57 research outputs found

    Th2 cells are essential for modulation of vascular repair by allogeneic endothelial cells

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    Author Manuscript 2011 April 1.Background: Endothelial cells (ECs) embedded within 3-dimensional matrices (MEEC) control lumenal inflammation and intimal hyperplasia when placed in the vascular adventitia. Matrix embedding alters endothelial immunogenicity in vitro. T-helper (Th) cell-driven host immunity is an impediment of allogeneic grafts. We aimed to identify if modulation of Th balance would affect immune compatibility and endothelial regulation of vascular repair in vivo. Methods: Pigs (n = 4/group) underwent carotid artery balloon injury and were left untreated (Group 1) or received perivascular porcine MEEC implants (Group 2), 12 days of cyclosporine A (CsA; Group 3), or MEEC and CsA (Group 4). Host immune reactivity was analyzed after 28 and 90 days. Results: MEEC treatment induced formation of EC-specific immunoglobulin (Ig) G1 antibodies (41 ± 6 mean fluorescence intensity [MFI]) and differentiation of host splenocytes into Th2, but not Th1, cytokine-producing cells (interleukin [IL]-4, 242 ± 102; IL-10, 273 ± 114 number of spots). Concomitant CsA therapy reduced IgG1 antibody frequency (25 ± 2 MFI; p < 0.02) and Th2-cytokine producing splenocytes upon MEEC treatment (IL-4, 157 ± 19; IL-10, 124 ± 26 number of spots; p < 0.05). MEECs inhibited luminal occlusion 28 and 90 days after balloon injury (12 ± 7%) vs untreated controls (68 ± 14%; p < 0.001) but to a lesser extent with concomitant CsA treatment (34 ± 13%; p < 0.02 vs Group 2). Conclusions: MEECs do not induce a significant Th1-driven immune response but do enhance differentiation of splenocytes into cells producing Th2 cytokine. Reduction in this Th2 response reduces the vasoregulatory effects of allogeneic ECs after injury

    Revisiting mechanisms and functions of prenatal hormone-mediated maternal effects using avian species as a model

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    This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this record.Maternal effects can adaptively modulate offspring developmental trajectories in variable but predictable environments. Hormone synthesis is sensitive to environmental factors, and maternal hormones are thus a powerful mechanism to transfer environmental cues to the next generation. Birds have become a key model for the study of hormone-mediated maternal effects because the embryo develops outside the mother’s body, facilitating the measurement and manipulation of prenatal hormone exposure. At the same time, birds are excellent models for the integration of both proximate and ultimate approaches, which is key to a better understanding of the evolution of hormone-mediated maternal effects. Over the past two decades, a surge of studies on hormone-mediated maternal effects has revealed an increasing number of discrepancies. In this review, we discuss the role of the environment, genetic factors and social interactions in causing these discrepancies and provide a framework to resolve them. We also explore the largely neglected role of the embryo in modulating the maternal signal, as well as costs and benefits of hormone transfer and expression for the different family members. We conclude by highlighting fruitful avenues for future research that have opened up thanks to new theoretical insights and technical advances in the field

    Delivery Site of Perivascular Endothelial Cell Matrices Determines Control of Stenosis in a Porcine Femoral Stent Model

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    PURPOSE: High restenosis rates are a major limitation of peripheral interventions. Endothelial cells, grown within gelatin matrices and implanted onto the adventitia of injured vessels, inhibit stenosis in experimental models. To determine if this technology could be adapted for minimally invasive procedures, we compared the effects of cells in an implantable sponge to an injectable formulation and investigated the importance of delivery site in a stent model. MATERIALS AND METHODS: Stents were implanted in the femoral arteries of 30 pigs followed by perivascular implantation of sponges or injection of particles containing allogeneic endothelial cells. Controls received acellular matrices or nothing. The effects of delivery site were assessed by injecting cellular matrices into or adjacent to the perivascular tissue, or into the neighboring muscle. Animals were sacrificed after 28 days. Pre-sacrifice angiograms and tissue sections were evaluated for stenosis. RESULTS: Arteries treated with cellular matrices had a 55 – 63% decrease in angiographic stenosis (P<0.05) and a 38 – 43% reduction (P<0.05) in histologic stenoses compared to controls. Intimal area was greatest when cellular matrices were delivered into the muscle (6.35 ± 0.95 mm2) compared to into or adjacent to the perivascular tissue (4.05 ± 0.56 mm2 and 4.73 ± 0.53 mm2, respectively, P < 0.05). CONCLUSIONS: Perivascular endothelial-cell matrices reduced stenosis after stent-induced injury. The effects were not dependent on the formulation but appeared to be dependent upon delivery site. Minimally invasive injections of endothelial-cell matrices to the adventitia of arteries following peripheral interventions may decrease restenosis rates.National Institutes of Health (U.S.) (Grant GM 49039

