Brain tissue properties differentiate between motor and limbic basal ganglia circuits.

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome.

Evaluation of the chicken transcriptome by SAGE of B cells and the DT40 cell line

Background: The understanding of whole genome sequences in higher eukaryotes depends to a large degree on the reliable definition of transcription units including exon/intron structures, translated open reading frames (ORFs) and flanking untranslated regions. The best currently available chicken transcript catalog is the Ensembl build based on the mappings of a relatively small number of full length cDNAs and ESTs to the genome as well as genome sequence derived in silico gene predictions.Results: We use Long Serial Analysis of Gene Expression (LongSAGE) in bursal lymphocytes and the DT40 cell line to verify the quality and completeness of the annotated transcripts. 53.6% of the more than 38,000 unique SAGE tags (unitags) match to full length bursal cDNAs, the Ensembl transcript build or the genome sequence. The majority of all matching unitags show single matches to the genome, but no matches to the genome derived Ensembl transcript build. Nevertheless, most of these tags map close to the 3' boundaries of annotated Ensembl transcripts.Conclusions: These results suggests that rather few genes are missing in the current Ensembl chicken transcript build, but that the 3' ends of many transcripts may not have been accurately predicted. The tags with no match in the transcript sequences can now be used to improve gene predictions, pinpoint the genomic location of entirely missed transcripts and optimize the accuracy of gene finder software.

Evaluation of sample preparation methods and optimization of nickel determination in vegetable tissues

Nickel, although essential to plants, may be toxic to plants and animals. It is mainly assimilated by food ingestion. However, information about the average levels of elements (including Ni) in edible vegetables from different regions is still scarce in Brazil. The objectives of this study were to: (a) evaluate and optimize a method for preparation of vegetable tissue samples for Ni determination; (b) optimize the analytical procedures for determination by Flame Atomic Absorption Spectrometry (FAAS) and by Electrothermal Atomic Absorption (ETAAS) in vegetable samples and (c) determine the Ni concentration in vegetables consumed in the cities of Lorena and Taubaté in the Vale do Paraíba, State of São Paulo, Brazil. By means of the analytical technique for determination by ETAAS or FAAS, the results were validated by the test of analyte addition and recovery. The most viable method tested for quantification of this element was HClO4-HNO3 wet digestion. All samples but carrot tissue collected in Lorena contained Ni levels above the permitted by the Brazilian Ministry of Health. The most disturbing results, requiring more detailed studies, were the Ni concentrations measured in carrot samples from Taubaté, where levels were five times higher than permitted by Brazilian regulations.

Recommendations to reduce extremity and eye lens doses in interventional radiology and cardiology

The main aim of the Work Package 1 (WP1) of the ORAMED project, Collaborative Project (2008-2011), supported by the European Commission within its 7th Framework Programme, was to obtain a set of standardized data on extremity and eye lens doses for staff in interventional radiology and cardiology (IR/IC) workplaces and to recommend a series of guidelines on radiation protection in order to both guarantee and optimize staff protection. Within the project, coordinated measurements were performed in 34 hospitals in 6 European countries. Furthermore, simulations of the most representative workplaces in IR and IC were performed to determine the main parameters that influence the extremity and eye lens doses. The work presented in this paper shows the recommendations that were formulated by the results obtained from both measurements and simulations. The presented guidelines are directed to operators, assistant personnel, radiation protection officers and medical physics experts. They concern radiation protection issues, such as the use of room protective equipment, as well as the positioning of the extremity and eye lens dosemeters for routine monitoring.

Physiological and anatomical characteristics of leaves of two clones of guarana

The objective of this work was to analyze gas exchange, photosynthetic characteristics, photochemical efficiency of photosystem II and anatomical characteristics of young plant leaves of two guarana (Paullinia cupana) clones (BRS-CG372RC and BRS-CG611RL) growing under open field. The variables of gas exchange and fluorescence of chlorophyll a were evaluated in mature leaves. The values of photosynthesis and transpiration found for BRS-CG372RC were 27% greater and 80% lesser than values found for BRS-CG611RL, respectively. The values of stomatal conductance found for the clones BRS-CG372RC and BRS-CG611RL were in the order of 224 and 614 mmol mm-2 s-1, respectively. The values of photorespiration, rate of carboxylation and rate electron transport were greater in BRS-CG372RC. The clone BRS-CG372RC exhibited stomatal density 26% greater than BRS-CG611RL. However, the area of ostiolar opening was 42% greater in BRS-CG611RL. The values of the water use efficiency in BRS-CG372RC were 134% greater than in BRS-CG611RL. High stomatal density and low stomatal conductance can be important characteristics in the selection of the clones with a good ability to assimilate carbon and optimize the use of water.

