Σκοπός της ακτινοθεραπείας του μαστού μετά το χειρουργείο είναι να μειωθεί η πιθανότητα της τοπικής επανεμφάνισης της νόσου παρέχοντας ταυτόχρονα κατά το δυνατό μία ανώτερη αισθητική στον μαστό. Ο στόχος αυτός μπορεί να επιτευχθεί με να δοθεί η κατά το δυνατό μέγιστη δόση σε ολόκληρο το μαστό ενώ ταυτόχρονα η δόση στα γειτονικά από το μαστό όργανα (πνεύμονας, καρδιά και ο δίπλα μαστός) να είναι η μικρότερη δυνατή. Ως εκ τούτου, είναι πολύ σημαντική η ακριβής καθημερινή τοποθέτηση της ασθενούς σε θέση θεραπείας καθώς ακόμη και μικρές αποκλίσεις από την προτιθέμενη τοποθέτηση μπορεί να έχει σημαντικές δοσιμετρικές συνέπειες. Αλλαγές στη δοσιμετρία έχουν σημαντικές συνέπειες στην καλή κάλυψη του όγκου στόχου άρα και στην πιθανότητα ελέγχου του όγκου. Τα γεωμετρικά λάθη εμφανίζονται σαν αποκλίσεις μεταξύ της γεωμετρίας που επιθυμείτε να εφαρμοστεί σύμφωνα με το πλάνο της θεραπείας και της πραγματικής γεωμετρίας που εφαρμόζεται κατά την θεραπεία. Tα συστηματικά λάθη παριστάνουν την διαφορά μεταξύ του επιθυμητού πλάνου θεραπείας και του πλάνου που εφαρμόζεται ενώ οι αποκλίσεις που εμφανίζονται μεταξύ των συνεδριών αφορούν τα τυχαία λάθη. Οι αποκλίσεις αυτές μετρώνται καθημερινά με ένα σύστημα ηλεκτρονικής κινητής απεικόνισης και εν συνεχεία με κατάλληλη μέθοδο προβλέπονται, ελαχιστοποιούνται και ελέγχονται. Στην παρούσα εργασία σκοπός ήταν να μετρηθούν τα γεωμετρικά λάθη που εμφανίζονται κατά την τοποθέτηση της ασθενούς και να εκτιμηθεί η μεταβολή στη δόση που προκύπτει και οφείλεται στα λάθη της τοποθέτησης και ταυτόχρονα να εξαχθούν από τις μεταβολές αυτές φυσικές και βιολογικές παράμετροι. / The aim of breast radiotherapy after surgery is to reduce the probability of local recurrence while providing a superior breast cosmesis. The main purpose of radiotherapy is to give the maximum prescribed dose to the whole breast while at the same time minimizing the dose to the organs placed at the vicinity of breast (lung, heart, contralateral breast). Therefore, accuracy of daily set up for treatments is important because small spatial deviations from the intended set up may have important dosimetric consequences. Changes in dosimetry have implications for coverage of the target volume and hence for tumor control probability. Geometrical errors are presented as deviation between intended geometry of radiotherapy plan and real geometry of radiotherapy treatment. . Total set up error consists of systematic (Σ set up) and random component (σ set up). Systematic errors represent the recurring difference between intended and actual geometry while fraction-to-fraction variations are called random errors. Errors’ measuring for patients undergoing breast radiotherapy with electronic portal imaging device and afterwards a proper correction strategy enables to predict, minimize, and keep under control the amount for most of geometrical errors. The aim of this work was to determine these geometrical uncertainties and to evaluate dose perturbation due to setup error in tangential breast irradiation and as well as extract physical and biological parameters.

No description available.

