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Ligands d'acides nucléiques et fluorophores dérivés de benzothiazoles : synthèse et applications biologiques / Nucleic acid ligands and benzothiazole-based fluorophores : synthesis and biological applicationsSafir Filho, Mauro 14 December 2018 (has links)
L’interdisciplinarité est désormais inhérente à la recherche scientifique. L’essor des recherches dans le domaine médical a notamment favorisé cette interdisciplinarité. C'est dans ce contexte que s'inscrivent les travaux présentés dans ce manuscrit. En effet, ce dernier vise à la production de nouveaux outils adaptés à des problématiques des sciences de la vie. Ce manuscrit traite de spectroscopie de la fluorescence et de chimie des acides nucléiques. Il est divisé en deux sections : Dans la partie I, nous présentons de nouveaux fluorophores push-pull très brillants, non toxiques et pouvant être utilisé en cultures cellulaires. Ces composés, basés sur des motifs benzothiazoles, peuvent être modulés structurellement afin d'obtenir les propriétés photophysiques souhaitées. D'ailleurs, pour ces composés, une relation structure-propriétés photophysiques a été établie. Ensuite, en utilisant ces fluorophores, nous avons conçu de nouvelles sondes fluorescentes pour suivre l’activité enzymatique de la β-galactosidase. Cette dernière étant un marqueur de la sénéscence cellulaire, nous avons utilisé nos sondes pour détecter la sénescence, in vitro, par des méthodes de microscopie de fluorescence et de cytométrie en flux. La partie II de ce manuscrit est consacrée à la chimie des acides nucléiques. Tout d'abord nous y décrivons la préparation et l'évaluation de nouveaux ligands d’ARN ciblant le domaine IIId de l'IRES du VHC. Ces ligands présentent d'une part, un motif permettant de faire un triplet de base avec la séquence IIId afin d'apporter de la spécificité, et d'autre part, des fonctions aminées afin de stabiliser le triplet par interactions électrostatiques avec les phosphodiesters de IIId. Enfin, la dernière partie concerne le développement d'une nouvelle stratégie permettant la fonctionnalisation post-synthèse d'acides nucléiques en position anomère. Pour ce faire, nous avons conçu des plateformes phosphoramidites qui, une fois incorporées dans des brins oligonucléotidiques, peuvent être impliquées dans diverses réaction de glycosidation. / Interdisciplinary is an obvious feature of scientific research. Notably, the continuously expanding researches in the medical field fostered this interdisciplinarity. Within this context, the work presented here deals with fluorescence spectroscopy and nucleic acid chemistry and aims at providing new tools suited for applications in life sciences. This manuscript presents two sections. In Part I, we developed novel series of highly bright and non-toxic push-pull fluorophores, compatible with cellular applications. In fact, we describe new benzothiazole-based fluorophores that can be structurally modulated to provide dyes with tunable photophysical properties. Their structure-photophysics relationship is also reported. Next, using these fluorophores, we produced new fluorescent probes to monitor the enzymatic activity of the β-galactosidase. Of note, since β-galactosidase is a marker of cellular senescence, we also used our probes for the detection of early stages of cellular senescence using fluorescence microscopy and flow cytometry analysis. Part II of this manuscript is devoted to the chemistry of nucleic acids. First, we describe the preparation and evaluation of novel RNA ligands targeting the IIId domain of the HCV IRES. These ligands can make a base triplet with the IIId sequence to provide specificity, and harbour amino functions to stabilize the triplet by electrostatic interaction with the phosphodiesters of IIId. Finally, the last part concerns the development of a new strategy allowing the post-synthetic functionalization of nucleic acids at the anomeric position. To do this, we designed new phosphoramidite platforms that, once incorporated into oligonucleotide strands, can be involved in various glycosidation reactions.
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Návrh a realizace zařízení pro měření síly v tahu u SMD / Design and realization of the pull strength measuring device for SMDValíček, Jan January 2013 (has links)
This thesis deals with the design and implementation of a device for measuring pull strength by surface mounted devices (SMD). It analyzes the theory of pull strength testing of solder joints with emphasis on standard IEC 62137-1-3 and describes the selection of components utilized to create mechanical construction and electrical parts. These electronic parts made or innovated in this work were control system based on microcontroler Atmega164P, power circuit for stepper motor and communication of measure equipment TEST 321 with PC. The whole design is complemented by simulation of mechanical stress to the critical components using ANSYS. The conclusion summarizes the most important parameters of this equipment.