Deep-hole drilling process, monitoring system and sensors modifications

 In the drilling processes and especially deep-hole drilling process, the monitoring system and having control on mechanical parameters (e.g. Force, Torque,Vibration and Acoustic emission) are essential. The main focus of this thesis work is to study the characteristics of deep-hole drilling process, and optimize the monitoring system for controlling the process. The vibration is considered as a major defect area of the deep-hole drilling process which often leads to breakage of the drill, therefore by vibration analysis and optimizing the workpiecefixture, this area is studied by finite element method and the suggestions are explained. By study on a present monitoring system, and searching on the new sensor products, the modifications and recommendations are suggested for optimize the present monitoring system for excellent performance in deep-hole drilling process research and measurements.

Consensus recommendations on training and competing in the heat.

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimize performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimize performance is to heat acclimatize. Heat acclimatization should comprise repeated exercise-heat exposures over 1-2 weeks. In addition, athletes should initiate competition and training in a euhydrated state and minimize dehydration during exercise. Following the development of commercial cooling systems (e.g., cooling vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organizers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimizing the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events for hydration and body cooling opportunities when competitions are held in the heat.

Characterization of local and systemic immune-modulation in melanoma patients

Le mélanome cutané est un des cancers les plus agressifs et dont l'incidence augmente le plus en Suisse. Une fois métastatique, le pronostic de survie moyenne avec les thérapies actuelles est d'environ huit mois, avec moins de 5% de survie à cinq ans. Les récents progrès effectués dans la compréhension de la biologie de la cellule tumorale mais surtout dans l'importance du système immunitaire dans le contrôle de ce cancer ont permis le développement de nouveaux traitements novateurs et prometteurs. Ces thérapies, appelées immunothérapies, reposent sur la stimulation et l'augmentation de la réponse immunitaire à la tumeur. Alors que les derniers essais cliniques ont démontré l'efficacité de ces traitements chez les patients avec des stades avancés de la maladie, le contrôle de la maladie à long- terme est seulement atteint chez une minorité des patients. La suppression locale et systémique de la réponse immunitaire spécifique anti-tumorale apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Des études sur les souris ont montré que les vaisseaux lymphatiques joueraient un rôle primordial dans ce processus en induisant une tolérance immune, ce qui permettrait à la tumeur d'échapper au contrôle du système immunitaire et métastatiser plus facilement. Ces excitantes découvertes n'ont pas encore été établi et prouvé chez l'homme. Dans cette thèse, nous montrons pour la première fois que les vaisseaux lymphatiques sont directement impliqués dans la modulation de la réponse immunitaire au niveau local et systémique dans le mélanome chez l'homme. Ces récentes découvertes montrent le potentiel de combiner des thérapies visant le système lymphatique avec les immunothérapies actuellement utilisées afin d'améliorer le pronostic des patients atteint du mélanome. -- Cutaneous melanoma is one of the most invasive and metastatic human cancers and causes 75% of skin cancer mortality. Current therapies such as surgery and chemotherapy fail to control metastatic disease, and relapse occurs frequently due to microscopic residual lesions. It is, thus, essential to develop and optimize novel therapeutic strategies to improve curative responses in these patients. In recent decades, tumor immunologists have revealed the development of spontaneous adaptive immune responses in melanoma patients, leading to the accumulation of highly differentiated tumor-specific T cells at the tumor site. This remains one of the most powerful prognostic markers to date. Immunotherapies that augment the natural function of these tumor-specific T cells have since emerged as highly attractive therapeutic approaches to eliminate melanoma cells. While