Das Kernstueck der vorliegenden Arbeit ist die Betonung von kleinen Modulen als Schluesselkomponenten von biologischen Netzwerken. Unter den zahlreichen moeglichen Modulen scheinen besondere diejenigen interessant zu sein, welche die Rueckkopplungen realisieren und in regulatorischen Einheiten auftreten. Prozesse wie Genregulation, Differentiation oder Homeostasis benoetigen haeufig Autoregulation. Auf Grund dessen ist die detaillierte Kenntnis der dynamischen Eigenschaften von kleinen Modulen von groesserem Interesse. Es werden zwei biologische Systeme analysiert. Das erste beschaftigt sich mit dem Zellzyklus, das zweite Beispiel kommt aus der Immunologie und betrifft die Aktivierung von T-Zellen. Beide Modelle, d.h. ihre zugrundeliegende Netzwerke, lassen sich in Untereinheiten mit wohldefinierten Funktionen zerlegen. Diese Module entscheiden ueber das Verhalten des gesamten Netzwerkes. Mit anderen Worten, die von den Modulen getroffenen Entscheidungen, werden von dem gesamten System uebernommen. Bei der Analyse des Modells zum Zellzyklus wurde eine interessante Eigenschaft von gekoppelten Modulen deutlich, die wir dann getrennt behandelt haben. Seriell geschaltete Module mit positiver Rueckkopplung liefern ueberraschende Konstruktionsmoeglichkeiten fuer Systeme mit mehreren stabilen Gleichgewichtslagen. Obwohl nicht alle hier aufgestellten Hypothesen derzeit experimentell ueberpruefbar sind, es kann eine wichtige Aussage getroffen werden. Uebereinstimmende Strukturen und Mechanismen, die in verschiedenen biologischen Systemen vorkommen, bieten uns die Moeglichkeit einer Klassifizierung von biologischen Systemen bezueglich ihrer strukturellen Aehnlichkeiten. / The thesis emphasizes the importance of small modules as key components of biological networks. Especially, those which perform positive feedbacks seem to be involved in a number of regulatory units. Processes like gene regulation, differentiation and homeostasis often require autoregulation. Therefore, detailed knowledge of dynamics of small modules becomes nowadays an important subject of study. We analyze two biological systems: one regarding cell cycle regulation and one immunological example related to T-cell activation. Their underlying networks can be dissected into subunits with well defined functions. These modules decide about the behavior of the global network. In other words, they have decision taking function, which is inherited by the whole system. Stimulated by the cell cycle model and its interesting dynamics resulting from coupled modules, we analyzed the switching issue separately. Serial coupling of positive feedback circuits provides astonishing possibilities to construct systems with multiple stable steady states. Even though, in current stage, no exact experimental proof of all hypotheses is possible, one important observation can be made. Common structures and mechanisms found in different biological systems allow to classify biological systems with respect to their structural similarities.

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Diss. Naturwiss. Bern (kein Austausch). / Mit Sonderdrucken. Literaturverz.

Diss., Naturwissenschaften, Eidgenössische Technische Hochschule ETH Zürich, Nr. 16856, 2006.