Les cancers du sein chez les femmes et de la prostate chez les hommes sont les cancers les plus répandus au Canada. Un diagnostic précoce et un suivi de la thérapie bien adapté au type de cancer représentent des facteurs importants pour le traitement de ces maladies. La tomographie d'émission par positrons (TEP) permet de visualiser la distribution spatiale et temporelle de molécules radiomarquées. Le développement de nouveaux traceurs spécifiques à certains récepteurs surexprimés dans différents types de cancer permettrait d'améliorer le diagnostic à l'aide de l'imagerie TEP. La bombésine se lie à 3 types de récepteurs humains, dont le récepteur à relâche de gastrine (GRPR). Il est surexprimé dans 65% des cas de carcinomes canalaires in situ et 63% des tumeurs prostatiques. Le GRPR pourrait également être utilisé comme marqueur du caractère malin dans ces cas de cancer. Notre hypothèse est que les ligands radiomarqués ciblant le GRPR permettraient un meilleur diagnostic à partir de l'imagerie TEP et contribuerait au développement d'une médecine personnalisée. Le premier objectif de cette étude vise à évaluer les effets du radiométal utilisé pour marquer les molécules sur les propriétés physicochimiques des traceurs ciblant les GRPR. Un peptide modèle, le NOTA-PEG-BBN(6-14), a été marqué au [indice supérieur 64] Cu et au [indice supérieur 68] Ga. Ces études ont démontré que l'isotope utilisé pour le marquage influence l'affinité du peptide pour le GRPR et conséquemment son accumulation spécifique. Le deuxième objectif consiste à évaluer et comparer différents monomères et homodimères dérivés de la bombésine afin d'étudier le rôle de la valence du ligand sur la captation et la rétention tumorale ainsi que d'évaluer l'effet de la longueur de l'espaceur entre les deux ligands des homodimères de la bombésine sur la captation/rétention tumorale. Ainsi, le NOTA-PEGBBN(6-14) et deux homodimères ont été comparés in vitro et in vivo . Les composés homodimériques présentent une accumulation non-spécifique accrue au niveau des poumons, de la rate, du foie et des reins. De plus, le NOTA-dimère 2 possédant un plus long espaceur présente une accumulation spécifique augmentée au niveau du pancréas, un organe riche en GRPR, et une rétention supérieure au niveau des cellules tumorales prostatiques PC3 tant in vitro qu' in vivo chez les souris Balb/c nues xénogreffées.

Le travail de recherche présenté dans ce mémoire, concerne la synthèse et l'étude des propriétés de coordination du 64Cu par une nouvelle famille de ligands acycliques de type polyaminophosphonatés à fort potentiel en imagerie médicale, en particulier pour la tomographie par émission de positron TEP. Ce sujet a nécessité l'utilisation de méthodes analytiques telles que la potentiométrie, la spectrophotométrie et la spectrométrie de masse en mode electrospray pour les études thermodynamiques et des techniques de cinétique rapide a écoulement bloqué pour la détermination des vitesses de formation et de dissociation des complexes de Cu(II).Nous avons synthétisé quatre ligands (L1-L4) qui forment des complexes de formule CuL de forte stabilité et avec une bonne sélectivité pour le Cu(II) par rapport à d'autres métaux tels que Ni(II), Zn(II), Co(II) et Ga(III). La cinétique de complexation de Cu(II) s'est avérée rapide et elle suit un mécanisme à caractère dissociatif de type Eigen-Wilkins. Les complexes CuL formés avec cette série de ligand se caractérisent par une bonne inertie cinétique vis-à-vis de la démétallation et ils sont capables d'être réduit en présence de réducteurs biologiques tout en restant stables.Les complexes de lanthanides formés avec cette série de ligands sont très stables en milieu physiologique, en particulier ceux formés avec le ligand L1. Les complexes GdL1, GdL2 et GdL3 révèlent des relaxivités très intéressantes qui les désignent comme de futurs agents de contraste à fort potentiel en IRM.Le ligand L1 tetraphosphonaté a été fonctionnalisé par la présence de groupement réactif ce qui a permit le marquage de biomolécules, dont l'anticorps B28-13 anticorps anti-tenascineC pour la détection de tumeurs cancéreuses.