recent clinical trials have demonstrated great progress in the treatment of advanced stage melanoma, long-term disease control is still only achieved in a minority of patients. Local and systemic immune suppression by the tumor appears to be responsible, in part, for this poor clinical evolution. These facts underscore the need for a better analysis and characterization of immune- related pathways within the tumor microenvironment (TME), as well as at the systemic level. The overall goal of this thesis is, thus, to obtain greater insight into the complexity and heterogeneity of the TME in human melanoma, as well as to investigate immune modulation beyond the TME, which ultimately influences the immune system throughout the whole body. To achieve this, we established two main objectives: to precisely characterize local and systemic immune modulation (i) in untreated melanoma patients and (ii) in patients undergoing peptide vaccination or checkpoint blockade therapy with anti-cytotoxic T- lymphocyte-asisctaed protein-4 (CTLA-4) antibody. In the first and main part of this thesis, we analyzed lymphatic vessels in relation to anti-tumor immune responses in tissues from vaccinated patients using a combination of immunohistochemistry (IHC) techniques, whole slide scanning/analysis, and an automatic quantification system. Strikingly, we found that increased lymphatic vessel density was associated with high expression of immune suppressive molecules, low functionality of tumor-infiltrating CD8+ T cells and decreased cytokine production by tumor-antigen specific CD8+ T cells in the blood. These data revealed a previously unappreciated local and systemic role of lymphangiogenesis in modulating T cell responses in human cancer and support the use of therapies that target lymphatic vessels combined with existing and future T cell based therapies. In the second objective, we describe a metastatic melanoma patient who developed pulmonary sarcoid-like granulomatosis following repetitive vaccination with peptides and CpG. We demonstrated that the onset of this pulmonary autoimmune adverse event was related to the development of a strong and long-lasting tumor-specific CD8+ T cell response. This constitutes the first demonstration that a new generation tumor vaccine can induce the development of autoimmune adverse events. In the third objective, we assessed the use of Fourier Transform Infrared (FTIR) imaging to identify melanoma cells and lymphocyte subpopulations in lymph node (LN) metastasis tissues, thanks to a fruitful collaboration with researchers in Brussels. We demonstrated that the different cell types in metastatic LNs have different infrared spectral features allowing automated identification of these cells. This technic is therefore capable of distinguishing known and novel biological features in human tissues and has, therefore, significant potential as a tool for histopathological diagnosis and biomarker assessment. Finally, in the fourth objective, we investigated the role of colony- stimulating factor-1 (CSF-1) in modulating the anti-tumor response in ipilimumab-treated patients using IHC and in vitro co-cultures, revealing that melanoma cells produce CSF-1 via CTL-derived cytokines when attacked by cytotoxic T lymphocytes (CTLs), resulting in the recruitment of immunosuppressive monocytes. These findings support the combined use of CSF-1R blockade with T cell based immunotherapy for melanoma patients. Taken together, our results reveal the existence of novel mechanisms of immune modulation and thus promote the optimization of combination immunotherapies against melanoma. -- Le mélanome cutané est un des cancers humains les plus invasifs et métastatiques et est responsable de 75% de la mortalité liée aux cancers de la peau. Les thérapies comme la chirurgie et la chimiothérapie ont échoué à contrôler le mélanome métastatique, par ailleurs les rechutes sous ces traitements ont été montrées fréquentes. Il est donc essentiel de développer et d'optimiser de nouvelles stratégies thérapeutiques pour améliorer les réponses thérapeutiques de ces patients. Durant les dernières décennies, les immunologistes spécialisés dans les tumeurs ont démontré qu'un patient atteint du mélanome pouvait développer spontanément une réponse immune adaptative à sa tumeur et que l'accumulation de cellules T spécifiques tumorales au sein même de la tumeur était un des plus puissants facteurs pronostiques. Les immunothérapies qui ont