Gli obbiettivi di questa tesi di dottorato erano: i) valutare l’effetto di differenti condizioni ambientali sulla biologia ed epidemiologia di isolati di B. cinerea appartenenti alle sub-popolazioni transposa e vacuma, e ii) sviluppare un nuovo modello previsionale per predire il rischio di muffa grigia nei vigneti tra le fasi fenologiche di sviluppo delle infiorescenze e maturazione dei grappoli. Gli effetti della temperatura, durata di bagnatura e umidità relativa sulle infezioni di infiorescenze e bacche di Vitis vinifera sono stati valutati con inoculazioni artificiali di isolati di B. cinerea. Gli effetti della temperatura, attività dell’acqua, umidità relativa e composizione delle bacche di uva sulla germinazione dei conidi, crescita miceliale e produzione di conidi sono stati valutati su substrati artificiali. I risultati evidenziano che la capacità di causare infezioni varia con gli isolati indipendentemente dall’appartenenza alle sub-popolazioni transposa o vacuma. Inoltre, le risposte dei differenti isolati al variare delle condizioni ambientali risultano essere simili. Basandosi sui risultati ottenuti sono state sviluppate equazioni matematiche per spiegare l’effetto dei fattori ambientali sull’incidenza delle infezioni di infiorescenze e bacche, germinazione dei conidi, crescita miceliale e produzione di conidi. Un nuovo modello previsionale è stato sviluppato per predire le infezioni di Botrytis cinerea nei vigneti utilizzando le equazioni sviluppate e seguendo un approccio meccanicistico. Il modello è stato validato per 6 anni (2009-2014) in 13 vigneti localizzati in Italia e Francia. Il nuovo modello risulta essere più completo di quelli proposti finora in letteratura e può essere utilizzato per migliorare le strategie di controllo della muffa grigia nei vigneti. / The aims of this Doctoral work were: i) to investigate the effect of different environmental conditions on biology and epidemiology of B. cinerea strains belonging the two transposon types vacuma and transposa, and ii) develop a new weather-driven mechanistic model in order to predict risk of grey mould in vineyards from early growth of inflorescences to berry ripening. The effect of temperature, wetness duration and relative humidity on infection of Vitis vinifera inflorescences and berries was investigated by artificial inoculation of B. cinerea strains. The effect of temperature, water activity, relative humidity and grape berry composition on conidia germination, colony growth and conidial production was investigated in agar-medium. The results showed that the ability to cause infection was a strain rather than a transposon genotype attribute. Moreover, the general response to different environmental conditions is similar among different B. cinerea strains. Based on these data, equations were developed to account the combined effects of environmental factors on infection incidence, conidia germination, colony growth and conidial production. A new previsional model for Botrytis cinerea infections on grapevine was elaborated using the equations developed and following a mechanistic approach. The model was validated over a 6-year period (2009 to 2014) in 13 vineyards located in different grape-growing areas of Italy and France. The model is more complete than the others proposed in literature and represents an improvement to control grey mould in vineyards.

Abstract Lymphomas are a heterogeneous group of malignancies that arise from lymphatic tissues. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma sub-type. It is an aggressive malignancy with an increasing incidence. The prognosis of DLBCL has improved significantly, but problems also remain. The clinical significance of central nervous system (CNS) relapses has become increasingly important. As secondary CNSL (sCNSL) and primary CNS lymphoma (PCNSL) are known to have poor prognoses; the prevention of sCNSL is of crucial importance. Peripheral T-cell lymphomas (PTCL) are rare neoplasms and include several lymphoma subtypes that possess complex and also overlapping morphological and immunophenotypic characteristics. The identification of different entities has improved, but the biological knowledge remains scarce when compared to DLBCL. The optimal treatment schemas for PTCLs are still lacking and they have long been treated with the same therapies as B-cell lymphomas, mainly with suboptimal treatment results. The aim of this study was to identify poor prognostic markers in DLBCL and PTCLs and potential biological markers for the prediction of DLBCL CNS relapse. The study material included patients with systemic DLBCL without CNS affision (sDLBCL), sCNSL, PCNSL and PTCLs. The expression of epithelial-mesenchymal transition (EMT) transcription factors (TFs), chemokines and their receptors and adhesion-, migration- and inflammatory responses-associated molecules were studied by means of immunohistochemistry. IEM was used to verify the specific subcellular location of the studied molecules. GEP was performed on 12 PTCL samples in order to compare the poor prognosis group with the good prognosis group and on one sDLBCL and one sCNSL sample from the time of primary diagnosis. The EMT TFs were found to be expressed in both DLBCL and PTCLs, where they ultimately proved to have prognostic relevance as well. In PTCLs, these TFs were able to delineate a disease group with a specific gene-expression profile. CXCR4, CXCR5, ITGA10, PTEN and CD44 were found to be differently expressed between DLBCL cases with CNS affision when compared to those without CNS disease. These molecules seem to play a role in the development of CNS relapse and hopefully, if further verified, will lead towards the identification of biological markers for CNS relapse prediction. / Tiivistelmä Lymfoomat ovat heterogeeninen ryhmä imukudossyöpiä, joista diffuusi suurisoluinen B-solulymfooma (DLBCL) on yleisin alatyyppi. Se on aggressiivinen maligniteetti, jonka insidenssi on noussut viime vuosina. DLBCL potilaiden ennuste on parantunut merkittävästi, mutta yhä osa potilaista menehtyy tautiinsa. DLBCL:n keskushermostorelapsin kliininen merkitys on tänä päivänä aiempaa suurempi. Sekundaarisen keskushermostolymfooman (sCNSL) ja primaarin aivolymfooman (PCNSL) ennusteet ovat nykyhoidoilla huonoja, joten keskushermostorelapsin ennaltaehkäiseminen on tärkeää. Perifeeriset T-solulymfoomat (PTCLs) ovat ryhmä harvinaisia neoplasioita, joka sisältää useita eri alatyyppejä, joiden morfologiset ja immunofenotyyppiset ominaisuudet ovat monimuotoisia ja osin päällekkäisiä. Eri entiteettien indentifiointi on parantunut, mutta PTCL:ien biologinen tietämys on yhä DLBCL:aa heikompaa. PTCL:ien optimaalinen hoito ei ole selvillä ja tätä tautiryhmää on pitkään hoidettu samoilla hoidoilla kuin DLBCL:aa, mutta huonommilla hoitotuloksilla. Tutkimuksen tavoitteena oli löytää huonon ennusteen markkereita, joilla myös pystyttäisiin ennustamaan DLBCL:n keskushermostorelapsia. Aineisto koostui DLBCL, sCNSL, PCNSL ja PTCL näytteistä. Immunohistokemiallisilla värjäyksillä tutkittiin epiteliaalis-mesenkymaalisen transition (EMT) transkriptiotekijöitä (TF), kemokiinireseptoreita sekä adheesioon-, migraatioon ja inflammaatioon assosioituja molekyylejä. Immunoelektronimikroskopialla varmennettiin molekyylien lokalisaatio soluissa. Geeniekspressioprofiloinnilla (GEP) verrattiin kahdentoista hyvän ja huonon ennusteen ryhmään kuuluvan PTCL näytteen välisiä geeniekspressioeroja sekä kahden DLBCL potilaan näytteitä, joista toiselle kehittyi keskushermostorelapsi. EMT TF:ien ekspressiota nähtiin DLBCL ja PTCL näytteissä, joissa niillä myös todettiin olevan ennusteellista merkitystä. PTCL:ssa TF:t pystyivät erottelemaan tautiryhmän, jolla oli oma spesifinen geeniekspressioprofiilinsa. CXCR4, CXCR5, ITGA10, PTEN ja CD44 ekspressio oli erilaista systeemisissä DLBCL tapauksissa verrattuna sCNSL tapauksiin. Edellä mainituilla molekyyleillä näyttää olevan oma roolinsa keskushermostotaudin kehittymisessä ja jos nämä tulokset pystytään vahvistamaan tulevissa tutkimuksissa, johtavat ne toivottavasti kohti keskushermostorelapsiriskin tarkempaa tunnistamista.

