able to stimulate the heart rate to achieve the recommended values for the maintenance of physical fitness in accordance with the American College of Sports Medicine guidelines. We conclude that an exercise training program with the Nintendo Wii may improve physical fitness in people with multiple sclerosis. Moreover, these activities could improve affective status and perhaps maintain the individual engaged at treatment program.

  14. The B Cell Response to Foot-and-Mouth Disease Virus in Cattle following Sequential Vaccination with Multiple Serotypes.

    Science.gov (United States)

    Grant, Clare F J; Carr, B Veronica; Kotecha, Abhay; van den Born, Erwin; Stuart, David I; Hammond, John A; Charleston, Bryan

    2017-05-01

    Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype does not confer interserotype protection. However, some historical data have shown that interserotype protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study, we have investigated the kinetics of the FMDV-specific antibody-secreting cell (ASC) response following homologous and heterologous inactivated FMDV vaccination regimes. We have demonstrated that the kinetics of the B cell response are similar for all four FMDV serotypes tested following a homologous FMDV vaccination regime. When a heterologous vaccination regime was used with the sequential inoculation of three different inactivated FMDV serotypes (O, A, and Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The studies also revealed that the local lymphoid tissue had detectable FMDV-specific ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to inactivated FMDV capsid. IMPORTANCE We have demonstrated the development of intraserotype response following a sequential vaccination regime of four different FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid tissue, further evidence of a TI-2 response to FMDV. Copyright © 2017 American Society for Microbiology.

  15. Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.; Opresko, Lee; Coffey, Robert J.; Zangar, Richard C.; Wiley, H. S.

    2008-11-14

    REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

  16. Plastic responses of a sessile prey to multiple predators: a field and experimental study.

    Directory of Open Access Journals (Sweden)

    Philipp Emanuel Hirsch

    Full Text Available Theory predicts that prey facing a combination of predators with different feeding modes have two options: to express a response against the feeding mode of the most dangerous predator, or to express an intermediate response. Intermediate phenotypes protect equally well against several feeding modes, rather than providing specific protection against a single predator. Anti-predator traits that protect against a common feeding mode displayed by all predators should be expressed regardless of predator combination, as there is no need for trade-offs.We studied phenotypic anti-predator responses of zebra mussels to predation threat from a handling-time-limited (crayfish and a gape-size-limited (roach predator. Both predators dislodge mussels from the substrate but diverge in their further feeding modes. Mussels increased expression of a non-specific defense trait (attachment strength against all combinations of predators relative to a control. In response to roach alone, mussels showed a tendency to develop a weaker and more elongated shell. In response to crayfish, mussels developed a harder and rounder shell. When exposed to either a combination of predators or no predator, mussels developed an intermediate phenotype. Mussel growth rate was positively correlated with an elongated weaker shell and negatively correlated with a round strong shell, indicating a trade-off between anti-predator responses. Field observations of prey phenotypes revealed the presence of both anti-predator phenotypes and the trade-off with growth, but intra-specific population density and bottom substrate had a greater influence than predator density.Our results show that two different predators can exert both functionally equivalent and inverse selection pressures on a single prey. Our field study suggests that abiotic factors and prey population density should be considered when attempting to explain phenotypic diversity in the wild.

  17. Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

    Directory of Open Access Journals (Sweden)

    Justin A. Roby

    2014-01-01

    Full Text Available Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV, Japanese encephalitis virus (JEV, yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA derived from the 3' untranslated region (UTR. sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated.

  18. Middle school science teachers' reaction and pedagogical response to high stakes accountability: A multiple case study

    Science.gov (United States)

    Tse, Kenneth

    The purpose of this study was to understand how science teachers reacted to the high stakes accountability and standardized testing in California. In a multiple case study of middle and intermediate schools in Southern California, four research questions focused on the perceptions of secondary science teachers and how they responded to the changes in the accountability specifically geared towards science as a content area, the pedagogical skills teachers were using both outside and inside of the classroom that impact instruction, the pedagogical training received that related specifically to the content standards, the tools or impediments that existed for teachers to successfully utilize these pedagogical methods and types of support and assistance the school site administration and/or school district offered in learning about the California Science Standards and the STAR test. Interviews were conducted with multiple middle/intermediate school teachers, science department chairpersons and school site administrators to gather information about what the classroom teachers were doing pedagogically to improve student performance on the STAR tests. Moreover, the study described the issues that supported the professional development of the teacher and what schools and districts were doing to support them.

  19. Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Schabel, Christoph; Horger, Marius; Kum, Sara [Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Weisel, Katja [Department of Internal Medicine II – Hematology & Oncology, Eberhard-Karls-University Tuebingen, Otfried-Müller-Str. 5, 72076 Tuebingen (Germany); Fritz, Jan [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Baltimore, MD 21287 (United States); Ioanoviciu, Sorin D. [Department of Internal Medicine, Clinical Municipal Hospital Timisoara, Gheorghe Dima Str. 5, 300079 Timisoara (Romania); Bier, Georg, E-mail: georg.bier@med.uni-tuebingen.de [Department of Neuroradiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

    2016-12-15

    Highlights: • A simplified method for response monitoring of multiple myeloma is proposed. • Medullary bone lesions of all limbs were included and analysed. • Diameters of ≥2 medullary bone lesions are sufficient for therapy monitoring. - Abstract: Introduction: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its time consumption for proper evaluation. Objective: To establish simplified response criteria by correlating size and CT attenuation changes of medullary multiple myeloma lesions in the appendicular skeleton with the course of lytic bone lesions in the entire skeleton. Furthermore to evaluate these criteria with respect to established hematological myeloma-specific parameters for the prediction of treatment response to bortezomib or lenalidomide. Materials and methods: Non-enhanced reduced-dose whole-body CT examinations of 78 consecutive patients (43 male, 35 female, mean age 63.69 ± 9.2 years) with stage III multiple myeloma were retrospectively re-evaluated. On per patient basis, size and mean CT attenuation of 2–4 representative lesions in the limbs were measured at baseline and at a follow-up after a mean of 8 months. Results were compared with the course of lytical bone lesions as well with that of specific hematological biomarkers. Myeloma response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Testing for correlation between response of medullary lesions (Resp

  20. Multiple stressor effects on marine infauna: responses of estuarine taxa and functional traits to sedimentation, nutrient and metal loading

    KAUST Repository

    Ellis, Joanne

    2017-09-14

    Sedimentation, nutrients and metal loading to coastal environments are increasing, associated with urbanization and global warming, hence there is a growing need to predict ecological responses to such change. Using a regression technique we predicted how maximum abundance of 20 macrobenthic taxa and 22 functional traits separately and interactively responded to these key stressors. The abundance of most taxa declined in response to sedimentation and metal loading while a unimodal response was often associated with nutrient loading. Optimum abundances for both taxa and traits occurred at relatively low stressor levels, highlighting the vulnerability of estuaries to increasing stressor loads. Individual taxa were more susceptible to stress than traits, suggesting that functional traits may be less sensitive for detecting changes in ecosystem health. Multiplicative effects were more common than additive interactions. The observed sensitivity of most taxa to increasing sedimentation and metal loading and the documented interaction effects between multiple stressors have important implications for understanding and managing the ecological consequences of eutrophication, sedimentation and contaminants on coastal ecosystems.

  1. Single Parents and the Work Setting: The Impact of Multiple Job and Homelife Responsibilities.

    Science.gov (United States)

    Burden, Dianne S.

    1986-01-01

    Examines the impact of combined work/family responsibilities on single-parent employees. Results indicated that parent employees, but particularly single female parents, were at risk for high job-family role strain and reduced levels of well-being. In spite of increased strain, however, single parents exhibited high levels of job satisfaction and…

  2. Multiple bottlenecks in hierarchical control of action sequences: what does "response selection" select in skilled typewriting?

    Science.gov (United States)

    Yamaguchi, Motonori; Logan, Gordon D; Li, Vanessa

    2013-08-01

    Does response selection select words or letters in skilled typewriting? Typing performance involves hierarchically organized control processes: an outer loop that controls word level processing, and an inner loop that controls letter (or keystroke) level processing. The present study addressed whether response selection occurs in the outer loop or the inner loop by using the psychological refractory period (PRP) paradigm in which Task1 required typing single words and Task2 required vocal responses to tones. The number of letters (string length) in the words was manipulated to discriminate selection of words from selection of keystrokes. In Experiment 1, the PRP effect depended on string length of words in Task1, suggesting that response selection occurs in the inner loop. To assess contributions of the outer loop, the influence of string length was examined in a lexical-decision task that also involves word encoding and lexical access (Experiment 2), or to-be-typed words were preexposed so outer-loop processing could finish before typing started (Experiment 3). Response time for Task2 (RT2) did not depend on string length with lexical decision, and RT2 still depended on string length with typing preexposed strings. These results support the inner-loop locus of the PRP effect. In Experiment 4, typing was performed as Task2, and the effect of string length on typing RT interacted with stimulus onset asynchrony superadditively, implying that another bottleneck also exists in the outer loop. We conclude that there are at least two bottleneck processes in skilled typewriting. 2013 APA, all rights reserved

  3. Assessment of a mussel as a metal bioindicator of coastal contamination: Relationships between metal bioaccumulation and multiple biomarker responses

    International Nuclear Information System (INIS)

    Chandurvelan, Rathishri; Marsden, Islay D.; Glover, Chris N.; Gaw, Sally

    2015-01-01

    This is the first study to use a multiple biomarker approach on the green-lipped mussel, Perna canaliculus to test its feasibility as a bioindicator of coastal metal contamination in New Zealand (NZ). Mussels were collected from six low intertidal sites varying in terms of anthropogenic impacts, within two regions (West Coast and Nelson) of the South Island of NZ. Trace elements, including arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn), were measured in the gills, digestive gland, foot and mantle, and in the surface sediments from where mussels were collected. Metal levels in the sediment were relatively low and there was only one site (Mapua, Nelson) where a metal (Ni) exceeded the Australian and New Zealand Interim Sediment Quality Guideline values. Metal levels in the digestive gland were generally higher than those from the other tissues. A variety of biomarkers were assessed to ascertain mussel health. Clearance rate, a physiological endpoint, correlated with metal level in the tissues, and along with scope for growth, was reduced in the most contaminated site. Metallothionein-like protein content and catalase activity in the digestive gland, and catalase activity and lipid peroxidation in the gill, were also correlated to metal accumulation. Although there were few regional differences, the sampling sites were clearly distinguishable based on the metal contamination profiles and biomarker responses. P. canaliculus appears to be a useful bioindicator species for coastal habitats subject to metal contamination. In this study tissue and whole organism responses provided insight into the biological stress responses of mussels to metal contaminants, indicating that such measurements could be a useful addition to biomonitoring programmes in NZ. - Highlights: • Multiple biomarker responses were measured in mussels from 6 sites. • Metal content of mussel tissues correlated with specific biomarker responses. • Clearance rate

  4. Assessment of a mussel as a metal bioindicator of coastal contamination: Relationships between metal bioaccumulation and multiple biomarker responses

    Energy Technology Data Exchange (ETDEWEB)

    Chandurvelan, Rathishri, E-mail: rch118@uclive.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Marsden, Islay D., E-mail: islay.marsden@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Glover, Chris N., E-mail: chris.glover@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Gaw, Sally, E-mail: sally.gaw@canterbury.ac.nz [Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand)

    2015-04-01

    This is the first study to use a multiple biomarker approach on the green-lipped mussel, Perna canaliculus to test its feasibility as a bioindicator of coastal metal contamination in New Zealand (NZ). Mussels were collected from six low intertidal sites varying in terms of anthropogenic impacts, within two regions (West Coast and Nelson) of the South Island of NZ. Trace elements, including arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn), were measured in the gills, digestive gland, foot and mantle, and in the surface sediments from where mussels were collected. Metal levels in the sediment were relatively low and there was only one site (Mapua, Nelson) where a metal (Ni) exceeded the Australian and New Zealand Interim Sediment Quality Guideline values. Metal levels in the digestive gland were generally higher than those from the other tissues. A variety of biomarkers were assessed to ascertain mussel health. Clearance rate, a physiological endpoint, correlated with metal level in the tissues, and along with scope for growth, was reduced in the most contaminated site. Metallothionein-like protein content and catalase activity in the digestive gland, and catalase activity and lipid peroxidation in the gill, were also correlated to metal accumulation. Although there were few regional differences, the sampling sites were clearly distinguishable based on the metal contamination profiles and biomarker responses. P. canaliculus appears to be a useful bioindicator species for coastal habitats subject to metal contamination. In this study tissue and whole organism responses provided insight into the biological stress responses of mussels to metal contaminants, indicating that such measurements could be a useful addition to biomonitoring programmes in NZ. - Highlights: • Multiple biomarker responses were measured in mussels from 6 sites. • Metal content of mussel tissues correlated with specific biomarker responses. • Clearance rate

  5. Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.

    Science.gov (United States)

    Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J; Cho, Hearn Jay

    2010-01-29

    The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.

  6. Changes in the potential multiple cropping system in response to climate change in China from 1960-2010.

    Science.gov (United States)

    Liu, Luo; Xu, Xinliang; Zhuang, Dafang; Chen, Xi; Li, Shuang

    2013-01-01

    The multiple cropping practice is essential to agriculture because it has been shown to significantly increase the grain yield and promote agricultural economic development. In this study, potential multiple cropping systems in China are calculated based on meteorological observation data by using the Agricultural Ecology Zone (AEZ) model. Following this, the changes in the potential cropping systems in response to climate change between the 1960s and the 2010s were subsequently analyzed. The results indicate that the changes of potential multiple cropping systems show tremendous heterogeneity in respect to the spatial pattern in China. A key finding is that the magnitude of change of the potential cropping systems showed a pattern of increase both from northern China to southern China and from western China to eastern China. Furthermore, the area found to be suitable only for single cropping decreased, while the area suitable for triple cropping increased significantly from the 1960s to the 2000s. During the studied period, the potential multiple cropping index (PMCI) gap between rain-fed and irrigated scenarios increased from 18% to 24%, which indicated noticeable growth of water supply limitations under the rain-fed scenario. The most significant finding of this research was that from the 1960s to the 2000s climate change had led to a significant increase of PMCI by 13% under irrigated scenario and 7% under rain-fed scenario across the whole of China. Furthermore, the growth of the annual mean temperature is identified as the main reason underlying the increase of PMCI. It has also been noticed that across China the changes of potential multiple cropping systems under climate change were different from region to region.

  7. Chemosensory perception, symptoms and autonomic responses during chemical exposure in multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Andersson, Linus; Claeson, Anna Sara; Dantoft, Thomas Meinertz

    2016-01-01

    Purpose: Multiple chemical sensitivity (MCS) is a prevalent medically unexplained symptom characterized by symptom reactions to everyday chemical exposure below hygienic thresholds. The aim of this study was to investigate the expressions of hyper-reactivity in MCS during whole-body exposure to low...... concentrations of the odorant n-butanol. Methods: We exposed 18 participants with MCS and 18 non-ill controls to a low concentration of the odorant n-butanol using an exposure chamber. The first 10 min constituted blank exposure, after which the n-butanol concentration increased and reached a plateau at 11.5 mg....../m3. Results: MCS participants, compared with controls, reported greater perceived odor intensities, more unpleasantness to the exposure and increasing symptoms over time. MCS participants also expressed higher pulse rate and lower pulse rate variability than controls did. No group differences were...

  8. Immunomodulatory effects and adaptive immune response to daratumumab in multiple myeloma

    DEFF Research Database (Denmark)

    Krejcik, Jakub; Casneuf, T.; Nijhof, I.

    2015-01-01

    (range) was 64 (31-84) years and median time from diagnosis was 5.12 (0.77-23.77) years. Seventy-six percent of patients had received >3 prior therapies and 91% were refractory to their last treatment. Clinical response was evaluated using IMWG consensus recommendations. Peripheral blood (PB) samples...... assays. T-cell subpopulation counts were modelled over time with linear mixed modelling. Two group comparisons were performed using non-parametric Wilcoxon rank sum tests. Results: Data from 148 patients receiving 16 mg/kg DARA in GEN501 (n = 42) and Sirius (n = 106) were analyzed for changes in immune...... response. In PB, robust mean increases in CD3+ (44%), CD4+ (32%) and CD8+ (62%) T-cell counts per 100 days were seen with DARA treatment. However, responding evaluable patients (n = 45) showed significantly greater increases from baseline than nonresponders (n = 93) in CD3+ (P = 0.00012), CD4+ (P = 0...

  9. Plant eco-physiological responses to multiple environmental and climate changes

    Energy Technology Data Exchange (ETDEWEB)

    Rost Albert, K.

    2009-03-15

    The current global changes of temperature, precipitation, atmospheric CO{sub 2} and UV-B radiation impact in concert ecosystems and processes in an unpredictable way. Therefore multifactor experimentation is needed to unravel the variability in strength of these drivers, whether the factors act additively or synergistically and to establish cause-effect relations between ecosystem processes. This thesis deals with heath plant responses to global change factors (the CLIMAITE project). In a Danish temperate heath ecosystem elevated CO{sub 2}, experimental summer drought, and passive nighttime warming was applied in all combinations (based on the scenario for Denmark anno 2075) and the responses after one year of treatment were investigated through a growing season in Hairgrass (Deschampsia flexousa) and Heather (Calluna vulgaris). In a high arctic heath ecosystem situated in NE-Greenland UV-B exclusion experiments were conducted on Salix arctica and Vaccinium uliginosum during six years. Responses of photosynthesis performance were characterized on the leaf scale by means of leaf gas-exchange (A/Ci curves), chlorophyll-a fluorescence, leaf nitrogen, carbon and delta13C and secondary compounds. The main findings were 1) The different growth strategies of the evergreen Calluna versus the opportunistic bi-phasic Deschampsia affects the photosynthesis response to drought and autumn warming; 2) Elevated CO{sub 2} and warming synergistically increase photosynthesis in spring and autumn; 3) Summer drought decreased photosynthesis in both species, but where Calluna maintained photosynthetic metabolism then major proportion of grass leaves wilted down; 4) Elevated CO{sub 2} did not decrease stomatal conductance, but the treatments affected soil water content positively, pointing to the complex water relations when plants of contrasting growth strategy co-occur; 5) Water availability affected the magnitude of photosynthesis to a higher degree than warming and elevated CO{sub 2

  10. Item difficulty of multiple choice tests dependant on different item response formats – An experiment in fundamental research on psychological assessment

    Directory of Open Access Journals (Sweden)

    KLAUS D. KUBINGER

    2007-12-01

    Full Text Available Multiple choice response formats are problematical as an item is often scored as solved simply because the test-taker is a lucky guesser. Instead of applying pertinent IRT models which take guessing effects into account, a pragmatic approach of re-conceptualizing multiple choice response formats to reduce the chance of lucky guessing is considered. This paper compares the free response format with two different multiple choice formats. A common multiple choice format with a single correct response option and five distractors (“1 of 6” is used, as well as a multiple choice format with five response options, of which any number of the five is correct and the item is only scored as mastered if all the correct response options and none of the wrong ones are marked (“x of 5”. An experiment was designed, using pairs of items with exactly the same content but different response formats. 173 test-takers were randomly assigned to two test booklets of 150 items altogether. Rasch model analyses adduced a fitting item pool, after the deletion of 39 items. The resulting item difficulty parameters were used for the comparison of the different formats. The multiple choice format “1 of 6” differs significantly from “x of 5”, with a relative effect of 1.63, while the multiple choice format “x of 5” does not significantly differ from the free response format. Therefore, the lower degree of difficulty of items with the “1 of 6” multiple choice format is an indicator of relevant guessing effects. In contrast the “x of 5” multiple choice format can be seen as an appropriate substitute for free response format.

  11. DNA methylation–based immune response signature improves patient diagnosis in multiple cancers

    Science.gov (United States)

    Jeschke, Jana; Bizet, Martin; Calonne, Emilie; Dedeurwaerder, Sarah; Garaud, Soizic; Koch, Alexander; Larsimont, Denis; Salgado, Roberto; Van den Eynden, Gert; Willard Gallo, Karen; Defrance, Matthieu; Sotiriou, Christos

    2017-01-01

    BACKGROUND. The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS. MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas. RESULTS. The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression–based immune markers, respectively. The MeTIL signature also improved the prediction of survival in other malignancies, including melanoma and lung cancer. Furthermore, the MeTIL signature predicted differences in survival for malignancies in which TILs were not known to have a prognostic value. Finally, we showed that MeTIL markers can be determined by bisulfite pyrosequencing of small amounts of DNA from formalin-fixed, paraffin-embedded tumor tissue, supporting clinical applications for this methodology. CONCLUSIONS. This study highlights the power of DNA methylation to evaluate tumor immune responses and the potential of this approach to improve the diagnosis and treatment of breast and other cancers. FUNDING. This work was funded by the Fonds National de la Recherche Scientifique (FNRS) and Télévie, the INNOVIRIS Brussels Region BRUBREAST Project, the IUAP P7/03 program, the Belgian “Foundation against Cancer,” the Breast Cancer Research Foundation (BCRF), and the Fonds Gaston Ithier

  12. The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

    Directory of Open Access Journals (Sweden)

    Natalia O. Kalinina

    2018-02-01

    Full Text Available The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribosepolymerase (PARP, which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses.

  13. The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

    Science.gov (United States)

    Kalinina, Natalia O.; Makarova, Svetlana; Makhotenko, Antonida; Love, Andrew J.; Taliansky, Michael

    2018-01-01

    The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribose)polymerase (PARP), which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses. PMID:29479362

  14. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Directory of Open Access Journals (Sweden)

    Yoon-Dong Park

    2016-08-01

    Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

  15. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2012-05-01

    Full Text Available Brendon J Coventry, Martin L AshdownDiscipline of Surgery, University of Adelaide, Royal Adelaide Hospital and Faculty of Medicine, University of Melbourne, AustraliaAbstract: Over 50 years of cancer therapy history reveals complete clinical responses (CRs from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained?Over some 20 years, realization that (1 chronic inflammation is intricately associated with cancer, and (2 the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of "final common pathways" of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This "missing" aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer

  16. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

  17. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    International Nuclear Information System (INIS)

    Chandra, Sudeshna; Noronha, Glen; Dietrich, Sascha; Lang, Heinrich; Bahadur, Dhirendra

    2015-01-01

    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH 2 CH 2 C(O)O(CH 2 CH 2 O) 9 CH 3 and CH 2 CH 2 C(O)O(CH 2 CH 2 O) 2 C 2 H 5 , respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe 3 O 4 ) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells

  18. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Sudeshna; Noronha, Glen [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India); Dietrich, Sascha; Lang, Heinrich [Technische Universität Chemnitz, Institute of Chemistry, Straße der Nationen 62, d-09111 Chemnitz (Germany); Bahadur, Dhirendra, E-mail: dhirenb@iitb.ac.in [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India)

    2015-04-15

    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 9}CH{sub 3} and CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 2}C{sub 2}H{sub 5}, respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe{sub 3}O{sub 4}) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells.

  19. Efficacy of multiple anticancer therapies may depend on host immune response

    Directory of Open Access Journals (Sweden)

    Kritika Karri

    2017-06-01

    Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

  20. Combining item response theory with multiple imputation to equate health assessment questionnaires.

    Science.gov (United States)

    Gu, Chenyang; Gutman, Roee

    2017-09-01

    The assessment of patients' functional status across the continuum of care requires a common patient assessment tool. However, assessment tools that are used in various health care settings differ and cannot be easily contrasted. For example, the Functional Independence Measure (FIM) is used to evaluate the functional status of patients who stay in inpatient rehabilitation facilities, the Minimum Data Set (MDS) is collected for all patients who stay in skilled nursing facilities, and the Outcome and Assessment Information Set (OASIS) is collected if they choose home health care provided by home health agencies. All three instruments or questionnaires include functional status items, but the specific items, rating scales, and instructions for scoring different activities vary between the different settings. We consider equating different health assessment questionnaires as a missing data problem, and propose a variant of predictive mean matching method that relies on Item Response Theory (IRT) models to impute unmeasured item responses. Using real data sets, we simulated missing measurements and compared our proposed approach to existing methods for missing data imputation. We show that, for all of the estimands considered, and in most of the experimental conditions that were examined, the proposed approach provides valid inferences, and generally has better coverages, relatively smaller biases, and shorter interval estimates. The proposed method is further illustrated using a real data set. © 2016, The International Biometric Society.

  1. Cuttlefish dynamic camouflage: responses to substrate choice and integration of multiple visual cues.

    Science.gov (United States)

    Allen, Justine J; Mäthger, Lydia M; Barbosa, Alexandra; Buresch, Kendra C; Sogin, Emilia; Schwartz, Jillian; Chubb, Charles; Hanlon, Roger T

    2010-04-07

    Prey camouflage is an evolutionary response to predation pressure. Cephalopods have extensive camouflage capabilities and studying them can offer insight into effective camouflage design. Here, we examine whether cuttlefish, Sepia officinalis, show substrate or camouflage pattern preferences. In the first two experiments, cuttlefish were presented with a choice between different artificial substrates or between different natural substrates. First, the ability of cuttlefish to show substrate preference on artificial and natural substrates was established. Next, cuttlefish were offered substrates known to evoke three main camouflage body pattern types these animals show: Uniform or Mottle (function by background matching); or Disruptive. In a third experiment, cuttlefish were presented with conflicting visual cues on their left and right sides to assess their camouflage response. Given a choice between substrates they might encounter in nature, we found no strong substrate preference except when cuttlefish could bury themselves. Additionally, cuttlefish responded to conflicting visual cues with mixed body patterns in both the substrate preference and split substrate experiments. These results suggest that differences in energy costs for different camouflage body patterns may be minor and that pattern mixing and symmetry may play important roles in camouflage.

  2. Evaluation of the Multiple Sclerosis Walking Scale-12 (MSWS-12) in a Dutch sample: Application of item response theory.

    Science.gov (United States)

    Mokkink, Lidwine Brigitta; Galindo-Garre, Francisca; Uitdehaag, Bernard Mj

    2016-12-01

    The Multiple Sclerosis Walking Scale-12 (MSWS-12) measures walking ability from the patients' perspective. We examined the quality of the MSWS-12 using an item response theory model, the graded response model (GRM). A total of 625 unique Dutch multiple sclerosis (MS) patients were included. After testing for unidimensionality, monotonicity, and absence of local dependence, a GRM was fit and item characteristics were assessed. Differential item functioning (DIF) for the variables gender, age, duration of MS, type of MS and severity of MS, reliability, total test information, and standard error of the trait level (θ) were investigated. Confirmatory factor analysis showed a unidimensional structure of the 12 items of the scale, explaining 88% of the variance. Item 2 did not fit into the GRM model. Reliability was 0.93. Items 8 and 9 (of the 11 and 12 item version respectively) showed DIF on the variable severity, based on the Expanded Disability Status Scale (EDSS). However, the EDSS is strongly related to the content of both items. Our results confirm the good quality of the MSWS-12. The trait level (θ) scores and item parameters of both the 12- and 11-item versions were highly comparable, although we do not suggest to change the content of the MSWS-12. © The Author(s), 2016.

  3. CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

    Science.gov (United States)

    Romme Christensen, Jeppe; Komori, Mika; von Essen, Marina Rode; Ratzer, Rikke; Börnsen, Lars; Bielekova, Bibi; Sellebjerg, Finn

    2018-05-01

    Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

  4. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

    Directory of Open Access Journals (Sweden)

    Levitt DG

    2014-09-01

    Full Text Available David G Levitt,1 Michael D Levitt2 1Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA; 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB and unconjugated bilirubin (UB. While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis, and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert's, Dubin–Johnson, Crigler–Najjar, Rotor syndromes. Novel aspects of this review include: 1 quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2 detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3 discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4 pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5 role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6 insights concerning the clinical interpretation of bilirubin measurements.Keywords: liver, conjugation, diazo, albumin, Rotor

  5. Dynamics of habitat selection in birds: adaptive response to nest predation depends on multiple factors.

    Science.gov (United States)

    Devries, J H; Clark, R G; Armstrong, L M

    2018-05-01

    According to theory, habitat selection by organisms should reflect underlying habitat-specific fitness consequences and, in birds, reproductive success has a strong impact on population growth in many species. Understanding processes affecting habitat selection also is critically important for guiding conservation initiatives. Northern pintails (Anas acuta) are migratory, temperate-nesting birds that breed in greatest concentrations in the prairies of North America and their population remains below conservation goals. Habitat loss and changing land use practices may have decoupled formerly reliable fitness cues with respect to nest habitat choices. We used data from 62 waterfowl nesting study sites across prairie Canada (1997-2009) to examine nest survival, a primary fitness metric, at multiple scales, in combination with estimates of habitat selection (i.e., nests versus random points), to test for evidence of adaptive habitat choices. We used the same habitat covariates in both analyses. Pintail nest survival varied with nest initiation date, nest habitat, pintail breeding pair density, landscape composition and annual moisture. Selection of nesting habitat reflected patterns in nest survival in some cases, indicating adaptive selection, but strength of habitat selection varied seasonally and depended on population density and landscape composition. Adaptive selection was most evident late in the breeding season, at low breeding densities and in cropland-dominated landscapes. Strikingly, at high breeding density, habitat choice appears to become maladaptive relative to nest predation. At larger spatial scales, the relative availability of habitats with low versus high nest survival, and changing land use practices, may limit the reproductive potential of pintails.