pour but d'augmenter les fonctions naturelles de ces cellules T spécifiques tumorales ont donc émergé comme des approches thérapeutiques très attractives pour éliminer les cellules du mélanome. Alors que les derniers essais cliniques ont démontré un progrès important dans le traitement des formes avancées du mélanome, le contrôle de la maladie à long-terme est seulement atteint chez une minorité des patients. La suppression immune locale et systémique apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Ces considérations soulignent la nécessité de mieux analyser et caractériser les voies immunitaires non seulement au niveau local dans le microenvironement tumoral mais aussi au niveau systémique dans le sang des patients. Le but de cette thèse est d'obtenir une plus grande connaissance de la complexité et de l'hétérogénéité du microenvironement tumoral dans les mélanomes mais aussi d'investiguer la modulation immunitaire au delà du microenvironement tumoral au niveau systémique. Afin d'atteindre ce but, nous avons établi deux objectifs principaux : caractériser précisément la modulation locale et systémique du système immunitaire (i) chez les patients atteints du mélanome qui n'ont pas reçu de traitement et (ii) chez les patients qui ont été traités soit par des vaccins soit par des thérapies qui bloquent les points de contrôles. Dans la première et majeure partie de cette thèse, nous avons analysé les vaisseaux lymphatiques en relation avec la réponse immunitaire anti-tumorale dans les tissus des patients vaccinés grâce à des techniques d'immunohistochimie et de quantification informatisé et automatique des marquages. Nous avons trouvé qu'une densité élevée de vaisseaux lymphatiques dans la tumeur était associée à une plus grande expression de molécules immunosuppressives ainsi qu'à une diminution de la fonctionnalité des cellules T spécifiques tumoral dans la tumeur et dans le sang des patients. Ces résultats révèlent un rôle jusqu'à là inconnu des vaisseaux lymphatiques dans la modulation directe du système immunitaire au niveau local et systémique dans les cancers de l'homme. Cette recherche apporte finalement des preuves du potentiel de combiner des thérapies visant le système lymphatique avec des autres immunothérapies déjà utilisées en clinique. Dans le second objectif, nous rapportons le cas d'un patient atteint d'un mélanome avec de multiples métastases qui a développé à la suite de plusieurs vaccinations répétées et consécutives avec des peptides et du CpG, un évènement indésirable sous la forme d'une granulomatose pulmonaire sarcoid-like. Nous avons démontré que l'apparition de cet évènement était intimement liée au développement d'une réponse immunitaire durable et spécifique contre les antigènes de la tumeur. Par là- même, nous prouvons pour la première fois que la nouvelle génération de vaccins est aussi capable d'induire des effets indésirables auto-immuns. Pour le troisième objectif, nous avons voulu savoir si l'utilisation de la spectroscopie infrarouge à transformée de Fourier (IRTF) était capable d'identifier les cellules du mélanome ainsi que les différents sous-types cellulaires dans les ganglions métastatiques. Grâce à nos collaborateurs de Bruxelles, nous avons pu établir que les diverses composantes cellulaires des ganglions atteints par des métastases du mélanome présentaient des spectres infrarouges différents et qu'elles pouvaient être identifiées d'une façon automatique. Cette nouvelle technique permettrait donc de distinguer des caractéristiques biologiques connues ou nouvelles dans les tissus humains qui auraient des retombées pratiques importantes dans le diagnostic histopathologique et dans l'évaluation des biomarqueurs. Finalement dans le dernier objectif, nous avons investigué le rôle du facteur de stimulation des colonies (CSF-1) dans la modulation de la réponse immunitaire anti-tumorale chez les patients qui ont été traités par l'Ipilimumab. Nos expériences in vivo au niveau des tissus tumoraux et nos co-cultures in vitro nous ont permis de démontrer que les cytokines secrétées par les cellules T spécifiques anti-tumorales induisaient la sécrétion de CSF-1 dans les cellules du mélanome ce qui résultait en un recrutement de monocytes immunosuppresseurs. Dans son ensemble, cette thèse révèle donc l'existence de nouveaux mécanismes de modulation de la réponse immunitaire anti-tumorale et propose de nouvelles optimisations de combinaison d'immunothérapies contre le mélanome.