    De juridische en praktische kaders bij het hergebruiken van digitale publieke geografische informatie

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    Digitalisering van overheidsinformatie biedt ongekende mogelijkheden om informatie snel en eenvoudig uit te wisselen en te integreren met andere informatie. Bestaande werkprocessen worden zo efficiënter en effectiever en het geeft een basis voor de ontwikkeling van nieuwe producten en toepassingen. Deze ontwikkelingen hebben misschien wel de grootste vlucht genomen op het gebied van de geografische informatie. Geografische informatie is informatiedie verbonden is aan een plaats op de aarde. Het verbindt locatie, tijd en kenmerken van die locatie. Bekende toepassingen die gebruik maken van geografische informatie zijn Google Earth en navigatieproducten van TomTom en Garmin. Ook in het publieke domein wordt veelvuldig gebruik gemaakt van geografische informatie. Hoewel deze informatie soms wordt ingekocht bijderden, wordt veel geografische informatie door de overheid zelf, of door derden in opdracht van de overheid, ingewonnen en verwerkt. Deze geografische overheidsinformatie blijkt naast gebruik voor de uitvoering van de publieke taak vaak ook geschikt voor andere doeleinden: het zogenaamde hergebruik van geografische overheidsinformatie.Het economisch potentieel van hergebruik van overheidsinformatie wordt geschat op waarden variërend tussen de €27 miljard en €68 miljard waarvan een significant deel door het economisch potentieel van geografische overheidsinformatie wordt gedekt. Anno 2011 blijft het hergebruik echter sterk achter bij deze schattingen uit het begin van deze eeuw.Dit hoofdstuk zal ingaan op de juridische kaders voor het hergebruik van geografische overheidsinformatie. Het hoofdstuk zal tevens mogelijke problemen identificeren waarmee hergebruikers te maken hebben en oplossingsrichtingen formuleren vanuit het perspectief van de hergebruiker.AuteursversieOLD Geo-information and Land Developmen

    Reflexes of Finiteness in Romance

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    This dissertation investigates the concept of finiteness across Romance, a theoretical notion very frequently used within linguistics although still poorly understood (Ledgeway 2007:335). Various Romance verb forms and clauses which are not readily classifiable as either finite or non-finite are examined, such as personal and inflected infinitives, as well as Balkan-style subjunctives in Romanian, Salentino, and southern Calabrian, morphologically finite verb forms which behave syntactically as non-finite verbs. First the categorial status of irrealis complements is studied; it is argued that both non-finite (the Romance infinitival complementisers deriving from Latin AD and DE) and irrealis complementisers (southern Calabrian mu, Salentino cu, Upper southern Italian che and Romanian să) are spurious categories. Specifically, it is shown that AD, DE, mu and cu can head variously sized clauses with different degrees of syntactic finiteness and that the morphological form of the verb does not seem to influence the clause size nor the degree of finiteness. Romanian să-clauses, on the other hand, are consistently CPs. It is thus concluded that there is no cross-linguistic correlation between finiteness and clause size. Second, the diachrony of these irrealis complementisers is analysed as well; they all result from a process of downwards (re)grammaticalisation, whereby grammatical elements originating in the C-domain come to occupy the lowest position of the CP, and, in the case of mu and cu, also come to head smaller complements and thus to occupy lower functional heads. This process is accompanied by a reanalysis from phrase (XP) to head (X) with concomitant phonological reduction. Third, it is shown that, unlike finite verbs, non-finite and semi-finite verb forms consistently move to a high position within the clause. This is also true of subjunctives; all have a common feature that requires the verb be moved to the edge of the inflectional domain. This movement renders the regular subject position SpecTP unavailable in most of these cases. The central proposal of the dissertation is that finiteness is not a linguistic primitive, but should be broken down into the anchoring of both Tense and Person. Both allow for different degrees of anchoring to the speech act (independent, dependent, or absent). There is an asymmetrical relationship between the two: only when Tense anchoring takes place, can Person anchoring obtain too. The combination of both anchoring mechanisms yields a scalar view of finiteness that matches more closely the wide range of semi-finite and non-finite forms explored in the dissertation. It is the dependent anchoring which triggers non-finite and semi-finite verbs to move high, while the absence of this anchoring automatically renders reduced complements non-finite. Finally, only when both anchoring mechanisms act completely independently does a fully finite clause obtain