  6. Serological response to influenza vaccination among children vaccinated for multiple influenza seasons.

    Directory of Open Access Journals (Sweden)

    Sajjad Rafiq

    Full Text Available To evaluate if, among children aged 3 to 15 years, influenza vaccination for multiple seasons affects the proportion sero-protected.Participants were 131 healthy children aged 3-15 years. Participants were vaccinated with trivalent inactivated seasonal influenza vaccine (TIV over the 2005-06, 2006-07 and 2007-8 seasons. Number of seasons vaccinated were categorized as one (2007-08; two (2007-08 and 2006-07 or 2007-08 and 2005-06 or three (2005-06, 2006-07, and 2007-08. Pre- and post-vaccination sera were collected four weeks apart. Antibody titres were determined by hemagglutination inhibition (HAI assay using antigens to A/Solomon Islands/03/06 (H1N1, A/Wisconsin/67/05 (H3N2 and B/Malaysia/2506/04. The proportions sero-protected were compared by number of seasons vaccinated using cut-points for seroprotection of 1:40 vs. 1:320. The proportions of children sero-protected against H1N1 and H3N2 was high (>85% regardless of number of seasons vaccinated and regardless of cut-point for seroprotection. For B Malaysia there was no change in proportions sero-protected by number of seasons vaccinated; however the proportions protected were lower than for H1N1 and H3N2, and there was a lower proportion sero-protected when the higher, compared to lower, cut-point was used for sero-protection.The proportion of children sero-protected is not affected by number of seasons vaccinated.

  7. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

    Science.gov (United States)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

    2018-02-20

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

  8. Seismic response analysis of a piping system subjected to multiple support excitations in a base isolated NPP building

    International Nuclear Information System (INIS)

    Surh, Han-Bum; Ryu, Tae-Young; Park, Jin-Sung; Ahn, Eun-Woo; Choi, Chul-Sun; Koo, Ja Choon; Choi, Jae-Boong; Kim, Moon Ki

    2015-01-01

    Highlights: • Piping system in the APR 1400 NPP with a base isolation design is studied. • Seismic response of piping system in base isolated building are investigated. • Stress classification method is examined for piping subjected to seismic loading. • Primary stress of piping is reduced due to base isolation design. • Substantial secondary stress is observed in the main steam piping. - Abstract: In this study, the stress response of the piping system in the advanced power reactor 1400 (APR 1400) with a base isolation design subjected to seismic loading is addressed. The piping system located between the auxiliary building with base isolation and the turbine building with a fixed base is considered since it can be subjected to substantial relative support movement during seismic events. First, the support responses with respect to the base characteristic are investigated to perform seismic analysis for multiple support excitations. Finite element analyses are performed to predict the piping stress response through various analysis methods such as the response spectrum, seismic support movement and time history method. To separately evaluate the inertial effect and support movement effect on the piping stress, the stress is decomposed into a primary and secondary stress using the proposed method. Finally, influences of the base isolation design on the piping system in the APR 1400 are addressed. The primary stress based on the inertial loading is effectively reduced in a base isolation design, whereas a considerable amount of secondary stress is generated in the piping system connecting a base isolated building with a fixed base building. It is also confirmed that both the response spectrum analysis and seismic support movement analysis provide more conservative estimations of the piping stress compared to the time history analysis

  9. Plant eco-physiological responses to multiple environmental and climate changes

    DEFF Research Database (Denmark)

    Albert, Kristian Rost

    2009-01-01

    arctic plants in both short and long term (Paper V, VII, VIII); 9) Ambient UV-B decreased net photosynthesis via effects on PSII performance in combination with effects on Calvin Cycle (Paper V, VII); 10) Current UV-B level is a important factor affecting high arctic plants, particularly in years......The current global changes of temperature, precipitation, atmospheric CO2 and UV-B radiation impact in concert ecosystems and processes in an unpredictable way. Therefore multifactor experimentation is needed to unravel the variability in strength of these drivers, whether the factors act...... additively or synergistically and to establish cause-effect relations between ecosystem processes. This thesis deals with heath plant responses to global change factors (the CLIMAITE project). In a Danish temperate heath ecosystem elevated CO2, experimental summer drought, and passive nighttime warming...

  10. Multiple redox states of multiheme cytochromes may enable bacterial response to changing redox environments

    Science.gov (United States)

    Arbour, T.; Wrighton, K. C.; Mullin, S. W.; Castelle, C.; Luef, B.; Gilbert, B.; Banfield, J. F.

    2013-12-01

    Multiheme c-type cytochromes (MHCs) are key components in electron-transport pathways that enable some microorganisms to transfer electron byproducts of metabolism to a variety of minerals. As a response to changes in mineral redox potential, microbial communities may shift their membership, or individual organisms may adjust protein expression. Alternatively, the ability to respond may be conferred by the innate characteristics of certain electron-transport-chain components. Here, we used potentiostat-controlled microbial fuel cells (MFCs) to measure the timescale of response to imposed changes in redox conditions, thus placing constraints on the importance of these different mechanisms. In the experiments, a solid electrode acts as an electron-accepting mineral whose redox potential can be precisely controlled. We inoculated duplicate MFCs with a sediment/groundwater mixture from an aquifer at Rifle, Colorado, supplied acetate as an electron donor, and obtained stable, mixed-species biofilms dominated by Geobacter and a novel Geobacter-related family. We poised the anode at potentials spanning the range of natural Fe(III)-reduction, then performed cyclic voltammetry (CV) to characterize the overall biofilm redox signature. The apparent biofilm midpoint potential shifted directly with anode set potential when the latter was changed within the range from about -250 to -50 mV vs. SHE. Following a jump in set potential by 200 mV, the CV-midpoint shift by ~100 mV over a timescale of ~30 minutes to a few hours, depending on the direction of the potential change. The extracellular electron transfer molecules, whose overall CV signature is very similar to those of purified MHCs, appear to span a broad redox range (~200 mV), supporting the hypothesis that MHCs confer substantial redox flexibility. This flexibility may be a principle reason for the abundance of MHCs expressed by microorganisms capable of extracellular electron transfer to minerals.

  11. Testing For The Linearity of Responses To Multiple Anthropogenic Climate Forcings

    Science.gov (United States)

    Forest, C. E.; Stone, P. H.; Sokolov, A. P.

    To test whether climate forcings are additive, we compare climate model simulations in which anthropogenic forcings are applied individually and in combination. Tests are performed with different values for climate system properties (climate sensitivity and rate of heat uptake by the deep ocean) as well as for different strengths of the net aerosol forcing, thereby testing for the dependence of linearity on these properties. The MIT 2D Land-Ocean Climate Model used in this study consists of a zonally aver- aged statistical-dynamical atmospheric model coupled to a mixed-layer Q-flux ocean model, with heat anomalies diffused into the deep ocean. Following our previous stud- ies, the anthropogenic forcings are the changes in concentrations of greenhouse gases (1860-1995), sulfate aerosol (1860-1995), and stratospheric and tropospheric ozone (1979-1995). The sulfate aerosol forcing is applied as a surface albedo change. For an aerosol forcing of -1.0 W/m2 and an effective ocean diffusitivity of 2.5 cm2/s, the nonlinearity of the response of global-mean surface temperatures to the combined forcing shows a strong dependence on climate sensitivity. The fractional change in decadal averages ([(TG + TS + TO) - TGSO]/TGSO) for the 1986-1995 period compared to pre-industrial times are 0.43, 0.90, and 1.08 with climate sensitiv- ities of 3.0, 4.5, and 6.2 C, respectively. The values of TGSO for these three cases o are 0.52, 0.62, and 0.76 C. The dependence of linearity on climate system properties, o the role of climate system feedbacks, and the implications for the detection of climate system's response to individual forcings will be presented. Details of the model and forcings can be found at http://web.mit.edu/globalchange/www/.

  12. Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Nestler, Holger; Groh, Ksenia J.; Schönenberger, René; Behra, Renata; Schirmer, Kristin; Eggen, Rik I.L.; Suter, Marc J.-F.

    2012-01-01

    The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

  13. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    International Nuclear Information System (INIS)

    Manek, Aditya K.; Ferrari, Maud C.O.; Niyogi, Som; Chivers, Douglas P.

    2014-01-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors

  14. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Manek, Aditya K., E-mail: aditya.manek@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada); Ferrari, Maud C.O. [Department of Biomedical Sciences, WCVM, University of Saskatchewan, Saskatoon, SK S7N 5B4 (Canada); Niyogi, Som; Chivers, Douglas P. [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada)

    2014-04-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors.

  15. Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Nestler, Holger [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Groh, Ksenia J.; Schoenenberger, Rene; Behra, Renata [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); Schirmer, Kristin [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); EPF Lausanne, School of Architecture, Civil and Environmental Engineering, 1015 Lausanne (Switzerland); Eggen, Rik I.L. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Suter, Marc J.-F., E-mail: suter@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland)

    2012-04-15

    The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

  16. Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Kishore Malyavantham

    Full Text Available To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC, relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression.The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS, 128 secondary progressive MS (SP-MS, 33 primary progressive MS (PP-MS and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed.The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b, respectively. Antibodies against CSF114(Glc, KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies.Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.

  17. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding.

    Directory of Open Access Journals (Sweden)

    Janet Chamberlain

    Full Text Available Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1 signaling in the vessel wall would raise arterial blood pressure and promote atheroma.Apoe(-/- and Apoe(-/-/IL-1R1(-/- mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-/IL-R1(-/- mice had a reduced blood pressure and significantly less atheroma than Apoe(-/- mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p < 0.05. This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress.The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man.

  18. Multiple phenological responses to climate change among 42 plant species in Xi'an, China.

    Science.gov (United States)

    Dai, Junhu; Wang, Huanjiong; Ge, Quansheng

    2013-09-01

    Phenological data of 42 woody plants in a temperate deciduous forest from the Chinese Phenological Observation Network (CPON) and the corresponding meteorological data from 1963 to 2011 in Xi'an, Shaanxi Province, China were collected and analyzed. The first leaf date (FLD), leaf coloring date (LCD) and first flower date (FFD) are revealed as strong biological signals of climatic change. The FLD, LCD and FFD of most species are sensitive to average temperature during a certain period before phenophase onset. Regional precipitation also has a significant impact on phenophases of about half of the species investigated. Affected by climate change, the FLD and FFD of these species have advanced by 5.54 days and 10.20 days on average during 2003-2011 compared with the period 1963-1996, respectively. Meanwhile, the LCD has delayed by 10.59 days, and growing season length has extended 16.13 days. Diverse responses of phenology commonly exist among different species and functional groups during the study period. Especially for FFD, the deviations between the above two periods ranged from -20.68 to -2.79 days; biotic pollination species showed a significantly greater advance than abiotic pollination species. These results were conducive to the understanding of possible changes in both the structure of plant communities and interspecific relationships in the context of climate change.

  19. Response function of NaI(Tl) detectors and multiple backscattering of gamma rays in aluminium

    International Nuclear Information System (INIS)

    Sabharwal, Arvind D.; Singh, Manpreet; Singh, Bhajan; Sandhu, B.S.

    2008-01-01

    The response function, converting the observed pulse-height distribution of a NaI(Tl) detector to a true photon spectrum, is obtained experimentally with the help of an inverse matrix approach. The energy of gamma-ray photons continuously decreases as the number of scatterings increases in a sample having finite dimensions when one deals with the depth of the sample. The present experiments are undertaken to study the effect of target thickness on intensity distribution of gamma photons multiply backscattered from an aluminium target. A NaI(Tl) gamma-ray detector detects the photons backscattered from the aluminium target. The subtraction of analytically estimated singly scattered distribution from the observed intensity distribution (originating from interactions of primary gamma-ray photons with the target) results in multiply backscattered events. We observe that for each incident gamma photon energy, the number of multiply backscattered photons increases with increase in target thickness and then saturates at a particular target thickness called the saturation thickness (depth). Saturation thickness for multiply backscattering of gamma photons is found to decrease with increase in energy of incident gamma-ray photons

  20. Environmental emergency response plans (EERPs): A single plan approach to satisfy multiple regulations

    International Nuclear Information System (INIS)

    Muzyka, L.

    1995-01-01

    Conrail is a freight railroad operating in twelve northeast and midwestern states transporting goods and materials over 11,700 miles of railroad. To repair, maintain, rebuild, and manufacture locomotives and rail cars, and to maintain the track, right of way, bridges, tunnels and other structures, Conrail uses petroleum products, solvents and cleaners. These products are stored in hundreds of storage tanks in and around the yards and right of way. To power the trains, locomotives are fueled with diesel fuel. With large volumes of fuel, lubricants, solvents and cleaners, safe and efficient handling of petroleum and chemicals is crucial to avoid negative impacts on the environment. Conrail recently revisited the issue of environmental emergency response planning. In an attempt to assure full compliance with a myriad of federal, state, and local regulation, a ''single plan approach'' was chosen. Single plans for each facility, coined EERPs, were decided on after careful review of the regulations, and evaluation of the company's operational and organizational needs

  1. C14-Crash. The C14-method and dendrochronology, unveiling the illusion. 2. rev. ed.; C14-Crash. Das Ende der Illusion, mit Radiokarbonmethode und Dendrochronologie datieren zu koennen

    Energy Technology Data Exchange (ETDEWEB)

    Bloess, C.; Niemitz, H.U.

    2000-07-01

    In this second edition of the book, which was published almost three years after the first edition, the authors reiterate and substantiate their doubts as to the basic theories underlying the radiocarbon dating method and the applicability of dendrochronology. (orig/CB) [German] In dieser zweiten Auflage des Buches, die knapp drei Jahre nach der ersten erschien, vertiefen die Autoren ihre Zweifel an den grundlegenden Theorien und den bisherigen Resultaten der Radiokarbonmethode und der Dendrochronologie. (orig./CB)

  2. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Ashdown, Martin L

    2012-01-01

    Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained? Over some 20 years, realization that (1) chronic inflammation is intricately associated with cancer, and (2) the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of “final common pathways” of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This “missing” aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer therapy. This aspect has been somewhat obscured and has been “lost in translation” to date

  3. [The value of serum heavy/light chain immunoassay to assess therapeutic response in patients with multiple myeloma].

    Science.gov (United States)

    Yu, X C; Su, W; Zhuang, J L

    2018-04-14

    Objective: To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM). Methods: A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection. Results: ①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC. Conclusion: Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.

  4. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

    Directory of Open Access Journals (Sweden)

    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  5. Recent research and applications of numerical simulation for dynamic response of long-span bridges subjected to multiple loads.

    Science.gov (United States)

    Chen, Zhiwei; Chen, Bo

    2014-01-01

    Many long-span bridges have been built throughout the world in recent years but they are often subject to multiple types of dynamic loads, especially those located in wind-prone regions and carrying both trains and road vehicles. To ensure the safety and functionality of these bridges, dynamic responses of long-span bridges are often required for bridge assessment. Given that there are several limitations for the assessment based on field measurement of dynamic responses, a promising approach is based on numerical simulation technologies. This paper provides a detailed review of key issues involved in dynamic response analysis of long-span multiload bridges based on numerical simulation technologies, including dynamic interactions between running trains and bridge, between running road vehicles and bridge, and between wind and bridge, and in the wind-vehicle-bridge coupled system. Then a comprehensive review is conducted for engineering applications of newly developed numerical simulation technologies to safety assessment of long-span bridges, such as assessment of fatigue damage and assessment under extreme events. Finally, the existing problems and promising research efforts for the numerical simulation technologies and their applications to assessment of long-span multiload bridges are explored.

  6. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

    Energy Technology Data Exchange (ETDEWEB)

    Cazenave, Jimena, E-mail: jcazenave@inali.unl.edu.a [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A. [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Wunderlin, Daniel A. [Dto. Bioquimica Clinica-CIBICI-CONICET, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre esq Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

    2009-11-15

    This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

  7. Improvement of fatigue in multiple sclerosis by physical exercise is associated to modulation of systemic interferon response.

    Science.gov (United States)

    Mulero, Patricia; Almansa, Raquel; Neri, María José; Bermejo-Martin, Jesús Francisco; Archanco, Miguel; Arenillas, Juan Francisco; Téllez, Nieves

    2015-03-15

    Mechanisms underlying multiple sclerosis (MS) fatigue and the causes of the beneficial effect of exercise on this symptom are not clarified. Our aim was to evaluate gene expression profiles in MS patients who improved their fatigue status after an exercise program and to compare them with healthy controls (HC). Gene expression in whole blood was profiled at baseline in 7 HC and also in 7 fatigued-MS patients. Patients underwent an exercise program for 6 months, and their fatigue status and gene expression profiles were again analyzed. MS patients showed a significant activation of genes participating in the systemic interferon response in comparison with HC that disappeared at the end of the program. Our results provide a biological basis for the observed benefit of exercise in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

    Directory of Open Access Journals (Sweden)

    Hiroki Hashida

    2017-01-01

    Full Text Available It has been reported that many patients with lung metastasis of colorectal cancer (CRC underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI plus bevacizumab (BV therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped.

  9. Histopathological analysis of the therapeutic response to cryotherapy with liquid nitrogen in patients with multiple actinic keratosis.

    Science.gov (United States)

    Oliveira, Marina Câmara de; Trevisan, Flávia; Pinto, Clovis Antônio Lopes; Xavier, Célia Antônia; Pinto, Jaqueline Campoi Calvo Lopes

    2015-01-01

    Actinic keratoses are premalignant lesions of the skin caused by excessive sun exposure. Lesions may become mainly squamous cell carcinoma. Cryotherapy with liquid nitrogen is one of the main treatments. In order to evaluate the response of actinic keratosis to cryotherapy by histopathology, two lesions were selected in each of 14 patients with multiple actinic keratoses. In one lesion a biopsy was performed and in the other lesion a biopsy was performed after cryotherapy. Subsequently, both biopsies were compared histologically. Of the thirteen patients who completed the study, the best results were obtained in lesions undergoing cryotherapy concerning the atypia of keratinocytes, epithelial thickness and corneal layer and lymphocytic infiltrate. Despite the small number of patients, it was concluded that, if performed correctly, cryotherapy has high efficacy in the treatment of actinic keratoses.

  10. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

    International Nuclear Information System (INIS)

    Cazenave, Jimena; Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A.; Wunderlin, Daniel A.

    2009-01-01

    This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

  11. Comparison of lipid peroxidation and catalase response in invasive dreissenid mussels exposed to single and multiple stressors.

    Science.gov (United States)

    Nowicki, Carly J; Kashian, Donna R

    2018-02-14

    Dreissenid mussels Dreissena bugensis (quagga mussel) and Dreissena polymorpha (zebra mussel) are prolific invasive species to the freshwaters of the United States and Western Europe. In the Great Lakes, D. polymorpha has initially dominated the system since its invasion in the mid-1980s; however, recently D. bugensis has displaced D. polymorpha as the dominant species. Dreissena bugensis has several competitive advantages over D. polymorpha, including greater tolerances to deeper and colder waters and lower respiration rates. Nevertheless, physiological differences between the species remain largely unknown. The oxidative stress response is a mechanism used by all organisms to mitigate environmental stress by reducing oxygen radicals in the body, and comparing this mechanism between similar species can be useful for understanding how different species compete in aquatic environments. We compared oxidative stress biomarkers (lipid peroxidation [LPO] and catalase [CAT] activity) in mussels after exposure to 4 stressors (i.e., high densities, temperature, hypoxia, and polychlorinated biphenyls [PCBs]) independently and in combinations of 2 stressors. Overall, D. bugensis had lower LPO and CAT activity than D. polymorpha when exposed to single stressors; however, in multiple stressor treatments D. bugensis had increased LPO, especially with high temperatures and PCBs. The lower lipid damage in D. bugensis compared with D. polymorpha under single stressor conditions may come at the cost of the ability to respond to multiple stressors. Environ Toxicol Chem 2018;9999:1-12. © 2018 SETAC. © 2018 SETAC.

  12. High Agreement was Obtained Across Scores from Multiple Equated Scales for Social Anxiety Disorder using Item Response Theory.

    Science.gov (United States)

    Sunderland, Matthew; Batterham, Philip; Calear, Alison; Carragher, Natacha; Baillie, Andrew; Slade, Tim

    2018-04-10

    There is no standardized approach to the measurement of social anxiety. Researchers and clinicians are faced with numerous self-report scales with varying strengths, weaknesses, and psychometric properties. The lack of standardization makes it difficult to compare scores across populations that utilise different scales. Item response theory offers one solution to this problem via equating different scales using an anchor scale to set a standardized metric. This study is the first to equate several scales for social anxiety disorder. Data from two samples (n=3,175 and n=1,052), recruited from the Australian community using online advertisements, were utilised to equate a network of 11 self-report social anxiety scales via a fixed parameter item calibration method. Comparisons between actual and equated scores for most of the scales indicted a high level of agreement with mean differences <0.10 (equivalent to a mean difference of less than one point on the standardized metric). This study demonstrates that scores from multiple scales that measure social anxiety can be converted to a common scale. Re-scoring observed scores to a common scale provides opportunities to combine research from multiple studies and ultimately better assess social anxiety in treatment and research settings. Copyright © 2018. Published by Elsevier Inc.

  13. Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

    Directory of Open Access Journals (Sweden)

    Mezei Z

    2012-10-01

    Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

  14. Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency.

    Science.gov (United States)

    Cornelius, Nanna; Frerman, Frank E; Corydon, Thomas J; Palmfeldt, Johan; Bross, Peter; Gregersen, Niels; Olsen, Rikke K J

    2012-08-01

    Riboflavin-responsive forms of multiple acyl-CoA dehydrogenation deficiency (RR-MADD) have been known for years, but with presumed defects in the formation of the flavin adenine dinucleotide (FAD) co-factor rather than genetic defects of electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). It was only recently established that a number of RR-MADD patients carry genetic defects in ETF-QO and that the well-documented clinical efficacy of riboflavin treatment may be based on a chaperone effect that can compensate for inherited folding defects of ETF-QO. In the present study, we investigate the molecular mechanisms and the genotype-phenotype relationships for the riboflavin responsiveness in MADD, using a human HEK-293 cell expression system. We studied the influence of riboflavin and temperature on the steady-state level and the activity of variant ETF-QO proteins identified in patients with RR-MADD, or non- and partially responsive MADD. Our results showed that variant ETF-QO proteins associated with non- and partially responsive MADD caused severe misfolding of ETF-QO variant proteins when cultured in media with supplemented concentrations of riboflavin. In contrast, variant ETF-QO proteins associated with RR-MADD caused milder folding defects when cultured at the same conditions. Decreased thermal stability of the variants showed that FAD does not completely correct the structural defects induced by the variation. This may cause leakage of electrons and increased reactive oxygen species, as reflected by increased amounts of cellular peroxide production in HEK-293 cells expressing the variant ETF-QO proteins. Finally, we found indications of prolonged association of variant ETF-QO protein with the Hsp60 chaperonin in the mitochondrial matrix, supporting indications of folding defects in the variant ETF-QO proteins.

  15. Candidate Gene Study of TRAIL and TRAIL Receptors: Association with Response to Interferon Beta Therapy in Multiple Sclerosis Patients

    Science.gov (United States)

    Órpez-Zafra, Teresa; Pinto-Medel, María Jesús; Oliver-Martos, Begoña; Ortega-Pinazo, Jesús; Arnáiz, Carlos; Guijarro-Castro, Cristina; Varadé, Jezabel; Álvarez-Lafuente, Roberto; Urcelay, Elena; Sánchez-Jiménez, Francisca

    2013-01-01

    TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset (AAO) and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10−4, pc = 0.048, OR = 0.30). This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A), a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells) were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS. PMID:23658636

  16. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

    Science.gov (United States)

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

    1993-04-01

    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

  17. Candidate gene study of TRAIL and TRAIL receptors: association with response to interferon beta therapy in multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Carlos López-Gómez

    Full Text Available TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset (AAO and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10(-4, pc = 0.048, OR = 0.30. This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A, a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS.

  18. Dendro-chronological analysis of fossilised wood in order to reconstruct the post-ice-age history of glaciers; Dendrochronologische Auswertung fossiler Hoelzer zur Rekonstruktion der nacheiszeitlichen Gletschergeschichte

    Energy Technology Data Exchange (ETDEWEB)

    Holzhauser, H.

    2008-07-01

    Around the middle of the 19th century, alpine glaciers advanced to their last maximum extension within the Holocene (the last 11'600 years). Some of the glaciers, especially the Great Aletsch and Gorner, penetrated deeply into wooded land and destroyed numerous trees. Not only were trees destroyed but also valuable arable farmland, alpine farm buildings and dwelling houses. Since the last maximum extension in the 19th century the retreat of the glaciers has accelerated revealing, within the glacier forefields, the remainders of trees once buried. Some of this fossil wood is found in the place where it grew (in situ). Often the wood dates back to a time before the last glacier advance, most of it is several thousands of years old because glacial advance and retreat periods occurred repeatedly within the Holocene. This paper shows the characteristics of fossil wood and how it can be analysed to reconstruct glacial history. It will be demonstrated how glacier length variation can be exactly reconstructed with help of dendrochronology. Thanks to the very exact reconstruction of the glacier length change during the advance periods in the 14th and 16th centuries, the velocities of both the Gorner and Great Aletsch glaciers can be estimated. They range between 7-8 and 20 m per year, in the case of the Gorner glacier, and between 7-8 and 36 m per year, in the case of the Great Aletsch glacier. (author)

  19. Dendrochronologically dated pine stumps document phase-wise bog expansion at a northwest German site between ca. 6700 and ca. 3400 BC

    Science.gov (United States)

    Maike Achterberg, Inke Elisabeth; Eckstein, Jan; Birkholz, Bernhard; Bauerochse, Andreas; Leuschner, Hanns Hubert

    2018-01-01

    The investigated northwest German mire site at Totes Moor is densely covered with subfossil pine stumps (Pinus sylvestris L.) from the fen-bog transition. This facilitates the spatio-temporal reconstruction of mire development, which is based on 212 in situ tree stumps in the case study presented here. Six dendrochronologically dated site chronologies together cover 2345 years between 6703 and 3403 BC. The gaps in between are 6 to 550 years long. Additionally, a floating chronology of 309 years, containing 30 trees, was radiocarbon-dated to the beginning of the 7th millennium cal BC. Peat-stratigraphical survey was carried out additionally, and elevations a.s.l. were determined at several locations. Tree dying-off phases, which indicate water level rise at the site, mostly in context of the local fen-bog transition, are evident for ca. 6600-6450, ca. 6350-5750, ca. 5300-4900, ca. 4700-4550, ca. 3900-3850, ca. 3700-3600, ca. 3500-3450 and ca. 3400 BC. The spatial distribution of the dated in situ trees illustrates the phase-wise expansion of raised bog over fen peat at the site. The documented bog expansion pulses likely correspond to climatic wet sifts.

  20. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas.

    Science.gov (United States)

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis.

  1. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas.

    Directory of Open Access Journals (Sweden)

    Szymon Ciapała

    Full Text Available Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics, some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i small size of samples that affects their representativeness, (ii spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis.

  2. Growth and Its Relationship to Individual Genetic Diversity of Mountain Hemlock (Tsuga mertensiana at Alpine Treeline in Alaska: Combining Dendrochronology and Genomics

    Directory of Open Access Journals (Sweden)

    Jeremy S. Johnson

    2017-11-01

    Full Text Available Globally, alpine treelines are characterized as temperature-limited environments with strong controls on tree growth. However, at local scales spatially heterogeneous environments generally have more variable impacts on individual patterns of tree growth. In addition to the landscape spatial heterogeneity there is local variability in individual tree genetic diversity (level of individual heterozygosity. It has been hypothesized that higher individual heterozygosity will result in more consistent patterns of growth. In this article, we combine genomics and dendrochronology to explore the relationship between individual genetic diversity and tree growth at a mountain hemlock (Tsuga mertensiana Bong. Carr alpine treeline on the Kenai Peninsula, Alaska, USA. We correlated average observed individual heterozygosity with average tree-ring width and variance in tree-ring width within individuals to test the hypothesis that trees with higher individual heterozygosity will also have more consistent growth patterns, suggesting that they may be more resilient to climate and environmental fluctuations at the alpine treeline. Our results showed that there was no significant relationship between tree growth and individual heterozygosity. However, there was a significant positive relationship between average tree-ring width and variance in tree-ring width implying that overall, fast growing trees in stressful environments, such as the alpine treeline, grow unstably regardless of the level of individual heterozygosity.