DETECTION AND QUANTIFICATION OF PHYTOCHEMICAL MARKERS OF Ilex paraguariensis BY LIQUID CHROMATOGRAPHY

Ilex paraguariensis (yerba-mate) is used as a beverage, and its extract requires adequate quality control methods in order to guarantee quality and safe use. Strategies to develop and optimize a chromatographic method to quantify theobromine, caffeine, and chlorogenic acid in I. paraguariensis extracts were evaluated by applying a quality by design (QbD) model and ultra high-performance liquid chromatography (UHPLC). The presence of these three phytochemical markers in the extracts was evaluated using UHPLC-MS and was confirmed by the chromatographic bands in the total ion current traces (m/z of 181.1 [M+H]+, 195.0 [M+H]+, and 353.0 [M−H]−, respectively). The developed method was then transferred to a high-performance liquid chromatography (HPLC) platform, and the three phytochemical markers were used as external standards in the validation of a method for analyses of these compounds in extracts using a diode array detector (DAD). The validated method was applied to quantify the chlorogenic acid, caffeine, and theobromine in the samples. HPLC-DAD chromatographic fingerprinting was also used in a multivariate approach to process the entire data and to separate the I. paraguariensis extracts into two groups. The developed method is very useful for qualifying and quantifying I. paraguariensis extracts.

A Development and Application of a Three-Dimensional Model for a CFB Gasifier

The developing energy markets and rising energy system costs have sparked the need to find new forms of energy production and increase the self-sufficiency of energy production. One alternative is gasification, whose principles have been known for decades, but it is only recently when the technology has become a true alternative. However, in order to meet the requirements of modern energy production methods, it is necessary to study the phenomenon thoroughly. In order to understand the gasification process better and optimize it from the viewpoint of ecology and energy efficiency, it is necessary to develop effective and reliable modeling tools for gasifiers. The main aims of this work have been to understand gasification as a process and furthermore to develop an existing three-dimensional circulating fluidized bed modeling tool for modeling of gasification. The model is applied to two gasification processes of 12 and 50 MWth. The results of modeling and measurements have been compared and subsequently reviewed. The work was done in co-operation with Lappeenranta University of Technology and Foster Wheeler Energia Oy.

Early Life Intestinal Microbiota in Health and in Atopic Eczema

Decrease in microbial contacts in affluent societies is considered to lie behind the rise in allergic and other chronic inflammatory diseases during the last decades. Indeed, deviations in the intestinal microbiota composition and diversity have been associated with several diseases, such as atopic eczema. However, there is no consensus yet on what would constitute a beneficial or harmful microbiota. The aim of this thesis was to study the microbiota development in healthy infants and to characterize intestinal microbiota signatures associated with disease status and severity in infants with atopic eczema. The methodological aim was to compare and optimize methods for DNA extraction from fecal samples to be used in high-throughput microbiota analyses. It was confirmed that the most critical step in successful microbial DNA extraction from fecal samples is the mechanical cell lysis procedure. Based on this finding, an efficient semi-automated extraction process was developed that can be scaled for use in high-throughput platforms such as phylogenetic microarray used in this series of studies. By analyzing a longitudinal motherchild cohort for 3 years it was observed that the microbiota development is a gradual process, where some bacterial groups reach the degree of adult-type pattern earlier than others. During the breast-feeding period, the microbiota appeared to be relatively simple, while major diversification was found to start during the weaning process. By the age of 3 years, the child’s microbiota composition started to resemble that of an adult, but the bacterial diversity has still not reached the full diversity, indicating that the microbiota maturation extends beyond this age. In addition, at three years of age, the child’s microbiota was more similar to mother’s microbiota than to microbiota of nonrelated women.In infants with atopic eczema, a high total microbiota diversity and abundance of butyrate-producing bacteria was found to correlate with mild symptoms at 6 months. At 18 months, infants with mild eczema had significantly higher microbiota diversity and aberrant microbiota composition when compared to healthy controls at the same age. In conclusion, the comprehensive phylogenetic microarray analysis of early life microbiota shows the synergetic effect of vertical transmission and shared environment on the intestinal microbiota development. By the age of three years, the compositional development of intestinal microbiota is close to adult level, but the microbiota diversification continues beyond this age. In addition, specific microbiota signatures are associated with the existence and severity of atopic eczema and intestinal microbiota seems to have a role in alleviating the symptoms of this disease.

