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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
191

Motivation ur ett studie- och yrkesvägledarperspektiv - En studie om faktorer och arbetssätt som inverkar på elevers motivation

Wahlin, Emmy, Trevik, Sanna January 2018 (has links)
Uppsatsens syfte är att undersöka hur studie- och yrkesvägledare på yrkesprogram resonerar kring elevers motivation i förhållande till deras skolgång. I inledningen presenteras forskning som påvisar att yrkeselever har bristande studiemotivation och svårt att uppnå en examen. I samband med detta synliggörs att vetskapen om hur studie- och yrkesvägledare kan bidra i motivationsarbetet är bristfällig och att ytterligare studier fordras för att klargöra hur vägledare kan bidra i arbetet. Mot bakgrund av detta formulerade vi följande frågeställningar; Vilka faktorer anser studie- och yrkesvägledarna har inverkan på elevers motivationsnivå och på vilket sätt talar studie- och yrkesvägledarna om sitt arbetssätt och sin yrkesroll i relation till dessa faktorer? Vi har använt oss av kvalitativ metod där sju yrkesverksamma studie- och yrkesvägledare på yrkesprogram har intervjuats. Det empiriska materialet analyserades utifrån motivationsteorin Self-Determination Theory som beskriver de tre motivationsbehoven känsla av autonomi, kompetens och samhörighet. Vårt resultat visar att motivation tillskrivs stor betydelse av samtliga informanter och att det finns flera faktorer som inverkar på elevernas motivation, något som vägledarna anser att de i olika utsträckning kan arbeta med. En styrd gymnasieskola influerad av mål- och betygssättning utgör utmaningar i arbetet med att få elever motiverade för sin skolgång. Dock ger vägledarna flera exempel på hur de kan arbeta för att skapa en stödjande kontext där eleven står i fokus.
192

Palindromes in finite and infinite words / Palindromi u konačnim i beskonačnim rečima

Bašić Bojan 30 September 2012 (has links)
<p>In the thesis we are concerned with actual problems on palindromic subwords and palindromic factors of finite and infinite words. The main course of the research are the ways of determining which of two given words is &ldquo;more palindromic&rdquo; than the other one, that is, defining a measure for the degree of &ldquo;palindromicity&rdquo; of a word. Particularly, we pay attention to two actual approaches: the so-called MP-ratio and the so-called <em>palindromic defect</em>, and answer several open questions about them.<br /><br />Namely, concerning the MP-ratio, a few plausible-looking question have been asked in the literature, which would have, if answered positively, made computations of MP-ratios significantly simpler. We add one more related question to these ones, and then show that, rather unexpectedly, all these questions have negative answer.<br /><br />Concerning the palindromic defect, the main result of this work is a construction of an infinite class of infinite words that have several properties that were sought after in some recent works in this area. Among the most interesting facts is that that all these words are aperiodic words of a finite positive defect, having the set of factors closed under reversal---in some recent works, the construction of even a single word having these properties turned out to be quite hard. Using these words, which we are calling <em>highly potential words</em>, we check the validity of several open&nbsp; conjectures, and for several of them we find out that they are false.</p> / <p> U tezi razmatramo aktuelne probleme u vezi s palindromskim podrečima i palindromskim faktorima konačnih i beskonačnih reči. Glavni pravac istraživanja jesu kriterijumi za određivanje koja od dve date reči je &bdquo;palindromičnija&ldquo; od druge, tj. određivanje stepena &bdquo;palindromičnosti&ldquo; date reči. Akcenat stavljamo na dva aktuelna pristupa: tzv. <em>MP-razmeru</em> i tzv. <em>palindromski defekt</em>, i odgovaramo na vi&scaron;e otvorenih pitanja u vezi s njima.<br /> <br /> Naime, u vezi sa MP-razmerom u literaturi je postavljeno vi&scaron;e pitanja, intuitivno uverljivih, koja bi, u slučaju pozitivnog razre&scaron;enja, znatno pojednostavila izračunavanje MP-razmere. Ovim pitanjima dodajemo jo&scaron; jedno srodno, a zatim pokazujemo da, prilično neočekivano, sva ova pitanja imaju negativan odgovor.<br /> <br /> U vezi s palindromskim defektom, glavni rezultat rada je konstrukcija beskonačne klase beskonačnih reči koje imaju vi&scaron;e osobina za kojima je iskazana potreba u skora&scaron;njim radovima iz ove oblasti. Među najzanimljivije spada činjenica da su sve aperiodične reči konačnog pozitivnog defekta, i da im je skup faktora zatvoren za preokretanje &ndash; u nekim skora&scaron;njim radovima konstrukcija makar jedne reči s ovim osobinama pokazala se kao prilično te&scaron;ka. Pomoću ovih reči, koje nazivamo <em>visokopotencijalne reči</em>, ispitujemo validnost vi&scaron;e otvorenih hipoteza, i za vi&scaron;e njih ustanovljavamo da nisu validne.</p>
193

