Dissertations / Theses on the topic 'Bio priming'

Dendritic cells (DC) have the unique capacities to induce primary T cell responses. In mice, CD8α+DC are specialized to cross-prime CD8+ T-cells and produce IL-12 that promotes cytotoxicity. Human BDCA-3+DC share several relevant characteristics with CD8α+DC, but the capacities of human DC subsets to induce CD8+ T cell responses are incompletely understood. Here we compared CD1c+mDC1, BDCA-3+mDC2 and plasmacytoid DC (pDC) in peripheral blood and lymphoid tissues for phenotype, cytokine production and their capacities to prime cytotoxic T cells. mDC1 were surprisingly the only human DC that secreted high amounts of IL-12p70, but they required combinational Toll-like receptor (TLR) stimulation. mDC2 and pDC produced IFN-λ and IFN-α, respectively. Importantly, mDC1 and mDC2 required different combinations of TLR-ligands to cross-present protein antigens to CD8+ T cells. pDC were inefficient, and also expressed lower levels of MHC- and co-stimulatory molecules. Nevertheless, all DC induced CD8+ memory T-cell expansions upon licensing by CD4+ T cells, and primed naive CD8+ T-cells following appropriate TLR stimulation. However, since mDC1 produced IL-12 they induced the highest levels of cytotoxic molecules. In conclusion, CD1c+mDC1 are the relevant source of IL-12 for naïve T cells, and are fully equipped to cross-prime cytotoxic T cell responses.

Background: Diabetes is a global health issue on the rise. Besides genetics as a cause of diabetes, diet, weight and lifestyle are amongst the main factors. Due to the modernized society, new technology and risks, there has been a shift in responsibility of safety and health. As a part of a health promoting policy development during the last few decades there has also been a natural de-authorization of health knowledge and expertise. Governmental expertise has been decentralized to the society and so has the responsibilities. Traces of this new health paradigm can be seen in the media discourse. It has been seen in studies of the reporting of diabetes in North American press, that societal factors – such as labor market, health care and infrastructure – often get veiled by individuals’ responsibility and guilt due to lifestyle and life choices. This affects how individuals feel about their life situation and how the public perceive them.     Method and material: A quantitative content analysis was performed on 112 articles from six Swedish broadsheet and tabloid newspapers. The articles were coded with variables measuring article theme, dominant framing of diabetes´ causes and whose responsibility, what arguments are used and what agents with dignity can be seen. Excerpts from the articles were also analyzed with qualitative tools as modality and argumentation analysis. Results: Similarities between the Swedish and the North American newspapers were discovered. Societal factors and structures as causes and means of responsibilities were not as prominent as those aiming for the individual. The responsibility of the society was also reported to a much greater extent than society as a factor contributing to cause diabetes. This can be considered a sign of the health promoting strategy and the individualism that is rooted in modernization, industrialization and economic liberalization. Doctors and scientists were given dignity as often as celebrities and private citizens, which indicates the de-authorization of health knowledge and the further use of scientists and doctors as a truth repository in media. Several of the articles concern the critique of the diabetes unawareness and predominant individual responsibility that was the outset of this study. Celebrities and private citizens were frequently given dignity in these cases. In their criticizing, high modality contributed to a strong authority in their knowledge.<br>Grund för forskningsfrågan: Diabetes av olika slag drabbar ett växande antal människor världen över. Sjukdomen tros främst bero på genetik och omgivande faktorer så som livsstil, vilken påverkas av den omgivande miljön. Det har visat sig i studier av rapportering kring sjukdomen i bland annat nordamerikansk press att samhälleliga faktorer ofta hamnar i skymundan och att skulden och ansvaret för sjukdomen framstår ligga hos individen och dess egenvalda livsstil. Detta kan bero på en hälsofrämjande strategi som setts växa fram under de senaste decennierna, som en reaktion på effekterna av teknisk utveckling, modernisering och marknadskrafter. Strategin har inneburit en naturlig av-auktorisering av hälsokunskapen och individualisering av ansvaret. Detta hälsoparadigm återspeglas i medierna.   Studien: Denna studie undersöker rapporteringen av diabetes i svensk press, genom en kvantitativ innehållsanalys av 112 artiklar från sex svenska dags- och kvällstidningar. Materialet kodades med variabler för bland annat artikeltema, dominant gestaltning av orsak samt ansvar för diabetes, vilka argument som förekommer och vilka aktörer som tillskrivs dignitet i sammanhanget. Detta kompletterades med en kvalitativ analys av några textutdrag från materialet, med verktyg och begrepp från och argumentationsanalys samt det lingvistiska begreppet modalitet.   Resultat: Det framträder stora likheter mellan de svenska tidningarna och de nordamerikanska. Samhällsstrukturer som orsak till och ansvar för diabetes framgår inte i samma utsträckning som individens roll. Samhällets ansvar för sjukdomen framgår dock i större utsträckning än dess skuld, vilket går i linje med individualiseringen av hälsoansvaret. Läkare och professorer tillsammans förekommer med dignitet i ungefär lika många artiklar som privatpersoner och kändisar tillsammans, vilket indikerar avauktoriseringen av hälsokunskapen, och den fortsatta användningen av läkare och professorer som ett slags ”sanningsvittnen”. I flera artiklar framträder just den kritik mot okunskap kring sjukdomen och hur individerna själva måste arbeta för att förändra läget, en utgångspunkt för denna studie. Kändisar och privatpersoner fick i dessa fall dignitet. I deras kritiserande av andra uttalanden de inte höll med i, agerade hög modalitet en faktor som gav dem auktoritet i sina uttalanden.