Submitted by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2016-09-23T12:09:04Z No. of bitstreams: 1 texto completo.pdf: 703627 bytes, checksum: 193b0cc47fc6514482df37f3b075f580 (MD5) / Made available in DSpace on 2016-09-23T12:09:04Z (GMT). No. of bitstreams: 1 texto completo.pdf: 703627 bytes, checksum: 193b0cc47fc6514482df37f3b075f580 (MD5) Previous issue date: 2000-07-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os processos que regulam a alocação de carbono para os órgãos vegetais e as sementes em desenvolvimento são muito importantes no desenvolvimento das plantas. Na maioria dos vegetais, o nutriente translocado mais importante é a sacarose, e a compreensão da biologia molecular, da bioquímica e da fisiologia de seu transporte é um problema central na biologia vegetal. Recentemente, foi isolado, em um laboratório da Universidade Federal de Viçosa, Viçosa-MG, um cDNA de uma biblioteca de expressão de sementes de soja que codifica um homólogo da proteína de ligação à sacarose (SBP), denominado S-64. Para analisar a função desse homólogo de SBP, tabacos transgênicos foram obtidos, introduzindo-se genes quiméricos que continham a região codificadora do gene s-64, ligado ao promotor 35S-CaMV, na orientação senso ou anti-senso via transformação mediada por Agrobacterium sp. O acúmulo do homólogo de SBP aumentou em tabacos que superexpressaram o gene s-64, assim como a expressão anti-senso do gene s-64 levou ao decréscimo nos níveis da proteína endógena. As plantas anti-senso desenvolveram sintomas característicos de uma inibição do transporte de sacarose à longa distância e apresentaram crescimento e desenvolvimento vegetal reduzidos. Em contraste, as plantas que continham a construção senso revelaram tendência de crescimento mais rápido e aceleração do desenvolvimento floral. O desempenho no desenvolvimento das plantas transgênicas foi correlacionado com a taxa fotossintética, sob condições normais de irradiância. Enquanto a taxa de fotossíntese nas linhagens anti-senso diminuiu, nas linhagens senso ela aumentou. Além disto, tanto a repressão anti-senso quanto a superexpressão senso do homólogo de SBP alteraram o particionamento de carboidratos em folhas maduras. Na geração seguinte, as plantas transgênicas senso e anti-senso revelaram diferentes padrões de expressão do gene s-64. Enquanto nas plantas senso não foi observado aumento no acúmulo da proteína, nas plantas anti-senso uma forte inibição de S-64/SBP persistiu. Além disto, as plantas transgênicas anti-senso R1 tiveram um reduzido crescimento vegetativo e radicular, acompanhado de um florescimento tardio. Seguindo esse padrão, a taxa fotossintética das folhas jovens e maduras diminuiu, o que evidencia uma possível diminuição no carregamento e, ou, descarregamento do floema. Um reduzido peso seco total e radicular, assim como experimentos de enxertia, forneceu evidências de que o gene s-64 está diretamente envolvido no descarregamento do floema. Coletivamente, esses resultados indicam que a proteína S-64 é funcionalmente análoga à proteína de ligação à sacarose e representa um importante componente da via de translocação de sacarose em plantas. / The processes that regulate carbon allocation to various organs in the developing seed is very important in plant development. In most plants, the morg important translocated nutrient is sucrose and, thus, understanding the molecular biology, biochemistry, and physiology of sucrose transport is a central problem in plant biology. A sucrose binding protein (SBP) homologue, designated S-64, was isolated and transgenic tobacco plants were obtained by introducing chimeric genes containing the S-64 coding region linked to the 35S CaMV promoter, either in the sense or antisense orientation, via Agrobacterium tumefaciens- mediated transformation. The accumulation of the SBP homologue was increased in transgenic plants expressing the heterologous sbp gene, whereas those expressing the antisense construct had reduced levels of the protein. The antisense transgenic plants developed symptoms characteristic of an inhibition of sucrose translocation and displayed a reduction in plant growth and development. In contrast, overexpression of the protein accelerated plant growth and the onset of flowering induction. The overall developmental performance of the transgenic plants was correlated with their photosynthetic rate under normal conditions. While photosynthesis in the antisense lines was decreased, in the sense lines photosynthetic rates were increased. Furthermore, both antisense repression and overexpression of the SBP homologue in transgenic lines altered carbohydrate partitioning in mature leaves. On the following generation, both sense and antisense plants revealed different S-64 expression patterns. While the sense plants had no overexpression when compared to control plants, the antisense plants was significantly inhibited by the SBP homologue gene. According to previous results, the antisense plants have a reduced vegetative growth accompanied by a late flowering. The photosynthesis was reduced on young and mature leaves from antisense plants supporting a possible decrease on loading and/or unloading of the phloem. A reduced root growth and dry weight, associated with grafting experiments showed strong evidences that gene is directly involved on phloem unloading. Taken together, these results indicate that S-64 protein is functionally analogous to sucrose binding protein, representing an important component of the sucrose translocation pathway in plants. / Não foi localizado o cpf do autor.

