Riparian vegetation is one of the most complex and abundant ecosystems in the world and it provides important ecosystem services. These services are affected by electricity production from hydropower dams. Hydropower accounts for 16% of the global electricity production and almost 50% in Sweden. One effect of hydropower is sub-daily fluctuations of water level caused by the turbines being turned on and off according to electricity demand. This is referred to as hydropeaking and has largely unknown effects on the fluvial ecosystem, and especially on the riparian vegetation. No studies have been made on the effects of hydropeaking on riparian vegetation. In this study, three native plants (Carex acuta, Betula pubescens and Salix phylicifolia x myrsinifolia) and one non-native plant (Helianthus annuus) were used as indicators (i.e., phytometers) for the effects of hydropeaking along two rivers from northern Sweden; one used for hydropower production and the other free flowing. From each of the four species, seedlings of two sizes and seeds were transplanted into five different river reaches and bank elevations along a hydropeaking gradient from none to high hydropeaking intensity. C. acuta and S. phylicifolia x myrsinifolia showed significant positive relationships to the hydropeaking gradient, likely due to their natural high tolerance to frequent inundation events. Therefore, they are suitable for restoration of river shores along reaches affected by hydropeaking. In contrast, B. pubescens was negatively related to the hydropeaking gradient, losing leaves and biomass with increasing hydropeaking intensities. It turned out to be the most sensitive species among the ones used in the experiment making it suitable as an indicator. H. annuus showed no response and therefore did not serve as impact indicator or for restoration. Germination for all native species was significantly lower along the reaches affected by hydropeaking which indicates a strong connection between hydropeaking and germination. These findings showed that recruitment becomes a bottleneck in riparian communities’ conservation along rivers affected by hydropeaking, and highlight the importance of mitigation actions focused on favoring riparian species seeds’ germination.

Small cell lung cancer (SCLC) is characterised by rapid growth, early metastatic spread and poor long-term survival. The tumour is initially sensitive to chemotherapy and thus objective response rates are high. Unfortunately, this response is often short-lived and SCLC recurs with acquired drug resistance, resulting in early patient death. Despite intensive chemo- and radiotherapy regimes survival has not improved significantly in 20 years. Prior research suggests a critical role for the tumour microenvironment in the pathogenesis of other cancers. Therefore, investigating interactions between SCLC cells and components of the tumour stroma may identify novel therapeutic targets. This thesis demonstrates that extracellular matrix (ECM) proteins present in the tumour microenvironment protect SCLC cells in vitro from chemo- and radiotherapy induced cell cycle arrest and apoptosis via cell surface β1 integrins. Pharmacological and genetic inhibition of phosphoinositol-3 kinase signalling abrogates this effect, defining a central role for this pathway in SCLC de novo drug resistance. Furthermore, the protective effect of ECM occurs without alteration in chemotherapy-induced DNA damage allowing SCLC cells to survive with new genetic defects. Integrin-mediated drug resistance has been shown to be important in other tumours and thus development of strategies to inhibit this pathway may yield new anti-cancer treatments. The design of targeted agents to down-regulate integrin-ECM interaction requires an in depth understanding of the intracellular signals that modulate integrin affinity. Two such pathways are investigated in this thesis. 1) H-Ras, a dominant suppressor of integrin affinity, acts in part through phosphorylation of Erk. Data presented here demonstrate that H-Ras also suppresses integrins through a phospholipase-C epsilon (PLCε)-dependent pathway, thus explaining discrepancies in prior data and confirming a physiological role for this recently identified phospholipase. 2) The Notch signalling pathway has been shown to have important roles in both development and cancer. It is shown here that activation of Notch signalling increases β1 integrin affinity and can protect SCLC cells from chemotherapyinduced apoptosis. However the mechanisms appear to be different; Notch-1 modulates integrin activation through the small GTPase R-Ras and Notch-2 promotes SCLC cell survival. These results define a new Notch pathway, a novel integrin modulator and a potential therapeutic target in SCLC cells. In addition to ECM proteins, the tumour microenvironment contains immune cells that may contribute to cancer growth. The cellular composition of the SCLC stroma is poorly understood. The data presented here indicate that the microenvironment of SCLC is infiltrated by lymphocytes and macrophages, the degree of which independently predicts patient survival. This suggests that the host immune system may be able to suppress SCLC growth. It is well recognised that patients with SCLC have defects in cellular immunity which correlate with survival. An in vitro coculture model was used to investigate the underpinning mechanisms, showing SCLC cells can suppress CD4+ T-cell proliferation and macrophage CD86 expression. Furthermore, preliminary data suggest a role for a soluble factor released by SCLC cells that up-regulates CD4+ T-cell production of IL-10. The work in this thesis implies a complex interaction between SCLC cells, ECM and immune cells in the tumour microenvironment. Manipulation of these pathways may have important therapeutic implications. Further investigation is required to understand the mechanisms of this interplay, which may in part be aided by prospective analysis of patient tumour samples and an in vivo model of SCLC.