Sjuksköterskors upplevelse av moralisk stress : En deskriptiv litteraturstudie

Östergren, Jonny, Sjöberg, Gunilla January 2020 (has links)
Bakgrund: Stress är vanligt förekommande hos yrkesverksamma sjuksköterskor och nämns som en grundläggande orsak till psykisk ohälsa och ökat antal sjukskrivningar. Arbetsmiljöverket rapporterar in yrkesrelaterad stress som den vanligaste sjukskrivningsorsaken bland vårdpersonal. Moralisk stress definieras som situationer då vi vet vad som är rätt att göra, men institutionella begränsningar gör det i princip omöjligt att göra det rätta. Syfte: Att beskriva sjuksköterskors upplevelser av moralisk stress. Metod: En deskriptiv litteraturstudie med tematisk dataanalysmetod som utgår från 13 vetenskapliga artiklar som svarar på studiens syfte.  Huvudresultat: Resultatet visade att när det finns brister i behandlingen som patienterna erhåller och kvaliteten på vården sviktar upplever många sjuksköterskor moralisk stress. Det visade även att samarbetssituationer, kommunikationsbrister och kontakter med anhöriga kan vara källor till moralisk stress. Den moraliska stressen utlöstes i de situationer där sjuksköterskor upplever att patienterna blir lidande och då sjuksköterskan upplever att hon inte kan agera på det sätt som är bäst för patienten. Som en konsekvens av den moraliska stressen upplever sjuksköterskorna flera varierande negativa känslor, där frustration är den mest frekventa känslan. Slutsats: Upplevelser av moralisk stress är vanligt förekommande bland kliniskt arbetande sjuksköterskor. Den moraliska stressen uppkommer i situationer där sjuksköterskor inte kan agera på det sätt som sjuksköterskorna anser är rätt. Som en konsekvens av den moraliska stressen upplever sjuksköterskorna flera olika negativa känslor. Genom att få en förståelse för vad moralisk stress är, hur den uppkommer och hur den yttrar sig känslomässigt kan sjuksköterskor lättare hantera sina egna reaktioner då de upplever moralisk stress. / Background: Stress is common among nurses and is mentioned as a fundamental cause of an increased number of sick leaves and mental illness. The Swedish Work Environment Authority reports occupational stress as the most common cause of sick leave among healthcare professionals. Moral distress is defined as situations when we know what is right to do, but when institutional limitations make it impossible to do the right thing. Aim: The aim of this study was to describe nurses' experience of moral distress.  Methods: A descriptive literature study with a thematic data analysis method based on 13 scientific articles that answer the aim. Main results: The result revealed that deficiencies in the treatment that patients receive and the quality of care declines, many nurses experience moral distress. It also revealed that cooperation situations, deficiencies in communication and contacts with relatives can be sources of moral distress. The moral distress is triggered in the situations where nurses feel that the patients are suffering and when the nurse feels that she cannot act in the best way for the patient. As a consequence of the moral distress, the nurses experience several varying negative emotions, where frustration is the most frequent emotions. Conclusion: Experiences of moral distress are common among clinically working nurses. The moral distress arises in situations where nurses can’t act in a way that the nurses think is right. As a consequence of the moral distress, the nurses experience several different negative emotions. By gaining an understanding of what moral distress is, how it arises and how it manifests emotionally, nurses can more easily manage their own reactions when they experience moral distress.
194