&nbsp;&nbsp;&nbsp; Luminescentni nanokristali (nanofosfori) na bazi fluorapatita (FAP-a) dopirani elementima retkih zemalja idealni su kontrastni agenti za bio-medicinske primene, kao &scaron;to su detekcije, snimanja, praćenja i terapije ćelija kancera. Kancer je jedna od najče&scaron;ćih bolesti modernog doba čiji uspeh lečenja zavisi od rane dijagnostike i neinvazivnog tretmana. Luminescentne nanočestice mogu uneti inovativnu paradigmu u lečenje kancera kombinovanjem biosnimanja, dijagnostike i tretmana. Za studije fluorescentnih biosnimanja nanokristali fluorapatita dopirani retkim zemljama kao kontrastni agenti pružaju značajne prednosti u vidu velikih kontrasta i dugotrajnosti luminescencije, i &scaron;to je jo&scaron; važnije visoke biokompatibilnosti, netoksičnosti i bioaktivnosti. Glavni ciljevi ove doktorske disertacije su sinteza novih luminescentnih multifotonskih bionanomaterijala na bazi fluorapatita dopiranih jonima prazeodimijuma (Pr³⁺), njihova karakterizacija i evaluacija&nbsp; primene za fluorescentna biosnimanja kancera. Sintezom nanoprahova u umerenim uslovima metodom ko-precipitacije, a potom su&scaron;enjem na 110 ^oC i kalcinacijom na temperaturama od 700 i 1000 ^oC očekuje se pronalaženje najboljih uslova za dobijanje novih nanofosfora koji bi na&scaron;li i različite bio-medicinske primene u oblasti fluorescentnih biosnimanja. Proučavane su tri vrste PrFAP nanokristala, sa 0,1%, 0,5% i 1% atomskih procenta Pr³⁺, zajedno sa nedopiranim FAP kontrolnim uzorkom. Nivoi energije aktivator jona Pr³⁺ sadrže metastabilna multipletna stanja koja nude mogućnosti efikasnih emisionih linija u vi&scaron;e boja u FAP nanokristalima, kao i u infracrvenoj i ultravioletnoj oblasti spektra. Metodom ko-precipitacije na sobnoj temperaturi (25 ^oC), a potom su&scaron;enjem na 110 ^oC, sintetisani su monofazni heksagonalni nanokristali PrFAPs nepravilnog sfernog oblika. Termičkom analizom sintetisanih uzoraka, na&nbsp;osnovu detektovanih temperaturnih opsega procesa dekarbonacije i dehidroksilacije, utvrđene su temperature kalcinacije od 700 i 1000 oC. Termička analiza i karakterizacija uzoraka su pokazale da Pr³⁺ joni dovode do stabilizacije FAP strukture na vi&scaron;im temperaturama, &scaron;to je pripisano unosu lantanoidnih jona sa specifičnim magnetnim osobinama u sistem i stvaranju jačih privlačnih sila sa O^2-anjonima. Nanokristali su&scaron;eni na 100 ^oC i kalcinisani na 1000 ^oC, zbog prisustva defekata kristalne re&scaron;etke koji zadržavaju emisiju Pr³⁺ jona, nisu pokazali luminescentne karakteristike od značaja za primene u medicinskim fluorescentnim biosnimanjima. Kalcinacijom uzoraka na 700 ^oC izrađen je novi tip aktiviranih fluorapatitnih nanokristala dopiranih prazeodimijumom (PrFAPa) sa ekscitaciono-emisionim profilima u vidljivom delu spektra. Fizičko-hemijska karakterizacija potvrdila je sferne kristale heksagonalne strukture do nanometrske veličine od oko 20 nm. Kvantno-hemijske kalkulacije predvidele su da se joni Pr³⁺ ugrađuju u kristalnu re&scaron;etku FAP nanokristala na položaju Ca2 (6h), &scaron;to je praćeno deformacijama pozicije F^- jona. Pretpostavljeni mehanizam supstitucije je jedan jon Pr³⁺ za jedan Ca²⁺, s delimičnom supstitucijom anjona F^&ndash; sa O^2&ndash; i OH^&ndash; i stvaranjem vakansi usled postizanja neutralnosti sistema. Rezultati in vitro biokompatibilnosti i hemokompatibilnosti pokazali su da nanokristali PrFAPa nisu toksični za žive ćelije. Pored toga, internalizacija PrFAPa nanokristala od strane ćelija kancera kože (A431) i pluća (A549) je proučavana kori&scaron;ćenjem konfokalne mikroskopije i mikroskopije &scaron;irokog polja zasnovane na fluorescenciji. Nanokristali pokazuju karakterističnu zelenu emisiju na 545 nm (³P₀&rarr;³H₅ tranzicija Pr³⁺ jona) i narandžastu emisiju na 600 nm (¹D₂&rarr;³H₄), koje su kori&scaron;ćene za razlikovanje od pozadinske autofluorescencije ćelije. Studije dobijenih slika konfokalnom mikroskopijom u plavom, zelenom i crvenom kanalu su otkrile da nanokristali mogu da prepoznaju ćelijsku povr&scaron;inu i da se lepe za nju, ali nisu potvrdile ulazak nanokristala u ćelije. Mikroskopija &scaron;irokog polja je detektovala emisione prelaze u zelenoj i narandžastoj boji i potvrdila da luminescentni signal dolazi iz unutra&scaron;njosti ćelija. Kori&scaron;ćenjem rezonantne ekscitacije od 488 nm i emisije od 600 nm PrFAPa nanokristala, konfokalnom mikroskopijom ekstrahovan je signal fluorescencije iz unutra&scaron;njosti ćelija kancera. Ortogonalne projekcije u 3D konfokalnim ravnima pokazuju da su nanokristali u stanju da uđu u ćelije kancera i da se raspoređuju po citoplazmi. Sveukupno, ovako dobijeni nanokristali PrFAPa su biokompatibilni i od testiranih uzoraka, aktivirani nanokristali dopirani sa 0,5% Pr³⁺ pokazuju najvi&scaron;e potencijala za primenu u medicinskim fluorescentnim biosnimanjima kao kontrastni agenti.