Thesis (MA)--University of Stellenbosch, 2001. / ENGLISH ABSTRACT: Suicide is currently one of the leading causes of death in many countries, and is still stigmatized to some extent in some cultures. As bereavement by suicide is a very difficult loss to adjust to, this study aims at creating a better understanding of the adjustment process that survivors of suicide have to go through. The study focuses on the impact of this kind of bereavement on family members and other people touched by the loss of someone to suicide. The needs of the bereaved have to be researched so that a suitable intervention programme can be developed to lessen the severity of the aftermath for survivors of suicide. Supportive aftercare (postvention) may also help prevent further tragedies following in the wake of suicide. The severity and stigma of suicide often contribute to the isolation of nuclear family members in their grief at a time when societal support would have been most helpful. Suicide touches the lives of people of all ages. Some may have special needs such as parents who lose a child to suicide or children whose parent has committed suicide. Better knowledge and understanding of the experiences of these survivors may guide caregivers to assist them with their bereavement and adjustment process as well as assist them in acquiring the necessary coping skills to work through the guilt, fears, anger, regrets and sorrow associated with their tragic loss. A review of the relevant literature is presented with pertinent hypotheses to inform further research to develop a suitable intervention programme for survivors of suicide in the nuclear family. A questionnaire is also presented that may guide interviewing of people affected by suicide in the family. / AFRIKAANSE OPSOMMING: Selfmoord lS tans een van die leidende oorsake van sterfte in baie lande van die wereld. Die verlies van 'n geliefde aan selfmoord is baie moeilik om te verwerk, en hierdie studie beoog om beter begrip vir hierdie proses te bewerkstellig. Daardeur kan die samelewing meer bewus word van die impak van selfmoord op die naasbestaandes van iemand wat as gevolg van selfrnoord gesterf het. Die spesifieke behoeftes van die treurendes moet nagevors word sodat toepaslike intervensieprograrnme uitgewerk kan word, wat kan bydra om die impak van selfmoord op naasbestaandes to help versag. Ondersteuning aan naasbestaandes na selfmoord kan die voorkoms van verdere tragedies in die gesin help voorkom. Die geweldige impak asook die stigma van selfmoord van 'n gesinslid dra dikwels by tot isolasie van die kemgesin tydens hul routydperk,juis terwyl hulle dit die nodigste het. Selfrnoord raak mense van aile ouderdomme, elk met hul eiesoortige behoeftes, soos ouers wie se kind selfmoord gepleeg het of kinders van wie 'n ouer gesterf het as gevolg van selfmoord. Beter kennis en begrip van die ervarings van naasbestaandes kan hulpverleners lei om bedroefdes te help met hul rouproses en aanpassing, asook hulle bystaan om die nodige hanteringsvaardighede te verwerf sodat hulle die samehangende skuldgevoelens, vrese, woe de, berou en verdriet kan verwerk. 'n Oorsig van die toepaslike literatuur word aangebied met pertinente hipoteses om verdere navorsing toe te lig in die ontwikkeling van 'n toepaslike intervensieprogram vir naasbestaandes na selfmoord in die kemgesin. 'n Vraelys word aangebied wat onderhoudvoering met naasbestaandes kan lei.

published_or_final_version / abstract / Economics and Finance / Master / Master of Philosophy

published_or_final_version / abstract / Statistics and Actuarial Science / Master / Master of Philosophy

published_or_final_version / Statistics and Actuarial Science / Master / Master of Philosophy