    Thiamin pyrophosphate (TPP) analogues as selective inhibitors for TPP-dependent enzymes

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    De begeleider en/of auteur heeft geen toestemming gegeven tot het openbaar maken van de scriptie. The supervisor and/or the author did not authorize public publication of the thesis.

    Research Report 1: Substrate analysis and studies on the kinetic mechanism of 5-hydroxymethyl-furfural oxidase

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    De begeleider en/of auteur heeft geen toestemming gegeven tot het openbaar maken van de scriptie. The supervisor and/or the author did not authorize public publication of the thesis.

    Myocardial drug distribution generated from local epicardial application: Potential impact of cardiac capillary perfusion in a swine model using epinephrine

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    Prior studies in small mammals have shown that local epicardial application of inotropic compounds drives myocardial contractility without systemic side effects. Myocardial capillary blood flow, however, may be more significant in larger species than in small animals. We hypothesized that bulk perfusion in capillary beds of the large mammalian heart not only enhances drug distribution after local release, but also clears more drug from the tissue target than in small animals. Epicardial (EC) drug releasing systems were used to apply epinephrine to the anterior surface of the left heart of swine in either point-sourced or distributed configurations. Following local application or intravenous (IV) infusion at the same dose rates, hemodynamic responses, epinephrine levels in the coronary sinus and systemic circulation, and drug deposition across the ventricular wall, around the circumference and down the axis, were measured. EC delivery via point-source release generated transmural epinephrine gradients directly beneath the site of application extending into the middle third of the myocardial thickness. Gradients in drug deposition were also observed down the length of the heart and around the circumference toward the lateral wall, but not the interventricular septum. These gradients extended further than might be predicted from simple diffusion. The circumferential distribution following local epinephrine delivery from a distributed source to the entire anterior wall drove drug toward the inferior wall, further than with point-source release, but again, not to the septum. This augmented drug distribution away from the release source, down the axis of the left ventricle, and selectively toward the left heart follows the direction of capillary perfusion away from the anterior descending and circumflex arteries, suggesting a role for the coronary circulation in determining local drug deposition and clearance. The dominant role of the coronary vasculature is further suggested by the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue.American Heart Association (09SDG2060320)Society for Cardiovascular Anesthesiologists (Starter Grant)National Institutes of Health (U.S.) (NIH grant R01 GM-49039)Deshpande Center for Technological Innovatio

    De haven van Rades (Tunesië)

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    Nabij Tunis, de hoofdstad van Tunesië (Noord-Afrika), bevinden zich drie haventerreinen die gezamenlijk het complex Tunis/La Goulette/Radès vormen. De haven van Tunis wordt binnenkort gesloten voor commercieel scheepvaartverkeer. De in 1986 geopende haven van Radès is opgebouwd uit twee aparte haventerreinen, een gespecialiseerd terrein voor de overslag van bulkgoederen en een general cargo-gedeelte voor de overslag van stukgoederen vervoerd door conventionele general cargo-schepen, ro-ro- en containerschepen. In 1993 bedroeg de hoeveelheid overgeslagen general cargo 1,1 miljoen ton. De vervoersprognoses voor de komende jaren duiden op een toename in transport over zee van goederen van en naar de haven van Radès. Met name op het gebied van ro-ro- en containeroverslag wordt een sterke toename verwacht, mede door de overname van een deel van de overslag van de haven van Tunis. In combinatie met de huidige lange wacht- en verblijftijden van schepen en goederen in deze haven, wordt aangenomen dat de haven dit aanbod in de toekomst niet meer zal kunnen verwerken. Om dit te voorkomen zal de haven van Radès zich verder moeten ontwikkelen en een aantal aanpassingen moeten ondergaan. In dit afstudeerwerk, dat wordt verricht in samenwerking met het ingenieursbureau DHV, wordt ingegaan op de ontwikkeling van het general cargo-deel van de haven van Radès. Aan de hand van de gesignaleerde huidige problemen en de verkeersprognose voor de komende jaren, wordt een masterplan opgesteld voor deze haven. Hierbij wordt gebruik gemaakt van een computersimulatiemodel, om op die wijze sneller en beter inzicht te krijgen in de gevolgen en effecten van bepaalde ingrepen.Hydraulic EngineeringCivil Engineering and Geoscience

