Non-genomic signalling of the retinoic X receptor through inhibition of Gq signalling in human platelets

Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) gamma, PPARbeta, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXRalpha and RXRbeta. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families.

Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets

Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) gamma, PPAR beta, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXR alpha, and RXR beta. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families. (C) 2007 by The American Society of Hematology.

A combined statistical and dynamical approach for downscaling large-scale footprints of European windstorms

The occurrence of mid-latitude windstorms is related to strong socio-economic effects. For detailed and reliable regional impact studies, large datasets of high-resolution wind fields are required. In this study, a statistical downscaling approach in combination with dynamical downscaling is introduced to derive storm related gust speeds on a high-resolution grid over Europe. Multiple linear regression models are trained using reanalysis data and wind gusts from regional climate model simulations for a sample of 100 top ranking windstorm events. The method is computationally inexpensive and reproduces individual windstorm footprints adequately. Compared to observations, the results for Germany are at least as good as pure dynamical downscaling. This new tool can be easily applied to large ensembles of general circulation model simulations and thus contribute to a better understanding of the regional impact of windstorms based on decadal and climate change projections.

Estimation of wind storm impacts over Western Germany under future climate conditions using a statistical-dynamical downscaling approach

A statistical–dynamical regionalization approach is developed to assess possible changes in wind storm impacts. The method is applied to North Rhine-Westphalia (Western Germany) using the FOOT3DK mesoscale model for dynamical downscaling and ECHAM5/OM1 global circulation model climate projections. The method first classifies typical weather developments within the reanalysis period using K-means cluster algorithm. Most historical wind storms are associated with four weather developments (primary storm-clusters). Mesoscale simulations are performed for representative elements for all clusters to derive regional wind climatology. Additionally, 28 historical storms affecting Western Germany are simulated. Empirical functions are estimated to relate wind gust fields and insured losses. Transient ECHAM5/OM1 simulations show an enhanced frequency of primary storm-clusters and storms for 2060–2100 compared to 1960–2000. Accordingly, wind gusts increase over Western Germany, reaching locally +5% for 98th wind gust percentiles (A2-scenario). Consequently, storm losses are expected to increase substantially (+8% for A1B-scenario, +19% for A2-scenario). Regional patterns show larger changes over north-eastern parts of North Rhine-Westphalia than for western parts. For storms with return periods above 20 yr, loss expectations for Germany may increase by a factor of 2. These results document the method's functionality to assess future changes in loss potentials in regional terms.

Explosive development of winter storm Xynthia over the subtropical North Atlantic Ocean

In winter of 2009–2010 south-western Europe was hit by several destructive windstorms. The most important was Xynthia (26–28 February 2010), which caused 64 reported casualties and was classified as the 2nd most expensive natural hazard event for 2010 in terms of economic losses. In this work we assess the synoptic evolution, dynamical characteristics and the main impacts of storm Xynthia, whose genesis, development and path were very uncommon. Wind speed gusts observed at more than 500 stations across Europe are evaluated as well as the wind gust field obtained with a regional climate model simulation for the entire North Atlantic and European area. Storm Xynthia was first identified on 25 February around 30° N, 50° W over the subtropical North Atlantic Ocean. Its genesis occurred on a region characterized by warm and moist air under the influence of a strong upper level wave embedded in the westerlies. Xynthia followed an unusual SW–NE path towards Iberia, France and central Europe. The role of moist air masses on the explosive development of Xynthia is analysed by considering the evaporative sources. A lagrangian model is used to identify the moisture sources, sinks and moisture transport associated with the cyclone during its development phase. The main supply of moisture is located over an elongated region of the subtropical North Atlantic Ocean with anomalously high SST, confirming that the explosive development of storm Xynthia had a significant contribution from the subtropics.

Can dynamically downscaled windstorm footprints be improved by observations through a probabilistic approach?

Windstorms are a main feature of the European climate and exert strong socioeconomic impacts. Large effort has been made in developing and enhancing models to simulate the intensification of windstorms, resulting footprints, and associated impacts. Simulated wind or gust speeds usually differ from observations, as regional climate models have biases and cannot capture all local effects. An approach to adjust regional climate model (RCM) simulations of wind and wind gust toward observations is introduced. For this purpose, 100 windstorms are selected and observations of 173 (111) test sites of the German Weather Service are considered for wind (gust) speed. Theoretical Weibull distributions are fitted to observed and simulated wind and gust speeds, and the distribution parameters of the observations are interpolated onto the RCM computational grid. A probability mapping approach is applied to relate the distributions and to correct the modeled footprints. The results are not only achieved for single test sites but for an area-wide regular grid. The approach is validated using root-mean-square errors on event and site basis, documenting that the method is generally able to adjust the RCM output toward observations. For gust speeds, an improvement on 88 of 100 events and at about 64% of the test sites is reached. For wind, 99 of 100 improved events and ~84% improved sites can be obtained. This gives confidence on the potential of the introduced approach for many applications, in particular those considering wind data.