Cupriavidus metallidurans CH34 est la bactérie Gram négative considérée comme organisme-modèle pour l’étude de la résistance aux métaux lourds. Notre travail a porté sur sa résistance au cuivre, codée par les gènes cop du plasmide pMOL30. Ces gènes, responsables des différentes étapes de la résistance (compartimentation des systèmes d’efflux entre périplasme et cytoplasme, modification de valence, et d’autres fonctions totalement inconnues) ont suscité notre intérêt. On distingue dans l’îlot cop des gènes codant pour des fonctions de résistance proprement dite (essentiellement par détoxication active du cytoplasme et du périplasme). En effet, les mutants de copSRABCD, copF, et dans une moindre mesure copJ et copE deviennent sensibles. Les phénotypes des mutants divergent toutefois suivant que la mutation soit sur un cosmide qui ne porte que l’îlot (pMOL1024) ou dans son plasmide d’origine (pMOL30). Un second groupe de mutants (copVTMK, copG, copL, copQ) se distingue par un phénotype plus résistant ou identique à la souche parente, sauf autour de la CMI. Ces gènes interviendraient donc à la CMI pour assurer la résistance la plus élevée et le maintien d'un état viable latent. La présence de l’îlot cop permet de contenir le taux d’oxygène radicalaire qui reste à un taux basal lorsque les cellules sont adaptées au cuivre environnent. Après un choc de Cu (ou stress aigu), l’îlot cop répond de façon « explosive » au stress, en consommant l’énergie du potentiel membranaire et en augmentant fortement l’activité de la chaîne respiratoire. La résistance au cuivre est inductible, mais de façon différenciée pour la souche sauvage (CH34) et celle qui ne porte qu l’îlot cop (AE1744) : la CMI de CH34 triple après adaptation au cuivre, alors que celle d’AE1744 est inchangée. Après un choc de Cu, la résistance au cuivre est plus fortement induite pour AE1744 que pour CH34. Ces observations suggèrent que l’îlot cop ait été sélectionné pour sa capacité à répondre à un stress aigu puis intégré dans un ensemble de gènes plus vaste qui répond à des impératifs de stress chronique. L’analyse biochimique de CopI, une petite protéine bleue à cuivre, montre qu’elle porte un site analogue à celui des oxydases multicuivre. Son rôle pourrait dès lors être celui d’une réductase multicuivre. La protéine CopK lie de façon très spécifique le Cu(I) et il semble que la liaison du cuivre modifie sa structure. L’analyse écologique a montré que des homologues de copK pourraient être présents dans l’ADN extrait de la terre de biotopes chargés en cuivre, et dans les souches cuprorésistantes qu’on y trouve. La contribution majeure de cette thèse est de montrer que l’effet d’un stress métallique ne se résume pas à deux états physiologiques « mort ou vif ». Il y a lieu de considérer des états transitoires (choc de Cu, adaptation au métal, survie autour de la CMI, persistance) où interviennent des gènes spécifiques dans un ou plusieurs états donnés. Les résultats biochimiques et physiologiques ne nous éclairent pas encore assez sur les interconversions Cu(I)/Cu(II) ni sur les flux de cations notamment vers l'espace extracellulaire. Cette thèse ouvre des perspectives sur des mécanismes (protection à la CMI, phénotype persistant) assurant la survie des bactéries ou leur potentiel de recolonisation lors d'une diminution de la pression toxique : les gènes copT, copV, copK, copM, copB, copG, copL et copQ semblent impliqués dans ces fonctions.

Clustered failure time data often arise in biomedical and clinical studies where potential correlation among survival times is induced in a cluster. In this thesis, we develop a class of marginal models for right censored clustered failure time data and propose a novel generalized estimating equation approach in a likelihood-based context. We first investigate a semiparametric proportional hazards model for clustered survival data and derive the large sample properties of the regression estimators. The finite sample studies demonstrate that the good applicability of the proposed method as well as the substantial efficiency improvement in comparison with the existing marginal model for clustered survival data. Another important feature of failure time data we will consider in this thesis is a possible fraction of cured subjects. To accommodate the potential cure fraction, we consider a proportional hazards mixture cure model for clustered survival data with long-term survivors and develop a set of estimating equations by incorporating working correlation matrices in an EM algorithm. The dependence among the cure statuses and among the survival times of uncured patients within clusters are modeled by working correlation matrices in the estimating equations. For the parametric proportional hazards mixture cure model, we show that the estimators of the regression parameters and the parameter in the baseline hazard function are consistent and asymptotically normal with a sandwich covariance matrix that can be consistently estimated. A numerical study presents that the proposed estimation method is comparable with the existing parametric marginal method. We also extend the proposed generalized estimating equation approach to a semiparametric proportional hazards mixture cure model where the baseline survival function is nonparametrically specified. A bootstrap method is used to obtain the variances of the estimates. The proposed method is evaluated by a simulation study from which we observe a noticeable efficiency gain of the proposed method over the existing semiparametric marginal method for clustered failure time data with a cure fraction. / Thesis (Ph.D, Mathematics & Statistics) -- Queen's University, 2013-01-30 21:23:48.968

