Interactions between cocoa flavanols and inorganic nitrate: additive effects on endothelial function at achievable dietary amounts

Dietary intervention studies have shown that flavanols and inorganic nitrate can improve vascular function, suggesting that these two bioactives may be responsible for beneficial health effects of diets rich in fruits and vegetables. We aimed to study interactions between cocoa flavanols (CF) and nitrate, focusing on absorption, bioavailability, excretion, and efficacy to increase endothelial function. In a double-blind randomized, dose-response crossover study, flow-mediated dilation (FMD) was measured in 15 healthy subjects before and at 1, 2, 3, and 4 h after consumption of CF (1.4-10.9 mg/kg bw) or nitrate (0.1-10 mg/kg bw). To study flavanol-nitrate interactions, an additional intervention trial was performed with nitrate and CF taken in sequence at low and high amounts. FMD was measured before (0 h) and at 1h after ingestion of nitrate (3 or 8.5 mg/kg bw) or water. Then subjects received a CF drink (2.7 or 10.9 mg/kg bw) or a micro- and macronutrient-matched CF-free drink. FMD was measured at 1, 2, and 4 h thereafter. Blood and urine samples were collected and assessed for CF and nitric oxide (NO) metabolites with HPLC and gas-phase reductive chemiluminescence. Finally, intragastric formation of NO after CF and nitrate consumption was investigated. Both CF and nitrate induced similar intake-dependent increases in FMD. Maximal values were achieved at 1 h postingestion and gradually decreased to reach baseline values at 4 h. These effects were additive at low intake levels, whereas CF did not further increase FMD after high nitrate intake. Nitrate did not affect flavanol absorption, bioavailability, or excretion, but CF enhanced nitrate-related gastric NO formation and attenuated the increase in plasma nitrite after nitrate intake. Both flavanols and inorganic nitrate can improve endothelial function in healthy subjects at intake amounts that are achievable with a normal diet. Even low dietary intake of these bioactives may exert relevant effects on endothelial function when ingested together.

Platelet signaling: a complex interplay between inhibitory and activatory networks

The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators. This article is protected by copyright. All rights reserved.

Decadal predictions with the HiGEM high resolution global coupled climate model: description and basic evaluation

This paper describes the development and basic evaluation of decadal predictions produced using the HiGEM coupled climate model. HiGEM is a higher resolution version of the HadGEM1 Met Office Unified Model. The horizontal resolution in HiGEM has been increased to 1.25◦ × 0.83◦ in longitude and latitude for the atmosphere, and 1/3◦ × 1/3◦ globally for the ocean. The HiGEM decadal predictions are initialised using an anomaly assimilation scheme that relaxes anomalies of ocean temperature and salinity to observed anomalies. 10 year hindcasts are produced for 10 start dates (1960, 1965,..., 2000, 2005). To determine the relative contributions to prediction skill from initial conditions and external forcing, the HiGEM decadal predictions are compared to uninitialised HiGEM transient experiments. The HiGEM decadal predictions have substantial skill for predictions of annual mean surface air temperature and 100 m upper ocean temperature. For lead times up to 10 years, anomaly correlations (ACC) over large areas of the North Atlantic Ocean, the Western Pacific Ocean and the Indian Ocean exceed values of 0.6. Initialisation of the HiGEM decadal predictions significantly increases skill over regions of the Atlantic Ocean,the Maritime Continent and regions of the subtropical North and South Pacific Ocean. In particular, HiGEM produces skillful predictions of the North Atlantic subpolar gyre for up to 4 years lead time (with ACC > 0.7), which are significantly larger than the uninitialised HiGEM transient experiments.

Intracellular trafficking, localization, and mobilization of platelet-borne thiol isomerases

OBJECTIVE: Thiol isomerases facilitate protein folding in the endoplasmic reticulum, and several of these enzymes, including protein disulfide isomerase and ERp57, are mobilized to the surface of activated platelets, where they influence platelet aggregation, blood coagulation, and thrombus formation. In this study, we examined the synthesis and trafficking of thiol isomerases in megakaryocytes, determined their subcellular localization in platelets, and identified the cellular events responsible for their movement to the platelet surface on activation. APPROACH AND RESULTS: Immunofluorescence microscopy imaging was used to localize protein disulfide isomerase and ERp57 in murine and human megakaryocytes at various developmental stages. Immunofluorescence microscopy and subcellular fractionation analysis were used to localize these proteins in platelets to a compartment distinct from known secretory vesicles that overlaps with an inner cell-surface membrane region defined by the endoplasmic/sarcoplasmic reticulum proteins calnexin and sarco/endoplasmic reticulum calcium ATPase 3. Immunofluorescence microscopy and flow cytometry were used to monitor thiol isomerase mobilization in activated platelets in the presence and absence of actin polymerization (inhibited by latrunculin) and in the presence or absence of membrane fusion mediated by Munc13-4 (absent in platelets from Unc13dJinx mice). CONCLUSIONS: Platelet-borne thiol isomerases are trafficked independently of secretory granule contents in megakaryocytes and become concentrated in a subcellular compartment near the inner surface of the platelet outer membrane corresponding to the sarco/endoplasmic reticulum of these cells. Thiol isomerases are mobilized to the surface of activated platelets via a process that requires actin polymerization but not soluble N-ethylmaleimide-sensitive fusion protein attachment receptor/Munc13-4-dependent vesicular-plasma membrane fusion.