  3. Efficient sparse matrix-matrix multiplication for computing periodic responses by shooting method on Intel Xeon Phi

    Science.gov (United States)

    Stoykov, S.; Atanassov, E.; Margenov, S.

    2016-10-01

    Many of the scientific applications involve sparse or dense matrix operations, such as solving linear systems, matrix-matrix products, eigensolvers, etc. In what concerns structural nonlinear dynamics, the computations of periodic responses and the determination of stability of the solution are of primary interest. Shooting method iswidely used for obtaining periodic responses of nonlinear systems. The method involves simultaneously operations with sparse and dense matrices. One of the computationally expensive operations in the method is multiplication of sparse by dense matrices. In the current work, a new algorithm for sparse matrix by dense matrix products is presented. The algorithm takes into account the structure of the sparse matrix, which is obtained by space discretization of the nonlinear Mindlin's plate equation of motion by the finite element method. The algorithm is developed to use the vector engine of Intel Xeon Phi coprocessors. It is compared with the standard sparse matrix by dense matrix algorithm and the one developed by Intel MKL and it is shown that by considering the properties of the sparse matrix better algorithms can be developed.

  4. MULTIPLE BIOMARKER RESPONSE IN THE MUSSEL, PERNA PERNA TO ASSESS THE MARINE QUALITY IN THE BIG CASABLANCA AREA

    Directory of Open Access Journals (Sweden)

    LAILA EL JOURMI

    2014-03-01

    Full Text Available The aim of this study is to assess the marine environment quality in the Big Casablanca area. A number of biochemical markers were measured in the brown mussel, Perna perna, sampled from four sampling sites characterized by a different degree of contamination and human impacts. As biochemical indices; Catalase (CAT, Glutathione S-transferase (GST, Acetylcholinesterase (AChE, as well as Malondialdehyde (MDA and Metallothioneine (MT were evaluated in whole soft tissues of mussels collected from the selected sites. The biomarkers showed statistically significant differences at the polluted sites when compared to the control ones. Our data indicated that CAT and GST activity, MDA and MT concentration in whole mussel bodies, are a higher and significant (p < 0.05 in mussels collected at polluted sites when compared to specimen sampled from control ones. In contrary the response of AChE activity was significantly (p<0.05 inhibited in mussels from polluted sites when compared to control values. The multiple biomarker responses obtained for October 2010 and 2011, clearly demonstrate the potential presence of different contaminants in Site1 and Site2 reflecting the intensity of pollution in these areas.

  5. Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality.

    Science.gov (United States)

    Martínez-López, Joaquín; Paiva, Bruno; López-Anglada, Lucía; Mateos, María-Victoria; Cedena, Teresa; Vidríales, María-Belén; Sáez-Gómez, María Auxiliadora; Contreras, Teresa; Oriol, Albert; Rapado, Inmaculada; Teruel, Ana-Isabel; Cordón, Lourdes; Blanchard, María Jesús; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Cueto-Felgueroso, Cecilia; Orfao, Alberto; Bladé, Joan; San Miguel, Jesús F; Lahuerta, Juan José

    2015-08-13

    Stringent complete response (sCR) criteria are used in multiple myeloma as a deeper response category compared with CR, but prospective validation is lacking, it is not always clear how evaluation of clonality is performed, and is it not known what the relative clinical influence is of the serum free light chain ratio (sFLCr) and bone marrow (BM) clonality to define more sCR. To clarify this controversy, we focused on 94 patients that reached CR, of which 69 (73%) also fulfilled the sCR criteria. Patients with sCR displayed slightly longer time to progression (median, 62 vs 53 months, respectively; P = .31). On analyzing this contribution to the prognosis of sFLCr or clonality, it was found that the sFLCr does not identify patients in CR at distinct risk; by contrast, low-sensitive multiparametric flow cytometry (MFC) immunophenotyping (2 colors), which is equivalent to immunohistochemistry, identifies a small number of patients (5 cases) with high residual tumor burden and dismal outcome; nevertheless, using traditional 4-color MFC, persistent clonal BM disease was detectable in 36% of patients, who, compared with minimal residual disease-negative cases, had a significantly inferior outcome. These results show that the current definition of sCR should be revised. © 2015 by The American Society of Hematology.

  6. A small graphene oxide sheet/polyvinylidene fluoride bilayer actuator with large and rapid responses to multiple stimuli.

    Science.gov (United States)

    Xu, Guochuang; Zhang, Miao; Zhou, Qinqin; Chen, Hongwu; Gao, Tiantian; Li, Chun; Shi, Gaoquan

    2017-11-16

    A high-performance actuator should be able to deliver large-shape deformations, fast actuations and sensitive responses to multiple stimuli. Here, we report such an actuator constructed from one layer of polyvinylidene fluoride (PVDF) with a high coefficient of thermal expansion (CTE), and another layer of small sheets of graphene oxide (SGO) with a negative CTE. The opposite deformations of both actuation layers make the SGO/PVDF bilayer actuator highly sensitive to the temperature stimulus with a large bending sensitivity of 1.5 cm -1 °C -1 . Upon irradiation with 60 mW cm -2 infrared light, this SGO/PVDF bilayer actuator displayed an extremely rapid tip displacement rate of 140 mm s -1 . Furthermore, this actuator can also sensitively respond to moisture because of its SGO layer, showing a curvature change from -22 to 13 cm -1 upon changing the relative humidity (RH) from 11% to 86%. This actuator can generate a contractile or relaxed stress 18 times that of mammalian skeletal muscle, under light irradiation or moisture with a response time as short as 1 s, being capable of lifting an object with a weight 80 times that of itself. Furthermore, it also showed excellent stability and repeatability.

  7. The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response

    International Nuclear Information System (INIS)

    Tiwari, Abhinav; Igoshin, Oleg A; Balázsi, Gábor; Gennaro, Maria Laura

    2010-01-01

    Bacterial persistence is the phenomenon in which a genetically identical fraction of a bacterial population can survive exposure to stress by reduction or cessation of growth. Persistence in mycobacteria has been recently linked to a stress-response network, consisting of the MprA/MprB two-component system and alternative sigma factor σ E . This network contains multiple positive transcriptional feedback loops which may give rise to bistability, making it a good candidate for controlling the mycobacterial persistence switch. To analyze the possibility of bistability, we develop a method that involves decoupling of the network into transcriptional and post-translational interaction modules. As a result we reduce the dimensionality of the dynamical system and independently analyze input–output relations in the two modules to formulate a necessary condition for bistability in terms of their logarithmic gains. We show that neither the positive autoregulation in the MprA/MprB network nor the σ E -mediated transcriptional feedback is sufficient to induce bistability in a biochemically realistic parameter range. Nonetheless, inclusion of the post-translational regulation of σ E by RseA increases the effective cooperativity of the system, resulting in bistability that is robust to parameter variation. We predict that overexpression or deletion of RseA, the key element controlling the ultrasensitive response, can eliminate bistability

  8. Application of PET/CT in treatment response evaluation and recurrence prediction in patients with newly-diagnosed multiple myeloma.

    Science.gov (United States)

    Li, Ying; Liu, Junru; Huang, Beihui; Chen, Meilan; Diao, Xiangwen; Li, Juan

    2017-04-11

    Multiple myeloma (MM) causes osteolytic lesions which can be detected by 18F-fluorodeoxyglucose positron emission tomography/Computed tomography (18F-FDG PET/CT). We prospectively involve 96 Newly diagnosed MM to take PET/CT scan at scheduled treatment time (figure 1), and 18F-FDG uptake of lesion was measured by SUVmax and T/Mmax. All MM patients took bortezomib based chemotherapy as induction and received ASCT and maintenance. All clinical features were analyzed with the PET/CT image changes, and some relationships between treatment response and FDG uptakes changes were found: Osteolytic lesions of MM uptakes higher FDG than healthy volunteers, and this trend is more obvious in extramedullary lesions. Compared to X-ray, PET/CT was more sensitive both in discoering bone as well as extramedullary lesions. In newly diagnosed MM, several adverse clinical factors were related to high FDG uptakes of bone lesions. Bone lesion FDG uptakes of MM with P53 mutation or with hypodiploidy and complex karyotype were also higher than those without such changes. In treatment response, PET/CT showed higher sensitivity in detecting tumor residual disease than immunofixation electrophoresis. But in relapse prediction, it might show false positive disease recurrences and the imaging changes might be influenced by infections and hemoglobulin levels. PET/CT is sensitive in discovering meduallary and extrameduallary lesions of MM, and the 18F-FDG uptake of lesions are related with clinical indictors and biological features of plasma cells. In evaluating treatment response and survival, PET/CT showed its superiority. But in predicting relapse or refractory, it may show false positive results.

  9. Gene Cluster Responsible for Secretion of and Immunity to Multiple Bacteriocins, the NKR-5-3 Enterocins

    Science.gov (United States)

    Ishibashi, Naoki; Himeno, Kohei; Masuda, Yoshimitsu; Perez, Rodney Honrada; Iwatani, Shun; Wilaipun, Pongtep; Leelawatcharamas, Vichien; Nakayama, Jiro; Sonomoto, Kenji

    2014-01-01

    Enterococcus faecium NKR-5-3, isolated from Thai fermented fish, is characterized by the unique ability to produce five bacteriocins, namely, enterocins NKR-5-3A, -B, -C, -D, and -Z (Ent53A, Ent53B, Ent53C, Ent53D, and Ent53Z). Genetic analysis with a genome library revealed that the bacteriocin structural genes (enkA [ent53A], enkC [ent53C], enkD [ent53D], and enkZ [ent53Z]) that encode these peptides (except for Ent53B) are located in close proximity to each other. This NKR-5-3ACDZ (Ent53ACDZ) enterocin gene cluster (approximately 13 kb long) includes certain bacteriocin biosynthetic genes such as an ABC transporter gene (enkT), two immunity genes (enkIaz and enkIc), a response regulator (enkR), and a histidine protein kinase (enkK). Heterologous-expression studies of enkT and ΔenkT mutant strains showed that enkT is responsible for the secretion of Ent53A, Ent53C, Ent53D, and Ent53Z, suggesting that EnkT is a wide-range ABC transporter that contributes to the effective production of these bacteriocins. In addition, EnkIaz and EnkIc were found to confer self-immunity to the respective bacteriocins. Furthermore, bacteriocin induction assays performed with the ΔenkRK mutant strain showed that EnkR and EnkK are regulatory proteins responsible for bacteriocin production and that, together with Ent53D, they constitute a three-component regulatory system. Thus, the Ent53ACDZ gene cluster is essential for the biosynthesis and regulation of NKR-5-3 enterocins, and this is, to our knowledge, the first report that demonstrates the secretion of multiple bacteriocins by an ABC transporter. PMID:25149515

  10. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Daniela F Angelini

    Full Text Available It has long been known that multiple sclerosis (MS is associated with an increased Epstein-Barr virus (EBV seroprevalence and high immune reactivity to EBV and that infectious mononucleosis increases MS risk. This evidence led to postulate that EBV infection plays a role in MS etiopathogenesis, although the mechanisms are debated. This study was designed to assess the prevalence and magnitude of CD8+ T-cell responses to EBV latent (EBNA-3A, LMP-2A and lytic (BZLF-1, BMLF-1 antigens in relapsing-remitting MS patients (n = 113 and healthy donors (HD (n = 43 and to investigate whether the EBV-specific CD8+ T cell response correlates with disease activity, as defined by clinical evaluation and gadolinium-enhanced magnetic resonance imaging. Using HLA class I pentamers, lytic antigen-specific CD8+ T cell responses were detected in fewer untreated inactive MS patients than in active MS patients and HD while the frequency of CD8+ T cells specific for EBV lytic and latent antigens was higher in active and inactive MS patients, respectively. In contrast, the CD8+ T cell response to cytomegalovirus did not differ between HD and MS patients, irrespective of the disease phase. Marked differences in the prevalence of EBV-specific CD8+ T cell responses were observed in patients treated with interferon-β and natalizumab, two licensed drugs for relapsing-remitting MS. Longitudinal studies revealed expansion of CD8+ T cells specific for EBV lytic antigens during active disease in untreated MS patients but not in relapse-free, natalizumab-treated patients. Analysis of post-mortem MS brain samples showed expression of the EBV lytic protein BZLF-1 and interactions between cytotoxic CD8+ T cells and EBV lytically infected plasma cells in inflammatory white matter lesions and meninges. We therefore propose that inability to control EBV infection during inactive MS could set the stage for intracerebral viral reactivation and disease relapse.

  11. Contrasting Responses of the Humboldt Current Ecosystem between the Holocene and MIS5e Interglacials Revealed from Multiple Sediment Records

    Science.gov (United States)

    Salvatteci, R.; Schneider, R. R.; Blanz, T.; Martinez, P.; Crosta, X.

    2016-12-01

    The Humboldt Current Ecosystem (HCE) off Peru yields about 10% of the global fish catch, producing more fish per unit area than any other region in the world. The high productivity is maintained by the upwelling of cold, nutrient-rich water from the oxygen minimum zone (OMZ), driven by strong trade winds. However, the potential impacts of climate change on upwelling dynamics and oceanographic conditions in the near future are uncertain, threatening local and global economies. Here, we unravel the response of the HCE to contrasting climatic conditions during the last two interglacials (i.e. Holocene and MIS5e) providing an independent insight about the relation between climatic factors and upwelling and productivity dynamics. For this purpose, we used multiple cores to reconstruct past changes in OMZ and upwelling intensity, productivity and fish biomass variability. Chronologies for the Holocene were obtained by multiple 14C ages and laminae correlations among cores, while for the MIS5e they were mainly done by correlation of prominent features in several proxies with other published records. We used a multiproxy approach including alkenones to reconstruct sea surface temperatures, δ15N as a proxy for water column denitrification, redox sensitive metals as proxies for sediment redox conditions, and diatom and fish debris assemblages to reconstruct ecological changes. The results show a very different response of the HCE to climate conditions during the last 2 interglacials, likely driven by changes in Tropical Pacific dynamics. During the Holocene we find that 1) the Late Holocene exhibits higher multi-centennial scale variability compared to the Early Holocene, 2) increased upwelling and a weak OMZ during the mid-Holocene, and 3) long term increase in productivity (diatoms and fishes) from the Early to the Late Holocene. During the MIS5e we find an 1) intense OMZ, 2) strong water column stratification, 3) high siliceous biomass, and 4) low fish biomass compared

  12. Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in Caenorhabditis elegans.

    Science.gov (United States)

    Kitazono, Tomohiro; Hara-Kuge, Sayuri; Matsuda, Osamu; Inoue, Akitoshi; Fujiwara, Manabi; Ishihara, Takeshi

    2017-10-18

    invertebrates. We found that in Caenorhabditis elegans hermaphrodite, the noncell autonomous regulations of forgetting of olfactory adaptation is regulated by three conserved proteins: a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2: and its ligand, HEN-1. MACO-1 and SCD-2/HEN-1, working in coordination, accelerate forgetting by controlling sensory responses in parallel. Furthermore, temporal regulation of neuronal activity is important for proper forgetting. We suggest that multiple pathways may coordinately and temporally regulate forgetting through control of sensory responses. This study should lead to a better understanding of forgetting in higher organisms. Copyright © 2017 the authors 0270-6474/17/3710240-12$15.00/0.

  13. Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis.

    Science.gov (United States)

    Teter, Barbara; Agashivala, Neetu; Kavak, Katelyn; Chouhfeh, Lynn; Hashmonay, Ron; Weinstock-Guttman, Bianca

    2014-06-01

    Factors driving disease-modifying therapy (DMT) switch behavior are not well understood. The objective of this paper is to identify patient characteristics and clinical events predictive of therapy switching in patients with suboptimal response to DMT. This retrospective study analyzed patients with relapsing-remitting multiple sclerosis (MS) and a suboptimal response to initial therapy with either interferon β or glatiramer acetate. Suboptimal responders were defined as patients with ≥1 MS event (clinical relapse, worsening disability, or MRI worsening) while on DMT. Switchers were defined as those who changed DMT within six to 12 months after the MS event. Of 606 suboptimal responders, 214 (35.3%) switched therapy. Switchers were younger at symptom onset (p = 0.012), MS diagnosis (p = 0.004), DMT initiation (p < 0.001), and first MS event (p = 0.011) compared with nonswitchers. Compared with one relapse alone, MRI worsening alone most strongly predicted switch behavior (odds ratio 6.3; 95% CI, 3.1-12.9; p < 0.001), followed by ≥2 relapses (2.8; 95% CI, 1.1-7.3; p = 0.040), EDSS plus MRI worsening (2.5; 95% CI, 1.1-5.9; p = 0.031) and EDSS worsening alone (2.2; 95% CI, 1.2-4.1; p = 0.009). Younger patients with disease activity, especially MRI changes, are more likely to have their therapy switched sooner than patients who are older at the time of MS diagnosis and DMT initiation. © The Author(s) 2013.

  14. The integration of multiple independent data reveals an unusual response to Pleistocene climatic changes in the hard tick Ixodes ricinus.

    Science.gov (United States)

    Porretta, Daniele; Mastrantonio, Valentina; Mona, Stefano; Epis, Sara; Montagna, Matteo; Sassera, Davide; Bandi, Claudio; Urbanelli, Sandra

    2013-03-01

    In the last few years, improved analytical tools and the integration of genetic data with multiple sources of information have shown that temperate species exhibited more complex responses to ice ages than previously thought. In this study, we investigated how Pleistocene climatic changes affected the current distribution and genetic diversity of European populations of the tick Ixodes ricinus, an ectoparasite with high ecological plasticity. We first used mitochondrial and nuclear genetic markers to investigate the phylogeographic structure of the species and its Pleistocene history using coalescent-based methods; then we used species distribution modelling to infer the climatic niche of the species at last glacial maximum; finally, we reviewed the literature on the I. ricinus hosts to identify the locations of their glacial refugia. Our results support the scenario that during the last glacial phase, I. ricinus never experienced a prolonged allopatric divergence in separate glacial refugia, but persisted with interconnected populations across Southern and Central Europe. The generalist behaviour in host choice of I. ricinus would have played a major role in maintaining connections between its populations. Although most of the hosts persisted in separate refugia, from the point of view of I. ricinus, they represented a continuity of 'bridges' among populations. Our study highlights the importance of species-specific ecology in affecting responses to Pleistocene glacial-interglacial cycles. Together with other cases in Europe and elsewhere, it contributes to setting new hypotheses on how species with wide ecological plasticity coped with Pleistocene climatic changes. © 2013 Blackwell Publishing Ltd.

  15. Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

    Science.gov (United States)

    Casoni, F; Merelli, E; Bedin, R; Sola, P; Bertolotto, A; Faglioni, P

    2004-01-01

    Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

  16. Optimization and modeling of spot welding parameters with simultaneous multiple response consideration using multi objective Taguchi method and RSM

    Energy Technology Data Exchange (ETDEWEB)

    Muhammad, Nora Siah; Manurung Yupiter HP; Hafidzi, Moham Mad; Abas, Sun Haji Kiyai; Tham, Ghalib; Haru Man, Esa [Universiti Teknologi MARA (UiTM), Selangor (Malaysia)

    2012-08-15

    This paper presents an alternative method to optimize process parameters of resistance spot welding (RSW) towards weld zone development. The optimization approach attempts to consider simultaneously the multiple quality characteristics, namely weld nugget and heat affected zone (HAZ), using multi objective Taguchi method (MTM). The experimental study was conducted for plate thickness of 1.5mm under different welding current, weld time and hold time. The optimum welding parameters were investigated using the Taguchi method with L9 orthogonal array. The optimum value was analyzed by means of MTM, which involved the calculation of total normalized quality loss (TNQL) and multi signal to noise ratio (MSNR). A significant level of the welding parameters was further obtained by using analysis of variance (ANOVA). Furthermore, the first order model for predicting the weld zone development is derived by using response surface methodology (RSM). Based on the experimental confirmation test, the proposed method can be effectively applied to estimate the size of weld zone, which can be used to enhance and optimized the welding performance in RSW or other application.

  17. Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod

    Directory of Open Access Journals (Sweden)

    Andrea Harrer

    2015-09-01

    Full Text Available Fingolimod, an oral sphingosine 1-phosphate (S1P receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS. The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7 expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls, and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition.

  18. Optimization and modeling of spot welding parameters with simultaneous multiple response consideration using multi objective Taguchi method and RSM

    International Nuclear Information System (INIS)

    Muhammad, Nora Siah; Manurung Yupiter HP; Hafidzi, Moham Mad; Abas, Sun Haji Kiyai; Tham, Ghalib; Haru Man, Esa

    2012-01-01

    This paper presents an alternative method to optimize process parameters of resistance spot welding (RSW) towards weld zone development. The optimization approach attempts to consider simultaneously the multiple quality characteristics, namely weld nugget and heat affected zone (HAZ), using multi objective Taguchi method (MTM). The experimental study was conducted for plate thickness of 1.5mm under different welding current, weld time and hold time. The optimum welding parameters were investigated using the Taguchi method with L9 orthogonal array. The optimum value was analyzed by means of MTM, which involved the calculation of total normalized quality loss (TNQL) and multi signal to noise ratio (MSNR). A significant level of the welding parameters was further obtained by using analysis of variance (ANOVA). Furthermore, the first order model for predicting the weld zone development is derived by using response surface methodology (RSM). Based on the experimental confirmation test, the proposed method can be effectively applied to estimate the size of weld zone, which can be used to enhance and optimized the welding performance in RSW or other application

  19. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, T; Christensen, T; Hansen, H J

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...... effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays...

  20. Multiple stressor effects on marine infauna: responses of estuarine taxa and functional traits to sedimentation, nutrient and metal loading

    KAUST Repository

    Ellis, Joanne; Clark, D.; Atalah, J.; Jiang, W.; Taiapa, C.; Patterson, M.; Sinner, J.; Hewitt, J.

    2017-01-01

    loading and the documented interaction effects between multiple stressors have important implications for understanding and managing the ecological consequences of eutrophication, sedimentation and contaminants on coastal ecosystems.

  1. FADDEEV: A fortran code for the calculation of the frequency response matrix of multiple-input, multiple-output dynamic systems

    International Nuclear Information System (INIS)

    Owens, D.H.

    1972-06-01

    The KDF9/EGDON programme FADDEEV has been written to investigate a technique for the calculation of the matrix of frequency responses G(jw) describing the response of the output vector y from the multivariable differential/algebraic system S to the drive of the system input vector u. S: Ex = Ax + Bu, y = Cx, G(jw) = C(jw E - A ) -1 B. The programme uses an algorithm due to Faddeev and has been written with emphasis upon: (a) simplicity of programme structure and computational technique which should enable a user to find his way through the programme fairly easily, and hence facilitate its manipulation as a subroutine in a larger code; (b) rapid computational ability, particularly in systems with fairly large number of inputs and outputs and requiring the evaluation of the frequency responses at a large number of frequencies. Transport or time delays must be converted by the user to Pade or Bode approximations prior to input. Conditions under which the algorithm fails to give accurate results are identified, and methods for increasing the accuracy of the calculations are discussed. The conditions for accurate results using FADDEEV indicate that its application is specialized. (author)

  2. PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

    Science.gov (United States)

    Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

    2015-10-01

    To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

  3. Thermal management of a multiple mini-channel heat sink by the integration of a thermal responsive shape memory material

    International Nuclear Information System (INIS)

    Di Maio, E.; Mastrullo, R.; Mauro, A.W.; Toto, D.

    2014-01-01

    In this paper, a novel application of a thermo-responsive shape memory polymer (SMP) is proposed to smart-control the forced flow of water in a multi mini-channel heat sink. In particular, it is reported that millimeter-sized cylinders made of SMP could be used to smartly obstruct the fluid flow by adapting the flow cross section to the heat load to be removed. By integrating the sensing, the control and the actuation functions within a unique, millimeter-sized device, these micro-valves, unlike the traditional actuators normally used for flow control, could be easily embedded into small heat sinks, with significant space and energy saving, useful, in particular, in systems where several miniaturized components have to be cooled concurrently, such as the modern mainframes or the concentrated photovoltaic solar cells. Two possible configurations for the SMP were considered in this study: an “open” configuration, without any obstruction of the water flow free and an “obstructed” configuration, with the millimeter-sized cylinder partially occupying the mini-channel. A numerical, steady state analysis was carried out with water in single-phase forced convection, to determine the effect of these two states on the internal fluid flow characteristics under different conditions of heat flux and pressure drop and to evaluate the overall thermal behavior of the smart-controlled multiple mini-channel heat sink in terms of ability to control the temperature of the system and to reduce the energy consumption. -- Highlights: • A novel application of a SMP material is investigated for the thermal management of a heat sink. • Numerical simulations to find the matching of the heat sink and material system after regulation were carried out. • The investigated system is able to control the heat sink temperature. • Further analysis for system stability are required

  4. Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

    Science.gov (United States)

    Ding, Ru; Gao, Wenwu; He, Zhiqing; Wu, Feng; Chu, Yang; Wu, Jie; Ma, Lan; Liang, Chun

    2017-11-01

    Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4 + CXCR5 + T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4 + CXCR5 + T cells in CAD patients were examined. Data showed that circulating CD4 + CXCR5 + T cells in CAD patients were enriched with a PD-1 + CCR7 - subset, which was previously identified as the most potent in B cell help. The CD4 + CXCR5 + T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1 + population significantly reduced the cytokine secretion. Interestingly, the CD4 + CXCR5 + PD-1 - T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4 + CXCR5 + T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4 + CXCR5 + T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4 + CXCR5 + T cells as a therapeutic target should therefore be examined in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Intensified Sampling in Response to a Salmonella Heidelberg Outbreak Associated with Multiple Establishments Within a Single Poultry Corporation.

    Science.gov (United States)

    Green, Alice; Defibaugh-Chavez, Stephanie; Douris, Aphrodite; Vetter, Danah; Atkinson, Richard; Kissler, Bonnie; Khroustalev, Allison; Robertson, Kis; Sharma, Yudhbir; Becker, Karen; Dessai, Uday; Antoine, Nisha; Allen, Latasha; Holt, Kristin; Gieraltowski, Laura; Wise, Matthew; Schwensohn, Colin

    2018-03-01

    On June 28, 2013, the Food Safety and Inspection Service (FSIS) was notified by the Centers for Disease Control and Prevention (CDC) of an investigation of a multistate cluster of illnesses of Salmonella enterica serovar Heidelberg. Since case-patients in the cluster reported consumption of a variety of chicken products, FSIS used a simple likelihood-based approach using traceback information to focus on intensified sampling efforts. This article describes the multiphased product sampling approach taken by FSIS when epidemiologic evidence implicated chicken products from multiple establishments operating under one corporation. The objectives of sampling were to (1) assess process control of chicken slaughter and further processing and (2) determine whether outbreak strains were present in products from these implicated establishments. As part of the sample collection process, data collected by FSIS personnel to characterize product included category (whole chicken and type of chicken parts), brand, organic or conventional product, injection with salt solutions or flavorings, and whether product was skinless or skin-on. From the period September 9, 2013, through October 31, 2014, 3164 samples were taken as part of this effort. Salmonella percent positive declined from 19.7% to 5.3% during this timeframe as a result of regulatory and company efforts. The results of intensified sampling for this outbreak investigation informed an FSIS regulatory response and corrective actions taken by the implicated establishments. The company noted that a multihurdle approach to reduce Salmonella in products was taken, including on-farm efforts such as environmental testing, depopulation of affected flocks, disinfection of affected houses, vaccination, and use of various interventions within the establishments over the course of several months.

  6. New Literacies, Multiple Literacies, Unlimited Literacies: What Now, What Next, Where to? A Response to "Blue Listerine, Parochialism and ASL Literacy"

    Science.gov (United States)

    Paul, Peter V.

    2006-01-01

    This article is a response to "Blue Listerine, Parochialism, and ASL Literacy" (Czubek, 2006). The author presents his views on the concepts of literacy and the new and multiple literacies. In addition, the merits of print literacy and other types of literacies are discussed. Although the author agrees that there is an American Sign…

  7. Dynamic Testing of Analogical Reasoning in 5- to 6-Year-Olds : Multiple-Choice Versus Constructed-Response Training Items

    NARCIS (Netherlands)

    Stevenson, C.E.; Heiser, W.J.; Resing, W.C.M.

    2016-01-01

    Multiple-choice (MC) analogy items are often used in cognitive assessment. However, in dynamic testing, where the aim is to provide insight into potential for learning and the learning process, constructed-response (CR) items may be of benefit. This study investigated whether training with CR or MC

  8. Performance of Men and Women on Multiple-Choice and Constructed-Response Tests for Beginning Teachers. Research Report. ETS RR-04-48

    Science.gov (United States)

    Livingston, Samuel A.; Rupp, Stacie L.