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Marketingové aktivity ELKO Elektro s.r.o. / Marketing Activities of ELKO Elektro s.r.o.Kobližková, Markéta January 2015 (has links)
This diploma thesis deals proposals to improve the marketing activities of the company based on our assessment of the current situation. The theoretical part defines the various concepts of marketing mix and describes its tools. This section further describes communication mix and its individual parts. Analytical part is focused on assess the overal situation of a specific company. In the end of this thesis recommendations are proposed mainly for new communication mix.
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Synthesis, self-assembly and photophysical evaluation of fluorophores derived from acenes, heteroacenes and quinazolines / Synthèse, auto-assemblage et étude photophysique de fluorophores dérivés d'acènes, d'heteroacènes et de quinazolinesDoan, Thu Hong 26 January 2018 (has links)
Les semiconducteurs organiques (OSC) tels que les composés organiques photovoltaïques (OPVs), les diodes électroluminescentes organiques (OLEDs) ou encore les transistors organiques à effet de champ (OFETs) constituent un domaine de recherche très attractif en raison de leur potentiel en tant que couches actives dans les dispositifs optoélectroniques. Les composés aromatiques polycycliques ainsi que les hétéroaromatiques sont considérés comme des matériaux prometteurs pour les OSC en raison de leurs conductivités électriques potentielles, de leurs propriétés optiques ainsi que de leurs assemblages géométriques. Ces deux systèmes et leurs propriétés photophysiques ont été étudiés dans les trois chapitres de cette thèse. Dans le premier chapitre, une étude sur un ensemble d'acènes linéaires, angulaires et condensés consistant en des liens hétéroatomes avec des agrégations uniques a été décrite et analysée. Les hétéroacènes N-fusionnés angulaires et π-étendus sont la classe principale étudiée dans le deuxième chapitre. Leurs synthèses sont basées sur la réaction de couplage de Suzuki-Miyaura et la réaction de Cadogan. Outre les acènes et les hétéroacènes N-fusionnés, les N-hétéroaromatiques ont fait l'objet d'une attention particulière dans le domaine de matériaux. L'un d'entre eux est la classe des quinazolines utilisées comme partie acceptrice d'électrons dans les structures push-pull pour le transfert de charge intramoléculaire (TCI). L'étude des relations entre les structures dérivées du motif quinazoline de type donneur d'électron-accepteur-donneur (D-A-D) et leurs propriétés de photoluminescence est le principal travail mentionné dans le troisième chapitre. / Organic semiconductors (OSCs) are a highly attractive research field due to their potentials as active layers in optoelectronic devices such as organic field-effect transistors (OFETs), organic photovoltaic (OPVs) and organic light emitting diodes (OLEDs). Polycyclic aromatic compounds as well as heteroaromatics are considered as promising materials for OSCs due to their semi conductivity properties, optical properties and geometric structures. The mentioned systems and their photophysical properties were investigated in three chapters of my thesis. In the first chapter, a study on a set of linear, angular and condensed acenes consisting of heteroatom linkages with unique aggregations was described and analyzed. The angular and π-extended N-fused heteroacenes are the main class studied in the second chapter. Their synthesis is based on the Suzuki-Miyaura coupling and the Cadogan reactions. Besides acenes and N-fused heteroacenes, N-heteroaromatics have gained attention in material area. One of them is the quinazoline class that is known as an electron withdrawing unit in push-pull structures for intramolecular charge transfer (ICT). The investigation of the relationships between the electron donor-acceptor-donor (D-A-D) quinazoline-based structures and their photoluminescence properties is the main work mentioned in the third chapter.
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Inhibition traductionnelle du facteur de restriction APOBEC3G par la protéine Vif du VIH-1 : rôle d'une uORF dans la 5'-UTR de l'ARNm d'A3G et identification de facteurs cellulaires / Translational inhibition of the restriction factor APOBEC3G (A3G) by the HIV-1 Vif protein : role of a uORF in the 5'-UTR of A3G mRNA and identification of cellular factorsSeissler, Tanja 13 September 2019 (has links)
La protéine Vif du VIH-1 contrecarre le facteur de restriction APOBEC3G (A3G) en diminuant son niveau d'expression dans les cellules infectées. Ceci est mis en œuvre entre autres par l'inhibition de sa traduction, un mécanisme encore peu compris. La première partie de ma thèse contribue à la caractérisation d'une petite ORF (uORF) qui se situe dans la 5'-UTR de l'ARNm d'A3G et d'A3F en amont de leurs ORF respectives. Cette uORF s'est révélée cruciale pour la régulation de la traduction d'A3G en présence et absence de Vif. Dans la deuxième partie de cette thèse, différents protocoles ont été mis en œuvre pour identifier les protéines associées avec l'ARNm d'A3G, qui pourraient jouer un rôle dans le mécanisme d'inhibition traductionnelle d'A3G par Vif. Ainsi, plusieurs protéines ont été identifiées dont la présence sur l'ARNm d'A3G semble modulée par Vif. / The HIV-1 Vif protein counteracts the restriction factor APOBEC3G (A3G) by downregulating its expression level in infected cells. This is achieved in different ways, one of which is translational inhibition, a mechanism that is still poorly understood. The first part of my thesis contributes to the characterization of a small upstream ORF (uORF), that is found in the 5'-UTR of A3G and A3F mRNAs. This uORF has been found to be crucial for regulation of A3G translation and is necessary to allow Vif-mediated translational inhibition. In the second part of this thesis, different protocols have been set up in order to identify A3G mRNA-associated cellular proteins which might play a role in the mechanism of Vif-mediated translational inhibition. Several proteins, whose presence on A3G mRNA seems to be modulated by Vif have been identified.