&nbsp;&nbsp;<br>Luminescent nanocrystals (nanophosphorus) based on fluorapatite (FAP) doped with rare earth elements are ideal contrast agents for biomedical applications such as cancer cell detection, imaging, tracking and therapy. Cancer is one of the most common diseases of the modern times whose success of the cure depends on early diagnosis and non-invasive treatment. Luminescent nanoparticles can bring an innovative paradigm into the treatment of cancer by combining bioimaging, diagnostics and treatment. Rare earth doped fluorapatite nanocrystals as contrast agents for studies of fluorescence bioimaging, offer significant advantages in terms of high contrasts and long-term luminescence, and more importantly high biocompatibility, non-toxicity and bioactivity. The main objectives of this doctoral dissertation are the synthesis of novel luminescent multiphoton bionanomaterials based on fluorapatites doped with praseodymium ions (Pr³⁺), their characterization and evaluation of their application for cancer fluorescence bioimaging. Synthesis of nanopowders under moderate conditions by the co-precipitation method, followed by dried at 110 &deg;C and calcination at 700 and 1000 &deg;C, is expected to find the best conditions for obtaining new nanophosphors that would find different bio-medical applications in the field of fluorescence bioimaging. Three types of PrFAP nanocrystals were studied, with 0,1%, 0,5%, and 1% atomic percentages of Pr³⁺, together with an undoped FAP control sample. Energy levels of the Pr³⁺ ion activator contain metastable multiplet states that offer the possibility of efficient multi-color emission lines in FAP nanocrystals as well as in the infrared and ultraviolet regions of the spectrum. Single-phase hexagonal nanocrystals PrFAPs of irregular spherical shape were synthesized by the method of co-precipitation at room temperature (25 ^oC) and then drying at 110 ^oC. Thermal analysis of the synthesized samples, based on the detected temperature ranges of the decarbonation and dehydroxylation processes, determined calcination temperatures of 700 and 1000 ^oC. Thermal analysis with characterization showed that Pr³⁺ ions lead to stabilization of the FAP structure at higher temperatures,&nbsp;which was attributed to the entry of lanthanoid ions with specific magnetic properties into the system and the creation of stronger attractive forces with O^2- anions. Nanocrystals dried at 100 ^oC and calcined at 1000 ^oC, due to the presence of crystal lattice defects that quench the emission of Pr³⁺ ions, did not show luminescent characteristics of significance for applications in medical fluorescence imaging. Calcination of the samples at 700 ^oC produced a new type of activated praseodymium doped fluorapatite nanocrystals (PrFAPa) with excitation-emission profiles in the visible part of the spectrum. Physicochemical characterization confirmed spherical crystals of hexagonal structure up to a nanometer size of about 20 nm. Quantum-chemical calculations predicted that Pr³⁺ ions would be embedded in the crystal lattice of FAP nanocrystals at the Ca2 position (6h), which was followed by deformations of the F^- ion position. The assumed substitution mechanism is one Pr3+ ion for one Ca²⁺, with partial substitution of F^&ndash;anions with O^2&ndash; and OH^&ndash; and creation of vacancies due to achieving system neutrality. The results of in vitro biocompatibility and hemocompatibility showed that PrFAP nanocrystals were not toxic to living cells. In addition, the internalization of PrFAPa nanocrystals by skin (A431) and lung (A549) cancer cells was studied using fluorescence-based confocal microscopy and wide-field microscopy. The nanocrystals show characteristic green emission at 545 nm (³P₀&rarr;³H₅ transition of Pr³⁺ ion) and orange emission at 600 nm (¹D₂&rarr;³H₄), which we use to discriminate from cell autofluorescence. Studies of the images obtained by confocal microscopy in the blue, green, and red channels revealed that nanocrystals could recognize the cell surface and adhere to it, but they did not confirm the entry of nanocrystals into the cells. The wide-field microscopy detected emission transitions in green and orange color, and confirmed that the luminescent signal was coming from inside the cells. Using resonant excitation of PrFAP nanocrystals at 488 nm and emission of 600 nm, confocal microscopy extracted the fluorescence signal from inside the cancer cells. Orthogonal projections across 3D confocal stacks show that the nanocrystals are able to enter the cells positioning themselves within the cytoplasm. Overall, the obtained PrFAPa nanocrystals are biocompatible and of the tested types, the 0,5% Pr³⁺ doped nanocrystals show the highest promise as a tracking nanoparticle probe for bioimaging applications.

Thesis (B.Sc)--University of Hong Kong, 2005.<br>"A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2005." Also available in print.