    2004-01-01

    Some previous research results imply that women tend to perform better, relative to men, on constructed-response (CR) tests than on multiple-choice (MC) tests in the same subjects. An analysis of data from several tests used in the licensing of beginning teachers supported this hypothesis, to varying degrees, in most of the tests investigated. The…

  9. Dynamic Testing of Analogical Reasoning in 5- to 6-Year-Olds: Multiple-Choice versus Constructed-Response Training Items

    Science.gov (United States)

    Stevenson, Claire E.; Heiser, Willem J.; Resing, Wilma C. M.

    2016-01-01

    Multiple-choice (MC) analogy items are often used in cognitive assessment. However, in dynamic testing, where the aim is to provide insight into potential for learning and the learning process, constructed-response (CR) items may be of benefit. This study investigated whether training with CR or MC items leads to differences in the strategy…

  10. Co-loading and intestine-specific delivery of multiple antioxidants in pH-responsive microspheres based on TEMPO-oxidized polysaccharides

    NARCIS (Netherlands)

    Shi, Mengxuan; Bai, Jie; Zhao, Liyun; Yu, Xinrui; Liang, Jingjing; Liu, Ying; Norde, Willem; Li, Yuan

    2017-01-01

    In this study, pH-responsive microspheres loaded with multiple antioxidants were developed for intestine-specific delivery and exhibited synergistic activity. They consist of chitosan (CS)-coated microspheres made of TEMPO-oxidized Konjac glucomannan (OKGM) polymers, of which the carboxyl (COO−)

  11. Effect of response format on cognitive reflection: Validating a two- and four-option multiple choice question version of the Cognitive Reflection Test.

    Science.gov (United States)

    Sirota, Miroslav; Juanchich, Marie

    2018-03-27

    The Cognitive Reflection Test, measuring intuition inhibition and cognitive reflection, has become extremely popular because it reliably predicts reasoning performance, decision-making, and beliefs. Across studies, the response format of CRT items sometimes differs, based on the assumed construct equivalence of tests with open-ended versus multiple-choice items (the equivalence hypothesis). Evidence and theoretical reasons, however, suggest that the cognitive processes measured by these response formats and their associated performances might differ (the nonequivalence hypothesis). We tested the two hypotheses experimentally by assessing the performance in tests with different response formats and by comparing their predictive and construct validity. In a between-subjects experiment (n = 452), participants answered stem-equivalent CRT items in an open-ended, a two-option, or a four-option response format and then completed tasks on belief bias, denominator neglect, and paranormal beliefs (benchmark indicators of predictive validity), as well as on actively open-minded thinking and numeracy (benchmark indicators of construct validity). We found no significant differences between the three response formats in the numbers of correct responses, the numbers of intuitive responses (with the exception of the two-option version, which had a higher number than the other tests), and the correlational patterns of the indicators of predictive and construct validity. All three test versions were similarly reliable, but the multiple-choice formats were completed more quickly. We speculate that the specific nature of the CRT items helps build construct equivalence among the different response formats. We recommend using the validated multiple-choice version of the CRT presented here, particularly the four-option CRT, for practical and methodological reasons. Supplementary materials and data are available at https://osf.io/mzhyc/ .

  12. Motor and sensory responses after percutaneous tibial nerve stimulation in multiple sclerosis patients with lower urinary tract symptoms treated in daily practice.

    Science.gov (United States)

    Zecca, C; Digesu, G A; Robshaw, P; Puccini, F; Khullar, V; Tubaro, A; Gobbi, C

    2014-03-01

    Posterior tibial nerve stimulation (PTNS) is an effective treatment option for lower urinary tract symptoms (LUTS) in multiple sclerosis (MS) patients. Patients with MS and LUTS unresponsive to medical treatment received PTNS for 12 weeks after saline urodynamics to evaluate the prevalence of motor, sensory and combined responses during PTNS and to determine whether the type of response can predict treatment outcome. LUTS were also assessed using a 3-day bladder diary, patient perception of bladder condition (PPBC) questionnaire, patient perception of intensity of urgency scale (PPIUS), Kings Health QOL questionnaire (KHQ) and Overactive Bladder Questionnaire (OAB-q) before and after treatment. Patients were considered as "responders" if they reported an improvement >50% in their LUTS according to the PPBC. Sensory, motor and combined sensory/motor responses were compared between responders and non-responders. Eighty-three patients were included. 61% (51/83) of patients were responders. Sensory, motor and combined sensory/motor responses were found in 64% (53/83), 6% (5/83) and 30% (25/83) of patients respectively. A sensory response alone, or in combination with a motor response, was better associated with a successful outcome than the presence of a motor response alone (P = 0.001). A sensory response, either alone or in combination with a motor response, is more frequent and seems to be better associated with a successful outcome of PTNS than motor response alone. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  13. Time since death and decay rate constants of Norway spruce and European larch deadwood in subalpine forests determined using dendrochronology and radiocarbon dating

    Science.gov (United States)

    Petrillo, Marta; Cherubini, Paolo; Fravolini, Giulia; Marchetti, Marco; Ascher-Jenull, Judith; Schärer, Michael; Synal, Hans-Arno; Bertoldi, Daniela; Camin, Federica; Larcher, Roberto; Egli, Markus

    2016-03-01

    Due to the large size (e.g. sections of tree trunks) and highly heterogeneous spatial distribution of deadwood, the timescales involved in the coarse woody debris (CWD) decay of Picea abies (L.) Karst. and Larix decidua Mill. in Alpine forests are largely unknown. We investigated the CWD decay dynamics in an Alpine valley in Italy using the chronosequence approach and the five-decay class system that is based on a macromorphological assessment. For the decay classes 1-3, most of the dendrochronological samples were cross-dated to assess the time that had elapsed since tree death, but for decay classes 4 and 5 (poorly preserved tree rings) radiocarbon dating was used. In addition, density, cellulose, and lignin data were measured for the dated CWD. The decay rate constants for spruce and larch were estimated on the basis of the density loss using a single negative exponential model, a regression approach, and the stage-based matrix model. In the decay classes 1-3, the ages of the CWD were similar and varied between 1 and 54 years for spruce and 3 and 40 years for larch, with no significant differences between the classes; classes 1-3 are therefore not indicative of deadwood age. This seems to be due to a time lag between the death of a standing tree and its contact with the soil. We found distinct tree-species-specific differences in decay classes 4 and 5, with larch CWD reaching an average age of 210 years in class 5 and spruce only 77 years. The mean CWD rate constants were estimated to be in the range 0.018 to 0.022 y-1 for spruce and to about 0.012 y-1 for larch. Snapshot sampling (chronosequences) may overestimate the age and mean residence time of CWD. No sampling bias was, however, detectable using the stage-based matrix model. Cellulose and lignin time trends could be derived on the basis of the ages of the CWD. The half-lives for cellulose were 21 years for spruce and 50 years for larch. The half-life of lignin is considerably higher and may be more than

  14. Reconstructing disturbances and their biogeochemical consequences over multiple timescales

    Science.gov (United States)

    McLauchlan, Kendra K.; Higuera, Philip E.; Gavin, Daniel G.; Perakis, Steven S.; Mack, Michelle C.; Alexander, Heather; Battles, John; Biondi, Franco; Buma, Brian; Colombaroli, Daniele; Enders, Sara K.; Engstrom, Daniel R.; Hu, Feng Sheng; Marlon, Jennifer R.; Marshall, John; McGlone, Matt; Morris, Jesse L.; Nave, Lucas E.; Shuman, Bryan; Smithwick, Erica A.H.; Urrego, Dunia H.; Wardle, David A.; Williams, Christopher J.; Williams, Joseph J.

    2014-01-01

    Ongoing changes in disturbance regimes are predicted to cause acute changes in ecosystem structure and function in the coming decades, but many aspects of these predictions are uncertain. A key challenge is to improve the predictability of postdisturbance biogeochemical trajectories at the ecosystem level. Ecosystem ecologists and paleoecologists have generated complementary data sets about disturbance (type, severity, frequency) and ecosystem response (net primary productivity, nutrient cycling) spanning decadal to millennial timescales. Here, we take the first steps toward a full integration of these data sets by reviewing how disturbances are reconstructed using dendrochronological and sedimentary archives and by summarizing the conceptual frameworks for carbon, nitrogen, and hydrologic responses to disturbances. Key research priorities include further development of paleoecological techniques that reconstruct both disturbances and terrestrial ecosystem dynamics. In addition, mechanistic detail from disturbance experiments, long-term observations, and chronosequences can help increase the understanding of ecosystem resilience.

  15. Using dendrochronology to detect and attribute CO2-induced growth increases in P. menziesii and P. ponderosa in western North America

    Science.gov (United States)

    Stretch, V.; Gedalof, Z.; Berg, A. A.

    2010-12-01

    Increased atmospheric CO2 could increase photosynthetic rates and cause trees to use water more efficiently, thereby increasing overall growth rates relative to climatic limiting factors. CO2 fertilization has been found across a range of forest types; however results have been inconsistent and based on short-term studies. Long-term studies based on tree-rings have generally been restricted to a few sites and have produced conflicting results. An initial global analysis of tree-ring widths for evidence of increasing growth relative to drought suggested a small but highly significant proportion of trees exhibit increasing growth over the past 130 years. These growth increases could not be attributed to increasing water use efficiency, elevation effects, nitrogen deposition, or divergence. These results suggest that CO2 fertilization is occurring at some locations and may influence future forest dynamics but this does not appear to occur at all locations. The processes causing differential responses are the focus of this study. Here we illustrate response differences between Douglas-fir (Pseudotsuga menziesii) and ponderosa pine (Pinus ponderosa). Using multiple site chronologies from these species over western North America, we demonstrate several site-specific explanations for differential responses to CO2 fertilization, such as forest composition, density, slope, aspect, soil type, and position relative to range limits.

  16. A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules.

    Directory of Open Access Journals (Sweden)

    Susan Pereira Ribeiro

    Full Text Available Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8. Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.

  17. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

    Science.gov (United States)

    Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

    2015-04-15

    Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

  18. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

    Science.gov (United States)

    Niesvizky, Ruben; Jayabalan, David S; Christos, Paul J; Furst, Jessica R; Naib, Tara; Ely, Scott; Jalbrzikowski, Jessica; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Larow, April; Lent, Richard; Mark, Tomer; Cho, Hearn J; Shore, Tsiporah; Tepler, Jeffrey; Harpel, John; Schuster, Michael W; Mathew, Susan; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

    2008-02-01

    This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

  19. Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

    OpenAIRE

    Lauer, Georg M.; Ouchi, Kei; Chung, Raymond T.; Nguyen, Tam N.; Day, Cheryl L.; Purkis, Deborah R.; Reiser, Markus; Kim, Arthur Y.; Lucas, Michaela; Klenerman, Paul; Walker, Bruce D.

    2002-01-01

    The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel...

  20. 76 FR 33155 - Safety Zones; Multiple Firework Displays in Captain of the Port, Puget Sound Area of Responsibility

    Science.gov (United States)

    2011-06-08

    ... Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not create an environmental risk to health or risk to safety that may disproportionately affect children...-AA00 Safety Zones; Multiple Firework Displays in Captain of the Port, Puget Sound Area of...

  1. The Multiple-Choice Model: Some Solutions for Estimation of Parameters in the Presence of Omitted Responses

    Science.gov (United States)

    Abad, Francisco J.; Olea, Julio; Ponsoda, Vicente

    2009-01-01

    This article deals with some of the problems that have hindered the application of Samejima's and Thissen and Steinberg's multiple-choice models: (a) parameter estimation difficulties owing to the large number of parameters involved, (b) parameter identifiability problems in the Thissen and Steinberg model, and (c) their treatment of omitted…

  2. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high).......A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  3. A DNA vaccine encoding multiple HIV CD4 epitopes elicits vigorous polyfunctional, long-lived CD4+ and CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Daniela Santoro Rosa

    Full Text Available T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+ T cells are important for the generation and maintenance of functional CD8(+ cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18, capable of eliciting broad CD4(+ T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+/CD8(+ T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+ and CD8(+ T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2 simultaneously in response to HIV-1 peptides. For CD4(+ T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2. The vaccine also generated long-lived central and effector memory CD4(+ T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+ T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+ T cells and antibody responses- elicited by other HIV immunogens.

  4. Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

    Science.gov (United States)

    Feletar, Marie; Hall, Stephen; Bird, Paul

    2016-01-01

    To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

  5. Is response to fire influenced by dietary specialization and mobility? A comparative study with multiple animal assemblages.

    Directory of Open Access Journals (Sweden)

    Xavier Santos

    Full Text Available Fire is a major agent involved in landscape transformation and an indirect cause of changes in species composition. Responses to fire may vary greatly depending on life histories and functional traits of species. We have examined the taxonomic and functional responses to fire of eight taxonomic animal groups displaying a gradient of dietary and mobility patterns: Gastropoda, Heteroptera, Formicidae, Coleoptera, Araneae, Orthoptera, Reptilia and Aves. The fieldwork was conducted in a Mediterranean protected area on 3 sites (one unburnt and two burnt with different postfire management practices with five replicates per site. We collected information from 4606 specimens from 274 animal species. Similarity in species composition and abundance between areas was measured by the Bray-Curtis index and ANOSIM, and comparisons between animal and plant responses by Mantel tests. We analyze whether groups with the highest percentage of omnivorous species, these species being more generalist in their dietary habits, show weak responses to fire (i.e. more similarity between burnt and unburnt areas, and independent responses to changes in vegetation. We also explore how mobility, i.e. dispersal ability, influences responses to fire. Our results demonstrate that differences in species composition and abundance between burnt and unburnt areas differed among groups. We found a tendency towards presenting lower differences between areas for groups with higher percentages of omnivorous species. Moreover, taxa with a higher percentage of omnivorous species had significantly more independent responses of changes in vegetation. High- (e.g. Aves and low-mobility (e.g. Gastropoda groups had the strongest responses to fire (higher R scores of the ANOSIM; however, we failed to find a significant general pattern with all the groups according to their mobility. Our results partially support the idea that functional traits underlie the response of organisms to environmental

  6. Is response to fire influenced by dietary specialization and mobility? A comparative study with multiple animal assemblages.

    Science.gov (United States)

    Santos, Xavier; Mateos, Eduardo; Bros, Vicenç; Brotons, Lluís; De Mas, Eva; Herraiz, Joan A; Herrando, Sergi; Miño, Àngel; Olmo-Vidal, Josep M; Quesada, Javier; Ribes, Jordi; Sabaté, Santiago; Sauras-Yera, Teresa; Serra, Antoni; Vallejo, V Ramón; Viñolas, Amador

    2014-01-01

    Fire is a major agent involved in landscape transformation and an indirect cause of changes in species composition. Responses to fire may vary greatly depending on life histories and functional traits of species. We have examined the taxonomic and functional responses to fire of eight taxonomic animal groups displaying a gradient of dietary and mobility patterns: Gastropoda, Heteroptera, Formicidae, Coleoptera, Araneae, Orthoptera, Reptilia and Aves. The fieldwork was conducted in a Mediterranean protected area on 3 sites (one unburnt and two burnt with different postfire management practices) with five replicates per site. We collected information from 4606 specimens from 274 animal species. Similarity in species composition and abundance between areas was measured by the Bray-Curtis index and ANOSIM, and comparisons between animal and plant responses by Mantel tests. We analyze whether groups with the highest percentage of omnivorous species, these species being more generalist in their dietary habits, show weak responses to fire (i.e. more similarity between burnt and unburnt areas), and independent responses to changes in vegetation. We also explore how mobility, i.e. dispersal ability, influences responses to fire. Our results demonstrate that differences in species composition and abundance between burnt and unburnt areas differed among groups. We found a tendency towards presenting lower differences between areas for groups with higher percentages of omnivorous species. Moreover, taxa with a higher percentage of omnivorous species had significantly more independent responses of changes in vegetation. High- (e.g. Aves) and low-mobility (e.g. Gastropoda) groups had the strongest responses to fire (higher R scores of the ANOSIM); however, we failed to find a significant general pattern with all the groups according to their mobility. Our results partially support the idea that functional traits underlie the response of organisms to environmental changes caused

  7. The response of amino acid cycling to global change across multiple biomes: Feedbacks on soil nitrogen availability

    Science.gov (United States)

    Brzostek, E. R.; Finzi, A. C.

    2010-12-01

    The cycling of organic nitrogen (N) in soil links soil organic matter decomposition to ecosystem productivity. Amino acids are a key pool of organic N in the soil, whose cycling is sensitive to alterations in microbial demand for carbon and N. Further, the amino acids released from the breakdown of protein by proteolytic enzymes are an important source of N that supports terrestrial productivity. The objective of this study was to measure changes in amino acid cycling in response to experimental alterations of precipitation and temperature in twelve global change experiments during the 2009 growing season. The study sites ranged from arctic tundra to xeric grasslands. The treatments experimentally increased temperature, increased or decreased precipitation, or some combination of both factors. The response of amino acid cycling to temperature and precipitation manipulations tended to be site specific, but the responses could be placed into a common framework. Changes in soil moisture drove a large response in amino acid cycling. Precipitation augmentation in xeric and mesic sites increased both amino acid pool sizes and production. However, treatments that decreased precipitation drove decreases in amino acid cycling in xeric sites, but led to increases in amino acid cycling in more mesic sites. Across sites, the response to soil warming was horizon specific. Amino acid cycling in organic rich horizons responded positively to warming, while negative responses were exhibited in lower mineral soil horizons. The variable response likely reflects a higher availability of protein substrate to sustain high rates of proteolytic enzyme activity in organic rich horizons. Overall, these results suggest that soil moisture and the availability of protein substrate may be important factors that mediate the response of amino acid cycling to predicted increases in soil temperatures.

  8. The combination of energy-dependent internal adaptation mechanisms and external factors enables Listeria monocytogenes to express a strong starvation survival response during multiple-nutrient starvation.

    Science.gov (United States)

    Lungu, Bwalya; Saldivar, Joshua C; Story, Robert; Ricke, Steven C; Johnson, Michael G

    2010-05-01

    The goal of this study was to characterize the starvation survival response (SSR) of a wild-type Listeria monocytogenes 10403S and an isogenic DeltasigB mutant strain during multiple-nutrient starvation conditions over 28 days. This study examined the effects of inhibitors of protein synthesis, the proton motive force, substrate level phosphorylation, and oxidative phosphorylation on the SSR of L. monocytogenes 10403S and a DeltasigB mutant during multiple-nutrient starvation. The effects of starvation buffer changes on viability were also examined. During multiple-nutrient starvation, both strains expressed a strong SSR, suggesting that L. monocytogenes possesses SigB-independent mechanism(s) for survival during multiple-nutrient starvation. Neither strain was able to express an SSR following starvation buffer changes, indicating that the nutrients/factors present in the starvation buffer could be a source of energy for cell maintenance and survival. Neither the wild-type nor the DeltasigB mutant strain was able to elicit an SSR when exposed to the protein synthesis inhibitor chloramphenicol within the first 4 h of starvation. However, both strains expressed an SSR when exposed to chloramphenicol after 6 h or more of starvation, suggesting that the majority of proteins required to elicit an effective SSR in L. monocytogenes are likely produced somewhere between 4 and 6 h of starvation. The varying SSRs of both strains to the different metabolic inhibitors under aerobic or anaerobic conditions suggested that (1) energy derived from the proton motive force is important for an effective SSR, (2) L. monocytogenes utilizes an anaerobic electron transport during multiple-nutrient starvation conditions, and (3) the glycolytic pathway is an important energy source during multiple-nutrient starvation when oxygen is available, and less important under anaerobic conditions. Collectively, the data suggest that the combination of energy-dependent internal adaptation mechanisms

  9. Dynamics of anti-MSP3 and Pfs230 antibody responses and multiplicity of infection in asymptomatic children from southern Ghana

    DEFF Research Database (Denmark)

    Amoah, Linda E; Acquah, Festus K; Ayanful-Torgby, Ruth

    2018-01-01

    BACKGROUND: During a Plasmodium infection, exposure of human host immune cells to both the asexual and the sexual stages of the parasite elicit immune responses. These responses may be protective and prevent the development of high parasitaemia and its associated clinical symptoms, or block...... the transmission of malaria to an uninfected person. This study aimed at examining the dynamics of naturally acquired immune responses against the asexual and sexual forms of Plasmodium falciparum as well as assessing differences in the multiplicity of infection (MOI) in asymptomatic Ghanaian children living...... 2015. Filter paper blood blots (DBS) as well as thick and thin blood smears were made from finger-pricked blood at each visit. Plasmodium falciparum parasite prevalence was determined by microscopy and PCR. Serum eluted from the DBS were used to assess anti-Pfs230 (sexual stage) and anti-MSP3 (asexual...

  10. Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients.

    Directory of Open Access Journals (Sweden)

    Johannes Ehler

    Full Text Available Experience with therapeutic plasma exchange (TPE for acute relapses in clinically isolated syndrome (CIS or multiple sclerosis (MS patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18-69 years.Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS scoring.A clinical response to TPE was observed in 65 out of 90 patients (72.2%, with marked improvement in 18 (20.0% and moderate improvement in 47 out of 90 patients (52.2%. The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001. Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001, no disease modifying drugs (p = 0.017, gadolinium-positive (Gd+ MRI lesions (p = 0.001 and EDSS ≤ 5.0 before TPE (p = 0.014. In the multiple logistic regression analysis only the detection of Gd+ MRI lesions was significantly altered (p = 0.004.Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd+ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.

  11. The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models.

    Science.gov (United States)

    Palsson, Sirus; Hickling, Timothy P; Bradshaw-Pierce, Erica L; Zager, Michael; Jooss, Karin; O'Brien, Peter J; Spilker, Mary E; Palsson, Bernhard O; Vicini, Paolo

    2013-09-28

    The complexity and multiscale nature of the mammalian immune response provides an excellent test bed for the potential of mathematical modeling and simulation to facilitate mechanistic understanding. Historically, mathematical models of the immune response focused on subsets of the immune system and/or specific aspects of the response. Mathematical models have been developed for the humoral side of the immune response, or for the cellular side, or for cytokine kinetics, but rarely have they been proposed to encompass the overall system complexity. We propose here a framework for integration of subset models, based on a system biology approach. A dynamic simulator, the Fully-integrated Immune Response Model (FIRM), was built in a stepwise fashion by integrating published subset models and adding novel features. The approach used to build the model includes the formulation of the network of interacting species and the subsequent introduction of rate laws to describe each biological process. The resulting model represents a multi-organ structure, comprised of the target organ where the immune response takes place, circulating blood, lymphoid T, and lymphoid B tissue. The cell types accounted for include macrophages, a few T-cell lineages (cytotoxic, regulatory, helper 1, and helper 2), and B-cell activation to plasma cells. Four different cytokines were accounted for: IFN-γ, IL-4, IL-10 and IL-12. In addition, generic inflammatory signals are used to represent the kinetics of IL-1, IL-2, and TGF-β. Cell recruitment, differentiation, replication, apoptosis and migration are described as appropriate for the different cell types. The model is a hybrid structure containing information from several mammalian species. The structure of the network was built to be physiologically and biochemically consistent. Rate laws for all the cellular fate processes, growth factor production rates and half-lives, together with antibody production rates and half-lives, are provided. The

  12. Step responses of a torsional system with multiple clearances: Study of vibro-impact phenomenon using experimental and computational methods

    Science.gov (United States)

    Oruganti, Pradeep Sharma; Krak, Michael D.; Singh, Rajendra

    2018-01-01

    Recently Krak and Singh (2017) proposed a scientific experiment that examined vibro-impacts in a torsional system under a step down excitation and provided preliminary measurements and limited non-linear model studies. A major goal of this article is to extend the prior work with a focus on the examination of vibro-impact phenomena observed under step responses in a torsional system with one, two or three controlled clearances. First, new measurements are made at several locations with a higher sampling frequency. Measured angular accelerations are examined in both time and time-frequency domains. Minimal order non-linear models of the experiment are successfully constructed, using piecewise linear stiffness and Coulomb friction elements; eight cases of the generic system are examined though only three are experimentally studied. Measured and predicted responses for single and dual clearance configurations exhibit double sided impacts and time varying periods suggest softening trends under the step down torque. Non-linear models are experimentally validated by comparing results with new measurements and with those previously reported. Several metrics are utilized to quantify and compare the measured and predicted responses (including peak to peak accelerations). Eigensolutions and step responses of the corresponding linearized models are utilized to better understand the nature of the non-linear dynamic system. Finally, the effect of step amplitude on the non-linear responses is examined for several configurations, and hardening trends are observed in the torsional system with three clearances.

  13. Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta-regression analysis.

    Science.gov (United States)

    Mainou, Maria; Madenidou, Anastasia-Vasiliki; Liakos, Aris; Paschos, Paschalis; Karagiannis, Thomas; Bekiari, Eleni; Vlachaki, Efthymia; Wang, Zhen; Murad, Mohammad Hassan; Kumar, Shaji; Tsapas, Apostolos

    2017-06-01

    We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: a retrospective study

    Directory of Open Access Journals (Sweden)

    Cefaro Luca

    2009-10-01

    Full Text Available Abstract Background Neutralizing antibodies (NAbs against Interferon beta (IFNβ are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNβ treatment. Methods We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNβ during the treatment period. Patients were classified as: group A, developing ≥ 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNβ formulations for at least one year. NAbs positivity was defined as NAbs titre ≥ 20 TRU. Results Seventeen patients (12.1% were NAbs positive. NAbs positivity correlated with poorer clinical response (p Conclusion The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNβ.

  15. Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

    Science.gov (United States)

    Zandveld, Jelle; van den Heuvel, Joost; Mulder, Maarten; Brakefield, Paul M; Kirkwood, Thomas B L; Shanley, Daryl P; Zwaan, Bas J

    2017-11-01

    Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits. We showed that flies were able to respond quickly to diet fluctuations throughout life span by drastically changing their transcription. Importantly, by measuring the response of multiple life-history traits we were able to decouple groups of genes associated with life span or reproduction, life-history traits that often covary with a diet change. A coexpression network analysis uncovered which genes underpin the separate and shared regulation of these life-history traits. Our study provides essential insights to help unravel the genetic architecture mediating life-history responses to diet, and it shows that the flies' whole genome transcription response is highly plastic. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  16. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

    Science.gov (United States)

    Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

    2012-06-29

    The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

  17. Soluble serum VCAM-1, whole blood mRNA expression and treatment response in natalizumab-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Petersen, E R; Søndergaard, H B; Oturai, A B

    2016-01-01

    Background Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum...... levels of a panel of immunomarkers, associated with natalizumab-treatment, are not sensitive markers of MS disease activity. However, decreased expression of pro-inflammatory HLX1 and IL1B and increased expression of immunoregulatory EBI3 may indicate a less pathogenic immune activation status...

  18. The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers

    DEFF Research Database (Denmark)

    Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik

    2015-01-01

    , haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative...... integrative discrimination index (RIDI). RESULTS: SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses...

  19. Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis.

    Science.gov (United States)

    Liu, Ying; Tan, Huiling; Tian, Hui; Liang, Chunyang; Chen, She; Liu, Qinghua

    2011-11-04

    The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2)-nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence-specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjögren's syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

    Science.gov (United States)

    Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

    2013-01-01

    A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

  1. How entorhinal grid cells may learn multiple spatial scales from a dorsoventral gradient of cell response rates in a self-organizing map.

    Directory of Open Access Journals (Sweden)

    Stephen Grossberg

    Full Text Available Place cells in the hippocampus of higher mammals are critical for spatial navigation. Recent modeling clarifies how this may be achieved by how grid cells in the medial entorhinal cortex (MEC input to place cells. Grid cells exhibit hexagonal grid firing patterns across space in multiple spatial scales along the MEC dorsoventral axis. Signals from grid cells of multiple scales combine adaptively to activate place cells that represent much larger spaces than grid cells. But how do grid cells learn to fire at multiple positions that form a hexagonal grid, and with spatial scales that increase along the dorsoventral axis? In vitro recordings of medial entorhinal layer II stellate cells have revealed subthreshold membrane potential oscillations (MPOs whose temporal periods, and time constants of excitatory postsynaptic potentials (EPSPs, both increase along this axis. Slower (faster subthreshold MPOs and slower (faster EPSPs correlate with larger (smaller grid spacings and field widths. A self-organizing map neural model explains how the anatomical gradient of grid spatial scales can be learned by cells that respond more slowly along the gradient to their inputs from stripe cells of multiple scales, which perform linear velocity path integration. The model cells also exhibit MPO frequencies that covary with their response rates. The gradient in intrinsic rhythmicity is thus not compelling evidence for oscillatory interference as a mechanism of grid cell firing. A response rate gradient combined with input stripe cells that have normalized receptive fields can reproduce all known spatial and temporal properties of grid cells along the MEC dorsoventral axis. This spatial gradient mechanism is homologous to a gradient mechanism for temporal learning in the lateral entorhinal cortex and its hippocampal projections. Spatial and temporal representations may hereby arise from homologous mechanisms, thereby embodying a mechanistic "neural relativity" that

  2. P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways.

    Science.gov (United States)

    Qu, Yan; Dubyak, George R

    2009-06-01

    Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of non-classical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell-cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

  3. catcher: A Software Program to Detect Answer Copying in Multiple-Choice Tests Based on Nominal Response Model

    Science.gov (United States)

    Kalender, Ilker

    2012-01-01

    catcher is a software program designed to compute the [omega] index, a common statistical index for the identification of collusions (cheating) among examinees taking an educational or psychological test. It requires (a) responses and (b) ability estimations of individuals, and (c) item parameters to make computations and outputs the results of…

  4. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T

    NARCIS (Netherlands)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; Van der Zwaag, W.

