Maintaining replication fork integrity is vital to preserve genomic stability and avoid cancer. Physical DNA damage and altered nucleotide or protein pools represent replication obstacles, generating replicative stress. Numerous cellular responses have evolved to ensure faithful DNA replication despite such challenges. Understanding those responses is essential to understand and prevent or treat replication-associated diseases, such as cancer. Re-priming is a mechanism to allow resumption of DNA synthesis past a fork-stalling lesion. This was recently suggested in yeast and explains the formation of gaps during DNA replication on damaged DNA. Using a combination of assays, we indicate the existence of re-priming also in human cells following UV irradiation. The gap left behind a re-primed fork must be stabilised to avoid replication-associated collapse. Our results show that the checkpoint signalling protein CHK1 is dispensable for stabilisation of replication forks after UV irradiation, despite its role in replication fork progression on UV-damaged DNA. It is not known what proteins are necessary for collapse of an unsealed gap or a stalled fork. We exclude one, previously suggested, endonuclease from this mechanism in UV-irradiated human fibroblasts. We also show that focus formation of repair protein RAD51 is not necessarily associated with cellular sensitivity to agents inducing replicative stress, in rad51d CHO mutant cells. Multiple factors are required for replication fork stability, also under unperturbed conditions. We identify the histone methyltransferase SET8 as an important player in the maintenance of replication fork stability. SET8 is required for replication fork progression, and depletion of SET8 led to the formation of replication-associated DNA damage. In summary, our results increase the knowledge about mechanisms and signalling at replication forks in unperturbed cells and after induction of replicative stress. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Submitted. Paper 2: Submitted. Paper 3: Manuscript. Paper 5: Submitted.

γδ T cells belong to the T cell lineage however they possess some innate like properties. γδ T cells recognize non-peptidic microbial and stress induced self antigens in a non-MHC restricted manner and are proposed to bridge the gap between innate and adaptive immunity. Dendritic epidermal T cells are a prototypic population of intraepithelial γδ T cells in murine skin. Found in the basal layer of epidermis in close contact with Langerhans cells and keratinocytes DETC facilitate vital immunological and physiological processes e.g. wound healing, homeostasis, tumour surveillance and regulation of inflammation. The purpose of this thesis was to elucidate whether γδ T cells and in particular DETC play a role in generation of adaptive immune responses to foreign cutaneous antigen (OVA) in the context of skin grafts. Skin grafting has long been established as a means to test cutaneous and epithelial immunity. To answer this question, γδ T cell knock-out mice (TCRδ-/-), transgenic K5mOva mice and a skin grafting model were used. It is shown in this study that in the absence of γδ in the skin and not in the circulation there is a lower rejection rate of OVA expressing skin grafts. This phenomenon is observed in both freshly placed and well healed grafts. To understand which part of the immune response is affected by the absence of γδ T cells the priming and effector phases of the immune response was examined in TCRδ-/- mice. The priming phase was studied using two approaches: the first approach was to test priming to maximal doses of subcutaneous antigen in conjunction with an adjuvant and the second approach involved testing priming to an antigen in the context of skin grafts (graft priming). Using ELISPOTs and CFSE proliferation assays we found that while administration of OVA in conjunction with an adjuvant (QuilA) via the subcutaneous route results in sufficient priming in γδ T cell knockout mice, cross priming to OVA in the context of - freshly placed and well healed skin grafts is impaired in TCRδ-/- mice. By immunizing TCRδ-/- mice prior to skin grafting or by transferring in vitro primed OT-I cells to RAG-/- mice grafted with K5mOVA or TCRδ-/-OVA skin it was shown that 100% of all OVA grafts are rejected regardless of presence or absence of γδ T cells, concluding that effector phase of the immune response is not affected in this model. The inability of DETC to perform the role of cross presentation leads to the hypothesis that DETC indirectly enhance this process by affecting professional antigen presenting cells (APC) of the skin. Based on the contribution of DETC to wound healing it was hypothesized that the migration of dendritic cells (DCs) from the skin grafts to the lymph nodes may be affected. When this hypothesis was tested using hapten sensitization and congenically marked skin grafts it was shown that migration of DCs from skin grafts is not affected by the absence of DETC. In another hypothesis the co-stimulatory markers CD40 and CD86 were examined on migrating DCs found in the skin draining lymph nodes of grafted mice and it was shown that expression levels of those molecules were lower on DCs from TCRδ-/- grafted mice compared to C57BL/6 control mice. In addition using cytometric bead array, we show that the cytokine milieu in TCRδ-/- skin and skin draining lymph nodes is different from that of wildtype C57 skin and this disparate cytokine profile may be contributing to the less efficient cross priming and graft rejection in TCRδ-/- mice.