Faktory ovlivňující genovou expresi u Bacillus subtilis / Factors affecting gene expression in Bacillus subtilis

Sudzinová, Petra January 2021 (has links)
Bacterial DNA-dependent RNA polymerase (RNAP) is a key enzyme of bacterial transcription. Its activity must be tightly regulated. This could be done on the level of promoter DNA topology recognition, by changing the intracellular levels of metabolites, or by binding proteins, known as transcription factors. Even though the RNAP regulatory network has been intensively studied for decades, new regulators are still being described. The main focus of this Thesis is to characterize some of them: i) HelD, a novel RNAP interacting factor, with so far unknown protein 3D structure; ii) RNase J1, an enzyme with a unique mechanism of functioning; iii) Spx, a major regulator of gene expression in Bacillus subtilis, with still new roles to be defined and iv) the effect of the topological state of promoters on transcription. We identified HelD as an interacting protein of RNAP in Bacillus subtilis and described its biochemical properties. It stimulates transcription in an ATP-dependent manner, by enhancing recycling of RNAP molecules (Publication I). We published the first insight into the HelD structure by SAXS (small angle X-ray scattering) and deepened the understanding of HelD domain composition (Publication III). And finally, we were able to solve the cryo-EM structure of HelD:RNAP complexes from...
195

Vnitrobuněčná a mezibuněčná regulace genové exprese u Gram-pozitivních bakterií / Intracellular and intercellular regulation of gene expression in Gram-positive bacteria.

Pospíšil, Jiří January 2021 (has links)
Bacteria, the most dominant organisms on Earth, are an everyday presence in our lives. Symbiotic bacteria, which are present in the digestive tract of animals, usually have a beneficial effect on the body. On the opposite side of the spectrum are pathogenic species that cause more or less serious diseases around the world. In order to fight pathogens effectively, it is necessary to learn as much as possible about the molecular mechanisms by which bacteria respond to their environment, and also about the types of communication within bacterial populations that allow them to react to environmental changes as "multicellular" organisms. This Thesis consists of two main parts. In the first part, selected aspects of bacterial gene expression are characterized, using Bacillus subtilis and Mycobacterium smegmatis as model organisms. DNA-dependent RNA polymerase (RNAP) is the enzyme that is responsible for transcription of DNA into RNA, and thus plays a key role in gene expression. This Thesis deals with the structure of bacterial RNAP and important auxiliary factors (proteins and RNA) that associate with this enzyme and modulate its function. In the second part, the focus is on cell-to-cell communication, revealing which factors/mechanisms, including gene expression, affect this process in B. subtilis....
196

Faktory ovlivňující genovou expresi u Bacillus subtilis / Factors affecting gene expression in Bacillus subtilis

Sudzinová, Petra January 2021 (has links)
Bacterial DNA-dependent RNA polymerase (RNAP) is a key enzyme of bacterial transcription. Its activity must be tightly regulated. This could be done on the level of promoter DNA topology recognition, by changing the intracellular levels of metabolites, or by binding proteins, known as transcription factors. Even though the RNAP regulatory network has been intensively studied for decades, new regulators are still being described. The main focus of this Thesis is to characterize some of them: i) HelD, a novel RNAP interacting factor, with so far unknown protein 3D structure; ii) RNase J1, an enzyme with a unique mechanism of functioning; iii) Spx, a major regulator of gene expression in Bacillus subtilis, with still new roles to be defined and iv) the effect of the topological state of promoters on transcription. We identified HelD as an interacting protein of RNAP in Bacillus subtilis and described its biochemical properties. It stimulates transcription in an ATP-dependent manner, by enhancing recycling of RNAP molecules (Publication I). We published the first insight into the HelD structure by SAXS (small angle X-ray scattering) and deepened the understanding of HelD domain composition (Publication III). And finally, we were able to solve the cryo-EM structure of HelD:RNAP complexes from...
197