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and

  5. Responses of Spartina alterniflora to Multiple Stressors: Changing Precipitation Patterns, Accelerated Sea Level Rise, and Nutrient Enrichment

    Science.gov (United States)

    Coastal wetlands, well recognized for their ecosystem services, have faced many threats throughout the United States and elsewhere. Managers require good information on responses of wetlands to the combined stressors that these habitats experience, or may in the future as a resul...

  6. Noninvasive pulse pressure variation and stroke volume variation to predict fluid responsiveness at multiple thresholds : a prospective observational study

    NARCIS (Netherlands)

    Vos, Jaap Jan; Poterman, Marieke; Papineau Salm, Pieternel; Van Amsterdam, Kai; Struys, Michel M. R. F.; Scheeren, Thomas W. L.; Kalmar, Alain F.

    2015-01-01

    Pulse pressure variation (PPV) and stroke volume variation (SVV) are dynamic preload variables that can be measured noninvasively to assess fluid responsiveness (FR) in anesthetized patients with mechanical ventilation. Few studies have examined the effectiveness of predicting FR according to the

  7. Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System Intervention

    DEFF Research Database (Denmark)

    Petrykiv, Sergei I; Laverman, Gozewijn Dirk; Persson, Frederik

    2017-01-01

    to angiotensin receptor blockers; n=5) or NSAIDs (n=1), changing from RAASi to NSAIDs (n=2), and changing from high to low sodium intake (n=5). A two-stage meta-analysis was conducted: Deming regression was conducted in each study to assess correlations in response, and individual study results were then meta...

  8. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Olpin, Simon E; Andresen, Brage S

    2007-01-01

    Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid, amino acid and choline metabolism that can result from defects in two flavoproteins, electron transfer flavoprotein (ETF) or ETF: ubiquinone oxidoreductase (ETF:QO). Some patients respond to pharmacological doses......; several had previously suffered cyclical vomiting. Urine organic acid and plasma acyl-carnitine profiles indicated MADD. Clinical and biochemical parameters were either totally or partly corrected after riboflavin treatment. All patients had mutations in the gene for ETF:QO. In one patient, we show...... that the ETF:QO mutations are associated with a riboflavin-sensitive impairment of ETF:QO activity. This patient also had partial deficiencies of flavin-dependent acyl-CoA dehydrogenases and respiratory chain complexes, most of which were restored to control levels after riboflavin treatment. Low activities...

  9. New literacies, multiple literacies, unlimited literacies: what now, what next, where to? A response to blue listerine, parochialism and ASL literacy.

    Science.gov (United States)

    Paul, Peter V

    2006-01-01

    This article is a response to Blue Listerine, Parochialism, and ASL Literacy (Czubek, 2006). The author presents his views on the concepts of literacy and the new and multiple literacies. In addition, the merits of print literacy and other types of literacies are discussed. Although the author agrees that there is an American Sign Language (ASL) literacy, he maintains that there should be a distinction between conversational "literacy" forms (speech and sign) and secondary literacy forms (reading and writing). It might be that cognitive skills associated with print literacy and, possibly, other captured literacy forms, are necessary for a technological, scientific-driven society such as that which exists in the United States.

  10. Invasive species information networks: Collaboration at multiple scales for prevention, early detection, and rapid response to invasive alien species

    Science.gov (United States)

    Simpson, Annie; Jarnevich, Catherine S.; Madsen, John; Westbrooks, Randy G.; Fournier, Christine; Mehrhoff, Les; Browne, Michael; Graham, Jim; Sellers, Elizabeth A.

    2009-01-01

    Accurate analysis of present distributions and effective modeling of future distributions of invasive alien species (IAS) are both highly dependent on the availability and accessibility of occurrence data and natural history information about the species. Invasive alien species monitoring and detection networks (such as the Invasive Plant Atlas of New England and the Invasive Plant Atlas of the MidSouth) generate occurrence data at local and regional levels within the United States, which are shared through the US National Institute of Invasive Species Science. The Inter-American Biodiversity Information Network's Invasives Information Network (I3N), facilitates cooperation on sharing invasive species occurrence data throughout the Western Hemisphere. The I3N and other national and regional networks expose their data globally via the Global Invasive Species Information Network (GISIN). International and interdisciplinary cooperation on data sharing strengthens cooperation on strategies and responses to invasions. However, limitations to effective collaboration among invasive species networks leading to successful early detection and rapid response to invasive species include: lack of interoperability; data accessibility; funding; and technical expertise. This paper proposes various solutions to these obstacles at different geographic levels and briefly describes success stories from the invasive species information networks mentioned above. Using biological informatics to facilitate global information sharing is especially critical in invasive species science, as research has shown that one of the best indicators of the invasiveness of a species is whether it has been invasive elsewhere. Data must also be shared across disciplines because natural history information (e.g. diet, predators, habitat requirements, etc.) about a species in its native range is vital for effective prevention, detection, and rapid response to an invasion. Finally, it has been our

  11. Rapid Induction of Multiple Terpenoid Groups by Ponderosa Pine in Response to Bark Beetle-Associated Fungi.

    Science.gov (United States)

    Keefover-Ring, Ken; Trowbridge, Amy; Mason, Charles J; Raffa, Kenneth F

    2016-01-01

    Ponderosa pine (Pinus ponderosa) is a major and widely distributed component of conifer biomes in western North America and provides substantial ecological and economic benefits. This tree is exposed to several tree-killing bark beetle-microbial complexes, including the mountain pine beetle (Dendroctonus ponderosae) and the phytopathogenic fungus Grosmannia clavigera that it vectors, which are among the most important. Induced responses play a crucial role in conifer defenses, yet these have not been reported in ponderosa pine. We compared concentrations of terpenes and a phenylpropanoid, two phytochemical classes with strong effects against bark beetles and their symbionts, in constitutive phloem tissue and in tissue following mechanical wounding or simulated D. ponderosae attack (mechanical wounding plus inoculation with G. clavigera). We also tested whether potential induced responses were localized or systemic. Ponderosa pines showed pronounced induced defenses to inoculation, increasing their total phloem concentrations of monoterpenes 22.3-fold, sesquiterpenes 56.7-fold, and diterpenes 34.8-fold within 17 days. In contrast, responses to mechanical wounding alone were only 5.2, 11.3, and 7.7-fold, respectively. Likewise, the phenylpropanoid estragole (4-allyanisole) rose to 19.1-fold constitutive levels after simulated attack but only 4.4-fold after mechanical wounding. Overall, we found no evidence of systemic induction after 17 days, which spans most of this herbivore's narrow peak attack period, as significant quantitative and compositional changes within and between terpenoid groups were localized to the wound site. Implications to the less frequent exploitation of ponderosa than lodgepole pine by D. ponderosae, and potential advantages of rapid localized over long-term systemic responses in this system, are discussed.

  12. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

    Science.gov (United States)

    Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

    2016-05-01

    The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study.

    Science.gov (United States)

    Martinez-Lopez, Joaquin; Fernández-Redondo, Elena; García-Sánz, Ramón; Montalbán, María Angeles; Martínez-Sánchez, Pilar; Pavia, Bruno; Mateos, María Victoria; Rosiñol, Laura; Martín, Marisa; Ayala, Rosa; Martínez, Rafael; Blanchard, María Jesus; Alegre, Adrian; Besalduch, Joan; Bargay, Joan; Hernandez, Miguel T; Sarasquete, María Eugenia; Sanchez-Godoy, Pedro; Fernández, Manuela; Blade, Joan; San Miguel, Jesús F; Lahuerta, Juan Jose

    2013-12-01

    Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly diagnosed MM patients from Grupo Español Multidisciplinar de Melanoma (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneous MFC. F-PCR at diagnosis was performed on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE rearrangements. The applicability of F-PCR was 91·5%. After induction therapy, 64 patients achieved molecular response and 66 non-molecular response; median progression-free survival (PFS) was 61 versus 36 months, respectively (P = 0·001). Median overall survival (OS) was not reached (NR) in molecular response patients (5-year survival: 75%) versus 66 months in the non-molecular response group (P = 0·03). The corresponding PFS and OS values for patients with immunophenotypic versus non-immunophenotypic response were 67 versus 42 months (P = 0·005) and NR (5-year survival: 95%) versus 69 months (P = 0·004), respectively. F-PCR analysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations in MM. © 2013 John Wiley & Sons Ltd.

  14. Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

    Science.gov (United States)

    Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

    2017-03-01

    In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Structural characterization of a novel full-length transcript promoter from Horseradish Latent Virus (HRLV) and its transcriptional regulation by multiple stress responsive transcription factors.

    Science.gov (United States)

    Khan, Ahamed; Shrestha, Ankita; Bhuyan, Kashyap; Maiti, Indu B; Dey, Nrisingha

    2018-01-01

    The promoter fragment described in this study can be employed for strong transgene expression under both biotic and abiotic stress conditions. Plant-infecting Caulimoviruses have evolved multiple regulatory mechanisms to address various environmental stimuli during the course of evolution. One such mechanism involves the retention of discrete stress responsive cis-elements which are required for their survival and host-specificity. Here we describe the characterization of a novel Caulimoviral promoter isolated from Horseradish Latent Virus (HRLV) and its regulation by multiple stress responsive Transcription factors (TFs) namely DREB1, AREB1 and TGA1a. The activity of full length transcript (Flt-) promoter from HRLV (- 677 to + 283) was investigated in both transient and transgenic assays where we identified H12 (- 427 to + 73) as the highest expressing fragment having ~ 2.5-fold stronger activity than the CaMV35S promoter. The H12 promoter was highly active and near-constitutive in the vegetative and reproductive parts of both Tobacco and Arabidopsis transgenic plants. Interestingly, H12 contains a distinct cluster of cis-elements like dehydration-responsive element (DRE-core; GCCGAC), an ABA-responsive element (ABRE; ACGTGTC) and as-1 element (TGACG) which are known to be induced by cold, drought and pathogen/SA respectively. The specific binding of DREB1, AREB1 and TGA1a to DRE, ABRE and as-1 elements respectively were confirmed by the gel-binding assays using H12 promoter-specific probes. Detailed mutational analysis of the H12 promoter suggested that the presence of DRE-core and as-1 element was indispensable for its activity which was further confirmed by the transactivation assays. Our studies imply that H12 could be a valuable genetic tool for regulated transgene expression under diverse environmental conditions.

  16. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hara, Naomi; Morata, Saori

    2016-01-01

    control ratio was also significantly increased. Maximal Protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired...... C57BL/6 mice were analyzed at either 6 hours or 24 hours. ROS-production was simultaneously measured in brain samples using fluorometry.Septic brain tissue exhibited an early increased uncoupling of respiration. Temporal changes between the two time points were diminutive and no difference in ROS...

  17. Lorazepam induces multiple disturbances in selective attention: attentional overload, decrement in target processing efficiency, and shifts in perceptual discrimination and response bias.

    Science.gov (United States)

    Michael, George Andrew; Bacon, Elisabeth; Offerlin-Meyer, Isabelle

    2007-09-01

    There is a general consensus that benzodiazepines affect attentional processes, yet only few studies have tried to investigate these impairments in detail. The purpose of the present study was to investigate the effects of a single dose of Lorazepam on performance in a target cancellation task with important time constraints. We measured correct target detections and correct distractor rejections, misses and false positives. The results show that Lorazepam produces multiple kinds of shifts in performance, which suggests that it impairs multipLe processes: (a) the evolution of performance over time was not the same between the placebo and the Lorazepam groups, with the Lorazepam affecting performance quite early after the beginning of the test. This is suggestive of a depletion of attentional resources during sequential attentional processing; (b) Lorazepam affected differently target and distractor processing, with target detection being the most impaired; (c) misses were more frequent under Lorazepam than under placebo, but no such difference was observed as far as false positives were concerned. Signal detection analyses showed that Lorazepam (d) decreased perceptual discrimination, and (e) reliably increased response bias. Our results bring new insights on the multiple effects of Lorazepam on selective attention which, when combined, may have deleterious effects on human performance.

  18. Multiple endocrine adenomatosis with Cushing's disease and the amenorrhea-galactorrhea syndrome responsive to proton beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Veseley, D.L.; Fass, F.H.

    1981-09-01

    Multiple endocrine adenomatosis (MEA) or neoplasia is a hereditary disorder consisting of tumors of hyperplasia of several endocrine glands. In MEA-1 the pituitary, parathyroids, and pancreatic islets are most frequently involved, while in MEA-2 the thyroid (medullary carcinoma of the thyroid), parathyroids,and adrenals (pheochromocytomas) are the endocrine glands most likely to be involved. Cushings's syndrome may occur in MEA-1 and has also been found in patients with MEA-2, where the cause of Cushing's syndrome is usually ectopic ACTH production from medullary carcinoma of the thyroid. Recently, there have been reports of amenorrhea-galactorrhea syndrome in patients with MEA-1, and confirmation that hyperprolactinemia is associated with this syndrom has been found in patients with MEA-1. The present report details a patient who has been followed up for 20 years since she first presented with amenorrhea and galactorrhea. Ten years after first being seen she was noted to have Cushing's syndrom and hyperparathyroidism due to parathyroid hyperplasia. Both the amenorrhea-galactorrhea syndrome and Cushing's sydrome disappeared with proton beam irradiation to the pituitary.

  19. Multiple endocrine adenomatosis with Cushing's disease and the amenorrhea-galactorrhea syndrome responsive to proton beam irradiation

    International Nuclear Information System (INIS)

    Veseley, D.L.; Fass, F.H.

    1981-01-01

    Multiple endocrine adenomatosis (MEA) or neoplasia is a hereditary disorder consisting of tumors of hyperplasia of several endocrine glands. In MEA-1 the pituitary, parathyroids, and pancreatic islets are most frequently involved, while in MEA-2 the thyroid (medullary carcinoma of the thyroid), parathyroids,and adrenals (pheochromocytomas) are the endocrine glands most likely to be involved. Cushings's syndrome may occur in MEA-1 and has also been found in patients with MEA-2, where the cause of Cushing's syndrome is usually ectopic ACTH production from medullary carcinoma of the thyroid. Recently, there have been reports of amenorrhea-galactorrhea syndrome in patients with MEA-1, and confirmation that hyperprolactinemia is associated with this syndrom has been found in patients with MEA-1. The present report details a patient who has been followed up for 20 years since she first presented with amenorrhea and galactorrhea. Ten years after first being seen she was noted to have Cushing's syndrom and hyperparathyroidism due to parathyroid hyperplasia. Both the amenorrhea-galactorrhea syndrome and Cushing's sydrome disappeared with proton beam irradiation to the pituitary

  20. Oxidative responsiveness to multiple stressors in the key Antarctic species, Adamussium colbecki: Interactions between temperature, acidification and cadmium exposure.

    Science.gov (United States)

    Benedetti, Maura; Lanzoni, Ilaria; Nardi, Alessandro; d'Errico, Giuseppe; Di Carlo, Marta; Fattorini, Daniele; Nigro, Marco; Regoli, Francesco

    2016-10-01

    High-latitude marine ecosystems are ranked to be among the most sensitive regions to climate change since highly stenothermal and specially adapted organisms might be seriously affected by global warming and ocean acidification. The present investigation was aimed to provide new insights on the sensitivity to such environmental stressors in the key Antarctic species, Adamussium colbecki, focussing also on their synergistic effects with cadmium exposure, naturally abundant in this area for upwelling phenomena. Scallops were exposed for 2 weeks to various combinations of Cd (0 and 40 μgL-1), pH (8.05 and 7.60) and temperature (-1 and +1 °C). Beside Cd bioaccumulation, a wide panel of early warning biomarkers were analysed in digestive glands and gills including levels of metallothioneins, individual antioxidants and total oxyradical scavenging capacity, onset of oxidative cell damage like lipid peroxidation, lysosomal stability, DNA integrity and peroxisomal proliferation. Results indicated reciprocal interactions between multiple stressors and their elaboration by a quantitative hazard model based on the relevance and magnitude of effects, highlighted a different sensitivity of analysed tissues. Due to cellular adaptations to high basal Cd content, digestive gland appeared more tolerant toward other prooxidant stressors, but sensitive to variations of the metal. On the other hand, gills were more affected by various combinations of stressors occurring at higher temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Multiple responses optimization in the development of a headspace gas chromatography method for the determination of residual solvents in pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Carla M. Teglia

    2015-10-01

    Full Text Available An efficient generic static headspace gas chromatography (HSGC method was developed, optimized and validated for the routine determination of several residual solvents (RS in drug substance, using a strategy with two sets of calibration. Dimethylsulfoxide (DMSO was selected as the sample diluent and internal standards were used to minimize signal variations due to the preparative step. A gas chromatograph from Agilent Model 6890 equipped with flame ionization detector (FID and a DB-624 (30 m×0.53 mm i.d., 3.00 µm film thickness column was used. The inlet split ratio was 5:1. The influencing factors in the chromatographic separation of the analytes were determined through a fractional factorial experimental design. Significant variables: the initial temperature (IT, the final temperature (FT of the oven and the carrier gas flow rate (F were optimized using a central composite design. Response transformation and desirability function were applied to find out the optimal combination of the chromatographic variables to achieve an adequate resolution of the analytes and short analysis time. These conditions were 30 °C for IT, 158 °C for FT and 1.90 mL/min for F. The method was proven to be accurate, linear in a wide range and very sensitive for the analyzed solvents through a comprehensive validation according to the ICH guidelines. Keywords: Headspace gas chromatography, Residual solvents, Pharmaceuticals, Surface response methodology, Desirability function

  2. The early supra-additive apoptotic response of R3327-G prostate tumors to androgen ablation and radiation is not sustained with multiple fractions

    International Nuclear Information System (INIS)

    Pollack, Alan; Ashoori, Faramarz; Sikes, Charles; Lim Joon, Daryl; Eschenbach, Andrew C. von; Zagars, Gunar K.; Meistrich, Marvin L.

    2000-01-01

    Purpose: The treatment of R3327-G tumor-bearing rats with androgen ablation (AA) via castration results in a supra-additive increase in apoptosis when 2-8 Gy γ-irradiation (RT) is given as a single dose 3-14 days afterwards. We report here the dose response and effect of multiple fractions on this supra-additive apoptotic response. Materials and Methods: Dunning R3327-G tumors were grown in the flanks of Copenhagen rats and the experiments were initiated at a tumor volume of 1.0-1.5 cc. Androgen ablation was achieved by castration 3 days prior to γ-irradiation. Apoptosis was measured with a terminal deoxynucleotidyl transferase dUTP-biotin nick end-labeling assay 6-h after RT, unless otherwise specified. Results: The dose response of the supra-additive apoptotic response was assessed by irradiating castrated animals with single doses of 2, 4, 8, or 16 Gy (n = 5 per group); tumor cell apoptosis at 6-h following irradiation was 2.4% ± 0.7% (± SEM), 4.2% ± 0.8%, 6.5% ± 1.4%, and 1.6% ± 0.3%, respectively. The RT only and AA only controls had < 1% apoptosis. The effect of fractionated RT on apoptosis was investigated to determine if the supra-additive apoptotic response was sustained with repeated 2-8 Gy fractions. When tumor-bearing animals were treated with repeated daily 2-Gy fractions, there was a reduction in the level of the supra-additive apoptotic response. After five 2-Gy fractions at 24-h intervals, apoptosis in the combined treated tumors was at levels seen in the AA controls. This raised the possibility that more than 24 h are required for recovery of the high supra-additive apoptotic levels seen after one fraction. When the interfraction interval was extended to 96 h, there was no significant increase in apoptosis over the additive effect of AA and RT. Although there was a decline in supra-additive apoptosis with repeated fractions, a dose response for tumor growth delay was evident for RT alone using 2.5-Gy fractions. Moreover, the combination of

  3. Pulsed Wave Doppler Ultrasound Is Useful to Assess Vasomotor Response in Patients with Multiple System Atrophy and Well Correlated with Tilt Table Study

    Directory of Open Access Journals (Sweden)

    Ke-Vin Chang

    2012-01-01

    Full Text Available The study aim was to assess sympathetic vasomotor response (SVR by using pulsed wave Doppler (PWD ultrasound in patients with multiple system atrophy (MSA and correlate with the tilt table study. We recruited 18 male patients and 10 healthy men as controls. The SVR of the radial artery was evaluated by PWD, using inspiratory cough as a provocative maneuver. The response to head-up tilt was studied by a tilt table with simultaneous heart rate and blood pressure recording. The hemodynamic variables were compared between groups, and were examined by correlation analysis. Regarding SVR, MSA patients exhibited a prolonged latency and less heart rate acceleration following inspiratory cough. Compared with the tilt table test, the elevation of heart rate upon SVR was positively correlated to the increase of heart rate after head-up tilt. The correlation analysis indicated that the magnitude of blood pressure drop from supine to upright was positively associated with the SVR latency but negatively correlated with the heart rate changes upon SVR. The present study demonstrated that blunted heart rate response might explain MSA's vulnerability to postural challenge. PWD may be used to predict cardiovascular response to orthostatic stress upon head-up tilt in MSA patients.

  4. Existence of multiple receptors in single neurons: responses of single bullfrog olfactory neurons to many cAMP-dependent and independent odorants.

    Science.gov (United States)

    Kashiwayanagi, M; Shimano, K; Kurihara, K

    1996-11-04

    The responses of single bullfrog olfactory neurons to various odorants were measured with the whole-cell patch clamp which offers direct information on cellular events and with the ciliary recording technique to obtain stable quantitative data from many neurons. A large portion of single olfactory neurons (about 64% and 79% in the whole-cell recording and in the ciliary recording, respectively) responded to many odorants with quite diverse molecular structures, including both odorants previously indicated to be cAMP-dependent (increasing) and independent odorants. One odorant elicited a response in many cells; e.g. hedione and citralva elicited the response in 100% and 92% of total neurons examined with the ciliary recording technique. To confirm that a single neuron carries different receptors or transduction pathways, the cross-adaptation technique was applied to single neurons. Application of hedione to a single neuron after desensitization of the current in response to lyral or citralva induced an inward current with a similar magnitude to that applied alone. It was suggested that most single olfactory neurons carry multiple receptors and at least dual transduction pathways.

  5. A note on the relationships between multiple imputation, maximum likelihood and fully Bayesian methods for missing responses in linear regression models.

    Science.gov (United States)

    Chen, Qingxia; Ibrahim, Joseph G

    2014-07-01

    Multiple Imputation, Maximum Likelihood and Fully Bayesian methods are the three most commonly used model-based approaches in missing data problems. Although it is easy to show that when the responses are missing at random (MAR), the complete case analysis is unbiased and efficient, the aforementioned methods are still commonly used in practice for this setting. To examine the performance of and relationships between these three methods in this setting, we derive and investigate small sample and asymptotic expressions of the estimates and standard errors, and fully examine how these estimates are related for the three approaches in the linear regression model when the responses are MAR. We show that when the responses are MAR in the linear model, the estimates of the regression coefficients using these three methods are asymptotically equivalent to the complete case estimates under general conditions. One simulation and a real data set from a liver cancer clinical trial are given to compare the properties of these methods when the responses are MAR.

  6. Atypical serum immunofixation patterns frequently emerge in immunomodulatory therapy and are associated with a high degree of response in multiple myeloma.

    Science.gov (United States)

    Mark, Tomer; Jayabalan, David; Coleman, Morton; Pearse, Roger N; Wang, Y Lynn; Lent, Richard; Christos, Paul J; Lee, Joong W; Agrawal, Yash P; Matthew, Susan; Ely, Scott; Mazumdar, Madhu; Cesarman, Ethel; Leonard, John P; Furman, Richard R; Chen-Kiang, Selina; Niesvizky, Ruben

    2008-12-01

    The M-protein is the major reference measure for response in multiple myeloma (MM) and its correct interpretation is key to clinical management. The emergence of oligoclonal banding is recognized as a benign finding in the postautologous stem cell transplantation setting (ASCT) for MM but its significance during non-myeloablative therapy is unknown. In a study of the immunomodulatory combination BiRD, (lenalidomide and dexamethasone with clarithromycin), we frequently detected the emergence of mono- and oligo-clonal immunoglobulins unrelated to the baseline diagnostic M-protein. The new M-proteins seen on serum immunofixation electrophoresis were clearly different in either heavy or light chain component(s) from the original M-spike protein and were termed atypical serum immunofixation patterns (ASIPs). Overall, 24/72 (33%) patients treated with BiRD developed ASIPs. Patients who developed ASIPs compared with patients treated with BiRD without ASIPs, had a significantly greater overall response (100% vs. 85%) and complete response rates (71% vs. 23%). ASIPs were not associated with new clonal plasma cells or other lymphoproliferative processes, and molecular remissions were documented. This is the first time this phenomenon has been seen with regularity in non-myeloablative therapy for MM. Analogous to the ASCT experience, ASIPs do not signal incipient disease progression, but rather herald robust response.

  7. Farmer responses to multiple stresses in the face of global change: Assessing five case studies to enhance adaptation

    Science.gov (United States)

    Nicholas, K. A.; Feola, G.; Lerner, A. M.; Jain, M.; Montefrio, M.

    2013-12-01

    The global challenge of sustaining agricultural livelihoods and yields in the face of growing populations and increasing climate change is the topic of intense research. The role of on-the-ground decision-making by individual farmers actually producing food, fuel, and fiber is often studied in individual cases to determine its environmental, economic, and social effects. However, there are few efforts to link across studies in a way that provides opportunities to better understand empirical farmer behavior, design effective policies, and be able to aggregate from case studies to a broader scale. Here we synthesize existing literature to identify four general factors affecting farmer decision-making: local technical and socio-cultural contexts; actors and institutions involved in decision-making; multiple stressors at broader scales; and the temporal gradient of decision-making. We use these factors to compare five cases that illustrate agricultural decision-making and its impacts: cotton and castor farming in Gujarat, India; swidden cultivation of upland rice in the Philippines; potato cultivation in Andean Colombia; winegrowing in Northern California; and maize production in peri-urban central Mexico. These cases span a geographic and economic range of production systems, but we find that we are able to make valid comparisons and draw lessons common across all cases by using the four factors as an organizing principle. We also find that our understanding of why farmers make the decisions they do changes if we neglect to examine even one of the four general factors guiding decision-making. This suggests that these four factors are important to understanding farmer decision-making, and can be used to guide the design and interpretation of future studies, as well as be the subject of further research in and of themselves to promote an agricultural system that is resilient to climate and other global environmental changes.

  8. The main component of an alarm pheromone of kissing bugs plays multiple roles in the cognitive modulation of the escape response

    Directory of Open Access Journals (Sweden)

    Sebastián eMinoli

    2013-07-01

    Full Text Available Innate responses in animals can be modulated by experience. Disturbed adults of the triatomine bug Triatoma infestans release an alarm pheromone (AP that elicits an escape response in conspecific larvae. The main component of this AP, the isobutyric acid (IsoAc, alone has already shown to generate an escape response in this species. However, not much is known about the modulation of this behavior by non-associative and associative cognitive processes. We present here evidences of the cognitive capacities of T. infestans larvae in an escape context under different conditioning paradigms, including IsoAc in different roles. We show that: 1 the duration of a pre-exposure to IsoAc plays a main role in determining the type of non-associative learning expressed: short time pre-exposures elicit a sensitization while a longer pre-exposure time triggers a switch from repellence to attractiveness; 2 a simple pre-exposure event is enough to modulate the escape response of larvae to the AP and to its main component: IsoAc; 3 IsoAc and the AP are perceived as different chemical entities; 4 an association between IsoAc and an aversive stimulus can be created under a classical conditioning paradigm; 5 an association between IsoAc and a self-action can be generated under an operant conditioning. These results evince that IsoAc can attain multiple and different cognitive roles in the modulation of the escape response of triatomines and show how cognitive processes can modulate a key behavior for surviving, as it is the escaping response in presence of a potential danger in insects.

  9. Microarray analysis of the transcriptional response to single or multiple doses of ionizing radiation in human subcutaneous fibroblasts

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Overgaard, Jens; Alsner, Jan

    2005-01-01

    cell lines after various ionizing radiation (IR) schemes in order to provide information on potential targets for prevention and to suggest candidate genes for SNP association studies aimed at predicting individual risk of radiation-induced morbidity. PATIENTS AND METHODS: Thirty different human......BACKGROUND AND PURPOSE: Transcriptional profiling of fibroblasts derived from breast cancer patients might improve our understanding of subcutaneous radiation-induced fibrosis. The aim of this study was to get a comprehensive overview of the changes in gene expression in subcutaneous fibroblast...... fibroblast cell lines were included in the study, and two different radiation schemes; single dose experiments with 3.5 Gy or fractionated with 3 x 3.5 Gy. Expression analyses were performed on unexposed and exposed cells after different time points. The IR response was analyzed using the statistical method...