    Pathway for personality development: juvenile red knots vary more in diet and exploratory behaviour than adults

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    Selin Ersoy; Christine E. Beardsworth; Elif Duran; Marcel T.J. van der Meer; Theunis Piersma; Ton G. G. Groothuis & Allert Bijleveld Title: "Pathway for personality development: juvenile red knots vary more in diet and exploratory behaviour than adults" Authors: Selin Ersoy, Christine E. Beardsworth, Elif Duran, Marcel T.J. van der Meer, Theunis Piersma, Ton G. G. Groothuis, Allert I. Bijleveld GENERAL INFORMATION Titles of the Dataset: Juv-Adult_Expl_Allyears (Exploration speed (mean speed cm/sec) in mobile arena), isotope data (plasma and red blood cell) Date of the data collection: Catching between 14 August 2018 - 19 October 2021 3. Geographic location of data collection: Western Dutch Wadden Sea (53°15'N, 5°15'E) 4. Corresponding author information: Selin Ersoy, NIOZ Royal Netherlands Institute for Sea Research, Department of Coastal Systems, PO Box 59, 1790 AB Den Burg, Texel, The Netherlands, [email protected] METHODS Isotope data: Red blood cell and plasma d13C and d15N isotopes collected from the blood samples of red knots. Exploration speed: Movement tracjectories were collected from the recordings of the top camera during experiments in the mobile arena. We used the distance between estimated positions to calculate speed. Errors in the positioning algorithm were filtered by excluding speeds higher than 200 cm/s. An individual’s exploration speed was calculated as the average speed during each 20 min trial. The dataset includes two repeats of exploration speed. DATA & FILE OVERVIEW Juv-Adult_Expl_Allyears : Exploration speed repeated measures from Juvenile and Adult red knots Column 1: FB: Unique metal ring number of red knots. Ring were put on the legs Column 2: Exp: Repeat number of the exploration assay trials Column 3: Age: Adult (3) or juvenile (1) age Column 4: Mean: Exploratory score of individual measured in mobile arena (mean speed cm/sec) measured through automated tracking Column 5: Year: Year of the testing Isotope : Red blood cell and plasma d13C and d15N isotopes collected from the blood samples of juvenile and adult red knots Column 1: RingNr: Unique metal ring number of red knots. Ring were put on the legs Column 2: Type: Blood type plasma or red blood cell Column 3: Repeat: If there is a repeated samples of an individual Column 4: d15N: Nitrogen 15 Isotope value Column 5: d13C: Carbon 13 Isotope value Column 6: ProcessDate:Process date of blood samples Column 7: Comments: important commments about samples Column 8: AGE: Adult (3) or juvenile (1) age Column 9: CatchDate: Cathing date of the individuals Column 10: CATCH_YEAR: Catching year of the individuals (taken from CatchDate) SIBER-2021-12-21.csv: Isotope data was organised for SIBER analysis #https://cran.r-project.org/web/packages/SIBER/vignettes/Introduction-to-SIBER.html iso1: RingNr: Unique metal ring number of red knots. Ring were put on the legs iso2: Type: Blood type plasma or red blood cell group: equals to AGE in isotope dataset (1=Juvenile, 2=Second-calendar year which is not used for this study, 3=Adult) community: equals to CATCH_YEAR in isotope dataset (1= 2018, 3= 2019 *which are not used for this analyses, 2= 2021) R file includes code for all the statistics and visualization of the data
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