Immunotherapy represents a therapeutic option for subgroups of paediatric patients with leukaemia who, despite the impressing advances of the last decades in the field, still show a poor prognosis because of high risk-disease or relapse. A deeper understanding of how the immune system physiologically recognizes and eradicates tumour cells is mandatory. Peptidic antigens are of great interest in the field of immunotherapy because they could be used as vaccines to boost immunity. TEL/AML1 mutant protein, whose sequence is known, is the result of a balanced t(12;21) translocation which generates a fusion gene. Peptides can be artificially synthetized from TEL/AML1 fusion protein and their HLA-binding capacity and immunogenicity can be predicted through bioinformatic tools. This project aimed to investigate whether the excellent prognosis showed by patients who suffer from a B-lineage ALL harbouring the TEL/AML1 mutation could be related to an immune response against peptidic antigens derived from the TEL/AML1 mutant protein. For such purpose, 8 priming experiments were performed with healthy donors’ leucocytes. Six experiments were carried out according to a dendritic cells-mediated protocol, whereas two experiments were performed according to a beads-mediated protocol. Successfully primed lymphocytes (identified by mean of intracellular cytokines production) were selected through flow cytometric sorting and single-cell seeded in order to get T-cell clones. This was possible in 3 out of 8 priming experiments. Growing T-cell clones were tested after stimulation with peptides (or through tetramer staining) but they did not show enough specificity. We also tried to show an immune response against fusion peptides in peripheral blood leucocytes of patients who survived a TEL/AML1 positive B-lineage ALL, through exposure to peptides and a short course stimulation with cytokines. We tested 22 patients, but unfortunately we weren’t able to show an answer against fusion peptides in any of them. Possible reasons might be the lack of specificity of the activation markers we used to identify reactive cells, the not enough restrictive gates we used for sorting, the fact that the HLA super type B*07 (for which the restricted peptides had the best prediction score) was underrepresented in our patients’ cohort. We suggest to perform further experiments using new activation markers, such as CD25 or PD-L1, or different techniques to identify reactive cells (such as Elispot), to use more restrictive gates for sorting and to exploit the beads priming protocol. In order to sample such lymphocyte populations (i.e. antigen specific T-cells) with an extremely low frequency, a possibility may be collect repeatedly blood samples from the same patient at different time points. Further studies are warranted to test the hypothesis of an autologous, spontaneously arising immune response against TEL/AML1 fusion peptides as reason for the good prognosis of TEL/AML1 positive leukaemia. Another possible approach in order to validate fusion peptides might be to test them in a situation of HLA B*07 mismatch between lymphocytes and APCs. The clinical counterpart could be the generation of reactive T-cell clones, cloning of their TCR and its transduction in the patient’s or donor’s lymphocytes, the latter in the perspective of a post-hematopoietic stem cell transplantation adoptive immunotherapy.<br>L’immunoterapia costituisce un’opzione terapeutica per alcuni sottogruppi di pazienti con leucemia dell’età pediatrica i quali, nonostante i notevoli progressi degli ultimi decenni, ancora non mostrano una prognosi soddisfacente perché affetti da malattia ad alto rischio oppure da ricaduta. Una comprensione più profonda di come il sistema immunitario fisiologicamente riconosce ed elimina le cellule tumorali è essenziale. Gli antigeni peptidici sono di grande interesse nel settore dell’immunoterapia perché possono essere utilizzati come vaccini per potenziare l’immunità. La proteina mutante TEL/AML1, la cui sequenza è nota, è il risultato di una traslocazione bilanciata t(12;21) che genera un gene di fusione. Dalla proteina di fusione TEL/AML1 si possono sintetizzare artificialmente peptidi, la cui capacità di legare le molecole HLA ed immunogenicità si può prevedere attraverso strumenti bioinformatici. Questo progetto ha l’obiettivo di indagare se l’eccellente prognosi dei pazienti affetti da leucemia linfoblastica di linea B con la mutazione TEL/AML1 possa essere correlata ad una risposta immunologica nei confronti di peptide di fusion derivati dalla proteina mutante TEL/AML1. A tale scopo, sono stati realizzati 8 esperimenti di priming con leucociti di donatori sani. Sei sono stati realizzati secondo un protocollo mediato da cellule dendritiche, mentre altri due esperimenti sono stati condotti secondo un protocollo mediato da beads. I linfociti responsivi al processo di priming (identificati mediante la produzione intracellulare di citochine) sono stati selezionati mediante sorting citofluorimetrico e coltivati a singola cellula in modo da ottenete cloni T-cellulari. Ciò è stato possibile in 3 esprimenti su 8. I cloni T-cellulari con evidenza di crescita sono stati testati dopo re-stimolazione con i peptidi (o mediante tetramer-staining) ma non hanno dimostrato sufficiente specificità- Abbiamo inoltre provato a dimostrare una risposta immunologica nei confronti dei peptidi di fusione nei leucociti (da sangue periferico) di pazienti con leucemia linfoblastica di linea B TEL/AML1 positiva in remissione, mediante esposizione ai peptidi e una breve stimolazione con citochine. Sono stati testati 22 pazienti, ma purtroppo non è stato possibile evidenziare una risposta nei confronti dei peptidi di fusione in nessuno di loro. Possibili spiegazioni potrebbero essere la mancanza di specificità dei marcatori di attivazione che sono stati utilizzati per identificare le cellule reattive, i gate non sufficientemente restrittivi utilizzati per il sorting, il fatto che il supertipo HLA B*07 (i peptidi B*07 ristretti avevano il migliore score predittivo) era sotto-rappresentato nella coorte di pazienti presa in esame. Ci riproponiamo di realizzare ulteriori esperimenti utilizzando nuovi marcatori di attivazione, come CD25 o PD-L1, oppure differenti tecniche per identificare le cellule reattive (come l’Elispot), di usare gates più restrittivi per il sorting e di utilizzare esclusivamente il protocollo mediato da beads per il priming. Per riuscire a includere nel campione popolazioni linfocitarie (cellule T antigene-specifiche) la cui frequenza è estremamente bassa, una possibilità potrebbe essere eseguire prelievi ematici ripetuti nel tempo nello stesso paziente. Sono necessari ulteriori studi per testare l’ipotesi di una risposta immune autologa, spontanea, nei confronti dei peptidi di fusione TEL/AML1 come spiegazione della buona prognosi della leucemia linfoblastica di linea B TEL/AML1 positiva. Un altro possibile approccio per validare i peptidi di fusione potrebbe essere quello di testarli in una situazione di HLA B*07 mismatch tra linfociti ed APCs. La ricaduta clinica potrebbe essere la generazione di cloni T-cellulari dalle cellule reattive al priming, il clonaggio del loro TCR e la sua transduzione nei linfociti del paziente o del suo donatore, in quest’ultimo caso nella prospettiva di un’immunoterapia adottiva post-trapianto di cellule staminali ematopoietiche.