  10. Long-term dynamics of tropical walking sticks in response to multiple large-scale and intense disturbances.

    Science.gov (United States)

    Willig, Michael R; Presley, Steven J; Bloch, Christopher P

    2011-02-01

    Understanding the effects of disturbance and secondary succession on spatio-temporal patterns in the abundance of species is stymied by a lack of long-term demographic data, especially in response to infrequent and high intensity disturbances, such as hurricanes. Moreover, resistance and resilience to hurricane-induced disturbance may be mediated by legacies of previous land use, although such interactive effects are poorly understood, especially in tropical environments. We address these central issues in disturbance ecology by analyzing an extensive dataset, spanning the impacts of Hurricanes Hugo and Georges, on the abundance of a Neotropical walking stick, Lamponius portoricensis, in tabonuco rainforest of Puerto Rico during the wet and dry seasons from 1991 to 2007. By synthesizing data from two proximate sites in tabonuco forest, we show that resistance to Hurricane Hugo (97% reduction in abundance) was much less than resistance to Hurricane Georges (21% reduction in abundance). Based on a powerful statistical approach (generalized linear mixed-effects models with Poisson error terms), we documented that the temporal trajectories of abundance during secondary succession (i.e., patterns of resilience) differed between hurricanes and among historical land use categories, but that the effects of hurricanes and land use histories were independent of each other. These complex results likely arise because of differences in the intensities of the two hurricanes with respect to microclimatic effects (temperature and moisture) in the forest understory, as well as to time-lags in the response of L. portoricensis to changes in the abundance and distribution of preferred food plants (Piper) in post-hurricane environments.

  11. Tuning of the Lethal Response to Multiple Stressors with a Single-Site Mutation during Clinical Infection by Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Krishan Kumar

    2017-10-01

    Full Text Available The agr system of Staphylococcus aureus promotes invasion of host tissues, and as expected, agents that block agr quorum sensing have anti-infective properties. Paradoxically, agr-defective mutants are frequently recovered from patients, especially those persistently infected with S. aureus. We found that an agr deficiency increased survival of cultured bacteria during severe stress, such as treatment with gentamicin, ciprofloxacin, heat, or low pH. With daptomycin, deletion of agr decreased survival. Therefore, agr activity can be either detrimental or protective, depending on the type of lethal stress. Deletion of agr had no effect on the ability of the antimicrobials to block bacterial growth, indicating that agr effects are limited to lethal action. Thus, the effect of an agr deletion is on bacterial tolerance, not resistance. For gentamicin and daptomycin, activity can be altered by agr-regulated secreted factors. For ciprofloxacin, a detrimental function was downregulation of glutathione peroxidase (bsaA, an enzyme responsible for defense against oxidative stress. Deficiencies in agr and bsaA were epistatic for survival, consistent with agr having a destructive role mediated by reactive oxygen species. Enhanced susceptibility to lethal stress by wild-type agr, particularly antimicrobial stress, helps explain why inactivating mutations in S. aureus agr commonly occur in hospitalized patients during infection. Moreover, the agr quorum-sensing system of S. aureus provides a clinically relevant example in which a single-step change in the response to severe stress alters the evolutionary path of a pathogen during infection.

  12. Multiple-stimuli responsive bioelectrocatalysis based on reduced graphene oxide/poly(N-isopropylacrylamide) composite films and its application in the fabrication of logic gates.

    Science.gov (United States)

    Wang, Lei; Lian, Wenjing; Yao, Huiqin; Liu, Hongyun

    2015-03-11

    In the present work, reduced graphene oxide (rGO)/poly(N-isopropylacrylamide) (PNIPAA) composite films were electrodeposited onto the surface of Au electrodes in a fast and one-step manner from an aqueous mixture of a graphene oxide (GO) dispersion and N-isopropylacrylamide (NIPAA) monomer solutions. Reflection-absorption infrared (IR) and Raman spectroscopies were employed to characterize the successful construction of the rGO/PNIPAA composite films. The rGO/PNIPAA composite films exhibited reversible potential-, pH-, temperature-, and sulfate-sensitive cyclic voltammetric (CV) on-off behavior to the electroactive probe ferrocenedicarboxylic acid (Fc(COOH)2). For instance, after the composite films were treated at -0.7 V for 7 min, the CV responses of Fc(COOH)2 at the rGO/PNIPAA electrodes were quite large at pH 8.0, exhibiting the on state. However, after the films were treated at 0 V for 30 min, the CV peak currents became much smaller, demonstrating the off state. The mechanism of the multiple-stimuli switchable behaviors for the system was investigated not only by electrochemical methods but also by scanning electron microscopy and X-ray photoelectron spectroscopy. The potential-responsive behavior for this system was mainly attributed to the transformation between rGO and GO in the films at different potentials. The film system was further used to realize multiple-stimuli responsive bioelectrocatalysis of glucose catalyzed by the enzyme of glucose oxidase and mediated by the electroactive probe of Fc(COOH)2 in solution. On the basis of this, a four-input enabled OR (EnOR) logic gate network was established.

  13. Targeting Ongoing DNA Damage in Multiple Myeloma: Effects of DNA Damage Response Inhibitors on Plasma Cell Survival

    Directory of Open Access Journals (Sweden)

    Ana Belén Herrero

    2017-05-01

    Full Text Available Human myeloma cell lines (HMCLs and a subset of myeloma patients with poor prognosis exhibit high levels of replication stress (RS, leading to DNA damage. In this study, we confirmed the presence of DNA double-strand breaks (DSBs in several HMCLs by measuring γH2AX and RAD51 foci and analyzed the effect of various inhibitors of the DNA damage response on MM cell survival. Inhibition of ataxia telangiectasia and Rad3-related protein (ATR, the main kinase mediating the response to RS, using the specific inhibitor VE-821 induced more cell death in HMCLs than in control lymphoblastoid cells and U266, an HMCL with a low level of DNA damage. The absence of ATR was partially compensated by ataxia telangiectasia-mutated protein (ATM, since chemical inhibition of both kinases using VE-821 and KU-55933 significantly increased the death of MM cells with DNA damage. We found that ATM and ATR are involved in DSB repair by homologous recombination (HR in MM. Inhibition of both kinases resulted in a stronger inhibition that may underlie cell death induction, since abolition of HR using two different inhibitors severely reduced survival of HMCLs that exhibit DNA damage. On the other hand, inhibition of the other route involved in DSB repair, non-homologous end joining (NHEJ, using the DNA-PK inhibitor NU7441, did not affect MM cell viability. Interestingly, we found that NHEJ inhibition did not increase cell death when HR was simultaneously inhibited with the RAD51 inhibitor B02, but it clearly increased the level of cell death when HR was inhibited with the MRE11 inhibitor mirin, which interferes with recombination before DNA resection takes place. Taken together, our results demonstrate for the first time that MM cells with ongoing DNA damage rely on an intact HR pathway, which thereby suggests therapeutic opportunities. We also show that inhibition of HR after the initial step of end resection might be more appropriate for inducing MM cell death, since it

  14. An analytical/numerical correlation study of the multiple concentric cylinder model for the thermoplastic response of metal matrix composites

    Science.gov (United States)

    Pindera, Marek-Jerzy; Salzar, Robert S.; Williams, Todd O.

    1993-01-01

    The utility of a recently developed analytical micromechanics model for the response of metal matrix composites under thermal loading is illustrated by comparison with the results generated using the finite-element approach. The model is based on the concentric cylinder assemblage consisting of an arbitrary number of elastic or elastoplastic sublayers with isotropic or orthotropic, temperature-dependent properties. The elastoplastic boundary-value problem of an arbitrarily layered concentric cylinder is solved using the local/global stiffness matrix formulation (originally developed for elastic layered media) and Mendelson's iterative technique of successive elastic solutions. These features of the model facilitate efficient investigation of the effects of various microstructural details, such as functionally graded architectures of interfacial layers, on the evolution of residual stresses during cool down. The available closed-form expressions for the field variables can readily be incorporated into an optimization algorithm in order to efficiently identify optimal configurations of graded interfaces for given applications. Comparison of residual stress distributions after cool down generated using finite-element analysis and the present micromechanics model for four composite systems with substantially different temperature-dependent elastic, plastic, and thermal properties illustrates the efficacy of the developed analytical scheme.

  15. Multiple response optimization of the coagulation process for upgrading the quality of effluent from municipal wastewater treatment plant

    Science.gov (United States)

    Li, Na; Hu, Yi; Lu, Yong-Ze; Zeng, Raymond J.; Sheng, Guo-Ping

    2016-05-01

    To meet the high quality standard of receiving water, the coagulation process using polyferric chloride (PFC) was used to further improve the water quality of effluent from wastewater treatment plants. Uniform design (UD) coupled with response surface methodology (RSM) was adopted to assess the effects of the main influence factors: coagulant dosage, pH and basicity, on the removal of total organic carbon (TOC), NH4+-N and PO43--P. A desirability function approach was used to effectively optimize the coagulation process for the comprehensive removal of TOC, NH4+-N and PO43--P to upgrade the effluent quality in practical application. The optimized operating conditions were: dosage 28 mg/L, pH 8.5 and basicity 0.001. The corresponding removal efficiencies for TOC, NH4+-N and PO43--P were 77.2%, 94.6% and 20.8%, respectively. More importantly, the effluent quality could upgrade to surface water Class V of China through coagulation under optimal region. In addition, grey relational analysis (GRA) prioritized these three factors as: pH > basicity > dosage (for TOC), basicity > dosage > pH (for NH4+-N), pH > dosage > basicity (for PO43--P), which would help identify the most important factor to control the treatment efficiency of various effluent quality indexes by PFC coagulation.

  16. Measuring decision weights in recognition experiments with multiple response alternatives: comparing the correlation and multinomial-logistic-regression methods.

    Science.gov (United States)

    Dai, Huanping; Micheyl, Christophe

    2012-11-01

    Psychophysical "reverse-correlation" methods allow researchers to gain insight into the perceptual representations and decision weighting strategies of individual subjects in perceptual tasks. Although these methods have gained momentum, until recently their development was limited to experiments involving only two response categories. Recently, two approaches for estimating decision weights in m-alternative experiments have been put forward. One approach extends the two-category correlation method to m > 2 alternatives; the second uses multinomial logistic regression (MLR). In this article, the relative merits of the two methods are discussed, and the issues of convergence and statistical efficiency of the methods are evaluated quantitatively using Monte Carlo simulations. The results indicate that, for a range of values of the number of trials, the estimated weighting patterns are closer to their asymptotic values for the correlation method than for the MLR method. Moreover, for the MLR method, weight estimates for different stimulus components can exhibit strong correlations, making the analysis and interpretation of measured weighting patterns less straightforward than for the correlation method. These and other advantages of the correlation method, which include computational simplicity and a close relationship to other well-established psychophysical reverse-correlation methods, make it an attractive tool to uncover decision strategies in m-alternative experiments.

  17. Shifts in Arctic phenology in response to climate and anthropogenic factors as detected from multiple satellite time series

    International Nuclear Information System (INIS)

    Zeng, Heqing; Jia, Gensuo; Forbes, Bruce C

    2013-01-01

    There is an urgent need to reduce the uncertainties in remotely sensed detection of phenological shifts of high latitude ecosystems in response to climate changes in past decades. In this study, vegetation phenology in western Arctic Russia (the Yamal Peninsula) was investigated by analyzing and comparing Normalized Difference Vegetation Index (NDVI) time series derived from the Advanced Very High Resolution Radiometer (AVHRR), the Moderate Resolution Imaging Spectroradiometer (MODIS), and SPOT-Vegetation (VGT) during the decade 2000–2010. The spatial patterns of key phenological parameters were highly heterogeneous along the latitudinal gradients based on multi-satellite data. There was earlier SOS (start of the growing season), later EOS (end of the growing season), longer LOS (length of the growing season), and greater MaxNDVI from north to south in the region. The results based on MODIS and VGT data showed similar trends in phenological changes from 2000 to 2010, while quite a different trend was found based on AVHRR data from 2000 to 2008. A significantly delayed EOS (p < 0.01), thus increasing the LOS, was found from AVHRR data, while no similar trends were detected from MODIS and VGT data. There were no obvious shifts in MaxNDVI during the last decade. MODIS and VGT data were considered to be preferred data for monitoring vegetation phenology in northern high latitudes. Temperature is still a key factor controlling spatial phenological gradients and variability, while anthropogenic factors (reindeer husbandry and resource exploitation) might explain the delayed SOS in southern Yamal. Continuous environmental damage could trigger a positive feedback to the delayed SOS. (letter)

  18. Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study

    Directory of Open Access Journals (Sweden)

    Ulivi Paola

    2012-05-01

    Full Text Available Abstract Background KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC patients. As only 20% of KRAS wild type (WT patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR progression-free (PFS and overall survival (OS with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen. Methods 67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry. Results BRAF and PIK3CA mutations were independently associated with worse PFS (p = 0.006 and p = 0.028, respectively and OS (p = 0.008 and p = 0.029, respectively. No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for KRAS, BRAF and PIK3CA mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations. Conclusions BRAF and PIK3CA mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.

  19. Genome-Wide Association Mapping Reveals Multiple QTLs Governing Tolerance Response for Seedling Stage Chilling Stress in Indica Rice

    Directory of Open Access Journals (Sweden)

    Sharat K. Pradhan

    2017-04-01

    Full Text Available Rice crop is sensitive to cold stress at seedling stage. A panel of population representing 304 shortlisted germplasm lines was studied for seedling stage chilling tolerance in indica rice. Six phenotypic classes were exposed to six low temperature stress regimes under control phenotyping facility to investigate response pattern. A panel of 66 genotypes representing all phenotypic classes was used for ensuring genetic diversity, population structure and association mapping for the trait using 58 simple sequence repeat (SSR and 2 direct trait linked markers. A moderate level of genetic diversity was detected in the panel population for the trait. Deviation of Hardy-Weinberg's expectation was detected in the studied population using Wright's F statistic. The panel showed 30% variation among population and 70% among individuals. The entire population was categorized into three sub-populations through STRUCTURE analysis. This revealed tolerance for the trait had a common primary ancestor for each sub-population with few admix individuals. The panel population showed the presence of many QTLs for cold stress tolerance in the individuals representing like genome-wide expression of the trait. Nineteen SSR markers were significantly associated at chilling stress of 8°C to 4°C for 7–21 days duration. Thus, the primers linked to the seedling stage cold tolerance QTLs namely qCTS9, qCTS-2, qCTS6.1, qSCT2, qSCT11, qSCT1a, qCTS-3.1, qCTS11.1, qCTS12.1, qCTS-1b, and CTB2 need to be pyramided for development of strongly chilling tolerant variety.

  20. Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.

    Science.gov (United States)

    Hu, Chuanpu; Randazzo, Bruce; Sharma, Amarnath; Zhou, Honghui

    2017-10-01

    Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

  1. Immune response induced by Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis peptides in current and past infectious mononucleosis: a risk for multiple sclerosis?

    Science.gov (United States)

    Mameli, G; Madeddu, G; Cossu, D; Galleri, G; Manetti, R; Babudieri, S; Mura, M Stella; Sechi, L A

    2016-01-01

    Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) has been associated with increased risk of multiple sclerosis (MS). However, the mechanism linking these pathologies is unclear. Different reports indicate the association of EBV, and recently Mycobacterium avium subsp. paratuberculosis (MAP), with MS. For a better understanding of the role of these pathogens, the host response induced by selected antigenic peptides in subjects with a history of IM that significantly increases the risk of MS was investigated. Both humoral and cell-mediated response against peptides able to induce a specific immune activation in MS patients deriving from lytic and latent EBV antigens BOLF1(305-320), EBNA1(400-413), from MAP MAP_4027(18-32), MAP_0106c(121-132) and from human proteins IRF5(424-434) and MBP(85-98) in subjects with current and past IM were examined. EBNA1 and MAP_0106c peptides were able to induce a humoral immune response in subjects with a history of clinical IM in an independent manner. Moreover, these peptides were capable of inducing pro-inflammatory cytokine interferon γ by CD4+ and CD8+ T lymphocytes and interleukin 6 and tumour necrosis factor α by CD14+ monocyte cells. Our results highlight that EBV and MAP may be involved independently in the same causal process leading to MS in subjects with a history of IM. © 2015 EAN.

  2. In vivo quantification of response to treatment in patients with multiple myeloma by 1H magnetic resonance spectroscopy of bone marrow.

    Science.gov (United States)

    Oriol, Albert; Valverde, Daniel; Capellades, Jaume; Cabañas, Miquel E; Ribera, Josep-Maria; Arús, Carles

    2007-04-01

    Magnetic resonance imaging (MRI) is the gold standard non-invasive technique to detect malignant disease in the bone marrow. Proton magnetic resonance spectroscopy (MRS) can be performed as a quick adjunct to routine spinal MRI. We performed proton MRS to patients with multiple myeloma (MM) at diagnosis and after treatment to investigate the possible correlation of MRS data with response to therapy. Twenty-one patients with newly diagnosed MM underwent combined MRI/MRS explorations of a transverse center section in the fifth lumbar vertebral body. MRS was acquired with STEAM and 40 ms TE. Areas of unsuppressed water and lipid resonances were used to calculate the lipid-to-water ratio (LWR). No association was detected between initial LWRs and the clinical characteristics of patients. Post treatment MRS was available in 16 patients of whom 11 (69%) presented an LWR increase, this included all complete responders (8/8, 100%, P = 0.012). A post-treatment LWR value equal to or larger than one is proposed as a non-invasive marker of complete response to treatment. Only patients responding to treatment presented a significant increase in bone marrow LWR after therapy. MRS may provide an adequate quantification of response to chemotherapy in patients with MM.

  3. The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis.

    Science.gov (United States)

    Wunsch, Marie; Hohmann, Christopher; Milles, Bianca; Rostermund, Christina; Lehmann, Paul V; Schroeter, Michael; Bayas, Antonios; Ulzheimer, Jochen; Mäurer, Mathias; Ergün, Süleyman; Kuerten, Stefanie

    2016-04-23

    There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy.

  4. The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Marie Wunsch

    2016-04-01

    Full Text Available There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV infection and brain inflammation in multiple sclerosis (MS. Here, we tested MS patients during relapse (n = 11 and in remission (n = 19 in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT and enzyme-linked immunosorbent assay (ELISA. Cytomegalovirus (CMV was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy.

  5. Pharmacodynamic effects of steady-state fingolimod on antibody response in healthy volunteers: a 4-week, randomized, placebo-controlled, parallel-group, multiple-dose study.

    Science.gov (United States)

    Boulton, Craig; Meiser, Karin; David, Olivier J; Schmouder, Robert

    2012-12-01

    Fingolimod, a first-in-class oral sphingosine 1-phosphate receptor (S1PR) modulator, is approved in many countries for relapsing-remitting multiple sclerosis, at a once-daily 0.5-mg dose. A reduction in peripheral lymphocyte count is an expected consequence of the fingolimod mechanism of S1PR modulation. The authors investigated if this pharmacodynamic effect impacts humoral and cellular immunogenicity. In this double-blind, parallel-group, 4-week study, 72 healthy volunteers were randomized to steady state, fingolimod 0.5 mg, 1.25 mg, or to placebo. The authors compared T-cell dependent and independent responses to the neoantigens, keyhole limpet hemocyanin (KLH), and pneumococcal polysaccharides vaccine (PPV-23), respectively, and additionally recall antigen response (tetanus toxoid [TT]) and delayed-type hypersensitivity (DTH) to KLH, TT, and Candida albicans. Fingolimod caused mild to moderate decreases in anti-KLH and anti-PPV-23 IgG and IgM levels versus placebo. Responder rates were identical between placebo and 0.5-mg groups for anti-KLH IgG (both > 90%) and comparable for anti-PPV-23 IgG (55% and 41%, respectively). Fingolimod did not affect anti-TT immunogenicity, and DTH response did not differ between placebo and fingolimod 0.5-mg groups. Expectedly, lymphocyte count reduced substantially in the fingolimod groups versus placebo but reversed by study end. Fingolimod was well tolerated, and the observed safety profile was consistent with previous reports.

  6. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    Science.gov (United States)

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

  7. Tandem Autologous Stem Cell Transplantation for Multiple Myeloma Patients Based on Response to Their First Transplant—A Prospective Phase II Study

    Science.gov (United States)

    Byrne, Michael; Salmasinia, Donya; Leather, Helen; Cogle, Christopher R; Davis, Amy; Hsu, Jack W; Wiggins, Laura; Chang, Myron N; An, Qi; Wingard, John R; Moreb, Jan S

    2014-01-01

    In this prospective phase II clinical trial, multiple myeloma (MM) patients were randomized to receive a second (tandem) autologous stem cell transplantation (ASCT) based on whether they achieved a partial response or worse (≤PR) following initial ASCT (ASCT1). Patients who achieved a very good partial response or better (≥VGPR) had salvage ASCT at relapse. Seventy-five patients received conditioning therapy and ASCT1. A total of 44 patients (59%) achieved ≥VGPR, whereas 31 patients entered ≤PR and were offered tandem ASCT. In all, 20 patients agreed to tandem ASCT. Demographic and clinical characteristics were similar between the two cohorts except for median lactate dehydrogenase (LDH) (P = 0.0141) and percentage of marrow plasma cells before ASCT1 (P = 0.0047), both lower in the ≥VGPR group. Intent to treat analysis showed that patients who achieved ≥VGPR to ASCT1 had a trend toward improved progression-free survival (PFS) (37 vs. 26 months, P = 0.078) and superior overall survival (OS) (not reached vs. 50 months, P = 0.0073). Patients with ≤PR who declined tandem transplantation had shortened PFS (20 vs. 28 months, P = 0.05) but similar OS (53 vs. 57.5 months, P = 0.29) compared to those who received it. Thus, a favorable clinical response to ASCT1 identifies a low-risk group with superior long-term prognosis despite similar PFS. PMID:25232286

  8. USE OF NEUROFEEDBACK AND MINDFULNESS TO ENHANCE RESPONSE TO HYPNOSIS TREATMENT IN INDIVIDUALS WITH MULTIPLE SCLEROSIS: Results From a Pilot Randomized Clinical Trial.

    Science.gov (United States)

    Jensen, Mark P; Battalio, Samuel L; Chan, Joy F; Edwards, Karlyn A; Day, Melissa A; Sherlin, Leslie H; Ehde, Dawn M

    2018-01-01

    This pilot study evaluated the possibility that 2 interventions hypothesized to increase slower brain oscillations (e.g., theta) may enhance the efficacy of hypnosis treatment, given evidence that hypnotic responding is associated with slower brain oscillations. Thirty-two individuals with multiple sclerosis and chronic pain, fatigue, or both, were randomly assigned to 1 of 2 interventions thought to increase slow wave activity (mindfulness meditation or neurofeedback training) or no enhancing intervention, and then given 5 sessions of self-hypnosis training targeting their presenting symptoms. The findings supported the potential for both neurofeedback and mindfulness to enhance response to hypnosis treatment. Research using larger sample sizes to determine the generalizability of these findings is warranted.

  9. [A case of transverse colon cancer with multiple liver metastases and hepatic pedicle lymph node involvement showing pathological complete response by XELOX plus bevacizumab].

    Science.gov (United States)

    Mukai, Toshiki; Akiyoshi, Takashi; Koga, Rintaro; Arita, Junichi; Saiura, Akio; Ikeda, Atsushi; Nagasue, Yasutomo; Oikawa, Yoshinori; Yamakawa, Keiko; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi; Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Yamamoto, Chiriko; Yamaguchi, Toshiharu

    2012-12-01

    A 70-year-old woman was referred to our hospital because of abdominal pain. Abdominal computed tomography(CT)and colonoscopy revealed transverse colon cancer with multiple liver metastases, with involvement of the hepatic pedicle and superior mesenteric artery lymph nodes. The patient received eight courses of XELOX plus bevacizumab, and CT showed a decrease in the size of the liver metastases and hepatic pedicle lymphadenopathy. Right hemicolectomy, partial hepatectomy, and hepatic pedicle lymph node resection were performed. Histopathological examination of the resected tissue revealed no residual cancer cells, suggesting a pathological complete response. The patient remains well 7 months after operation, without any signs of recurrence. Surgical resection should be considered for patients with initially unresectable colon cancer with liver metastases and hepatic pedicle lymph nodes involvement if systemic chemotherapy is effective.

  10. Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response.

    Science.gov (United States)

    Kilaparty, Surya P; Agarwal, Rakhee; Singh, Pooja; Kannan, Krishnaswamy; Ali, Nawab

    2016-07-01

    Inositol polyphosphates represent a group of differentially phosphorylated inositol metabolites, many of which are implicated to regulate diverse cellular processes such as calcium mobilization, vesicular trafficking, differentiation, apoptosis, etc. The metabolic network of these compounds is complex and tightly regulated by various kinases and phosphatases present predominantly in the cytosol. Multiple inositol polyphosphate phosphatase 1 (Minpp1) is the only known endoplasmic reticulum (ER) luminal enzyme that hydrolyzes various inositol polyphosphates in vitro as well as in vivo conditions. However, access of the Minpp1 to cytosolic substrates has not yet been demonstrated clearly and hence its physiological function. In this study, we examined a potential role for Minpp1 in ER stress-induced apoptosis. We generated a custom antibody and characterized its specificity to study the expression of Minpp1 protein in multiple mammalian cells under experimentally induced cellular stress conditions. Our results demonstrate a significant increase in the expression of Minpp1 in response to a variety of cellular stress conditions. The protein expression was corroborated with the expression of its mRNA and enzymatic activity. Further, in an attempt to link the role of Minpp1 to apoptotic stress, we studied the effect of Minpp1 expression on apoptosis following silencing of the Minpp1 gene by its specific siRNA. Our results suggest an attenuation of apoptotic parameters following knockdown of Minpp1. Thus, in addition to its known role in inositol polyphosphate metabolism, we have identified a novel role for Minpp1 as a stress-responsive protein. In summary, our results provide, for the first time, a probable link between ER stress-induced apoptosis and Minpp1 expression.

  11. Detecting early response to cyclophosphamide treatment of RIF-1 tumors using selective multiple quantum spectroscopy (SelMQC) and dynamic contrast enhanced imaging.

    Science.gov (United States)

    Poptani, Harish; Bansal, Navin; Graham, Robert A; Mancuso, Anthony; Nelson, David S; Glickson, Jerry D

    2003-04-01

    The purpose of this study was to develop a reliable, noninvasive method for early detection of tumor response to therapy that would facilitate optimization of treatment regimens to the needs of the individual patient. In the present study, the effects of cyclophosphamide (Cp, a widely used alkylating agent) were monitored in a murine radiation induced fibrosarcoma (RIF-1) using in vivo (1)H NMR spectroscopy and imaging to evaluate the potential of these techniques towards early detection of treatment response. Steady-state lactate levels and Gd-DTPA uptake kinetics were measured using selective multiple quantum coherence (Sel-MQC) transfer spectroscopy and dynamic contrast enhanced imaging, respectively in RIF-1 tumors before, 24 and 72 h after 300 mg/kg of Cp administration. High-resolution (1)H NMR spectra of perchloric acid extracts of the tumor were correlated with lactate and glucose concentrations determined enzymatically. In vivo NMR experiments showed a decrease in steady-state lactate to water ratios (5.4 +/- 1.6 to 0.6 +/- 0.5, p < 0.05) and an increase in Gd-DTPA uptake kinetics following treatment response. The data indicate that decreases in lactate result from decreased glycolytic metabolism and an increase in tumor perfusion/permeability. Perchloric acid extracts confirmed the lower lactate levels seen in vivo in treated tumors and also indicated a higher glycerophosphocholine/phosphocholine (GPC/PC) integrated intensity ratio (1.39 +/- 0.09 vs 0.97 +/- 0.04, p < 0.01), indicative of increased membrane degradation following Cp treatment. Steady-state lactate levels provide metabolic information that correlates with changes in tumor physiology measured by Gd-DTPA uptake kinetics with high spatial and temporal resolution. Both of these parameters may be useful for monitoring early tumor response to therapy. Copyright 2003 John Wiley & Sons, Ltd.

  12. Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.