Utvecklingen för gröna tak i Stockholm stad / The development for green roofs in Stockholm city

Olofsson, Jakob January 2019 (has links)
Det råder idag en stor brist på information angående utvecklingen för gröna tak i Stockholms stad. Eftersom gröna tak har en stor potential att stödja stadens dagvattensystem, bidra till en ökad biologisk mångfald, minska buller samt förbättra luftkvalitet innebär att gröna tak stark kan kopplas till två av Sveriges miljömål nämligen god bebyggd miljö och ett rikt växt- och djurliv. På grund av denna potential vore det ofördelaktigt om gröna tak inte används fullt ut.  En inventering av gröna tak med hjälp av flygfoton har gjorts på en del av södra Stockholms stad för att avgöra hur mycket gröna tak som byggts de senaste nio åren jämfört med tidigare år. Området valdes på grund av stor åldersvariation i bebyggelsen för att kunna representera Stockholms stad som helhet bättre. Det har också genomförts 3 intervjuer, dels med representanter för Stockholms stad och dels från byggsektorn. Syftet med intervjuerna var att undersöka om det skett en ökning i byggandet samt orsaker till detta. Resultaten av inventeringen visar att det byggts lika många gröna tak de senaste nio åren som de byggts alla tidigare år i området. Intervjuerna visar på att det har skett en ökning av mängden byggda tak och att en av orsakerna till denna ökning har varit introduktionen av grönytefaktorn. Detta kan dock inte styrkas med någon befintligdata då sådan saknas för Stockholms stad som helhet. Utvecklingen för gröna tak utifrån denna studie framgår vara positiv dock för att helt kunna säkerställa gröna taks utveckling i Stockholm rekommenderas det att en mer utförlig inventering av hela Stockholms stads bestånd av gröna tak görs. / There is currently a great lack of information regarding the development of green roofs in Stockholm. Since green roofs have big potential to support the city's storm water system, contribute to increased biodiversity, reduce noise and improve air quality, green roofs can be strongly linked to two of Sweden's environmental goals, namely a good built environment and a rich plant and animal life. Because of this potential, it would be disadvantageous if green roofs were not fully used. An inventory of green roofs using aerial photos have been taken on a part of southern Stockholm to determine how much green roofs have been built over the past nine years compared to previous years. The area was chosen because of the large age variation in the buildings in order to better represent the city of Stockholm as a whole. There have also been 3 interviews conducted with representatives of the City of Stockholm and representatives from the construction sector. The purpose of the interviews was to investigate whether there has been an increase in construction and reasons for this. The results of the inventory show that as many green roofs have been built in the last nine years as has been built in the area all the previous years. The interviews show that there has been an increase in the amount of built roofs and that one of the reasons for this increase has been the introduction of the green area factor. However, this cannot be substantiated by any existing data, as such is missing for the City of Stockholm as a whole. The development for green roofs based on this study appears to be positive, however, in order to fully ensure the development of green roofs in Stockholm, it is recommended that a more detailed inventory of the entire Stockholm city stock of green roofs be made.
198

Synaptic arrangements and potential communication partners of \(Drosophila’s\) PDF-containing clock neurons within the accessory medulla / Synaptische Konstellationen und potentielle Kommunikationspartner von \(Drosophila’s\) PDF-enthaltenden Uhrneuronen innerhalb der akzessorischen Medulla