One means by which inhibitory control in selective attention may be studied is with the negative priming (NP) procedure. It is widely assumed that children are characterised by reduced capacity for inhibition (Diamond, 2002) and that inhibitory dysfunction is a key characteristic of children and adolescents with ADHD (Barkley, 1997). This should translate into reduced NP effects for these populations. In this dissertation, four studies using the NP procedure find no evidence for reduced inhibitory function in typical children or in adolescents with ADHD. Study 1 examined the magnitude of NP in children compared with adults. An important line of support for the idea that children suffer an inhibitory decrement has been based an empirical report suggesting that conceptual (identity or semantic) NP effects, assumed to reflect the by-product of distractor inhibition, while consistently found in adults are lacking in children (Tipper, Bourque, Anderson, & Brehaut, 1989). In Study 1, the opposite result was found. Study 2 compared NP effects between 7-year-old children and adults while replicating the respective methodologies of the only two studies to explore conceptual NP effects in developmental populations to date (Pritchard & Neumann, 2004, vs. Tipper et al., 1989) to determine the nature of the divergent results between these studies. In Study 2, it was found that distractor inhibition effects are comparable between children and adults when a NP task contains trials in which the distractor stimulus is consistently incongruent with the target stimulus, but that children may be more susceptible than adults to divide attention between target and distractor when a NP task contains a number of trials in which target selection difficulty is reduced. These are critical new findings, highlighting that reduced NP may often relate to methodological artifacts, and when considered in the light of current theories of NP, are also problematic for anti-inhibitory accounts of NP. Having distinguished more definitively the role of inhibition in developmental NP effects, Studies 3 and 4 explored whether the inhibitory process underpinning NP was implicated in young persons with ADHD. To date, evidence for NP in ADHD populations is equivocal. Study 3 found no evidence for a reduced NP effect in ADHD devoid of a corresponding diagnosis. Study 4 found that conduct and oppositional defiant disorders had the potential to confound the evaluation of NP in ADHD. Taken together, results in Studies 1 - 4 parallel very recent results in the literature on NP in older adults and adult psychopathology where presumed reductions of NP in these populations may also be accounted for by methodological artifacts (Buchner & Mayr, in press). It is concluded that NP may reflect a primitive and robust form of inhibitory processing, one that develops early and one that is often the last to deteriorate.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 86-90).