A reversal of climatic trends in the North Atlantic since 2005

In the mid-1990s the North Atlantic subpolar gyre warmed rapidly, which had important climate impacts, such as increased hurricane numbers, and changes to rainfall over Africa, Europe and North America. Evidence suggests that the warming was largely due to a strengthening of the ocean circulation, particularly the Atlantic Meridional Overturning Circulation (AMOC). Since the mid-1990s direct and indirect measurements have suggested a decline in the strength of the ocean circulation, which is expected to lead to a reduction in northward heat transport. Here we show that since 2005 a large volume of the upper North Atlantic Ocean has cooled significantly by approximately -0.45C or 1.5x10^22 J, reversing the previous warming trend. By analysing observations and a state-of-the-art climate model, we show that this cooling is consistent with a reduction in the strength of the ocean circulation and heat transport, linked to record low densities in the deep Labrador Sea. The low density in the deep Labrador Sea is primarily due to deep ocean warming since 1995, but a long-term freshening also played a role. The observed upper ocean cooling since 2005 is not consistent with the hypothesis that anthropogenic aerosols directly drive Atlantic temperatures.

Diel surface temperature range scales with lake size

Ecological and biogeochemical processes in lakes are strongly dependent upon water temperature. Long-term surface warming of many lakes is unequivocal, but little is known about the comparative magnitude of temperature variation at diel timescales, due to a lack of appropriately resolved data. Here we quantify the pattern and magnitude of diel temperature variability of surface waters using high-frequency data from 100 lakes. We show that the near-surface diel temperature range can be substantial in summer relative to long-term change and, for lakes smaller than 3 km2, increases sharply and predictably with decreasing lake area. Most small lakes included in this study experience average summer diel ranges in their near-surface temperatures of between 4 and 7°C. Large diel temperature fluctuations in the majority of lakes undoubtedly influence their structure, function and role in biogeochemical cycles, but the full implications remain largely unexplored.

The Autoimmune Regulator (AIRE), Which Is Defective in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients, Is Expressed in Human Epidermal and Follicular Keratinocytes and Associates With the Intermediate Filament Protein Cytokeratin 17

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is caused by mutation of the autoimmune regulator (AIRE) gene, is a highly variable disease characterized by multiple endocrine failure, chronic mucocutaneous candidiasis, and various ectodermal defects. AIRE is a transcriptional regulator classically expressed in medullary thymic epithelial cells, monocytes, macrophages, and dendritic cells. Previous studies have suggested that AIRE can shuttle between the nucleus and cytoplasm of cells, although its cytoplasmic functions are poorly characterized. Through mass spectrometry analysis of proteins co-immunoprecipitating with cytoplasmic AIRE, we identified a novel association of AIRE with the intermediate filament protein cytokeratin 17 (K17) in the THP-1 monocyte cell line. We confirmed AIRE expression in HaCaT epidermal keratinocytes, as well as its interaction with K17. Confocal microscopy of human fetal and adult scalp hair follicles demonstrated a cytoplasmic pattern of AIRE staining that moderately colocalized with K17. The cytoplasmic association of AIRE with the intermediate filament network in human epidermal and follicular keratinocytes may provide a new path to understanding the ectodermal abnormalities associated with the APECED syndrome. (Am J Pathol 2011, 178:983-988; DOI: 10.1016/j.ajpath.2010.12.007)

A real-time polymerase chain reaction assay for the identification and quantification of American Leishmania species on the basis of glucose-6-phosphate dehydrogenase

A real-time polymerase chain reaction (PCR) test was developed on the basis of the Leishmania glucose-6-phosphate dehydrogenase locus that enables identification and quantification of parasites. Using two independent pairs of primers in SYBR-Green assays, the test identified etiologic agents of cutaneous leishmaniasis belonging to both subgenera, Leishmania (Viannia) and Leishmania (Leishmania) in the Americas. Furthermore, use of TaqMan probes enables distinction between L. (V.) braziliensis or L. (V.) peruviania from the other L. (Viannia) species. All assays were negative with DNA of related trypanosomatids, humans, and mice. The parasite burden was estimated by normalizing the number of organisms per total amount of DNA in the sample or per host glyceraldehyde-3-phosphate dehydrogenase copies. The real-time PCR assay for L. (Leishmania) subgenus showed a good linear correlation with quantification on the basis of a limiting dilution assay in experimentally infected mice. The test successfully identifies and quantifies Leishmania in human biopsy specimens and represents a new tool to study leishmaniasis.