Effect of harvest at different times of day on the physical and chemical characteristics of vegetable-type soybean

The objective of this study was to evaluate the effect of harvest at different times of day on the chemical and physical characteristics of vegetable-type soybean BRS 267 cultivar, harvested at the R6 stage (seed development) and to compare it with that on the grains harvested at the R8 stage (maturation). The pods of the BRS 267 cultivar were harvested at the R6 stage (at 8:00 AM, 12:00 AM, and 6:00 PM), the color parameters were evaluated, and the grains were analyzed for chemical composition, activity inhibitor trypsin, phytic acid content, starch, sugars, fatty acids, and isoflavones. No differences were observed among the different harvest times in terms of the chemical constituents of vegetable-type soybean BRS 267 cultivar harvested at the R6 stage. Isoflavones content did not change with different harvest times, and the aglycone forms (daidzein, glycitein, and genistein) were found in smaller quantities at the R6 stage compared to the R8 stage. The color of the pods of soybean BRS 267 cultivar, harvested at the R6 stage did not change with different harvest times. The grains harvested at the R6 stage had lower protein content, phytic acid, and sucrose and higher levels of lipids, carbohydrates, starch, glucose, fructose, stachyose, and linolenic acids than those collected at the R8 stage. The different times of harvest did not affect the quality of the vegetable-type soybean BRS 267 cultivar harvested at stage R6. Nevertheless, it is recommended to harvest in the morning, when the temperature is milder, like other vegetables, to facilitate and optimize its marketing and in natura consumption.

Melanosomal targeting sequences from gp100 are essential for MHC class II-restricted endogenous epitope presentation and mobilization to endosomal compartments

CD4+ T lymphocytes play an important role in CD8+ T cell-mediated responses against tumors. Considering that about 20% of melanomas express major histocompatibility complex (MHC) class II, it is plausible that concomitant antigenic presentation by MHC class I and class II complexes shapes positive (helper T cells) or negative (regulatory T cells) anti-tumor responses. Interestingly, gp100, a melanoma antigen, can be presented by both MHC class I and class II when expressed endogenously, suggesting that it can reach endosomal/MHC class II compartments (MIIC). Here, we demonstrated that the gp100 putative amino-terminal signal sequence and the last 70 residues in carboxy-terminus, are essential for MIIC localization and MHC class II presentation. Confocal microscopy analyses confirmed that gp100 was localized in LAMP-1+ endosomal/MIIC. Gp100-targeting sequences were characterized by deleting different sections in the carboxy-terminus (residues 590 to 661). Transfection in 293T cells, expressing MHC class I and class II molecules, revealed that specific deletions in carboxy-terminus resulted in decreased MHC class II presentation, without effects on MHC class I presentation, suggesting a role in MIIC trafficking for these deleted sections. Then, we used these gp100-targeting sequences to mobilize the green fluorescent protein (GFP) to endosomal compartments, and to allow MHC class II and class I presentation of minimal endogenous epitopes. Thus, we concluded that these specific sequences are MIIC targeting motifs. Consequently, these sequences could be included in expression cassettes for endogenously expressed tumor or viral antigens to promote MHC class II and class I presentation and optimize in vivo T cell responses, or as an in vitro tool for characterization of new MHC class II epitopes.

Electrospinning and characterization of supramolecular poly(4-vinyl pyridine)-small molecule complexes