Thesis (B.Sc)--University of Hong Kong, 2005.<br>"A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2005." Also available in print.

Thesis (B.Sc)--University of Hong Kong, 2007.<br>"A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2007." Includes bibliographical references (p. 27-30). Also available in print.

The sagebrush steppe is a particularly sensitive ecosystem that is easily disturbed by fires, oil and gas extraction, woody-plant encroachment, and overgrazing. The natural regeneration of native species following a disturbance within this system is typically slow and sporadic, which allows invasive grasses to occupy the landscape. Attempts to assist the recovery of these landscapes through direct seeding is commonly met with poor success rates, particularly in lower elevation, drier sites. Novel seed enhancement technologies and planting techniques that mitigate limiting factors impairing restoration efforts may improve the likelihood of restoring these degraded areas. For chapter 1, we evaluated a solid-matrix priming technique, where bluebunch wheatgrass (Pseudoroegneria spicata) and Lewis flax (Linum lewisii) were primed and then the priming matrix and seed were pelleted together. We evaluated primed seed that had been incorporated into pellets at two field sites against seed that was pelleted but been left unprimed, and untreated seed (control). These three seed treatments were planted in the spring (mid-march) in shallow (2-cm) and deep (15-cm) furrows, in a complete factorial design. We found that primed seeds generally produced higher plant densities than control seed at the beginning of the growing season; however, its influence diminished towards the end of the growing season. We also found that deep furrows increased plant density throughout the growing season and even into the following year. The combination of priming and deep furrows outperformed control seed in shallow furrows in all measured metrics. For chapter 2, we evaluated a seed conglomeration technique for improving Wyoming big sagebrush (Artemisia tridentata ssp. Wyomingensis) emergence and survival under fall and winter plantings. The trial was implemented at five sites across Utah and Nevada in a randomized complete block-split-split plot design, with site, and planting season, comprising the split-plot factors. Each site and season combination was seeded with conglomerated and control seed. We found that in most cases, a fall seeding of Wyoming big sagebrush was either the same or more successful compared to planting on the snow in the winter, which is the current suggested practice. Our results also demonstrated that seed conglomeration produced higher plant densities compared to control seed throughout the growing season. The higher density of plants produced from conglomerates combined with the improved seed delivery provided by the conglomeration technique was estimated to offset the cost in producing conglomerates and reduce overall restoration costs by 41%.

Dans ce travail, nous étudions les mécanismes du changement de langue lors de la reconnaissance visuelle de mots chez des trilingues français /anglais /espagnol. Dans un premier temps, nous avons examiné les processus d’accès pour chacune des langues étudiées, indépendamment de la présentation des autres langues. Nous nous sommes ensuite interrogés sur les relations entre les langues et l’organisation lexicale sous-jacente dans la mémoire multilingue, ainsi que la mise en place des mécanismes cognitifs permettant de passer d’une langue à une autre. Dans cette perspective, nous avons réalisé trois séries d’expériences afin d’examiner l’influence mutuelle des langues et le coût cognitif consécutif à un changement de langue lors de la reconnaissance visuelle de mots isolés. Nous avons comparé le traitement de mots spécifiques à différentes langues (ayant un degré de recouvrement orthographique minimal) en faisant varier les situations de changement et en recueillant des données comportementales et chronométriques dans des tâches de décision lexicale, de catégorisation sémantique et d’amorçage sémantique par traduction. Les résultats mettent en évidence un ralentissement global du traitement dû au changement pour les trois langues. Nous avons également observé un coût cognitif suite à un changement de langue pour les trois langues, mais plus important lorsqu’il s’opère entre les deux langues les moins maîtrisées (L2 vers L3 et L3 vers L2). Les données obtenues confirment l’hypothèse d’unités lexicales intégrées au sein d’un même lexique dans la mémoire multilingue. Les résultats sont interprétés dans leur ensemble dans le cadre des principaux modèles de la mémoire bilingue/multilingue<br>The present work focuses on language switching mechanisms during visual word recognition in French / English / Spanish trilinguals. First, we examined access to processing for each language, independently from the presentation of other languages. Then, our concern was to determine the different relations between languages and the underlying lexical organization inside the multilingual memory, as well as the activation of cognitive mechanisms allowing language switching. With this goal in mind, we performed three series of experiments to examine the influences between the languages, and the cognitive cost subsequent to a language switching during visual word recognition. We compare the processing of non-cognate words belonging to the three languages, manipulating the language switching situations and recording behavioral and electrophysiological data during lexical decision, semantic categorization and semantic translation priming. Results of these experiments highlight a general slowdown of processing consecutive to a language switch for all languages. Moreover, we observed a cognitive cost related to language switching for all the three languages, but bilaterally larger when it concerns the two non-dominant languages (L2 to L3 and L3 to L2). The recording data confirms the hypothesis of lexical representations integrated into a shared lexicon of multilingual memory. The results are interpreted in the light of the main models accounting for bilingual memory