Extern Web-service-lösning vid SSAB Tunnplåt i Borlänge- för kommunikation med sina distributions lager

Detta examensarbete har utförts på SSAB- Tunnplåt i Borlänge under vårterminen 2004 och omfattar 10 veckors arbete.SSAB sköter idag sin kommunikation med distributionslagren via fax, telefon eller e-post. Eftersom detta är ett ganska tidskrävande kommunikationssätt, vill SSAB ha en smidigare och snabbare kommunikationslösning. Den lösning som SSAB vill ha är en extern Web-service-lösning för att upprätta en säker kommunikation med sina distributionslager.Parallellt med byggandet av Web-service-lösningen arbetades en förvaltningsmodell fram. Den beskriver hur förvaltningsorganisationen med dess rutiner kan se ut vid implementering av lösningen.För att skapa en säker förbindelse med Web-servicen skall en webbklient användas som i sin tur anropar en COM+ komponent. Detta för att kunna skicka med certifikatet ifrån webbklienten till webbservern där Web-servicen ligger. COM+ komponenten måste få tillgång till en användarprofil när den kommunicerar med Web-servicen. Detta för att kunna upprätta en SSL-förbindelse i det inledande skedet. SSL-förbindelsen skall läggas i den VPN-tunnel som mVPN tillhandahåller via WSSAL.

Utveckling av Hedlunds Hus AB webbplats

För att visa på nyttan av vad ett användartest kan erbjuda i samband med utveckling av en webbplats har vi i denna rapport tagit med alla stegen fram till och med utveckling i Vattenfallsmetoden, som är den metod som vi använt oss av. De föregående stegen i metoden är förstudie, analys och design. Förstudien valde vi att genomföra som ett användartest för att få fram vad användarna verkligen efterfrågade. Vi analyserade sedan resultatet av användartestet och gjorde en sammanfattning, men i den tog vi även hänsyn till det material som vi samlat in och vad de ansvariga på Hedlunds Hus AB efterfrågade. Detta resulterade i en lista med prioriterade funktioner och innehåll, som vi sedan utgick ifrån vid utveckling av webbplatsen. Vid utveckling av webbplatsen togs även hänsyn till det material som vi samlat in om webbutformning/design. Att använda sig av ett användartest i förstudiefasen tycker vi är ett bra sätt för att få fram vad användarna efterlyser och inte vad vi som webbutvecklare själva tror att användarna behöver.

Ungdomars tankar kring betydelsen av färg och form vid framställningen av en internationell webbtidning

När en grafisk profil för en spännande ny internationell webbtidning för ungdomar skall göras är det viktigt att tänka på hur färg och form påverkar våra känslor. Experiment med färg som har gjorts av ledande färgpsykologer och färgvetare som Goethe, Itten, Lüscher och Karl Ryberg bevisar att färg har en stor psykologisk påverkan på människan. Internet är ett väldigt effektiv kommunikationsmedium och för att kommunicera effektivt är det inte bara orden, utan även färgerna och formerna på webbsidorna som skall vara väl genomtänkta. Vilka färger kopplar ungdomar i Sverige och Chile ihop med vissa känslor? Vilka former kopplas ihop med samma känslor? Svaren på de frågorna sammanställdes och analyserades efter svaren på en enkät om färg och form som delades it till två högstadieskolor i Borlänge, Sverige och en i Santiago, Chile.

Den nya kassaregisterlagen

The government appointed in 2004 a special investigator with the objective to investigate the possibility of introducing a new law concerning implementation of obligatory cash registers with certain certification. This resulted in SOU 2005:35 ”Krav på kassaregister - Effektivare utredning av skattebrott” (Proposition 2006/07: 105). Following advice received from the respondents, the government has drafted a bill submitted to parliament in March 2007. Government bill 2006/07: 105 proposals for new law on cash registers, and submitted to parliament 2007th Act (2007:592) on the cash register was adopted by parliament in March that year and came into force on 1 January 2010. Earlier great opportunities for tax cheating has been available by various methods so as to simply not punch in a sale at the checkout, use the training function type, use receipt copies, manipulate register functions on its program level, using alternative programming etc. These opportunities are eliminated in the certified cash registers. Respondent traders believed the most part has not changed the competition or that the change will be relatively small. They also thought it was too early to see any change at this time. A tendency among traders we have asked is that they feel negatively for the costs it imposes, with the new registry and that they are skeptical about the expected impact of the law, among others due to the scarce resources spent on follow-up. The Swedish tax agency is responsible for control and the new systems make it easier for Tax control, but actual physical on-scene control must be performed to detect irregularities.