Hieke, Marie January 2019 (has links) (PDF)
Endogenous clocks regulate physiological as well as behavioral rhythms within all organisms. They are well investigated in D. melanogaster on a molecular as well as anatomical level. The neuronal clock network within the brain represents the center for rhythmic activity control. One neuronal clock subgroup, the pigment dispersing factor (PDF) neurons, stands out for its importance in regulating rhythmic behavior. These neurons express the neuropeptide PDF (pigment dispersing factor). A small neuropil at the medulla’s edge, the accessory medulla (AME), is of special interest, as it has been determined as the main center for clock control. It is not only highly innervated by the PDF neurons but also by terminals of all other clock neuron subgroups. Furthermore, terminals of the photoreceptors provide light information to the AME. Many different types of neurons converge within the AME and afterward spread to their next target. Thereby the AME is supplied with information from a variety of brain regions. Among these neurons are the aminergic ones whose receptors’ are expressed in the PDF neurons. The present study sheds light onto putative synaptic partners and anatomical arrangements within the neuronal clock network, especially within the AME, as such knowledge is a prerequisite to understand circadian behavior. The aminergic neurons’ conspicuous vicinity to the PDF neurons suggests synaptic communication among them. Thus, based on former anatomical studies regarding this issue detailed light microscopic studies have been performed. Double immunolabellings, analyses of the spatial relation of pre- and postsynaptic sites of the individual neuron populations with respect to each other and the identification of putative synaptic partners using GRASP reenforce the hypothesis of synaptic interactions within the AME between dopaminergic/ serotonergic neurons and the PDF neurons. To shed light on the synaptic partners I performed first steps in array tomography, as it allows terrific informative analyses of fluorescent signals on an ultrastructural level. Therefore, I tested different ways of sample preparation in order to achieve and optimize fluorescent signals on 100 nm thin tissue sections and I made overlays with electron microscopic images. Furthermore, I made assumptions about synaptic modulations within the neuronal clock network via glial cells. I detected their cell bodies in close vicinity to the AME and PDFcontaining clock neurons. It has already been shown that glial cells modulate the release of PDF from s-LNvs’ terminals within the dorsal brain. On an anatomical level this modulation appears to exist also within the AME, as synaptic contacts that involve PDF-positive dendritic terminals are embedded into glial fibers. Intriguingly, these postsynaptic PDF fibers are often VIIAbstract part of dyadic or even multiple-contact sites in opposite to prolonged presynaptic active zonesimplicating complex neuronal interactions within the AME. To unravel possible mechanisms of such synaptic arrangements, I tried to localize the ABC transporter White. Its presence within glial cells would indicate a recycling mechanism of transmitted amines which allows their fast re-provision. Taken together, synapses accompanied by glial cells appear to be a common arrangement within the AME to regulate circadian behavior. The complexity of mechanisms that contribute in modulation of circadian information is reflected by the complex diversity of synaptic arrangements that involves obviously several types of neuron populations / Endogene Uhren steuern sowohl physiologische als auch verhaltensbedingte Rhythmen bei allen Organismen. In D. melanogaster sind sie nicht nur