Orientador: Marco Eustáquio de Sá / Banca: Kuniko Iwamoto Haga / Banca: Marcelo Andreotti / Banca: Valdemir Antonio Laura / Banca: Ceci Castilho Custódio / Resumo: O uso de sementes de Brachiaria brizantha tem aumentado, no entanto a qualidade fisiológica das sementes disponibilizadas ao produtor é ainda um fator limitante para um bom desempenho das culturas. O objetivo do trabalho foi verificar os efeitos do condicionamento fisiológico (CF), escarificação química e diferentes períodos de envelhecimento artificial na qualidade fisiológica, superação de dormência e lixiviação de íons no exsudato do teste de condutividade elétrica, em sementes de B. brizantha cv. MG-5 Vitória. O trabalho foi conduzido no Laboratório de Análises de Sementes da Unesp - Campus de Ilha Solteira. O delineamento experimental utilizado foi o inteiramente casualizados e o estudo foi constituído por três experimentos. Experimento 1 - verificou-se o efeito do condicionamento osmótico (CO) com soluções mistas constituídas por Polietileno glicol 8000 + solução com nutriente ou regulador de crescimento ou bioestimulante e associação entres eles. Experimento 2 - verificou-se os efeitos de diferentes períodos de envelhecimento artificial. Experimento 3 - verificou-se os efeitos da escarificação química, diferentes períodos de envelhecimento artificial e CF. Conclui-se que o aumento dos teores de potássio e cálcio nas sementes é proporcionado através do CO com KNO3 e Ca(NO3)2, respectivamente. A escarificação química é um método eficaz para superação de dormência, porém as sementes apresentam menor potencial de armazenamento. A utilização da escarificação com um período curto de exposição à alta temperatura e umidade é eficaz para o aumento da expressão do vigor e superação de dormência das sementes. O CF com KNO3 atua positivamente na qualidade fisiológica das sementes e proporciona menor perda de constituintes celulares. O lixiviado de potássio parece ser um parâmetro adequado para a identificação da qualidade ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The use of Brachiaria brizantha seeds has been increased, yet the physiological quality of seed available to farmer is still a limiting factor for good crop performance. The objective was to investigate the effects of priming, chemical scarification and different periods of artificial aging on physiological quality, dormancy and leaching of ions in the exudate of the electrical conductivity test seeds of B. brizantha cv. MG-5 Vitória. The work was carried out at the Laboratory of Seed Analysis - Unesp Ilha Solteira. The experimental design was completely randomized and the study consisted of three experiments. Experiment 1 - it has the effect of priming mixed solutions consisting of polyethylene glycol 8000 + with nutrient solution or growth regulator or plant growth regulator and association among them. Experiment 2 - it has the effect of different periods of artificial aging. Experiment 3 - it has the effect of chemical scarification, different periods of aging and priming. We conclude that increased levels of potassium and calcium in the seed provided by the priming with KNO3 and Ca(NO3) 2, respectively. Chemical scarification is an effective method for breaking dormancy, but the seeds have a lower storage potential. The use of scarification with a short period of exposure to high temperature and humidity is effective to increase the expression of vigor and dormancy of seeds. Priming with KNO3 acts positively on seed physiological quality and provides lower loss of cellular constituents. The leaching of potassium seems to be a suitable parameter for identifying the physiological quality of seeds scarified B. brizantha / Doutor

abstract: An emerging body of literature suggests that humans likely have multiple threat avoidance systems that enable us to detect and avoid threats in our environment, such as disease threats and physical safety threats. These systems are presumed to be domain-specific, each handling one class of potential threats, and previous research generally supports this assumption. Previous research has not, however, directly tested the domain-specificity of disease avoidance and self-protection by showing that activating one threat management system does not lead to responses consistent only with a different threat management system. Here, the domain- specificity of the disease avoidance and self-protection systems is directly tested using the lexical decision task, a measure of stereotype accessibility, and the implicit association test. Results, although inconclusive, more strongly support a series of domain-specific threat management systems than a single, domain- general system / Dissertation/Thesis / Ph.D. Psychology 2011