La chimie supramoléculaire est basée sur l'assemblage non covalent de blocs simples, des petites molécules aux polymères, pour synthétiser des matériaux fonctionnels ou complexes. La poly(4-vinylpyridine) (P4VP) est l'une des composantes supramoléculaires les plus utilisées en raison de sa chaîne latérale composée d’une pyridine pouvant interagir avec de nombreuses espèces, telles que les petites molécules monofonctionnelles et bifonctionnelles, grâce à divers types d'interactions. Dans cette thèse, des assemblages supramoléculaires de P4VP interagissant par liaisons hydrogène avec de petites molécules sont étudiés, en ayant comme objectifs de faciliter l'électrofilage de polymères et de mieux comprendre et d'optimiser la photoréponse des matériaux contenant des dérivés d'azobenzène. Une nouvelle approche est proposée afin d'élargir l'applicabilité de l'électrofilage, une technique courante pour produire des nanofibres. À cet effet, un complexe entre la P4VP et un agent de réticulation bifonctionnel capable de former deux liaisons hydrogène, le 4,4'-biphénol (BiOH), a été préparé pour faciliter le processus d’électrofilage des solutions de P4VP. Pour mieux comprendre ce complexe, une nouvelle méthode de spectroscopie infrarouge (IR) a d'abord été développée pour quantifier l'étendue de la complexation. Elle permet de déterminer un paramètre clé, le rapport du coefficient d'absorption d'une paire de bandes attribuées aux groupements pyridines libres et liées par liaisons hydrogène, en utilisant la 4-éthylpyridine comme composé modèle à l’état liquide. Cette méthode a été appliquée à de nombreux complexes de P4VP impliquant des liaisons hydrogène et devrait être généralement applicable à d'autres complexes polymères. La microscopie électronique à balayage (SEM) a révélé l'effet significatif du BiOH sur la facilité du processus d’électrofilage de P4VP de masses molaires élevées et faibles. La concentration minimale pour former des fibres présentant des perles diminue dans le N, N'-diméthylformamide (DMF) et diminue encore plus lorsque le nitrométhane, un mauvais solvant pour la P4VP et un non-solvant pour le BiOH, est ajouté pour diminuer l'effet de rupture des liaisons hydrogène causé par le DMF. Les liaisons hydrogène dans les solutions et les fibres de P4VP-BiOH ont été quantifiées par spectroscopie IR et les résultats de rhéologie ont démontré la capacité de points de réticulation effectifs, analogues aux enchevêtrements physiques, à augmenter la viscoélasticité de solutions de P4VP pour mieux résister à la formation de gouttelettes. Cette réticulation effective fonctionne en raison d'interactions entre le BiOH bifonctionnel et deux chaînes de P4VP, et entre les groupements hydroxyles du BiOH complexé de manière monofonctionnelle. Des études sur d’autres agents de réticulation de faible masse molaire ont montré que la plus forte réticulation effective est introduite par des groupes d’acide carboxylique et des ions de zinc (II) qui facilitent le processus d’électrofilage par rapport aux groupements hydroxyles du BiOH. De plus, la sublimation est efficace pour éliminer le BiOH contenu dans les fibres sans affecter leur morphologie, fournissant ainsi une méthode élégante pour préparer des fibres de polymères purs dont le processus d’électrofilage est habituellement difficile. Deux complexes entre la P4VP et des azobenzènes photoactifs portant le même groupement tête hydroxyle et différents groupes queue, soit cyano (ACN) ou hydrogène (AH), ont été étudiés par spectroscopie infrarouge d’absorbance structurale par modulation de la polarisation (PM-IRSAS) pour évaluer l'impact des groupements queue sur leur performance lors de l'irradiation avec de la lumière polarisée linéairement. Nous avons constaté que ACN mène à la photo-orientation des chaînes latérales de la P4VP et des azobenzènes, tandis que AH mène seulement à une orientation plus faible des chromophores. La photo-orientation des azobenzènes diminue pour les complexes avec une teneur croissante en chromophore, mais l'orientation de la P4VP augmente. D'autre part, l'orientation résiduelle après la relaxation thermique augmente avec la teneur en ACN, à la fois pour le ACN et la P4VP, mais la tendance opposée est constatée pour AH. Ces différences suggèrent que le moment dipolaire a un impact sur la diffusion rotationnelle des chromophores. Ces résultats contribueront à orienter la conception de matériaux polymères contenant des azobenzène efficaces.

A Comaparison Study of EM and Physical Equivalent Circuit Modeling for MIM CMOS Capacitors

In this Letter a new physical model for metal-insulatormetal CMOS capacitors is presented. In the model the parameters of the circuit are derived from the physical structural details. Physical behaviors due to metal skin effect and inductance have been considered. The model has been confirmed by 3D EM simulator and design rules proposed. The model presented is scalable with capacitor geometry, allowing designers to predict and optimize quality factor. The approach has been verified for MIM CMOS capacitors