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Capteurs fluorescents à base de fluorène : nouvelles perspectives en synthèse et applications pour le marquage des acides nucléiques et en imagerie de la membrane cellulaire / Fluorene-based fluorescent markers : new insights in synthesis and applications into labeling of nucleic acids and imaging of cell membranesShaya, Janah 21 September 2016 (has links)
Le développement de nouvelles voies synthétiques permettant l’accès à des sondes à applications biologiques connaît un intérêt accru. Les travaux de cette thèse s’inscrivent dans ce cadre. Ils portent particulièrement sur les colorants « Push-pull » qui se caractérisent par leur sensibilité aux changements de leur environnement, leur faible cytotoxicité et leur photostabilité élevée. En outre, la synthèse de ces fluorènes est très exigeante. Nos travaux ont abouti à : 1) Des approches synthétiques concises pour accéder à des composés aromatiques aminés difficiles à synthétiser, celles-ci via des systèmes Pallado-catalysés optimisés impliquant une amination sélective et une synthèse séquentielle en « one pot », 2) La synthèse d'une bibliothèque vaste de fluorènes avec la diversification des groupements accepteur et donneur. 3) Des relations structure- propriétés photophysiques. 4) La synthèse de trois colorants avancés engendrant la première sonde de fluorènes spécifique aux membranes : un outil puissant pour étudier la structure et les dynamiques biophysiques de ces membranes. Le colorant optimal surpasse les caractéristiques des sondes couramment utilisées montrant : une absorption décalée vers le rouge attenant 405 nm en diode laser, une luminosité plus élevée diminuant la concentration du colorant pour la coloration de ~ 10-15 fois, une haute photo-stabilité, une forte sensibilité aux domaines liquides des membranes des cellules. 5) La Synthèse de 4 phosphoramidites marqués et leurs incorporations dans les oligonucléotides attestant une grande sensibilité aux milieux protiques et au pH. En duplex d'ADN, le colorant est efficace pour la différenciation des bases opposées. Une application du marqueur d'ADN fluorescent l’a testé comme un donneur pour le déplacement de Stokes dans une paire de FRET émissive en combinaison avec l’accepteur Dy681. Le FRET a démontré une augmentation ratiométrique dans la région proche infrarouge avec un décalage de 300 nm / Extensive research focuses on finding straightforward synthesis and prospective probes for biological applications. Push-pull dyes are of particular interest for various uses as biosensors for membranes and nucleic acids. These dyes are highly responsive to changes of their environments. Specifically, push-pull fluorenes exhibit low cytotoxicity and high photostability, but are not yet reported in the two mentioned applications. Furthermore, their synthesis is highly demanding. In this context, our work presents: 1) Step-economic and concise approaches to access challenging aminoaromatics via optimized air-stable Pd catalytic systems involving selective mono/di-amination and sequential one-pot synthesis, 2) Synthesis of a fluorene library varying the acceptor and the donor groups, 3) Structure-photophysics relationships, 4) Synthesis of three advanced dyes and concluding the first plasma membrane-specific fluorene probe that can be a powerful tool for studying the structure and biophysical dynamics of membranes. The optimal dye surpasses the features of commonly used probes showing: red-shifted absorption matching the 405 nm diode laser, higher brightness decreasing the dye concentration for staining by ~10-15 folds, high photostability, comparably strong sensitivity to liquid domains of cell membrane, and 5) Synthesis of 4 fluorene-labeled phosphoramidites and their site-specific ODN incorporations evidencing high sensitivity to protic media and pH. Labeled sequences exhibited a far-red emission with modest quantum yields in line with their strong charge transfer character. In DNA duplexes, the dye efficiently base-discriminated opposite cytidine and thymidine. A preliminary application of the DNA fluorescent marker involved testing it as a mega-Stokes shift donor in an emissive FRET pair in combination with Dy681 acceptor. The FRET demonstrated a ratiometric turn-on in NIR region with a shift of 300 nm
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Přistěhovalci nebo uprchlíci? Nový typ migrace z Mexika do Spojených států. / Immigrants or Refugees: A New Type of Exodus from Mexico to the United StatesKamal, Tereza January 2013 (has links)