auf molekularer sondern auch auf anatomischer Ebene bereits gut erforscht. Das neuronale Uhrnetzwerk im Gehirn stellt das Zentrum der Steuerung der rhythmischen Aktivität dar. Eine Uhrneuronengruppe sticht allein schon durch ihre besonderen anatomischen Eigenschaften hervor. Diese Neurone exprimieren das Neuropeptid PDF (pigment dispersing factor), welches zudem besonderen Einfluss auf die Lokomotionsaktivität der Fliege hat. Ein kleines Neuropil am Rande der Medulla, die akzessorische Medulla (AME) ist von besonderem Interesse, da neben seiner intensiven Innervation durch die PDF-Neurone auch Terminale aller anderen Uhrneuronengruppen zu finden sind. Zudem wird sie durch Terminale der Photorezeptoren mit Informatonen über die Lichtverhätnisse versorgt. Die AME erreichen des Weiteren Informationen aus vielen anderen Hirnregionen. Eine Vielzahl von Neuronentypen laufen in ihr zusammen, um sich anschließend wieder in verschiedenste Hirnareale zu verteilen. So wird die AME auch durchzogen von Fasern mit aminergem Inhalt, dessen Rezeptoren wiederum auf den PDF-Neuronen zu finden sind. Die vorliegende Arbeit gibt Aufschluss über vermutliche synaptische Partner und anatomische Anordnungen innerhalb des neuronalen Uhrnetzwerkes, insbesondere innerhalb der AME. Solch Wissen stellt eine Grundvoraussetzung dar, um zirkadianes Verhalten verstehen zu können. Die auffällige Nähe der aminergen Neurone zu den PDF Neuronen lässt eine synaptische Interaktion zwischen ihnen vermuten. Deshalb wurden basierend auf vorangegangen Studien detailiertere Untersuchungen dieser Thematik durchgeführt. So wird die Hypothese über synaptische Interaktionen innerhalb der AME zwischen dopaminergen/ serotonergen Neuronen und den PDF Neuronen bestärkt mittels Doppelimmunofärbungen, gegenüberstellende Analysen über die räumlichen Nähe von prä- und postsynaptischen Stellen der jeweiligen Neuronenpopulationen und durch die Identifikation vermutlicher synaptischer Partner unter Verwendung von GRASP. Zur möglichen Identifikation der synaptischen Partner unternahm ich erste Schritte in der Array Tomographie, welche hochinformative Analysen von fluoreszierenden Signalen auf einem ultrastrukturellen Level ermöglicht. Dazu testete ich verschieden Wege der Gewebepräparation, um Flureszenzsignale zu erhalten bzw. zu optimieren und bildete erste Überlagerungen der Fluoreszenz- und Elektronenmikrskopbilder. Die Auswertung der elektronenmikroskopischen Bilder erlaubten Mutmaßungen über mö- gliche synaptische Modulationen innerhalb des neuronalen Uhrnetzwerkes durch Gliazellen. Ihre Zellkörper fand ich in unmittelbarer Nähe zu den PDF Neuronen. Im dorsalen Hirn wurden neuronale Modulationen an den kleinen PDF Neuronen durch Gliazellen bereits festgestellt. Auf anatomischer Ebene scheint diese Modulation auch innerhalb der AME zu erfolgen, da synaptische Kontakte, welche PDF-positive Dendriten involvieren, von Gliafasern umgeben sind. Interessanterweise sind diese postsynaptischen PDF Fasern dabei oftmals Teil dyadischer oder sogar multipler Kontakte, die sich gegenüber einer ausgedehnten aktiven Zone befinden. Um mögliche Mechanismen solcher synaptischer Anordnungen zu erklären, versuchte ich den ABC Transporter White im Hirn von Drosophila zu lokalisieren. Seine Präsenz in Gliazellen würde auf einen Recyclingmechanismus hindeuten, welcher eine schnelle Wiederbereitstellung des Transmiters ermöglichen würde. Zusammengefasst scheinen Synapsen mit postsynaptischen PDF-Neuronen in Begleitung von Gliazellen, ein gebräuchliches synaptisches Arrangement innerhalb der AME dazustellen. Diese komplexe Diversität der synaptischen Anordnung reflektiert die komplexen Mechanismen, welche der Verarbeitung der zirkadianen Informationen zugrunde liegen
199