Entreprenörskap i skolan : Gymnasielärares attityd och inställning till begreppen entreprenörskap och entreprenöriellt lärande.

Undersökningens avsikt var att vinna kunskap om hur gymnasielärare förhåller sig till lanseringen av begreppet entreprenörskap i skolan. Uppsatsen klarlägger och systematiserar hur lärare beskriver innehållet i begreppen entreprenörskap och entreprenöriellt lärande och fördjupar sig även i hur lärarna ser på upprinnelsen till begreppens lansering i den svenska skolan. Undersökningen gör även en analys av möjliga entreprenöriella undervisningsmetoder samt de olika undervisningsrelaterade problem som lärarna anser att dessa metoder kan ge upphov till. Åtta kvalitativa intervjuer genomförda på en gymnasieskola i norra Sverige utgör basen för undersökningen. Studien nyttjar en abduktiv förståelseansats vilket betyder att analysen av det empiriska materialet kännetecknades av en pendelrörelse mellan en induktiv ansats och en deduktiv ansats. I arbetets resultatdel slås bland annat fast att begreppet entreprenöriellt lärande av lärarna ses som ett verktyg för undervisning i entreprenörskap. Det framgår även som tydligt att entreprenörskap främst sätts i samband med företagande och/eller kreativitet. Begreppet entreprenöriellt lärande uppfattas i sin tur som mer diffust och mindre värdeladdat än begreppet entreprenörskap. De undervisningsmetoder som lärarna ansåg vara förknippade med entreprenörskap betonade främst antingen undervisningsstrategier/undervisningsinnehåll eller undervisningsstruktur/undervisningsform. Med utgångspunkt i intervjupersonernas svar var det möjligt att klargöra att entreprenörskap, utifrån ett skolperspektiv, inte bör ses som något nytt. Samtliga lärare i undersökning utgick från redan befintliga tillvägagångssätt när de beskrev metoder för entreprenöriell undervisning. I och med att lärarna uppfattade att svagare elever, som av olika anledningar ofta kan ha svårare att finna kreativitet och initiativförmåga, som de elever som har svårast med den typ av undervisning som lärarna sätter i samband med entreprenörskap, klargör uppsatsen även att det är svagare elever som får störst problem med entreprenörskapsundervisning. De problem som lärarna ansåg att entreprenöriell undervisning kan resultera i sträckte sig sammantaget från elevorienterade problem till lärar- och skolorienterade problem. Allt som allt uppfattar lärarna att det är partipolitiska beslut och en övergripande samhällsutveckling som legat till grund för lanserandet av entreprenörskap i den svenska skolan. Denna slutsats sätter uppsatsen i samband med övergripande samhällsteoretiska uppslag av Manuel Castells och Richard Florida.

Variação, contato e mudança linguística em Moçambique e Cabo Verde : A concordância variável de número em sintagmas nominais do português

This study investigates variable noun phrase number agreement (VNA) in two second language varieties of Portuguese, spoken in Maputo, Mozambique and in Mindelo, Cape Verde. Quantitative VARBRUL analysis is carried out based on recordings made in Maputo and Mindelo 2007 and 2008. Previous quantitative studies on VNA in varieties of Brazilian Portuguese (Guy, 1981; Lopes, 2001; Andrade, 2003) as well as on VNA in first and second language varieties of Portuguese from São Tomé (Baxter, 2004; Figueiredo, 2008, 2010) indicate contact between Portuguese and African languages as the main origin of this phenomenon. VNA in Brazilian Portuguese is, however, interpreted by Scherre (1988) and Naro & Scherre (1993, 2007) as the result of language internal drift. Varieties of Portuguese from Mozambique and Cape Verde are particularly interesting to contrast in order to investigate influences from African languages on VNA, as in Mozambique Bantu languages are first languages of the vast majority of Portuguese speakers, whereas in Cape Verde, practically all Portuguese speakers are first language speakers of Cape Verdean Creole, whose substrates are West African, and not Bantu, languages. Comparison is also made with previous studies from Brazil and São Tomé. The results of this study comment previously postulated explanations for VNA in Portuguese in various ways. The analysis of the variables onset age and age stratum indicates that VNA in the analyzed varieties is a phenomenon linked to the acquisition of Portuguese as a second language and/or language contact rather than the result of internal drift. The fact that all the compared varieties tend to mark plural on pre-head components contradicts Bantu transfer as an explanation for this pattern, and raises the need to also consider more general explanations based on language contact. The basic structural similarity between the compared varieties suggests the existence of a grammatical restructuring continuum.