Conserved residues in protein are crucial for maintaining structure and function, either by direct involvement in chemistry or indirectly, by being essential for folding, stability and oligomerisation and are mostly clustered near active sites. The variability of sequences of the same protein from diverse organisms is a reflection of the selective pressures of evolution. Sequence conservation analysis with 3397 bacterial triosephosphate isomerase (TIM) sequences using Plasmodium falciparum (Pf) TIM as template, showed full conservation of ten residues, K12, T75, H95, E97, C126, E165, P166, G209, G210 and G228. The integrity of the enzyme active site, which lies near the dimer interface, makes TIM an obligatory dimer. Attempts to engineer active monomeric TIM have not been successful. The present study assesses the effects of mutations at fully conserved position 75 (Thr) and the highly conserved position 64 (Q: 3011, E: 383) near the dimer interface, using the recombinant Plasmodial enzyme. Residue 64, Gln in Pf, and T75 interact with the catalytic E97 and K12, respectively. Preliminary analysis of available crystal structures showed that Gln 64 takes part in a single intersubunit interaction and maintains the obligatory strained backbone angles of the catalytic K12 residue, while Thr 75 is involved in four intersusunit hydrogen bond interactions. This led to the hypothesis that mostly, Gln at position 64 is crucial for enzyme activity and Thr at position 75 for the integrity of the dimer. Biophysical and kinetic data are reported for four T75 (T75S/V/C/N) and two Q64 (Q64N/E) mutants. The major findings revealed that the mutations at position 64 have a significant effect on dimer integrity with a 1000 fold increase in the dimer dissociation constant compared to the wild type enzyme, while dimer stability was unimpaired for the T75 mutants. Concentration dependence of activity yielded an estimate of dimer dissociation constant (Kd) values (Q64N 73.7±9.2 nM and Q64E 44.6±8.4 nM). Enzyme activity values of the T75 mutants are comparable to the wild type, except for T75N which shows a 4-fold drop in activity. All four T75 mutants show a dramatic fall in activity between 35 °-45 °C. Crystal structure determination of the T75S/V/N mutant offers insights into the variation in local interactions with T75N showing the largest changes. These results were unanticipated emphasising the uncertainties involved in inferring functional and structural role for individual residues based only on analysis of interactions observed in crystal structures. Nanospray ionisation mass spectrometric studies has also been used to probe the oligomeric properties of the three mutant proteins Q64N, Q64E and T75S and the wild type enzyme in the gas phase. The gas phase distributions of dimeric and monomeric species have been examined under a wild range of collision energies (40 – 160 eV). The order in the gas phase, PfTIM wild type > T75S > Q64E ~ Q64N, together with the solution phase experiments described above establish the importance of Q64 and T75 in influencing stability and activity. Inhibition studies with a 27 residue synthetic dimer interface peptide and the Q64 mutants establish that the interaction between the protein and the peptide was facilitated in the case of monomeric species.