The XWS open access catalogue of extreme European windstorms from 1979 to 2012

The XWS (eXtreme WindStorms) catalogue consists of storm tracks and model-generated maximum 3 s wind-gust footprints for 50 of the most extreme winter windstorms to hit Europe in the period 1979–2012. The catalogue is intended to be a valuable resource for both academia and industries such as (re)insurance, for example allowing users to characterise extreme European storms, and validate climate and catastrophe models. Several storm severity indices were investigated to find which could best represent a list of known high-loss (severe) storms. The best-performing index was Sft, which is a combination of storm area calculated from the storm footprint and maximum 925 hPa wind speed from the storm track. All the listed severe storms are included in the catalogue, and the remaining ones were selected using Sft. A comparison of the model footprint to station observations revealed that storms were generally well represented, although for some storms the highest gusts were underestimated. Possible reasons for this underestimation include the model failing to simulate strong enough pressure gradients and not representing convective gusts. A new recalibration method was developed to estimate the true distribution of gusts at each grid point and correct for this underestimation. The recalibration model allows for storm-to-storm variation which is essential given that different storms have different degrees of model bias. The catalogue is available at www.europeanwindstorms.org.

Synthesis, Structural Characterization, and Biological Evaluation of Oxorhenium(V) Complexes with a Novel Type of Thiosemicarbazones Derived from N-[N `,N `-Dialkylamino(thiocarbonyl)]benzimidoyl Chlorides

Reactions of N-[N`,N`-diethylamino(thiocarbonyl)]benzimidoyl chloride with 4,4-dialkylthiosemicarbazides give a novel class of thiosemicarbazides/thiosemicarbazones, H(2)L, which causes a remarkable reduction of cell growth in in vitro experiments. These strong antiproliferative effects are also observed for oxorhenium(V) complexes of the general composition [ReOCl(L)], which are formed by reactions of the potentially tridentate ligands with (NBu(4))[ReOCl(4)]. A systematic substitution of the alkyl groups in the thiosemicarbazone building blocks of the ligands do not significantly influence the biological activity of the metal complexes, while the replacement of the chloro ligand by a PPh(3) ligand (by the replacement of the oxo unit by a nitrido ligand) completely terminated the cytotoxicity of the metal complexes.

Att leva med långvarig smärta vid fibromyalgi : Upplevelser, hantering och omvårdnad

Syftet med denna litteraturstudie var att beskriva hur människor med fibromyalgi upplever att leva med långvarig smärta, hur denna hanteras i det dagliga livet samt vilka omvårdnadshandlingar som upplevs betydelsefulla av fibromyalgidrabbade. Litteratursökningen genomfördes via Högskolan Dalarnas databaser ELIN, Blackwell Synergy och EBSCO HOST med hjälp av sökord i olika kombinationer. Tre artiklar söktes manuellt. Inklusionskriterierna var att artiklarna skulle vara vetenskapliga och skrivna på engelska, svenska, norska eller danska samt vara publicerade mellan 1997-2007. Artiklarna (n=16) kvalitetsgranskades med hjälp av granskningsmallar och de artiklar som var av hög eller medelhög kvalitet inkluderades. I resultatet framkom att den långvariga smärtan vid fibromyalgi upplevdes dominera medvetandet vilket kunde leda till känslor av ilska, hjälplöshet, frustration, irritation, desperation och utmattning. Flera delar av, eller i vissa fall hela kroppen, engagerades av smärtan. Exempel på strategier för att hantera smärtan var att använda sig av fysiska aktiviteter, avslappningsövningar, självdistrahering, alternativmedicinska behandlingar och att ha en positiv attityd. Den viktigaste formen av psykologiskt stöd var att bli lyssnad till och att få uttrycka sig utan att känna sig dömd. Vidare var praktiskt stöd, såsom assistans med hushållssysslor av stor betydelse. Att erhålla adekvat information om sjukdomstillståndet och prognosen upplevdes vara viktigt av fibromyalgidrabbade.

Nutritionsomvårdnad hos den äldre människan : Sjuksköterskans omvårdnadsansvar - en litteraturstudie

Syftet med denna studie var att undersöka kunskapsnivån gällande nutritionsarbete hos sjuksköterskor samt att undersöka vilka omvårdnadsåtgärder sjuksköterskor kan vidta som ansvariga för nutritionsarbetet. Metoden som användes var en litteraturstudie där 15 artiklar granskades. Att sjuksköterskor har bra kunskaper inom nutritionsomvårdnaden framkom i några studier. Sjuksköterskor ansåg till exempel att nutritionsplaner och dokumentationer av nutritionsomvårdnad var viktiga. De ansåg även att kosten var viktig för en god hälsa. Sjuksköterskor bedömde sig själva ha tillräckligt med kunskaper om vikten av en adekvat nutrition. Dock framkom även i många studier att nutritionsomvårdnaden brister. Trots att sjuksköterskor ansåg att kosten var en viktig del i omvårdnaden prioriterades den inte. Sjuksköterskor deltog sällan vid måltiderna och hade därför svårt att utföra ett gott nutritionsarbete. Dokumentationen visade sig i många studier vara bristfällig. Det visade sig även att sjuksköterskor inte ansåg sig själva ha tillräckligt med kunskap i nutritionsomvårdnaden. De omvårdnadsåtgärder som visat sig ge goda resultat var utbildningar till personalen angående nutritionsomvårdnad. Om sjuksköterskor är mer involverade i matserveringen får de bättre insikt i hur patienter äter och kan assistera, vilket bidrar till högre energiintag. Även patienterna kan med fördel involveras mer i sin nutrition vilket visat sig leda till ökat energiintag.