Klonale T-LGL-Zellen bei Patienten mit Rheumatoider Arthritis / Clonal T-LGL-cells in patients with rheumatoid arthritis

Junker, Lara Päldsom Rosemarie January 2021 (has links) (PDF)
Die Rheumatoide Arthritis ist eine häufig auftretende, chronisch entzündliche Systemerkrankung und wird bei bis zu einem Drittel der Patienten mit einer T-LGL-Leukämie diagnostiziert. Wie häufig klonale T-LGL-Zellen bei Patienten mit Rheumatoider Arthritis auftreten, ist ungeklärt. Ziel dieser Studie war es, die Oberflächenantigene der T-Lymphozyten in einem Patientenkollektiv mit Rheumatoider Arthritis zu bestimmen. Der Fokus lag dabei auf der Prävalenz von klonalen T-LGL-Zellexpansionen und möglichen Risikofaktoren. Hierfür wurden zwischen November 2013 und August 2015 527 Patienten mit Rheumatoider Arthritis mittels Durchflusszytometrie untersucht. Zur Bestätigung der Klonalität erfolgte bei Patienten mit auffälligem Immunphänotyp eine PCR (Polymerase-Kettenreaktion)-Analyse. Bei 19 Patienten konnte eine klonale T-LGL-Zellexpansion festgestellt werden, was einer Prävalenz von 3,6% entspricht. Das Auftreten von klonalen T-LGL-Zellen war mit einer TNFα-Inhibitoren-Therapie (p=0,01) und deren Dauer assoziiert (p=0,01). Ob die klonalen T-LGL-Zellen Ausdruck der Autoimmunerkrankung oder Vorläuferzellen einer T-LGL-Leukämie sind, bleibt offen. Die Patienten werden mit einer klonalen T-LGL-Zellexpansion unklarer Signifikanz beschrieben. / Rheumatoid arthritis is a common, chronic inflammatory systemic disease and is diagnosed in up to a third of patients with T-LGL leukemia. The frequency of clonal T-LGL-cells in patients with rheumatoid arthritis is unknown. The aim of this study was to determine surface antigens of T-lymphocytes in a collective of patients with rheumatoid arthritis. The focus was on the prevalence of clonal T-LGL cell expansion and possible risk factors. Therefore, 527 patients with rheumatoid arthritis were examined using flow cytometry between November 2013 and August 2015. To confirm clonality, a PCR (polymerase chain reaction) analysis was carried out in patients with an aberrant immune phenotype. A clonal T-LGL-cell expansion was found in 19 of those patients, which corresponds to a prevalence of 3,6%. The occurrence of clonal T-LGL-cells was associated with TNFα inhibitor therapy (p=0,01) and its duration (p=0,01). Whether the clonal T-LGL-cells are an expression of the autoimmune disease or precursor cells of T-LGL leukemia remains unclear. Therefore, those patients are described with a clonal T-LGL-cell expansion of uncertain significance.
200

Herstellung und Charakterisierung von anti-CD40- und anti-41BB-Fusionsproteinen mit PDL1-abhängiger agonistischer Aktivität / Production and characterization of anti-CD40 and anti-41BB fusion proteins with PDL1-dependent agonistic activity

Freiherr von Rotenhan, Stefan January 2022 (has links) (PDF)
In this work, bispecific antibodies were produced by coupling TNFR-specific antibodies with checkpoint inhibitors, tested for their functionality and compared with each other. This combination should enable a targeted TNFR activation in tumor tissue, where a high PDL1 expression is frequent and therefore the formation of oligomeric transactivating (TNFSF3-TNFRSF3)2 complexes should only occur there by binding to PDL1-expressing cells. These receptor-ligand complexes are a prerequisite for the agonistic activity of the antibodies. / In dieser Arbeit wurden bispezifische Antikörper durch Kopplung von TNFR-spezifischen Antikörpern mit Checkpoint-Inhibitoren hergestellt, auf ihre Funktionalität getestet und miteinander verglichen. Diese Kombination sollte eine gezielte TNFR-Aktivierung im Tumorgewebe ermöglichen, wo eine hohe PDL1-Expression häufig ist und daher die Bildung oligomerer transaktivierender (TNFSF3-TNFRSF3)2-Komplexe nur dort durch Bindung an PDL1-exprimierende Zellen erfolgen sollte. Diese Rezeptor-Liganden-Komplexe sind eine Voraussetzung für die agonistische Aktivität der Antikörper.

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