This paper uses event history analysis to investigate the effects of relatedness on three different outcomes of corporate venturing, identified as retention, termination, and spin-off. For this purpose, relatedness is defined as the degree to which the venture’s activity matches or overlaps with the parent’s activity. Drawing from literature on relational fit, we argue that highly related ventures would be retained, moderately related ones spun off, and unrelated ones would be probable candidates for termination. However, highly related ventures may be likely to pose internal threat to the parent, and consequently be candidates for termination for political reasons as well. This raises the average level of relatedness of terminated ventures above the average of spin-offs. The empirical findings derived from a sample consisting of 78 ventures launched and developed by a number of companies across the Swedish economy give support to our expectations. The highly related ventures were found to be either terminated or retained, moderately related ones were likely to be spun off, and unrelated ones typically faced termination. This supports our hypothesis that relatedness has an impact on how the internal venture is dealt with. We follow with implications for the practice of corporate venturing management.

Onkologinėmis ligomis suserga vis daugiau žmonių tiek Lietuvoje, tiek pasaulyje. Todėl svarbu išsiaiškinti veiksnius, kurie gali pagerinti ankstyvą diagnostiką, gydymą. Tyrimo tikslas: ištirti, ar IgM klasės specifiniai natūralūs antikūniai endotoksinai sąlygoja ilgesnį asmenų, sergančių gerklų ir ryklės vėžiu, išgyvenamumą Tyrimo uždaviniai: 1) Nustatyti, ar IgMNAE kiekis kraujo serume turi įtakos sergančiųjų gerklų ir ryklės vėžiu išgyvenamumui. 2) Įvertinti vėžio išplitimo stadijos (FIGO) ir IgMNAE kiekio kraujyje įtaką išgyvenamumui3)Ligos išplitimo stadijos (TNM) ir IgMNAE kiekio kraujyje įtaką išgyvenamumui. 4) Ląstelinio imuniteto ir IgMNAE kiekio kraujyje įtaką išgyvenamumui. 5) Iššorinių vėžio rizikos veiksnių (alkoholio ir rūkymo) ir IgMNAE kiekio įtaka išgyvenamumui. Metodai: naudotasi Navikų imunologinės laboratorijos 1988 – 1990 m. darbo žurnalais, Onkologijos institute esančiomis ambulatorinių kortelių ir vėžio registro duomenimis. Rinkti duomenys apie 78 vyrus, sergančius gerklų ir ryklės vėžiu. Duomenų analizė atlikta naudojantis SPSS 17.0 versijos statistiniu duomenų analizės paketu. Skirtumui tarp grupių įvertinti taikytas (Chi-kvadrato) metodas, Kruscal-Wallis H testas. Visoms hipotezėms tikrinti taikytas reikšmingumo lygmuo 0,05. Išgyvenamumo analizė atlikta naudojant Kaplan - Meier metodą. Rezultatai: Asmenims, kurie nerūko ar surūko nedidelį cigarečių kiekį per dieną didesnė galimybė, kad susidarys specifiniai IgMNAE p<0,05. Piktnaudžiaujantiems... [toliau žr. visą tekstą] / Cancer develops more and more people in Lithuania and the world. Therefore important to find out factors that may improve early diagnosis, treatment. The aim of research: To investigate, does the special natural IgM class antibodies to endotoxins leads longer people suffering from larynx and pharynx cancer survival The task of (the) research: 1. to establish, does IgMNAE content in blood affect survival of patients with larynx and pharynx cancer. 2. To assess the spread of cancer stage (FIGO) and IgMNAE content in blood influence to survival. 3. To investigate the of the disease stage (TNM) and IgMNAE content in blood influence to survival. 4.Cellular immunity and IgMNAE in blood influence to survival. 5. Investigate external cancer risk factors (smoking and alcohol) and IgMNAE content in blood influence to survival Methods: Was used tumor immunological laboratories 1988-1990 routine work “Cancer risk and oncological patients immunological researches” magazines, Vilnius University Oncology institute data of existing outpatients and cancer registry, following about: 78 trial men with larynx and pharynx cancer. Data analysis was performed using statistical package for data analysis SPSS version 17.0. To evaluate the difference between the groups used (chi-square) method), Kruscal-Wallis H test with values of p < 0,05 being defined as significant. Survival analysis was performed using the Kaplan-Meier method. Results: For patients with the blood of survival time median equal to... [to full text]