<p>Three main theoretical approaches to the study of the causation of prejudice can be distinguished within psychological research. The cognitive approach suggests that prejudice is a function of cognitive processes where stereotypic information about social groups, stored in memory, is automatically activated and affects people’s judgements and behavior toward members of the target group. The personality approach suggests that prejudice is a function of people’s personality characteristics. Finally, the social psychological approach emphasizes people’s group membership and group identification as the as major source of causation.</p><p>Previous research has almost entirely focused on only one approach of causation at a time. The focus has also shifted periodically – with attention paid to one approach at each period of time. The present thesis is an attempt to integrate these approaches and suggests an integrative model where the relative contribution of each approach could be assessed. The underlying assumption is that all three approaches are meaningful and that prejudice is a complex phenomenon that is best explained by taking into account all approaches jointly.</p><p>Examining the cognitive approach, Paper I revealed that people are knowledgeable of the cultural stereotypes and that stereotypic information is automatically activated and affects people’s judgments. Paper II (and Paper III) supported the personality approach and revealed that prejudice is highly related to primary personality characteristics and, in line with a central idea in this approach, different types of prejudice (ethnic prejudice, sexism, homophobia, and prejudice toward disabled people) are highly correlated. The results of Paper III revealed the importance of group membership and group identification, supporting the social psychology approach.</p><p>The findings are discussed in relation to previous research and the necessity to integrate various approaches and disciplines to explain psychological phenomena in general and prejudice in particular. Also, implications of the findings for prejudice prevention are discussed.</p>

This dissertation investigates how cognates are organized in the bilingual mental lexicon and examines whether orthography in one language, via phonological representations, influences the processing of cognates and false friends in the other language. In light of the framework of two well-known models of bilingual visual word recognition, the Bilingual Interactive Activation (BIA) and the Bilingual Interactive Activation Plus (BIA+), the premise is that there is activation from orthography to phonology across a bilingual’s two languages and that this activation is modulated by the degree of orthographic and phonological code overlap. Two objective metrics were used to assess crosslinguistic similarity of Portuguese-English cognates and false friends that were selected for a cross-language lexical decision task with masked priming. Dynamic time warping (DTW), an algorithm that was originally conceived to compare different speech patterns in automatic speech recognition and to measure acoustic similarity between two time-dependent sequences, was used to compute crosslinguistic phonological similarity. The Normalized Levenshtein Distance (NLD), an algorithm that calculates the minimum number of single-character insertions, deletions or substitutions required to change one word into another and normalizes the result by their lengths, was used to compute crosslinguistic orthographic similarity. Portuguese-English bilinguals who acquired their second language after reaching puberty, and English functional monolinguals who grew up speaking primarily English were recruited to participate in the experimental task. Based on collected reaction time and accuracy data, mixed-effects models analyses are used to estimate the individual effects of crosslinguistic orthographic, phonological and semantic similarity and the role each of them, along with English proficiency, word frequency and length play in the organization of the Portuguese-English bilingual mental lexicon.

The main metabolic pathway involved during an exercise of duration greater than 1 minute is the oxidative metabolism. The functional evaluation of oxidative metabolism is based on the analysis of two main functional indexes: O2max and O2 kinetics. These indexes are determined by a finite ability to deliver oxygen to the working muscles (central factor) and a limited ability of the muscles to extract oxygen (peripheral factor). The relative contribution of central and peripheral factors to the overall limitation of oxidative metabolism, yet remains controversial. Near Infrared Spectroscopy (NIRS) was recently added to the classical methods of muscle oxidative metabolism functional evaluation. NIRS is a non-invasive technology that continuously monitors changes (relative or absolute) in oxygenated and deoxygenated haemoglobin (HHb). NIRS HHb signal directly depends on the ratio between the muscular O2 utilization rate and the capillary O2 delivery in the region explored by the probe, providing a non-invasive estimate of the changes in O2 extraction occurring inside the muscles. The general aim of the thesis is to elucidate the relative contribution of central and peripheral factors in limiting oxidative metabolism by the application of non invasive techniques. We have proposed to modulate oxidative metabolism with different manipulations: 1) High fat diet; 2) Heavy intensity warm up and 3) two kinds of training: Aerobic and Isotonic. In the study #1 we used a high fat diet (HFdiet) to manipulate the peripheral factor in healthy young moderate trained males. Animal and human studies suggest that fat adaptation induces structural and functional muscle adaptations that may benefit oxidative metabolism. We tested the hypothesis that a long term HFdiet enhances oxidative metabolism by augmenting the muscle’s capacity to extract oxygen. 