Kristen Sionism : Myt som religiöst och politiskt verktyg

In this essay I focus on Christian Zionism, its roots and growth, to judge wether or not it is possible to look at Christian Zionism as a modern form of myth. To do that I have used Bruce Lincoln's definition: ideology in narrative form. I also ask the question whether this kind of religious conviction can be labeled as an extreme or become a danger to society. The conclusion I reach is that Christian Zionism and its broader context, dispensationalism, very well fits the definitions of modern myth that Lincoln offers. There is certainly a hierarcic ideology within Christian Zionism, and its narrative/myth have been ”negotiated between narrators and audiences over time”. The essay also shows that there is a risk concerning this particular form of religious conviction, it could become an extreme. Especially so when this alternative form of viewing reality and the future, is represented not only among ordinary citizens in the US, but also within the US Government and among military leaders.

Gerillakampanjer – karakteristika och reklambyråns arbetssätt : En djupintervjuundersökning med särskilt fokus på visuella gerillakampanjer

Syftet med denna studie var att genom semistrukturerade djupintervjuer, med särskild fokus på visuella gerillakampanjer, kartlägga de av byråerna benämnda karaktärsdragen för gerillakampanjer samt byråernas arbetssätt för dessa kampanjer.Fem semistrukturerade djupintervjuer genomfördes på respektive respondents arbetsplats utvalda genom ett kombinerat strategiskt och bekvämlighetsurval.Resultaten visade tydliga karaktärsdrag för en gerillakampanj. Utifrån dessa har följande definition tagits fram: en gerillakampanj kännetecknas av att den saknar köpt medieexponering och ofta karaktäriseras av en kreativ, ofta situations- och miljöanpassad, utformning som på egen hand väcker stort intresse eller uppmärksamhet relativt mot den nyttjade budgeten i syfte att skapa djupare relationer med mottagaren.Arbetssätten för en visuell gerillakampanj och vanliga gerillakampanjer skiljer sig inte nämnvärt mot arbetssätten för en traditionell reklamkampanj. Vid framtagandet av en gerillakampanj görs juridiska överväganden om huruvida lagöverträdelser kan komma att krävas. Det framkom även att spridningen i efterhand av en gerillakampanj var viktig för att få så stort genomslag som möjligt genom nyttjandet av traditionell media.

Motivations for knowledge sharing in virtual social networks: a comparative study between Brazil and France

Sociedades pós-modernas caracterizam-se pela transição de economias baseadas em ativos tangíveis para economias de conhecimento, onde indivíduos vivenciam uma imprescindível conectividade, mas ao mesmo tempo, experimentam um enfraquecimento das estruturas sociais, que tem generado uma crescente necessidade de se criar bases cognitivas e afetivas para a vida (Rheingold, 1992; Wasko & Farah, 2005; Arvidsson, 2008). Nesse cenário se desenvolve o fenômeno das redes sociais virtuais, agregando milhões de pessoas que compartilham mensagens de texto, imagens e vídeos todos os dias (Nielsen, 2012) fazendo com que organizações privadas foquem cada vez mais seus investimentos para acompanhar as novas tendências (McWilliam, 2000; Reichheld & Schefter, 2000; Yoo, Suh & Lee, 2002; Arvidsson, 2008). Consequentemente, uma das mais importantes questões que vem ganhando importância no meio academico e entre profissionais da área é justamente: por que as pessoas compartilham conhecimento online? (Monge, Fulk, Kalman, Flanigan, Parnassa & Rumsey, 1998; Lin, 2001) Por meio de uma metodologia de estudo de caso conduzida no Brasil e na França, este estudo objetiva produzir uma relevante revisão teórica acerca do tema, trazendo novas idéias de diferentes contextos, e propondo um modelo para avaliar as principais motivações que conduzem indivíduos a compartilhar conhecimento em redes sociais virtuais. Essas razões foram estruturadas em cinco dimensões: capital estrutural, cognitivo e relacional, motivações pessoais e razões monetárias (Nahapiet & Ghoshal, 1998; Wasko & Faraj, 2005; Chiu et al, 2006). As evidências sugerem que o processo de participar e compartilhar conhecimento em redes sociais virtuais é resultado de uma complexa combinação de motivações de orientação pessoal e coletiva, que parecem variar pouco de acordo com os diferentes objetivos e contextos dessas comunidades, onde as razões financeiras parecem ser secundárias.