Apart from trade and drug control, immigration is one of the three major issues affecting U.S. - Mexican relations. The U.S. today has more immigrants from Mexico alone than any other country in the world has from all other countries of the world. The scale of this human movement, the persistence and the large proportion of the unauthorized low skilled migrants, which dominated this flow for decades, make Mexican migration unique. The decision to migrate North has always been driven by economic motives; the prospect of higher wages and a better living standard have been the main push factors, until recently. Since 2007/2008 there has been a significant change in the character of Mexican migration. This can be attributed to several factors influencing the process at once, but the primary reason is the escalation of drug related violence on the Mexican side of the border. The focus of my thesis is to analyze the transformation of Mexican migration since 2007/2008. I argue these years have been a turning point in the dynamics of migration for two reasons. Firstly, in 2007 the American economy turned into recession, which significantly affected the flow of unauthorized migration. Secondly, in 2008 the drug related violence in Mexico spiked dramatically. This had a deterrent effect on the unauthorized...
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Vad motiverar olika generationer till att äga företag? : En studie baserad på individer i generationerna Millennials, Generation X och Baby BoomersNilsson, Olivia, Andersson, Mikaela January 2023 (has links)
Under de senaste åren har antalet företagare ökat i Sverige och på dagens arbetsmarknad befinner sig just nu fyra generationer. I denna studie fokuserar vi på de tre generationer som utgör den största delen av arbetsmarknaden; Millennials, Generation X och Baby Boomers. Dessa generationer skiljer sig åt beroende på olika faktorer som påverkat dem genom livet. Millennials är uppväxta i en tid där sociala medier har spelat en stor roll, Generation X växte upp med teknikens utveckling och Baby Boomers växte upp under ekonomisk tillväxt. I denna kvalitativa forskningsansats undersöks hur olika generationer motiveras av olika faktorer. Syftet med studien är att bidra med ny kunskap till tidigare forskning om vad som motiverar individer i olika generationer till att äga företag. Detta gör vi genom att besvara problemformuleringen “Hur skiljer sig motivatorerna åt mellan Millennials, Generation X och Baby Boomers vid valet att äga företag?” Insamlad teori redovisar relevant fakta om motivationsteori, inre och yttre motivation, push- och pull-perspektivet samt generationsskillnader. Arbetets teoretiska referensram är insamlad från vetenskapliga artiklar, hemsidor och litteratur. Vidare består arbetet av insamlat empiriskt material där mixed methods har använts i form av 49 enkäter samt sex semistrukturerade intervjuer, där respondenterna uppfyllt ett antal kriterier för att få medverka. Studiens slutsats visar att Millennials och Generation X båda drivs av inre motivation, exempelvis passion, vara sin egen chef, flexibilitet och att utvecklas. Baby Boomers drivs av yttre motivation, exempelvis ekonomisk vinning och familjeföretag. / In recent years, the number of entrepreneurs has increased in Sweden and there are currently four generations in today's labor market. In this study we focus on the three generations that make up the largest part of the labor market; Millennials, Generation X and Baby Boomers. These generations differ depending on various factors that have influenced them throughout life. Millennials grew up in an era where social media has played a big role, Generation X grew up with the advancement of technology and Baby Boomers grew up during economic growth. In this qualitative research approach we investigate how different generations are motivated by different factors. The purpose of the study is to contribute with new knowledge to previous research on what motivates individuals in different generations to own businesses. We do this by answering the research question "How do the motivators differ between Millennials, Generation X and Baby Boomers when choosing to own a business?" Collected theory presents relevant facts about motivation theory, intrinsic and extrinsic motivation, the push- and pull-perspective and generational differences. The work's theoretical frame of reference is collected from scientific articles, websites and literature. Furthermore, the work consists of collected empirical material where mixed methods have been used through 49 questionnaires and six semi-structured interviews, where the respondents met a number of criteria to participate. The study's conclusion shows that Millennials and Generation X are both driven by intrinsic motivation, such as passion, being their own boss, flexibility and developing. Baby Boomers are driven by extrinsic motivation, such as financial gain and family businesses.