22 young healthy moderately trained males (28±5 yrs, 53±6 ml*Kg-1*min-1) were randomly assigned to: Hdiet (HFD, 55% of calories from fat, 30% carbohydrate and 15% proteins) or control diet (C, 30, 55 and 15%) for 10 days. Before and after the diet the subjects performed an incremental cycling test to exhaustion and 3 step transitions at moderate intensity. Respiratory variables and heart rate (HR) were measured bbb. The maximal and submaximal response to exercise were evaluated ( O2, respiratory exchange ratio, R) and the kinetics of pulmonary O2 were fitted by a double exponential model. HF diet was associated with a shift in substrate selection towards a higher contribution of fat to the production of energy in the moderate intensity domain of exercise (reduced R). Furthermore, HFD increased the speed of adaptation of pulmonary O2 kinetics by the reduction of the time constant of the primary component. Our findings support the hypothesis that, in healthy young males, a 10-day high fat diet may increase the speed of adaptation of oxidative metabolism at the onset of a moderate intensity exercise by increasing the relative contribution of fats oxidation to ATP production. In the study #2 we applied heavy intensity warm-up (HWu) to manipulate O2 delivery in sedentary healthy older adults. HWu increases VO2 kinetics during successive moderate intensity transitions. We tested the hypothesis that such improvement is due to a better matching of O2 delivery to utilization within the working muscles. We tested the hypothesis that HWu improvement is due to a better matching of O2 delivery to utilization within the working muscles, rather than to an increase in O2 bulk delivery. In 21 healthy older adults (65.7 5 yrs) we measured contemporarily and non-invasively indexes of the overall speed of adaptation of the oxidative metabolism ( i.e. pulmonary O2 kinetic), of the bulk O2 delivery (i.e. ) and of the rate of muscle deoxygenation (i.e. HHb) during moderate intensity step transitions, either with (Wu) or without (nWu) prior Hwu. The local matching of O2 delivery to utilization was evaluated by the HHb/ O2 ratio index. The innovative findings of this study are: i) HWu does not modify the speed of adaptation of bulk O2 delivery (i.e. ) and TPR; ii) HWu reduces the “overshoot” of the HHb/ O2 ratio, suggesting a better matching of O2 delivery to O2 utilization. Our data are compatible with the hypothesis that, in older adults, HWu, may beneficially affect oxidative metabolism thanks to acute improvement of the local matching of O2 delivery to O2 utilization. The evidences of Study # 2 motivated us to apply a manipulation that modifies O2 delivery in an adaptive way. Thus in the study #3 we applied aerobic training (AT) to manipulate O2 delivery in sedentary healthy older adults. We tested the hypothesis that older adults may benefit from 12 weeks of AT mainly thanks to an adaptive enhancement of O2 delivery to the working muscles. 14 healthy elderly (66 ± 6 yrs) were tested before and after a 12-week training consisting of an AT or a control (remained sedentary). Subjects performed: the same test protocol described in study # 2. Cardio-respiratory variables were measured bbb and muscle oxygen extraction (HHb) was measured, at the vastus lateralis, by quantitative NIRS. We calculated the time delay and the time constant of both the primary component of the pulmonary O2 and of HHb. The main findings of this study wereAT: i) increased O2max and pulmonary O2 kinetics, preceded (Wu) or not (nWu) by HWu; ii) did not modify the speed of adaptation of muscle oxygen extraction (HHb kinetics); iii) abolished the HWu effect in pulmonary O2 kinetics; iv) attenuated HWu effect in muscle oxygen extraction kinetics; v) abolished the peak of the HHb/ O2 ratio. Our data are compatible with the hypothesis that, in older adults, AT may beneficially affect oxidative metabolism thanks to an adaptive improvement in the matching of O2 delivery to the local O2 utilization. The attenuation yet not an abolishment of the HWu effect in HHb kinetics suggested us an underlying limitation in muscle O2 extraction, unaffected by AT. Isotonic Training is known to increase strength and muscle mass in older adults. We tested the hypothesis that older adults may benefits from 12 weeks of isotonic + aerobic training (IT) thanks to an adaptive enhancement in O2 delivery and O2 utilization. 14 healthy elderly (66 ± 6 yrs) were tested before and after a 12-week training consisting of an isotonic training added to aerobic training (IT) or a control condition (remained sedentary). Subjects performed the test protocol described in study #2 and were measured the variables and analyzed data as described for study # 4 The main finding of this study was that IT produced at the lungs an attenuation of HWu effect (i.e.TD remained shorter). These results suggested that older adults can be beneficially affected by IT, however it is not enough to produce the necessary variations in muscle O2 delivery to completely avoid HWu effect. Furthermore at muscle level the variations IT supressed the HWu effect. Thus in agreement with our hypothesis isotonic training added to aerobic training was enough to eliminate completely the effect of priming exercise. Regarding nWu exercise, the effect of IT was a reduction in the HHb/ O2 ratio peak, suggestive of a better matching in O2 delivery to the O2 utilization following training. Our data are compatible with the hypothesis that in older adults oxidative metabolism may be beneficially affected by IT thanks to an adaptive improvement of the local O2 delivery and a further adaptations in the working muscle to O2 utilization. In summary, eucaloric high fat diet, priming and training (aerobic and isotonic) beneficially affect the speed of adaptation of oxidative matabolism at the onset of an exercise of moderate intensity. The observed benefits are related to a variable combination of adaptations in O2 delivery and utilization that have been non-invasively evaluated in our studies.<br>The main metabolic pathway involved during an exercise of duration greater than 1 minute is the oxidative metabolism. The functional evaluation of oxidative metabolism is based on the analysis of two main functional indexes: O2max and O2 kinetics. These indexes are determined by a finite ability to deliver oxygen to the working muscles (central factor) and a limited ability of the muscles to extract oxygen (peripheral factor). The relative contribution of central and peripheral factors to the overall limitation of oxidative metabolism, yet remains controversial. Near Infrared Spectroscopy (NIRS) was recently added to the classical methods of muscle oxidative metabolism functional evaluation. NIRS is a non-invasive technology that continuously monitors changes (relative or absolute) in oxygenated and deoxygenated haemoglobin (HHb). NIRS HHb signal directly depends on the ratio between the muscular O2 utilization rate and the capillary O2 delivery in the region explored by the probe, providing a non-invasive estimate of the changes in O2 extraction occurring inside the muscles. The general aim of the thesis is to elucidate the relative contribution of central and peripheral factors in limiting oxidative metabolism by the application of non invasive techniques. We have proposed to modulate oxidative metabolism with different manipulations: 1) High fat diet; 2) Heavy intensity warm up and 3) two kinds of training: Aerobic and Isotonic. In the study #1 we used a high fat diet (HFdiet) to manipulate the peripheral factor in healthy young moderate trained males. Animal and human studies suggest that fat adaptation induces structural and functional muscle adaptations that may benefit oxidative metabolism. We tested the hypothesis that a long term HFdiet enhances oxidative metabolism by augmenting the muscle’s capacity to extract oxygen. 