    Science.gov (United States)

    Dorigatti, Ilaria; Aguas, Ricardo; Donnelly, Christl A; Guy, Bruno; Coudeville, Laurent; Jackson, Nicholas; Saville, Melanie; Ferguson, Neil M

    2015-07-17

    The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the first dose. This study contributes to a better understanding of the immunological responses elicited by CYD-TDV. The recent availability of phase-3 data is a unique opportunity to further investigate the immunogenicity and efficacy of the CYD-TDV vaccine, especially in subjects with different levels of pre-existing immunity against DENV. Modelling multiple immunological outcomes with a single multivariate model offers advantages over traditional approaches, capturing correlations between response variables, and the statistical method adopted in this study can be applied to a variety of infections with interacting strains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Whole-body MRI quantitative biomarkers are associated significantly with treatment response in patients with newly diagnosed symptomatic multiple myeloma following bortezomib induction

    Energy Technology Data Exchange (ETDEWEB)

    Latifoltojar, Arash; Dikaios, Nikolaos [University College London, Centre for Medical Imaging, London (United Kingdom); Hall-Craggs, Margaret; Taylor, Stuart A.; Halligan, Steve; Punwani, Shonit [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospital, Department of Radiology, London (United Kingdom); Bainbridge, Alan; Sokolska, Magdalena [University College London Hospital, Department of Medical Physics and Bioengineering, London (United Kingdom); Rabin, Neil; Popat, Rakesh; Rismani, Ali; D' Sa, Shirley; Yong, Kwee [University College London Hospital, Department of Haematology, London (United Kingdom); Antonelli, Michela; Ourselin, Sebastien [University College London, Translational Imaging Group, Centre for Medical Imaging Computing, London (United Kingdom)

    2017-12-15

    To evaluate whole-body MRI (WB-MRI) parameters significantly associated with treatment response in multiple myeloma (MM). Twenty-one MM patients underwent WB-MRI at diagnosis and after two cycles of chemotherapy. Scans acquired at 3.0 T included T2, diffusion-weighted-imaging (DWI) and mDixon pre- and post-contrast. Twenty focal lesions (FLs) matched on DWI and post-contrast mDixon were selected for each time point. Estimated tumour volume (eTV), apparent diffusion coefficient (ADC), enhancement ratio (ER) and signal fat fraction (sFF) were derived. Clinical treatment response to chemotherapy was assessed using conventional criteria. Significance of temporal parameter change was assessed by the paired t test and receiver operating characteristics/area under the curve (AUC) analysis was performed. Parameter repeatability was assessed by interclass correlation (ICC) and Bland-Altman analysis of 10 healthy volunteers scanned at two time points. Fifteen of 21 patients responded to treatment. Of 254 FLs analysed, sFF (p < 0.0001) and ADC (p = 0.001) significantly increased in responders but not non-responders. eTV significantly decreased in 19/21 cases. Focal lesion sFF was the best discriminator of treatment response (AUC 1.0). Bone sFF repeatability was excellent (ICC 0.98) and better than bone ADC (ICC 0.47). WB-MRI derived focal lesion sFF shows promise as an imaging biomarker of treatment response in newly diagnosed MM. (orig.)

  14. Ovarian response to 150 µg corifollitropin alfa in a GnRH-antagonist multiple-dose protocol: a prospective cohort study.

    Science.gov (United States)

    Lerman, Tamara; Depenbusch, Marion; Schultze-Mosgau, Askan; von Otte, Soeren; Scheinhardt, Markus; Koenig, Inke; Kamischke, Axel; Macek, Milan; Schwennicke, Arne; Segerer, Sabine; Griesinger, Georg

    2017-05-01

    The incidence of low (18 oocytes) ovarian response to 150 µg corifollitropin alfa in relation to anti-Müllerian hormone (AMH) and other biomarkers was studied in a multi-centre (n = 5), multi-national, prospective, investigator-initiated, observational cohort study. Infertile women (n = 212), body weight >60 kg, underwent controlled ovarian stimulation in a gonadotrophin-releasing hormone-antagonist multiple-dose protocol. Demographic, sonographic and endocrine parameters were prospectively assessed on cycle day 2 or 3 of a spontaneous menstruation before the administration of 150 µg corifollitropin alfa. Serum AMH showed the best correlation with the number of oocytes obtained among all predictor variables. In receiver-operating characteristic analysis, AMH at a threshold of 0.91 ng/ml showed a sensitivity of 82.4%, specificity of 82.4%, positive predictive value 52.9%and negative predictive value 95.1% for predicting low response (area under the curve [AUC], 95% CI; P-value: 0.853, 0.769-0.936; <0.0001). For predicting high response, the optimal threshold for AMH was 2.58 ng/ml, relating to a sensitivity of 80.0%, specificity 82.1%, positive predictive value 42.5% and negative predictive value 96.1% (AUC, 95% CI; P-value: 0.871, 0.787-0.955; <0.0001). In conclusion, patients with serum AMH concentrations between approximately 0.9 and 2.6 ng/ml were unlikely to show extremes of response. Copyright © 2017. Published by Elsevier Ltd.

  15. Response

    Science.gov (United States)

    Higgins, Chris

    2012-01-01

    This article presents the author's response to the reviews of his book, "The Good Life of Teaching: An Ethics of Professional Practice." He begins by highlighting some of the main concerns of his book. He then offers a brief response, doing his best to address the main criticisms of his argument and noting where the four reviewers (Charlene…

  16. Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Sandra Hellberg

    2016-09-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

  17. Riboflavin-Responsive Multiple Acyl-CoA Dehydrogenase Deficiency Associated with Hepatoencephalomyopathy and White Matter Signal Abnormalities on Brain MRI.

    Science.gov (United States)

    Vieira, Päivi; Myllynen, Päivi; Perhomaa, Marja; Tuominen, Hannu; Keski-Filppula, Riikka; Rytky, Seppo; Risteli, Leila; Uusimaa, Johanna

    2017-06-01

    Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting both fatty acid and amino acid oxidation. It can manifest at any age, but riboflavin-responsiveness has mainly been described in less severely affected patients. We describe an infant with severe MADD presenting with profound hypotonia and hepatomegaly. Treatment with riboflavin improved his muscle strength, liver size, and biochemical markers. A homozygous mutation of electron transfer flavoprotein dehydrogenase ( ETFDH ) was found. His motor skills continued to progress until a fatal infection-triggered deterioration at the age of 34 months. We show changes in brain magnetic resonance imaging over the course of the disease, with profound white matter abnormalities during the deterioration phase. Aggregates of mitochondria with abnormal cristae in muscle electron microscopy were noticed already in infancy. An unusual lactate dehydrogenase (LDH) isoenzyme pattern with LDH-1 predominance was additionally observed. This case demonstrates riboflavin-responsiveness in a severely affected infant with both muscular and extramuscular involvement and further underlines the variable nature of this disease. Georg Thieme Verlag KG Stuttgart · New York.

  18. Evolution of resistance to a multiple-herbivore community: genetic correlations, diffuse coevolution, and constraints on the plant's response to selection.

    Science.gov (United States)

    Wise, Michael J; Rausher, Mark D

    2013-06-01

    Although plants are generally attacked by a community of several species of herbivores, relatively little is known about the strength of natural selection for resistance in multiple-herbivore communities-particularly how the strength of selection differs among herbivores that feed on different plant organs or how strongly genetic correlations in resistance affect the evolutionary responses of the plant. Here, we report on a field study measuring natural selection for resistance in a diverse community of herbivores of Solanum carolinense. Using linear phenotypic-selection analyses, we found that directional selection acted to increase resistance to seven species. Selection was strongest to increase resistance to fruit feeders, followed by flower feeders, then leaf feeders. Selection favored a decrease in resistance to a stem borer. Bootstrapping analyses showed that the plant population contained significant genetic variation for each of 14 measured resistance traits and significant covariances in one-third of the pairwise combinations of resistance traits. These genetic covariances reduced the plant's overall predicted evolutionary response for resistance against the herbivore community by about 60%. Diffuse (co)evolution was widespread in this community, and the diffuse interactions had an overwhelmingly constraining (rather than facilitative) effect on the plant's evolution of resistance. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  19. Multiple response optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry with sample injection as detergent emulsion

    International Nuclear Information System (INIS)

    Brum, Daniel M.; Lima, Claudio F.; Robaina, Nicolle F.; Fonseca, Teresa Cristina O.; Cassella, Ricardo J.

    2011-01-01

    The present paper reports the optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry (GF AAS) employing a strategy based on the injection of the samples as detergent emulsions. The method was optimized in relation to the experimental conditions for the emulsion formation and taking into account that the three analytes (Cu, Fe and Pb) should be measured in the same emulsion. The optimization was performed in a multivariate way by employing a three-variable Doehlert design and a multiple response strategy. For this purpose, the individual responses of the three analytes were combined, yielding a global response that was employed as a dependent variable. The three factors related to the optimization process were: the concentration of HNO 3 , the concentration of the emulsifier agent (Triton X-100 or Triton X-114) in aqueous solution used to emulsify the sample and the volume of solution. At optimum conditions, it was possible to obtain satisfactory results with an emulsion formed by mixing 4 mL of the samples with 1 mL of a 4.7% w/v Triton X-100 solution prepared in 10% v/v HNO 3 medium. The resulting emulsion was stable for 250 min, at least, and provided enough sensitivity to determine the three analytes in the five samples tested. A recovery test was performed to evaluate the accuracy of the optimized procedure and recovery rates, in the range of 88-105%; 94-118% and 95-120%, were verified for Cu, Fe and Pb, respectively.

  20. Multiple response optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry with sample injection as detergent emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Brum, Daniel M.; Lima, Claudio F. [Departamento de Quimica, Universidade Federal de Vicosa, A. Peter Henry Rolfs s/n, Vicosa/MG, 36570-000 (Brazil); Robaina, Nicolle F. [Departamento de Quimica Analitica, Universidade Federal Fluminense, Outeiro de S.J. Batista s/n, Centro, Niteroi/RJ, 24020-141 (Brazil); Fonseca, Teresa Cristina O. [Petrobras, Cenpes/PDEDS/QM, Av. Horacio Macedo 950, Ilha do Fundao, Rio de Janeiro/RJ, 21941-915 (Brazil); Cassella, Ricardo J., E-mail: cassella@vm.uff.br [Departamento de Quimica Analitica, Universidade Federal Fluminense, Outeiro de S.J. Batista s/n, Centro, Niteroi/RJ, 24020-141 (Brazil)

    2011-05-15

    The present paper reports the optimization for Cu, Fe and Pb determination in naphtha by graphite furnace atomic absorption spectrometry (GF AAS) employing a strategy based on the injection of the samples as detergent emulsions. The method was optimized in relation to the experimental conditions for the emulsion formation and taking into account that the three analytes (Cu, Fe and Pb) should be measured in the same emulsion. The optimization was performed in a multivariate way by employing a three-variable Doehlert design and a multiple response strategy. For this purpose, the individual responses of the three analytes were combined, yielding a global response that was employed as a dependent variable. The three factors related to the optimization process were: the concentration of HNO{sub 3}, the concentration of the emulsifier agent (Triton X-100 or Triton X-114) in aqueous solution used to emulsify the sample and the volume of solution. At optimum conditions, it was possible to obtain satisfactory results with an emulsion formed by mixing 4 mL of the samples with 1 mL of a 4.7% w/v Triton X-100 solution prepared in 10% v/v HNO{sub 3} medium. The resulting emulsion was stable for 250 min, at least, and provided enough sensitivity to determine the three analytes in the five samples tested. A recovery test was performed to evaluate the accuracy of the optimized procedure and recovery rates, in the range of 88-105%; 94-118% and 95-120%, were verified for Cu, Fe and Pb, respectively.

  1. Enhancement of juvenile Caribbean spiny lobsters: an evaluation of changes in multiple response variables with the addition of large artificial shelters.

    Science.gov (United States)

    Briones-Fourzán, Patricia; Lozano-Alvarez, Enrique; Negrete-Soto, Fernando; Barradas-Ortiz, Cecilia

    2007-03-01

    Shortage of natural crevice shelters may produce population bottlenecks in juvenile Caribbean spiny lobsters (Panulirus argus), a socially gregarious species. We conducted a field experiment to test enhancement of a local population of juvenile P. argus with the addition of artificial shelters ("casitas") that mimic large crevices (1.1 m(2) in surface area and 3.8 cm in height). Changes in density and biomass of juvenile lobsters 15-50 mm carapace length (CL) were assessed with a multiple before-after control-impact (MBACI) analysis. Separate analyses were also conducted on small (15-35 mm CL) and large (35.1-50 mm CL) juveniles to assess size-related effects. First, we carried out 13 lobster surveys on nine fixed 1-ha sites over a shallow reef lagoon ("before" period). Then, we deployed ten casitas in each of five sites and left four sites as controls, and conducted 22 further surveys ("after" period). Deployment of casitas resulted in a sixfold increase in juvenile density (76% contributed by small and 24% by large juveniles) and a sevenfold increase in biomass (40 and 60%, respectively). Capture-recapture results revealed that enhancement was achieved not by promoting individual growth but by increasing survival, persistence, and foraging ranges of small and large juveniles. Casitas both mitigated shortage of natural shelter and increased sociality, allowing for cohabitation of smaller, more vulnerable juveniles with larger conspecifics that have greater defensive abilities. Casitas may help enhance local populations of juvenile P. argus in Caribbean seagrass habitats, typically poor in natural crevice shelters. The use of MBACI and the simultaneous assessment of multiple interrelated response variables may be a powerful analytical approach to test shelter limitation in other species and to examine the function of structural habitat in other systems.

  2. Responses of female rock lizards to multiple scent marks of males: effects of male age, male density and scent over-marking.

    Science.gov (United States)

    Martín, José; López, Pilar

    2013-03-01

    Scent-marked substrates may inform conspecifics on the characteristics of territorial males. Scent-marks of male Carpetan rock lizards (Iberolacerta cyreni) affect space use of females, which by selecting an area may increase the probability of mating with the male that has scent-marked that area. However, males do not hold exclusive territories, and scent-marks of different individual males are often together. This may provide complex information from multiple sources on the social structure. Here, we examined female preference in response to scent marks of various males and combinations in a laboratory experiment. Females preferred areas scent-marked by territorial old males against those scent-marked by young satellite-sneaker males. This reflected the known preference of females for mating with old males. In a second experiment, females preferred areas scent-marked by two males to areas of similar size marked by a single male. This may increase the probability of obtaining multiple copulations with different males, which may favour sperm competition and cryptic female choice, or may be a way to avoid infertile males. Finally, when we experimentally over-marked the scent-marks of an old male with scent-marks of a young male, females did not avoid, nor prefer, the over-marked area, suggesting that the quality of the old male may override the presence of a satellite male. We suggest that, irrespective of the causes underlying why a female selects a scent-marked area, this strategy may affect her reproductive success, which may have the same evolutionary consequences that "direct" mate choice decisions of other animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Response

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Starting from a brief historical perspective on scientific discovery, this talk will review some of the theory and open problems of deep learning and describe how to design efficient feedforward and recursive deep learning architectures for applications in the natural sciences. In particular, the focus will be on multiple particle problems at different scales: in biology (e.g. prediction of protein structures), chemistry (e.g. prediction of molecular properties and reactions), and high-energy physics (e.g. detection of exotic particles, jet substructure and tagging, "dark matter and dark knowledge")

  4. Multiple Perspectives / Multiple Readings

    Directory of Open Access Journals (Sweden)

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  5. Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke

    2015-01-01

    Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for......-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.......Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used...... for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels...

  6. Response to heavy, non-floating oil spilled in a Great Lakes river environment: a multiple-lines-of-evidence approach for submerged oil assessment and recovery

    Science.gov (United States)

    Dollhopf, Ralph H.; Fitzpatrick, Faith A.; Kimble, Jeffrey W.; Capone, Daniel M.; Graan, Thomas P.; Zelt, Ronald B.; Johnson, Rex

    2014-01-01

    The Enbridge Line 6B pipeline release of diluted bitumen into the Kalamazoo River downstream of Marshall, MI in July 2010 is one of the largest freshwater oil spills in North American history. The unprecedented scale of impact and massive quantity of oil released required the development and implementation of new approaches for detection and recovery. At the onset of cleanup, conventional recovery techniques were employed for the initially floating oil and were successful. However, volatilization of the lighter diluent, along with mixing of the oil with sediment during flooded, turbulent river conditions caused the oil to sink and collect in natural deposition areas in the river. For more than three years after the spill, recovery of submerged oil has remained the predominant operational focus of the response. The recovery complexities for submerged oil mixed with sediment in depositional areas and long-term oil sheening along approximately 38 miles of the Kalamazoo River led to the development of a multiple-lines-of-evidence approach comprising six major components: geomorphic mapping, field assessments of submerged oil (poling), systematic tracking and mapping of oil sheen, hydrodynamic and sediment transport modeling, forensic oil chemistry, and net environmental benefit analysis. The Federal On-Scene Coordinator (FOSC) considered this information in determining the appropriate course of action for each impacted segment of the river. New sources of heavy crude oils like diluted bitumen and increasing transportation of those oils require changes in the way emergency personnel respond to oil spills in the Great Lakes and other freshwater ecosystems. Strategies to recover heavy oils must consider that the oils may suspend or sink in the water column, mix with fine-grained sediment, and accumulate in depositional areas. Early understanding of the potential fate and behavior of diluted bitumen spills when combined with timely, strong conventional recovery methods can

  7. Association of Odor Thresholds and Responses in Cerebral Blood Flow of the Prefrontal Area during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity.

    Directory of Open Access Journals (Sweden)

    Kenichi Azuma

    Full Text Available Multiple chemical sensitivity (MCS is a disorder characterized by nonspecific and recurrent symptoms from various organ systems associated with exposure to low levels of chemicals. Patients with MCS process odors differently than controls do. Previously, we suggested that this odor processing was associated with increased regional cerebral blood flow (rCBF in the prefrontal area during olfactory stimulation using near-infrared spectroscopic (NIRS imaging. The aim of this study was to investigate the association of odor thresholds and changes in rCBF during olfactory stimulation at odor threshold levels in patients with MCS. We investigated changes in the prefrontal area using NIRS imaging and a T&T olfactometer during olfactory stimulation with two different odorants (sweet and fecal at three concentrations (zero, odor recognition threshold, and normal perceived odor level in 10 patients with MCS and six controls. The T&T olfactometer threshold test and subjective assessment of irritating and hedonic odors were also performed. The results indicated that the scores for both unpleasant and pungent odors were significantly higher for those for sweet odors at the normal perceived level in patients with MCS than in controls. The brain responses at the recognition threshold (fecal odor and normal perceived levels (sweet and fecal odors were stronger in patients with MCS than in controls. However, significant differences in the odor detection and recognition thresholds and odor intensity score between the two groups were not observed. These brain responses may involve cognitive and memory processing systems during past exposure to chemicals. Further research regarding the cognitive features of sensory perception and memory due to past exposure to chemicals and their associations with MCS symptoms is needed.

  8. SYNTHESIS OF pH-RESPONSIVE AMPHIPHILIC DIBLOCK COPOLYMERS CONTAINING POLYISOBUTYLENE via OXYANION-INITIATED POLYMERIZATION AND THEIR MULTIPLE SELF-ASSEMBLY MORPHOLOGIES

    Institute of Scientific and Technical Information of China (English)

    Huai-chao Wang; Ming-zu Zhang; Pei-hong Ni; Jin-lin He; Ying Hao; Yi-xian Wu

    2013-01-01

    Two pH-responsive amphiphilic diblock copolymers,namely polyisobutylene-block-poly[2-(N,N-dimethylamino)ethyl methacrylate] (PIB-b-PDMAEMA) and polyisobutylene-block-poly(metharylic acid) (PIB-b-PMAA),were synthesized via oxyanion-initiated polymerization,and their multiple self-assembly behaviors have been studied.An exo-o1efin-terminated highly reactive polyisobutylene (HRPIB) was first changed to hydroxyl-terminated PIB (PIB-OH) via hydroboration-oxidation of C=C double bond in the chain end,and then reacted with KH to yield a potassium alcoholate of PIB (PIB-O-K+).PIB-O-K+ was immediately used as a macroinitiator to polymerize DMAEMA monomer,resulting in a cationic diblock copolymer PIB-b-PDMAEMA.With the similar synthesis procedure,the anionic diblock copolymer PIB-b-PMAA could be prepared via a combination of oxyanion-initiated polymerization of tert-butyl methacrylate (tBMA) and subsequent hydrolysis of tert-butyl ester groups in PtBMA block.The functional PIB and block copolymers have been fully characterized by 1H-NMR,FT-IR spectroscopy,and gel permeation chromatography (GPC).These samples allowed us to systematically investigate the effects of block composition on the pH responsivity and various self-assembled morphologies of the copolymers in THF/water mixed solvent.Transmission electron microscopy (TEM) images revealed that these diblock copolymers containing small amount of original PIB without exo-olefin-terminated group are able to self-assemble into micelles,vesicles with different particle sizes and cylindrical aggregates,depending on various factors including block copolymer composition,solvent polarity and pH value.

  9. Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

    Science.gov (United States)

    Ishii, Kiyoko; Komaki, Hirofumi; Ohkuma, Aya; Nishino, Ichizo; Nonaka, Ikuya; Sasaki, Masayuki

    2010-09-01

    We report an adolescent case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by intermittent nausea and depressive state as early symptoms. At the age of 12 years and 11 months, the patient experienced intermittent nausea and vomiting, and depressive state. She was on medication for depression for 5 months but it was ineffective. Brain magnetic resonance imaging showed disseminated high-intensity areas in the periventricular white matter and in the splenium of the corpus callosum on T2-weighted images and fluid-attenuated inversion-recovery images. Progressive muscle weakness occurred and blood creatine kinase level was found to be elevated. The muscle biopsy revealed lipid storage myopathy. Urine organic acid analysis and mutation analysis of the ETFDH gene confirmed the diagnosis of MADD. With oral supplements of riboflavin and l-carnitine, in addition to a high-calorie and reduced-fat diet, her clinical symptoms improved dramatically. Early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD. Copyright 2009 Elsevier B.V. All rights reserved.

  10. Multiple myeloma patients in long-term complete response after autologous stem cell transplantation express a particular immune signature with potential prognostic implication.

    Science.gov (United States)

    Arteche-López, A; Kreutzman, A; Alegre, A; Sanz Martín, P; Aguado, B; González-Pardo, M; Espiño, M; Villar, L M; García Belmonte, D; de la Cámara, R; Muñoz-Calleja, C

    2017-06-01

    The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4 + T-cells was lower in patients, whereas an increment in the percentage of CD4 + and CD8 + effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naïve cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

  11. Multiple Sclerosis and Vitamin D

    Science.gov (United States)

    ... Editors David C. Spencer, MD Steven Karceski, MD Multiple sclerosis and vitamin D Andrew J. Solomon, MD WHAT ... caused by improper immune responses (autoimmune diseases), including multiple sclerosis (MS). A recent Patient Page in Neurology provided ...

  12. {sup 11}C-Acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chieh; Tsai, Shu-Fan; Yen, Tzu-Chen [Chang Gung Memorial Hospital, Department of Nuclear Medicine and Molecular Imaging Center, Gueishan (China); Chang Gung University College of Medicine, Taoyuan (China); Ho, Chi-Lai [Hong Kong Sanatorium and Hospital, Department of Nuclear Medicine and Positron Emission Tomography, Hong Kong (China); Ng, Shu-Hang; Lin, Yu-Chun [Chang Gung University College of Medicine, Taoyuan (China); Chang Gung Memorial Hospital, Department of Diagnostic Radiology, Taoyuan (China); Wang, Po-Nan; Tang, Tzung-Chih [Chang Gung University College of Medicine, Taoyuan (China); Chang Gung Memorial Hospital, Department of Internal Medicine, Division of Hematology-Oncology, Taoyuan (China); Huang, Yenlin [Chang Gung University College of Medicine, Taoyuan (China); Chang Gung Memorial Hospital, Department of Anatomic Pathology, Taoyuan (China); Rahmouni, Alain [AP-HP, Groupe Henri-Mondor Albert-Chenevier, CHU Henri Mondor, Department of Radiology, Creteil (France)

    2014-01-15

    We investigated the potential value of {sup 11}C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with {sup 18}F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards. In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48-69 years) underwent dual-tracer {sup 11}C-ACT and {sup 18}F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUV{sub max}). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test. At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30-90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using {sup 11}C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p = 0.01). In contrast, a diagnosis of diffuse infiltration could be established using {sup 18}F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both {sup 11}C-ACT PET/CT and WB MRI, and in 10 patients on {sup 18}F-FDG PET/CT. Focal lesions demonstrated {sup 11}C-ACT uptake with a mean SUV{sub max} of 11.4 ± 3.3 (range 4.6-19.6, n = 59), which was significantly higher than the {sup 18}F-FDG uptake (mean SUV{sub max} 6.6 ± 3.1, range 2.3-13.7, n = 29; p < 0.0001). After treatment, the diffuse bone marrow {sup 11}C-ACT uptake showed a mean SUV{sub max} reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p = 0.01). PET/CT using {sup 11}C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using {sup 18}F-FDG, and may be

  13. 11C-Acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment

    International Nuclear Information System (INIS)

    Lin, Chieh; Tsai, Shu-Fan; Yen, Tzu-Chen; Ho, Chi-Lai; Ng, Shu-Hang; Lin, Yu-Chun; Wang, Po-Nan; Tang, Tzung-Chih; Huang, Yenlin; Rahmouni, Alain

    2014-01-01

    We investigated the potential value of 11 C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with 18 F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards. In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48-69 years) underwent dual-tracer 11 C-ACT and 18 F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUV max ). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test. At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30-90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using 11 C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p = 0.01). In contrast, a diagnosis of diffuse infiltration could be established using 18 F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both 11 C-ACT PET/CT and WB MRI, and in 10 patients on 18 F-FDG PET/CT. Focal lesions demonstrated 11 C-ACT uptake with a mean SUV max of 11.4 ± 3.3 (range 4.6-19.6, n = 59), which was significantly higher than the 18 F-FDG uptake (mean SUV max 6.6 ± 3.1, range 2.3-13.7, n = 29; p 11 C-ACT uptake showed a mean SUV max reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p = 0.01). PET/CT using 11 C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using 18 F-FDG, and may be valuable for response assessment. (orig.)

  14. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  15. Potencialidad de Prosopis ferox Griseb (Leguminosae, subfamilia: Mimosoideae para estudios dendrocronológicos en desiertos subtropicales de alta montaña Potential of Prosopis ferox Griseb (Leguminosae, subfamily: Mimosoideae for dendrochronological studies in high-montane subtropical deserts

    Directory of Open Access Journals (Sweden)

    MARIANO S. MORALES

    2001-12-01

    Full Text Available Debido a la escasez de especies con anillos anuales de crecimiento, la dendrocronología de regiones áridas de montañas tropicales y subtropicales está muy poco desarrollada. En este trabajo evaluamos el potencial de la especie arbórea Prosopis ferox,"churqui", para estudios dendrocronológicos analizando las características anatómicas del leño y las relaciones entre registros climáticos y cronologías de ancho de anillos de una colección realizada a 3.500 m, en la quebrada de Humahuaca (23°13' S, 65°20' O, Provincia de Jujuy, Argentina. Las observaciones microscópicas de cortes histológicos muestran que los anillos están claramente demarcados por una banda parenquimática terminal clara. Comparando la cronología estandarizada de ancho de anillos con los registros instrumentales de La Quiaca (22º06'S, 65º36'O, se observan correlaciones significativas con precipitaciones por encima de la media y temperaturas por debajo de la media durante los meses de verano (diciembre_marzo. Esto se interpreta como una relación positiva con la disponibilidad de agua en el suelo durante el período de crecimiento. Esta cronología representa no solamente el primer registro dendrocronológico desarrollado a partir de P. ferox, sino también la primera cronología de anillos de árboles en la provincia biogeográfica Prepuneña. La buena discriminación de los anillos anuales de crecimiento, la fuerte relación con variables climáticas, el amplio rango de distribución de la especie en el noroeste de Argentina y sur de Bolivia (20° a 25° S y la longevidad observada en individuos aislados (c. 500 años, hacen de P. ferox una especie muy promisoria para estudios dendroclimatológicos y dendroecológicos en desiertos subtropicales de alta montañaDue to the scarcity of species with annual tree rings, the use of dendrochronological techniques has received little attention in tropical and subtropical montane dry areas. In this study, we assess the

  16. The use of discriminant analysis for evaluation of early-response multiple biomarkers of radiation exposure using non-human primate 6-Gy whole-body radiation model

    Energy Technology Data Exchange (ETDEWEB)

    Ossetrova, N.I. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: ossetrova@afrri.usuhs.mil; Farese, A.M.; MacVittie, T.J. [Marlene and Stewart Greenebaum Cancer Center, Bressler Research Building, Room 7-039, University of Maryland-Baltimore, 655 West Baltimore Street, Baltimore, MD 21201 (United States); Manglapus, G.L.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    The present need to rapidly identify severely irradiated individuals in mass-casualty and population-monitoring scenarios prompted an evaluation of potential protein biomarkers to provide early diagnostic information after exposure. The level of specific proteins measured using immunodiagnostic technologies may be useful as protein biomarkers to provide early diagnostic information for acute radiation exposures. Herein we present results from on-going studies using a non-human primate (NHP) 6-Gy X-rays ( 0.13Gymin{sup -1}) whole-body radiation model. Protein targets were measured by enzyme-linked immunosorbent assay (ELISA) in blood plasma before, 1, and 2 days after exposure. Exposure of 10 NHPs to 6 Gy resulted in the up-regulation of plasma levels of (a) p21 WAF1/CIP1, (b) interleukin 6 (IL-6), (c) tissue enzyme salivary {alpha}-amylase, and (d) C-reactive protein. Data presented show the potential utility of protein biomarkers selected from distinctly different pathways to detect radiation exposure. A correlation analysis demonstrated strong correlations among different combinations of four candidate radiation-responsive blood protein biomarkers. Data analyzed with use of multivariate discriminant analysis established very successful separation of NHP groups: 100% discrimination power for animals with correct classification for separation between groups before and 1 day after irradiation, and 95% discrimination power for separation between groups before and 2 days after irradiation. These results also demonstrate proof-in-concept that multiple protein biomarkers provide early diagnostic information to the medical community, along with classical biodosimetric methodologies, to effectively manage radiation casualty incidents.