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Vägen ut ur gängkriminalitet : En studie om vägen ut ur gängkriminalitet och vilka faktorer som varit avgörande och upplevelsen av befintliga och saknade stödinsatser “Ju mer distans man får till det förflutna, desto mer växer det nya”Jaoshan, Sadaf, Rosales Stenbäck, Felicia January 2023 (has links)
Syftet med studien är att undersöka hur gängmedlemmar lyckats lämna sitt gäng. Denna kvalitativa studie undersöker fyra gängmedlemmars personliga resa ut ur sina respektive gäng, och hur de upplevde samhällsinsatser och ibland bristen på dem. Studien genomfördes med hjälp av semistrukturerade intervjuer som analyserades med en tematisk analys. Under litteratursökningens gång upptäcktes en märkbar kunskapslucka i tillgänglig forskning om hur människor lämnar kriminella gäng. Det finns dock studier gjorda om vägen in i ett gäng. Resultatet av intervjuerna har tolkats utifrån push- och pull-teorin och teorin om sociala band. Resultaten tyder på att majoriteten av de tillfrågade lämnade sina gäng på grund av rädsla för att bli skjutna, antingen för sig själv eller familjemedlemmar. En annan viktig anledning till att de tillfrågade lämnade sina gäng var för att de hade yttre motiv och möjligheter, såsom: en ny relation, att skaffa barn eller att flytta till en annan stad. Personer som har lämnat gängkriminalitet upplevde ofta samhällsinsatserna som otillräckliga och därmed bristande. Enligt deras upplevelse litade socialarbetaren inte helt på eller lyssnade på dem. Andra typer av insatser som respondenterna hade önskat var: familjebehandling i hemmet, mentorskap eller olika återinträdesinsatser för att bli bättre integrerade i samhället efter att ha lämnat ett gäng. Studien visade att det finns ett behov av ytterligare forskning gällande utfallet av olika insatser. Det behövs också ytterligare forskning kring socialarbetarens roll, vad de kan göra och vad de bör göra, för att underlätta vägen ut ur ett gäng. / The purpose of the study is to investigate how gang members succeeded in quitting their gang. This qualitative study examines the personal journey of four gang-members out of their respective gangs, and how they experienced the societal efforts and sometimes the lack of them. The study was carried out with the help of semi-structured interviews which were analyzed with a thematic analysis. Surprisingly, there was a noticeable gap in available research in how people leave criminal gangs. There are however studies done on the way into a gang. The result of the interviews have been interpreted based on the push- and pull-theory and the theory of social bonds. The results indicate that the majority of respondents left their gangs due to fear of getting shot, either themselves or family members. Another major reason why the respondents left their gangs is because they had other external motivations and opportunities, such as: a new relationship, having a child, or simply relocating to another city. However, the former gang members often experienced that societal interventions were lacking. In their experience the social worker didn't fully trust or listen to them. Examples of interventions that could have benefitted, according to the respondents, are: family treatment at home, mentorship, or re-entry interventions to get better integrated into society after leaving a gang. The study showed that there's a need for further research regarding the potential outcome of each type of intervention. There is also a need for further research regarding the role of social workers, what they can do, and what they should do, in order to facilitate the way out of a gang.
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Emigrationen från Medelstads härad 1870-1925. : En kvantitativ studie av emigrationen från Blekinge län till Danmark och Tyskland. / The emigration from Medelstads härad 1870-1925. : A quantitative study on emigration from Blekinge County to Denmark and Germany.Alritzson, Tuva January 2023 (has links)
This is a study on the emigration from Blekinge County with a focus on Medelstads härad to Denmark and Germany, during the period 1870-1925. By measuring statistics on how many people emigrated from Medelstads judicial district 13 parishes to Denmark and Germany respectively the aim is. To get a new perspective on the less known emigration. From this the study can continue to examine female and male emigration from the parishes of Backaryd, Edestad, Listerby and Ronneby. Furthermore, the study will examine the professional titles and other titles that the emigrants had when they chose to emigrate. Based on the results of the first questions, it is possible to see which similarities and differences are found between the emigration to Denmark and Germany. The results indicates the a greater number of emigrants went to Denmark than to Germnay. The results between the male and female emigration indicates that the female emigration was moe extensive than the male emigration both to Denmark and to Germany. Regarding the occupational titles, it can be determined that it was occupations that belonged to the working class that most emigrants had when they emigrated from Medelstads härad. From these results, it is possible to find similarities and differences betwwen the migration to Denmark and Germany.
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