22 young healthy moderately trained males (28±5 yrs, 53±6 ml*Kg-1*min-1) were randomly assigned to: Hdiet (HFD, 55% of calories from fat, 30% carbohydrate and 15% proteins) or control diet (C, 30, 55 and 15%) for 10 days. Before and after the diet the subjects performed an incremental cycling test to exhaustion and 3 step transitions at moderate intensity. Respiratory variables and heart rate (HR) were measured bbb. The maximal and submaximal response to exercise were evaluated ( O2, respiratory exchange ratio, R) and the kinetics of pulmonary O2 were fitted by a double exponential model. HF diet was associated with a shift in substrate selection towards a higher contribution of fat to the production of energy in the moderate intensity domain of exercise (reduced R). Furthermore, HFD increased the speed of adaptation of pulmonary O2 kinetics by the reduction of the time constant of the primary component. Our findings support the hypothesis that, in healthy young males, a 10-day high fat diet may increase the speed of adaptation of oxidative metabolism at the onset of a moderate intensity exercise by increasing the relative contribution of fats oxidation to ATP production. In the study #2 we applied heavy intensity warm-up (HWu) to manipulate O2 delivery in sedentary healthy older adults. HWu increases VO2 kinetics during successive moderate intensity transitions. We tested the hypothesis that such improvement is due to a better matching of O2 delivery to utilization within the working muscles. We tested the hypothesis that HWu improvement is due to a better matching of O2 delivery to utilization within the working muscles, rather than to an increase in O2 bulk delivery. In 21 healthy older adults (65.7 5 yrs) we measured contemporarily and non-invasively indexes of the overall speed of adaptation of the oxidative metabolism ( i.e. pulmonary O2 kinetic), of the bulk O2 delivery (i.e. ) and of the rate of muscle deoxygenation (i.e. HHb) during moderate intensity step transitions, either with (Wu) or without (nWu) prior Hwu. The local matching of O2 delivery to utilization was evaluated by the HHb/ O2 ratio index. The innovative findings of this study are: i) HWu does not modify the speed of adaptation of bulk O2 delivery (i.e. ) and TPR; ii) HWu reduces the “overshoot” of the HHb/ O2 ratio, suggesting a better matching of O2 delivery to O2 utilization. Our data are compatible with the hypothesis that, in older adults, HWu, may beneficially affect oxidative metabolism thanks to acute improvement of the local matching of O2 delivery to O2 utilization. The evidences of Study # 2 motivated us to apply a manipulation that modifies O2 delivery in an adaptive way. Thus in the study #3 we applied aerobic training (AT) to manipulate O2 delivery in sedentary healthy older adults. We tested the hypothesis that older adults may benefit from 12 weeks of AT mainly thanks to an adaptive enhancement of O2 delivery to the working muscles. 14 healthy elderly (66 ± 6 yrs) were tested before and after a 12-week training consisting of an AT or a control (remained sedentary). Subjects performed: the same test protocol described in study # 2. Cardio-respiratory variables were measured bbb and muscle oxygen extraction (HHb) was measured, at the vastus lateralis, by quantitative NIRS. We calculated the time delay and the time constant of both the primary component of the pulmonary O2 and of HHb. The main findings of this study wereAT: i) increased O2max and pulmonary O2 kinetics, preceded (Wu) or not (nWu) by HWu; ii) did not modify the speed of adaptation of muscle oxygen extraction (HHb kinetics); iii) abolished the HWu effect in pulmonary O2 kinetics; iv) attenuated HWu effect in muscle oxygen extraction kinetics; v) abolished the peak of the HHb/ O2 ratio. Our data are compatible with the hypothesis that, in older adults, AT may beneficially affect oxidative metabolism thanks to an adaptive improvement in the matching of O2 delivery to the local O2 utilization. The attenuation yet not an abolishment of the HWu effect in HHb kinetics suggested us an underlying limitation in muscle O2 extraction, unaffected by AT. Isotonic Training is known to increase strength and muscle mass in older adults. We tested the hypothesis that older adults may benefits from 12 weeks of isotonic + aerobic training (IT) thanks to an adaptive enhancement in O2 delivery and O2 utilization. 14 healthy elderly (66 ± 6 yrs) were tested before and after a 12-week training consisting of an isotonic training added to aerobic training (IT) or a control condition (remained sedentary). Subjects performed the test protocol described in study #2 and were measured the variables and analyzed data as described for study # 4 The main finding of this study was that IT produced at the lungs an attenuation of HWu effect (i.e.TD remained shorter). These results suggested that older adults can be beneficially affected by IT, however it is not enough to produce the necessary variations in muscle O2 delivery to completely avoid HWu effect. Furthermore at muscle level the variations IT supressed the HWu effect. Thus in agreement with our hypothesis isotonic training added to aerobic training was enough to eliminate completely the effect of priming exercise. Regarding nWu exercise, the effect of IT was a reduction in the HHb/ O2 ratio peak, suggestive of a better matching in O2 delivery to the O2 utilization following training. Our data are compatible with the hypothesis that in older adults oxidative metabolism may be beneficially affected by IT thanks to an adaptive improvement of the local O2 delivery and a further adaptations in the working muscle to O2 utilization. In summary, eucaloric high fat diet, priming and training (aerobic and isotonic) beneficially affect the speed of adaptation of oxidative matabolism at the onset of an exercise of moderate intensity. The observed benefits are related to a variable combination of adaptations in O2 delivery and utilization that have been non-invasively evaluated in our studies.