Den här uppsatsen har som syfte att utifrån Gun-Britt Sundströms roman Student -64 (1966) undersöka hur en författare genom beskrivningar av platser och rum formulerar en stadsmyt och därmed även konstruerar en viss identitet för personerna inom den. Utgångspunkten var att det finns en viss myt om Uppsala som studentstad, och att denna skildras i bland annat skönlitteraturen. Genom att fokusera på myten om studentstaden Uppsala och identiteten som student har också frågan om vilken funktion myten om staden har för studenten varit i fokus. För att genomföra undersökningen har en motivstudie baserat på rumsliga teman genomförts, som resulterade i en kartläggning över vilka platser som förekommer i romanen samt hur ofta de nämns. Det teoretiska ramverket som användes bestod huvudsakligen av Henri Lefebvres teorier om socialt rum och hur vi skapar rum genom tre olika slags erfarenheter: fysisk, mental och social, som vi får antingen genom rumsliga praktiker, representationer av rum eller genom representationella rum. Resultatet av undersökningen visar att Sundström i Student -64 gestaltar ett antal platser i Uppsala där protagonisten Sagas rumsliga praktiker kommer till uttryck. Platserna relateras till Sagas sociala erfarenhet och det hon som kallar för ”uppsalastämning”, vilket är en del av den historiska myten om Uppsala som Sundström anknyter till.  Därmed bidrar hon till att befästa myten genom att bygga på det representationella rum som är studentstaden Uppsala i sin helhet, samtidigt som hon omformulerar myten i en modern tolkning genom att skapa nya representationella rum. Dessa rum visar sig också möjliggöra en viss studentidentitet, samt en utveckling inom denna som i sig bidrar till att myten kan fortsätta leva.

I mitt examensarbete har jag valt att skriva om sats 1 ur Felix Mendelssohns violinkonsert. Jag har valt detta stycke för att jag tycker väldigt mycket om det och jag har lyssnat på violinkonserten sedan jag var ett litet barn. Syfte har varit att undersöka om utförandet av ett musikstycke kan påverkas av om man är ergonomiskt medveten eller inte. Jag fann intresse att skriva om ergonomi då jag har egna erfarenheter av att ha problem med spänningar och smärta i min kropp när jag övat (i synnerhet nacke, axlar och armar) och har insett att det kan vara sammanlänkat med ett bristande ergonomiskt medvetande i mitt fiolspel. Jag har velat undersöka om jag med ergonomiska övningar kan undvika spänningar och smärta. Jag har valt ut ett par passager ur stycket och undersökt vad det är för spänningar och smärta som uppkommer. Jag valde ut några ergonomiska övningar för nacke och axlar som förhindrar att spänningar uppstår och provade att se om övningarna kunde förbättra mitt framförande av passagerna. Övningarna gav ett mycket positivt resultat. Jag märkte en tydlig skillnad från tidigare: det krävdes bara ett par minuters ergonomiska övningar innan varje övningspass av de olika passagerna för att bli av med spänningarna och smärtan. Jag har känt mig mycket mer avslappnad i kroppen efter att jag praktiserat övningarna. Därför har jag absolut haft nytta av att undersöka detta ämne. Jag har blivit mer medveten om vilket viktigt verktyg ergonomin tillför till övningen. Dessa typer av övningar kommer jag använda mig av i framtiden i mitt musicerande. Förhoppningsvis kommer mitt arbete inspirera andra musiker att bli mer ergonomiskt medvetna. Detta är ett ämne vi inte ska underskatta.

Thesis (M. Dev.) -- University of Limpopo, 2017. / This study focuses on the legislative interventions for educators in ensuring the right of access to quality education in South Africa. It highlights the right of access to education as provided in section 29 of the Constitution of the Republic of South Africa. It examines the effect of poor education to the black majority and qualifications of educators during the apartheid period and how this has impacted black schools and learners. The structures, policies and programs of the apartheid are compared and contrasted to the post- apartheid (1994) structures, policies and programs. It argues that poor performance in black schools emanates from incapacity of educators in providing quality education. Although there was a radical transition in educational laws and programs from apartheid to post- apartheid, till date there are still challenges in the implementation of these policies and laws. The mini-dissertation recommends that government must capacitate and empower educators as this will enable them to deliver high standard pedagogy in black schools.

The diploma thesis is focused on the participation of older workers in the labour market of the European Union. Older people might be many times challenged by several obstacles or tougher employment conditions, compared to younger genera-tions. The objective of the diploma thesis is to recognize the dependence of the unemployment of age category 55-64 upon selected explanatory variables. At the beginning, theoretical reviews are presented. The multiple linear regression analy-sis is the main method used in the thesis. The model and its parameters are esti-mated by the Ordinary Least Squares method, and their statistical significance is further tested. There are several statistical tests and graphical outputs that are used for testing whether the estimated model meets all seven classical assump-tions.