  17. Non-invasive imaging provides spatiotemporal information on disease progression and response to therapy in a murine model of multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Simone S Riedel

    Full Text Available Multiple myeloma (MM is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI. Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase(+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase(+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring

  18. Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9months in a cohort study of Chinese infants.

    Science.gov (United States)

    Sturza, Julie; Silver, Monica K; Xu, Lin; Li, Mingyan; Mai, Xiaoqin; Xia, Yankai; Shao, Jie; Lozoff, Betsy; Meeker, John

    2016-01-01

    Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning. Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split). Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant's cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group. ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide

  19. The Effects of Nicotine on the Stimulation of the Cholinergic System and Immune Responses Changes in Animal Models of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    M Shahmoradi

    2016-06-01

    Full Text Available Background & aim: Lately, it has been demonstrated that the signaling by the α7 nicotinic receptors produces the anti-inflammatory condition in both macrophages and T cells. Moreover, activation of macrophages and T cells play an important role in multiple sclerosis (MS.  In the present study, the therapeutic effect of nicotine on experimental autoimmune encephalomyelitis (EAE, an animal model of MS, and its effects on T-helper cells responses was evaluated. Methods: In the present experimental study, EAE was induced by homogenised guinea pig spinal cord and complete Freund’s adjuvant in wistar rats. Animals were allocated in two therapeutic groups (n=7 per group. Treatment with nicotine (2.5 mg/kg-daily was started in treatment group when the treatment group developed a disability score (at day 12. At the same time, the control group received only the solvent with the same program. Signs of disease were recorded daily until the day 36 when animals were sacrificed. The Splenocytes were checked for proliferation by MTT test and cytokine production by ELISA. The level of nitric oxide in serum was checked by griess test. The data was analyzed using the Student t test and Mann-Whitney U. Results: Nicotine administration in the treatment group significantly reduced the clinical symptoms after the onset of symptoms. Simultaneously with the decrease of the level of serum nitric oxide, nicotine significantly decreased the pro-inflammatory cytokine IL-17 and IFN-γ. The levels of anti-inflammatory IL-10 were not changed significantly. Lymphocyte proliferation was significantly decreased in treatment group compared to control group Conclusion: The results of this study indicated that nicotine had immune modulatory effects and could be used to control MS disease.

  20. MULTIPLE OBJECTS

    Directory of Open Access Journals (Sweden)

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  1. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Christensen, Tove; Hansen, Hans Jacob

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...

  2. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  3. Multiple homicides.

    Science.gov (United States)

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  4. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  5. Multiple myeloma.

    LENUS (Irish Health Repository)

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  6. Multiple mononeuropathy

    Science.gov (United States)

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  7. Identification of new sensitive biomarkers for the in vivo response to interferon-beta treatment in multiple sclerosis using DNA-array evaluation

    DEFF Research Database (Denmark)

    Sellebjerg, F.; Krakauer, M.; Hesse, D.

    2009-01-01

    Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)-beta. NAbs impair the effect of treatment. The biological effect of IFN-beta can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other...

  8. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

    2008-01-01

    Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and...

  9. Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis

    DEFF Research Database (Denmark)

    Brudek, T.; Christensen, T.; Hansen, H.J.

    2004-01-01

    Retroviruses have been suggested as possible pathogenic factors in multiple sclerosis (MS), supported by the observation that endogenous retroviruses are activated in MS patients. Different members of the herpes family of which several are neurotropic have also been suggested as factors in MS pat...

  10. Quantifying the residual volume transport through a multiple-inlet system in response to wind forcing: The case of the western Dutch Wadden Sea

    NARCIS (Netherlands)

    Duran-Matute, M.; Gerkema, T.; Sassi, M.

    2016-01-01

    In multiple-inlet coastal systems like the western Dutch Wadden Sea, the tides (and their interaction with the bathymetry), the fresh water discharge, and the wind drive a residual flow through the system. In the current paper, we study the effect of the wind on the residual volume transport through

  11. [Responses of Picea likiangensis radial growth to climate change in the Small Zhongdian area of Yunnan Province, Southwest China].

    Science.gov (United States)

    Zhao, Zhi-Jiang; Tan, Liu-Yi; Kang, Dong-Wei; Liu, Qi-Jing; Li, Jun-Qing

    2012-03-01

    Picea likiangensis (Franch. ) Pritz. primary forest is one of the dominant forest types in the Small Zhongdian area in Shangri-La County of Yunnan Province. In this paper, the responses of P. likiangensis tree-ring width to climate change were analyzed by dendrochronological methods, and the dendrochronology was built by using relatively conservative detrending negative exponential curves or linear regression. Correlation analysis and response function analysis were applied to explore the relationships between the residual chronology series (RES) and climatic factors at different time scales, and pointer year analysis was used to explain the reasons of producing narrow and wide rings. In the study area, the radial growth of P. likiangensis and the increasing air temperature from 1990 to 2008 had definite 'abruption'. The temperature and precipitation in previous year growth season were the main factors limiting the present year radial growth, and especially, the temperature in previous July played a negative feedback role in the radial growth, while the sufficient precipitation in previous July promoted the radial growth. The differences in the temperature variation and precipitation variation in previous year were the main reasons for the formation of narrow and wide rings. P. likiangensis radial growth was not sensitive to the variation of PDSI.

  12. [Multiple meningiomas].

    Science.gov (United States)

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Arendt-Nielsen, Lars; Kupers, Ron

    2013-01-01

    BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor...

  14. A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance

    Directory of Open Access Journals (Sweden)

    Ali Bassam R

    2012-05-01

    Full Text Available Abstract Background We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26. Methods In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation. Results Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia. Conclusions We report the first missense homozygous disease-causing mutation in KIF7 and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients.

  15. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  16. Application of the Matrix Pencil Method for Estimating the SEM (Singularity Expansion Method) Poles of Source Free Transient Responses From Multiple Look Directions

    National Research Council Canada - National Science Library

    Sarkar, Tapan

    2000-01-01

    .... The SEM poles are independent of the angle at which the transient response is recorded. The only difference between the various waveforms are that the residues at the various poles are of different magnitudes...

  17. Multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  18. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  19. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  20. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  1. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  2. Multiple Sclerosis.

    Science.gov (United States)

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  3. Parenting Multiples

    Science.gov (United States)

    ... when your babies do. Though it can be hard to let go of the thousand other things you need to do, remember that your well-being is key to your ability to take care of your babies. What Problems Can Happen? It may be hard to tell multiple babies apart when they first ...

  4. Opportunities and applications of dendrochronology in Africa

    NARCIS (Netherlands)

    Gebrekirstos, A.; Bräuning, A.; Sass-Klaassen, U.; Mbow, C.

    2014-01-01

    Partly due to severe lack of instrumental climate data, the drivers of the African climate, their interactions and impacts are poorly understood. The paper demonstrates the prospects and applications of dendroecological and stable isotope techniques, such as to reconstruct climate variability,

  5. Results of the Dendrochronological Studies in Mongolia

    Directory of Open Access Journals (Sweden)

    Gordon C. Jacoby

    2003-06-01

    Full Text Available The Mongolian-AmericanTree-Ring Project was initiated in 1995 to develop longer climatic records in Mongolia and to help establish capabilities in Mongolia for independent tree-ring analyses. The records from old-aged trees can provide more complete information about the variations in the climate system and aid in planning for future changes or variations in climate. Many areas of Mongolia have been investigated and tree-ring samples collected. Dendroclimatic records of temperature extending back more than one thousand years and precipitation records of over 300 years have been developed. These records show that global warming is present in Mongolia and that variations in precipitation and stream-flow appear to show some solar influence. Scientists and students trained by ,the project are now engaged in tree-ring studies in various areas of Mongolia. The project is expected to continue for the next several years.

  6. Paleo-event data standards for dendrochronology

    Science.gov (United States)

    Elaine Kennedy Sutherland; P. Brewer; W. Gross

    2017-01-01

    Extreme environmental events, such as storm winds, landslides, insect infestations, and wildfire, cause loss of life, resources, and human infrastructure. Disaster riskreduction analysis can be improved with information about past frequency, intensity, and spatial patterns of extreme events. Tree-ring analyses can provide such information: tree rings reflect events as...

  7. Ecological response of Cedrus atlantica to climate variability in the Massif of Guetiane (Algeria

    Directory of Open Access Journals (Sweden)

    Said Slimani

    2014-12-01

    Full Text Available Aim of the study: The study analyzes the long-term response of Atlas cedar, Cedrus atlantica (Manneti, to climate variability. Area of study: Atlas cedar forest of Guetiane (Batna, Algeria.Material and methods: The dendrochronological approach was adopted. An Atlas cedar tree-ring chronology was established from twenty trees. The response of the species to climate variability was assessed through the pointer years (PYs, the common climate signal among the individual chronologies, expressed by the first component (PC1, the mean sensitivity (msx, and response function and correlations analysis involving the tree-ring index and climate data (monthly mean temperature and total precipitation.Results: The highest growth variability was registered from the second half of the 20th century. The lower than the mean PYs, the PC1, and the msx increased markedly during the studied period. Dramatic increases in the PC1 and msx were detected at the end of the 1970s, reflecting a shift towards drier conditions enhancing an increasing trend towards more synchronous response of trees to climate conditions. The response function and correlations analysis showed that tree growth was mainly influenced by precipitation variability.Research highlights: Our findings provide baseline knowledge concerning the ecological response of Atlas cedar to climate variability in in its southern distribution limit, where a high level of tree mortality has been observed during recent decades, coinciding with the driest period Algeria has ever experienced. This information is vital to support ongoing ecosystem management efforts in the region. Keywords: Atlas cedar; annual growth variability; dieback; dendrochronology

  8. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadzadehfar, Hojjat; Wegen, Simone; Yordanova, Anna; Kuerpig, Stefan; Eppard, Elisabeth; Wei, Xiao; Schlenkhoff, Carl; Essler, Markus [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fimmers, Rolf [University of Bonn, Institute for Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Hauser, Stefan [University Hospital Bonn, Department of Urology, Bonn (Germany)

    2017-08-15

    Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [{sup 177}Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation. Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA. Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles. (orig.)

  9. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [177Lu]Lu-PSMA-617.

    Science.gov (United States)

    Ahmadzadehfar, Hojjat; Wegen, Simone; Yordanova, Anna; Fimmers, Rolf; Kürpig, Stefan; Eppard, Elisabeth; Wei, Xiao; Schlenkhoff, Carl; Hauser, Stefan; Essler, Markus

    2017-08-01

    Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [ 177 Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation. Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA. Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles.

  10. Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

    Science.gov (United States)

    Niesvizky, Ruben; Mark, Tomer M; Ward, Maureen; Jayabalan, David S; Pearse, Roger N; Manco, Megan; Stern, Jessica; Christos, Paul J; Mathews, Lena; Shore, Tsiporah B; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E

    2013-03-15

    This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

  11. RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses.

    Science.gov (United States)

    Saha, Manujendra N; Jiang, Hua; Mukai, Asuka; Chang, Hong

    2010-11-01

    Mutations or deletions of p53 are relatively rare in multiple myeloma (MM), at least in newly diagnosed patients. Thus, restoration of p53 tumor suppressor function in MM by blocking the inhibitory role of murine double minute 2 (MDM2) is a promising and applicable therapeutic strategy. RITA and nutlin are two new classes of small molecule MDM2 inhibitors that prevent the p53-MDM2 interaction. Earlier reports showed p53-dependent activity of RITA in solid tumors as well as in leukemias. We and others recently described nutlin-induced apoptosis in MM cells, but it remains unclear whether RITA exerts antimyeloma activity. Here, we found that RITA activates the p53 pathway and induces apoptosis in MM cell lines and primary MM samples, preferentially killing myeloma cells. The activation of p53 induced by RITA was mediated through modulation of multiple apoptotic regulatory proteins, including upregulation of a proapoptotic protein (NOXA), downregulation of an antiapoptotic protein, Mcl-1, and activation of caspases through extrinsic pathways. Moreover, a number of key p53-mediated apoptotic target genes were identified by gene expression profiling and further validated by quantitative real-time PCR. Importantly, the combination of RITA with nutlin displayed a strong synergism on growth inhibition with the combination index ranging from 0.56 to 0.82 in MM cells. Our data support further clinical evaluation of RITA as a potential novel therapeutic intervention in MM. ©2010 AACR.

  12. Dendrochronology of species from Brazilian Araucaria Forest, Candoi, PR Dendrocronologia de espécies da Floresta Ombrófila Mista do Município de Candói, PR

    Directory of Open Access Journals (Sweden)

    Patricia Póvoa de Mattos

    2010-06-01

    Full Text Available In the present work the dendrochronological potential of six species of the Araucaria Forest is analyzed. The trunks of 20 trees were collected in Candoi, State of Parana, Brazil, from an area that belongs to
    ELEJOR, Centrais Elétricas do Rio Jordão, for the following species: Araucaria angustifolia, Clethra scabra, Cedrela lilloi, Ocotea porosa, Podocarpus lambertii and Sebastiania commersoniana (3 to 6, from each species. The trunks were sawed, and at breast height a sample was taken from the center of the board, from bark to bark, crossing the pith, for macroscopic analysis. These samples were dried and polished, making possible the recognition and measurement of growth rings The historical climatic data series were provided by SIMEPAR, the State weather institute. The trees presented diameter at breast height (DBH, varying from 14 cm to 40 cm, with age of 60 years, annual diameter increment of 0.6 cm, in average. Although the number of trees was small, it was possible to observe that the site was not limiting for the species, as the growth rings showed very low sensitivity.
    However, the very extreme growth condition of 1999 and 2000, when  occurred a very low precipitation period followed by a very severe winter, was registered in the growth ring series of most of the disks analyzedFoi analisado o potencial dendrocronológico de seis espécies da Floresta Ombrófila Mista (FOM.
    Foram coletados troncos em Candói, PR, em uma área pertencente a ELEJOR, Centrais Elétricas do Rio Jordão,
    sendo três a seis indivíduos das espécies: Araucaria angustifolia, Clethra scabra, Cedrela lilloi, Ocotea
    porosa, Podocarpus lambertii e Sebastiania commersoniana. Os troncos foram serrados, sendo retiradas amostras à altura do peito, da prancha central, de casca a casca, cruzando a medula, para análise macroscópica. Essas amostras foram secas e lixadas, possibilitando o reconhecimento e medição dos anéis de crescimento. A

  13. Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups.

    Science.gov (United States)

    Padhukasahasram, B; Yang, J J; Levin, A M; Yang, M; Burchard, E G; Kumar, R; Kwok, P-Y; Seibold, M A; Lanfear, D E; Williams, L K

    2014-08-01

    Inhaled short-acting beta-agonist (SABA) medication is commonly used in asthma patients to rapidly reverse airway obstruction and improve acute symptoms. We performed a genome-wide association study of SABA medication response using gene-based association tests. A linear mixed model approach was first used for single-nucleotide polymorphism associations, and the results were later combined using GATES to generate gene-based associations. Our results identified SPATA13-AS1 as being significantly associated with SABA bronchodilator response in 328 healthy African Americans. In replication, this gene was associated with SABA response among the two separate groups of African Americans with asthma (n=1073, P=0.011 and n=1968, P=0.014), 149 healthy African Americans (P=0.003) and 556 European Americans with asthma (P=0.041). SPATA13-AS1 was also associated with longitudinal SABA medication usage in the two separate groups of African Americans with asthma (n=658, P=0.047 and n=1968, P=0.025). Future studies are needed to delineate the precise mechanism by which SPATA13-AS1 may influence SABA response.

  14. Multiple Responses, Promising Results: Evidence-Based, Nonpunitive Alternatives to Zero Tolerance. Research-to-Results Brief. Publication #2011-09

    Science.gov (United States)

    Boccanfuso, Christopher; Kuhfeld, Megan

    2011-01-01

    In response to highly publicized violent incidents in schools, such as the Columbine High School massacre, school disciplinary policies have become increasingly severe. These policies have been implemented at the school, district, and state levels with the goal of ensuring the safety of students and staff. Many of these policies have one component…

  15. The occurrence of graft-versus-host disease is the major predictive factor for response to donor lymphocyte infusions in multiple myeloma

    NARCIS (Netherlands)

    Lokhorst, Henk M.; Wu, Kalung; Verdonck, Leo F.; Laterveer, Laurens L.; van de Donk, Niels W. C. J.; van Oers, Marinus H. J.; Cornelissen, Jan J.; Schattenberg, Anton V.

    2004-01-01

    The graft-versus-myeloma (GVM) effect of donor lymphocyte infusions (DLIs) is well established. We now report the outcome of DLI in 54 patients with relapsed myeloma following allogeneic transplantation. Twenty-eight patients (52%) responded, 19 patients (35%) with a partial response and 9 patients

  16. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma.

    NARCIS (Netherlands)

    Lokhorst, H.M.; Schmidt-Wolf, I.; Sonneveld, P.; Holt, B. van der; Martin, H.; Barge, R.; Bertsch, U.; Schlenzka, J.; Bos, G.M.; Croockewit, S.; Zweegman, S.; Breitkreutz, I.; Joosten, P.; Scheid, C.; Marwijk-Kooy, M. van; Salwender, H.J.; Oers, M.H. van; Schaafsma, R.; Naumann, R.; Sinnige, H.A.M.; Blau, I.; Delforge, M.; Weerdt, O. de; Wijermans, P.W.; Wittebol, S.; Duersen, U.; Vellenga, E.; Goldschmidt, H.

    2008-01-01

    In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001).

  17. Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex.

    Science.gov (United States)

    Thimm, Andreas; Funke, Klaus

    2015-02-15

    Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms). The effect increased with each of the five iTBS blocks applied. cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks. We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS-like effects with application of several blocks. Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (iTBS diminished the suppression of the second response evoked by paired PW or AW-PW stimulation at 20 ms intervals. The effects

  18. Multiple sclerosis

    International Nuclear Information System (INIS)

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  19. Environmental Response and Genomic Regions Correlated with Rice Root Growth and Yield under Drought in the OryzaSNP Panel across Multiple Study Systems.

    Directory of Open Access Journals (Sweden)

    Len J Wade

    Full Text Available The rapid progress in rice genotyping must be matched by advances in phenotyping. A better understanding of genetic variation in rice for drought response, root traits, and practical methods for studying them are needed. In this study, the OryzaSNP set (20 diverse genotypes that have been genotyped for SNP markers was phenotyped in a range of field and container studies to study the diversity of rice root growth and response to drought. Of the root traits measured across more than 20 root experiments, root dry weight showed the most stable genotypic performance across studies. The environment (E component had the strongest effect on yield and root traits. We identified genomic regions correlated with root dry weight, percent deep roots, maximum root depth, and grain yield based on a correlation analysis with the phenotypes and aus, indica, or japonica introgression regions using the SNP data. Two genomic regions were identified as hot spots in which root traits and grain yield were co-located; on chromosome 1 (39.7-40.7 Mb and on chromosome 8 (20.3-21.9 Mb. Across experiments, the soil type/ growth medium showed more correlations with plant growth than the container dimensions. Although the correlations among studies and genetic co-location of root traits from a range of study systems points to their potential utility to represent responses in field studies, the best correlations were observed when the two setups had some similar properties. Due to the co-location of the identified genomic regions (from introgression block analysis with QTL for a number of previously reported root and drought traits, these regions are good candidates for detailed characterization to contribute to understanding rice improvement for response to drought. This study also highlights the utility of characterizing a small set of 20 genotypes for root growth, drought response, and related genomic regions.

  20. T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs.

    Directory of Open Access Journals (Sweden)

    Andréa Barbosa de Melo

    Full Text Available The yellow fever vaccines (YF-17D-204 and 17DD are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env and nonstructural (NS proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4(+ and CD8(+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines.

  1. More Popsicle-Stick Multiplication.

    Science.gov (United States)

    Dunkels, Andrejs

    1982-01-01

    A way to use tongue depressors in a model of multiplication is presented. The original intent was to use the sticks to teach about fractions, but "mistakes" in student responses led to new ideas. It is felt that teachers should use the model in teaching multiplication. (MP)

  2. Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats

    Science.gov (United States)

    de Bakker, Chantal M. J.; Altman-Singles, Allison R.; Li, Yihan; Tseng, Wei-Ju; Li, Connie; Liu, X. Sherry

    2017-01-01

    Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on post-menopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, while other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that while rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. PMID:28109138

  3. Analysis of the pressure response of high angle multiple (HAM) fractures intersecting a welbore; Kokeisha multi fracture (HAM) kosei ni okeru atsuryoku oto kaiseki ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Ujo, S; Osato, K [Geothermal Energy Research and Development Co. Ltd., Tokyo (Japan); Arihara, N [Waseda University, Tokyo (Japan); Schroeder, R

    1996-05-01

    This paper reports pressure response analysis on wells piercing a high angle multi (HAM) fracture model. In this model which is defined on a three-dimensional space, a plurality of slanted fractures intersect with wells at high angles (however, intersection of fractures with each other is not considered). With respect to the pressure response analysis method using this model, the paper presents a basic differential equation on pressure drawdown and boundary conditions in the wells taking flows in the fractures pseudo-linear, as well as external boundary conditions in calculation regions (a reservoir spreads to an infinite distance, and its top and bottom are closed by non-water permeating beds). The paper also indicates that results of calculating a single vertical fracture model and a slanted fracture model by using a numerical computation program (MULFRAC) based on the above equations agree well respectively with the existing calculation results (calculations performed by Erlougher and Cinco et al). 5 refs., 6 figs.

  4. Viral suppression of multiple escape mutants by de novo CD8+ T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

    Directory of Open Access Journals (Sweden)

    Siliciano Robert F

    2011-08-01

    Full Text Available Abstract Elite suppressors or controllers (ES are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated at CTL epitopes, a single, dominant variant containing CTL escape mutations is typically seen in plasma during chronic infection. We describe an ES who developed seven distinct and rare escape variants at an HLA-B*57-restricted Gag epitope over a five year period. Interestingly, he developed proliferative, de novo CTL responses that suppressed replication of each of these variants. These responses, in combination with low viral fitness of each variant, may contribute to sustained elite control in this ES.

  5. Ad35 and ad26 vaccine vectors induce potent and cross-reactive antibody and T-cell responses to multiple filovirus species.

    Directory of Open Access Journals (Sweden)

    Roland Zahn

    Full Text Available Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35 was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,, two Marburg strains (Marburg Angola and Marburg Ravn and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26-Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years.

  6. Identification of Immunodominant Responses to the Plasmodium falciparum Antigens PfUIS3, PfLSA1 and PfLSAP2 in Multiple Strains of Mice.

    Directory of Open Access Journals (Sweden)

    Rhea J Longley

    Full Text Available Malaria, caused by the Plasmodium parasite, remains a serious global public health concern. A vaccine could have a substantial impact on eliminating this disease, alongside other preventative measures. We recently described the development of three novel, viral vectored vaccines expressing either of the antigens PfUIS3, PfLSA1 and PfLSAP2. Each vaccination regimen provided high levels of protection against chimeric parasite challenge in a mouse model, largely dependent on CD8+ T cells. In this study we aimed to further characterize the induced cellular immune response to these vaccines. We utilized both the IFNγ enzyme-linked immunosorbent spot assay and intracellular cytokine staining to achieve this aim. We identified immunodominant peptide responses for CD4+ and CD8+ T cells for each of the antigens in BALB/c, C57BL/6 and HLA-A2 transgenic mice, creating a useful tool for researchers for subsequent study of these antigens. We also compared these immunodominant peptides with those generated from epitope prediction software, and found that only a small proportion of the large number of epitopes predicted by the software were identifiable experimentally. Furthermore, we characterized the polyfunctionality of the induced CD8+ T cell responses. These findings contribute to our understanding of the immunological mechanisms underlying these protective vaccines, and provide a useful basis for the assessment of these and related vaccines as clinical constructs.

  7. The development of new environmental policies and processes in response to a crisis: the case of the multiple barrier approach for safe drinking water

    International Nuclear Information System (INIS)

    Plummer, Ryan; Velaniskis, Jonas; Grosbois, Danuta de; Kreutzwiser, Reid D.; Loe, Rob de

    2010-01-01

    While new environmental policies and procedures often are developed incrementally, they can also result from crises or other significant events. In situations where policies and procedures are introduced in response to a crisis, questions about the strengths and weaknesses of existing mechanisms, and the extent to which they can be used to address concerns, may be ignored. This paper explores the complexities of introducing new policies and processes where planning systems and procedures already exist. Drinking water source protection policies that are being developed in response to the tragic events in Walkerton, Ontario, Canada serve as the context for the inquiry. Three case study watersheds were selected to reflect the diversity of municipal jurisdictions and water supply systems in Ontario. A content analysis was undertaken on regulatory and non-regulatory policy documents to determine the extent to which they addressed elements of the multi-barrier approach for drinking water safety. Findings from the research reveal considerable evidence of the multi-barrier approach in the policy and guiding documents analyzed. Policy development in response to a crisis can advance progress on the issue of drinking water safety and coincide with emerging governance strategies. Policy effectiveness may be enhanced by considering existing policies as well as contextual and jurisdictional differences.

  8. The Arabidopsis thaliana RNA editing factor SLO2, which affects the mitochondrial electron transport chain, participates in multiple stress and hormone responses.

    Science.gov (United States)

    Zhu, Qiang; Dugardeyn, Jasper; Zhang, Chunyi; Mühlenbock, Per; Eastmond, Peter J; Valcke, Roland; De Coninck, Barbara; Oden, Sevgi; Karampelias, Michael; Cammue, Bruno P A; Prinsen, Els; Van Der Straeten, Dominique

    2014-02-01

    Recently, we reported that the novel mitochondrial RNA editing factor SLO2 is essential for mitochondrial electron transport, and vital for plant growth through regulation of carbon and energy metabolism. Here, we show that mutation in SLO2 causes hypersensitivity to ABA and insensitivity to ethylene, suggesting a link with stress responses. Indeed, slo2 mutants are hypersensitive to salt and osmotic stress during the germination stage, while adult plants show increased drought and salt tolerance. Moreover, slo2 mutants are more susceptible to Botrytis cinerea infection. An increased expression of nuclear-encoded stress-responsive genes, as well as mitochondrial-encoded NAD genes of complex I and genes of the alternative respiratory pathway, was observed in slo2 mutants, further enhanced by ABA treatment. In addition, H2O2 accumulation and altered amino acid levels were recorded in slo2 mutants. We conclude that SLO2 is required for plant sensitivity to ABA, ethylene, biotic, and abiotic stress. Although two stress-related RNA editing factors were reported very recently, this study demonstrates a unique role of SLO2, and further supports a link between mitochondrial RNA editing events and stress response.

  9. A neuro-data envelopment analysis approach for optimization of uncorrelated multiple response problems with smaller the better type controllable factors

    Science.gov (United States)

    Bashiri, Mahdi; Farshbaf-Geranmayeh, Amir; Mogouie, Hamed

    2013-11-01

    In this paper, a new method is proposed to optimize a multi-response optimization problem based on the Taguchi method for the processes where controllable factors are the smaller-the-better (STB)-type variables and the analyzer desires to find an optimal solution with smaller amount of controllable factors. In such processes, the overall output quality of the product should be maximized while the usage of the process inputs, the controllable factors, should be minimized. Since all possible combinations of factors' levels, are not considered in the Taguchi method, the response values of the possible unpracticed treatments are estimated using the artificial neural network (ANN). The neural network is tuned by the central composite design (CCD) and the genetic algorithm (GA). Then data envelopment analysis (DEA) is applied for determining the efficiency of each treatment. Although the important issue for implementation of DEA is its philosophy, which is maximization of outputs versus minimization of inputs, this important issue has been neglected in previous similar studies in multi-response problems. Finally, the most efficient treatment is determined using the maximin weight model approach. The perfo