Thesis (MEd)--Stellenbosch University, 2013. / Bibliography / ENGLISH ABSTRACT: The focus of this study is on Biology teachers in selected Namibian schools. The researcher seeks to understand how Biology teachers implement Environmental Education (EE) as part of the Biology curriculum as is mandated in the curriculum policy. Literature indicates that the EE curriculum and the science curriculum are underpinned by different philosophical and pedagogical perspectives. This prompts the research questions, and the subsequent research reported on in this thesis. During a case study guided by a qualitative interpretive paradigm, Biology teachers and Biology advisory teachers are interviewed about their experiences and actions and invited to make suggestions. In addition curriculum document analysis and observation are used. The data point to the aspects that can facilitate the implementation of EE in the curriculum, However the implementation of EE is associated with many obstacles and challenges. Teachers struggle to implement EE because of an inadequate understanding of EE and its underlying philosophy. Further enhancement of EE will also require the reduction of tensions between policy and practice, logistic barriers, and the gap between EE and science, while increasing the involvement of teachers in curriculum development, collegiality among teachers and principals, teachers and advisory teachers’ knowledge of EE, teachers and advisory teachers’ curriculum understanding and professional support. Teachers cannot achieve the objectives of EE unaided; therefore the establishment of EE co-coordinators in schools is suggested, since schools have failed to implement EE without such support. In addition, it is suggested that activity systems be studied in totality and that boundaries be crossed to enrich the outcome of EE. . Subject advisors are mandated by the government to support teachers experiencing problems, and it is suggested that ideas linked to the activity systems and activity theory be investigated and implemented to solve the problems. This should improve the implementation of EE as part of science teaching in the schools where the study was conducted and in other schools. / AFRIKAANSE OPSOMMING: Die fokus van hierdie studie was op biologie-onderwysers in geselekteerde Namibiese skole. Die navorser probeer om te verstaan hoe biologie-onderwysers Environmental Education (EE) implementeer as deel van die biologie van die kurrikulum wat in die kurrikulum beleid mandaat. Literatuur dui daarop dat die EE kurrikulum en die wetenskap kurrikulum word ondersteun deur "anders" filosofiese en pedagogiese perspektiewe wat die navorsing vrae gevra, en die daaropvolgende projek berig in hierdie tesis. Het egter Biologie-onderwysers se pre-diens onderwys sluit nie EE. Tydens 'n gevallestudie gelei deur 'n kwalitatiewe interpretatiewe paradigma, is biologie-onderwysers en biologie raadgewende onderwysers ondervra oor hul ervarings, aksies en voorstelle. Kurrikulum dokumente is ontleed en waarnemings van onderwysers in klaskamers in Benewens onderhoude en dokument-analise is gebruik. Data dui daarop dat die implementering word omring deur baie struikelblokke en uitdagings. EE is beperk tot opvoeding oor die omgewing en word gelei deur wetenskapsfilosofie. Dit lyk asof daar 'n gebrek aan begrip van EE en sy onderliggende filosofie deur onderwysers. Die meeste onderwysers noem baie struikelblokke as struikelblokke tot die implementering en dit sluit in logistieke hindernisse, en die gaping tussen EE en wetenskap, 'n gebrek van die betrokkenheid van onderwysers in kurrikulumontwikkeling, 'n gebrek van kollegialiteit onder onderwysers en skoolhoofde, gebrek aan onderwysers en raadgewende onderwysers se kurrikulum begrip en professionele ondersteuning. Terwyl, dokument-analise het gewys op die spanning tussen beleid en praktyk. Verdere data wys na die aspekte wat kan ondersteun as die inlywing van EE in die kurrikulum EE implementering, Biologie word gesien as 'n goeie voertuig vir EE, onderwysers benaderings is kennis van leerder, onderwysers se houding teenoor die implementering is positief. Advisory onderwysers kennis van hul algemene verantwoordelikhede, maar hulle lyk nie te verstaan hoe dit is van toepassing in EE weens gebrek aan EE kennis. Onderwysers kan nie die doel bereik sonder hulp, dus die vestiging van EE mede-koördineerders in skole word voorgestel, aangesien skole het misluk EE te implementeer sonder ondersteuning. Daarbenewens word dit voorgestel dat die aktiwiteit stelsels in totaliteit bestudeer word en dat die grense oorgesteek om die uitkoms te verryk. In hierdie verband, vakadviseurs mandaat deur die regering om onderwysers te ondersteun wat hindernisse ervaar, en daar word voorgestel dat die idees gekoppel aan die aktiwiteit en aktiwiteit-teorie ondersoek word en geïmplementeer word om die hindernisse aan te pak. Dit moet EE implementering te verbeter as deel van die wetenskap-onderrig in die skole waar die studie gedoen is.

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