Objetivos: O objetivo do nosso estudo foi verificar se a umidificação dos comprimidos com formulação brasileira de misoprostol vaginal aumenta a dilatação cervical antes da aspiração manual por vácuo (AMIU), em comparação com o uso de misoprostol seco nos abortos espontâneos no primeiro trimestre. O objetivo secundário foi verificar se houve correlação entre o pH vaginal e o grau de dilatação cervical usando um comprimido de misoprostol umedecido ou seco. Métodos: Estudo unicêntrico, duplo cego e randomizado, com 46 pacientes com aborto espontâneo de primeiro trimestre foram alocados aleatoriamente para o tratamento com 400 μg de misoprostol seco ou umedecido (com 200 μl de água destilada). Resultados: A dilatação cervical mediana (intervalo) nos grupos úmido e seco foi de 8 mm (6-12 mm) e 7 mm (5-10 mm), respectivamente ( p = 0,06). O tempo médio entre a inserção de misoprostol e a realização do procedimento não diferiu entre os grupos seco (406 min, intervalo 180-550 min) e molhado (448 min, intervalo 180-526 min) ( p = 0,1). Não foi encontrada correlação entre o pH vaginal e a dilatação cervical usando dados continuos ( p = 0.57; r = 0.08; intervalo de confiança de 95% -0.02, 0.3) ou dados dicotômicos (pH ≤5 /> 5, dilatação cervical ≥8 mm ou <8 mm; p = 0,8). Conclusão: Não foi observada diferença na dilatação cervical entre o uso de misoprostol umedecido e não umedecido antes do AMIU. / Objectives: The aim of our study was to ascertain whether moistening the Brazilian formulation of vaginal misoprostol tablets increases cervical dilation before manual vacuum aspiration (MVA), compared with use of dry misoprostol, in first-trimester miscarriage. The secondary objective was to ascertain whether there was any correlation between vaginal pH and the degree of cervical dilation using a moistened or dry misoprostol tablet. Methods: In a single-centre, double-blind, randomised trial, 46 patients with first-trimester miscarriage were randomly allocated to treatment with dry or moistened (with 200 μl distilled water) 400μg of misoprostol. Results: The median (range) cervical dilation in the wet and dry groups was 8 mm (6–12 mm) and 7 mm (5–10 mm), respectively (p=0.06). The median time between misoprostol insertion and carrying out the procedure did not differ between the dry (406 min, range 180–550 min) and wet (448 min, range 180–526 min) groups (p=0.1). No correlation was found between vaginal pH and cervical dilation using continuous data (p=0.57; r=0.08; 95% confidence interval -0.02, 0.3) or dichotomous data (pH ≤5/>5; cervical dilation ≥8 mm or <8 mm; p=0.8). Conclusion: No difference was observed in cervical dilation between moistened and non-moistened misoprostol use prior to MVA.

Det här är ett examensarbete i Informationsdesign med inriktning mot rumslig gestaltning. Syftet med studien är att skapa ett gestaltningsförslag till en utställning som kan bidra till en förståelse för cirkulär ekonomi. Av den anledningen undersöks vilka visuella element som kan stödja denna förståelse. Förslaget är anpassat specifikt till ReTuna Återbruksgalleria, men ska även kunna appliceras i andra miljöer.Studien baseras på teorier och tidigare forskning om cirkulär ekonomi, kognition, visuella representationer, konceptuella modeller, utställningsdesign, material och färg. Metoder som har genomförts är användartest, kvalitativ intervju och rumslig analys. Studien har resulterat i ett gestaltningsförslag för hur cirkulär ekonomi genom rumslig gestaltning kan kommuniceras.

Listeners identify talkers more accurately when they are familiar with both the sounds and words of the language being spoken. It is unknown whether lexical information alone can facilitate talker identification in the absence of familiar phonology. To dissociate the roles of familiar words and phonology, we developed English-Mandarin “hybrid” sentences, spoken in Mandarin, which can be convincingly coerced to sound like English when presented with corresponding subtitles (e.g., “wei4 gou3 chi1 kao3 li2 zhi1” becomes “we go to college”). Across two experiments, listeners learned to identify talkers in three conditions: listeners' native language (English), an unfamiliar, foreign language (Mandarin), and a foreign language paired with subtitles that primed native language lexical access (subtitled Mandarin). In Experiment 1 listeners underwent a single session of talker identity training; in Experiment 2 listeners completed three days of training. Talkers in a foreign language were identified no better when native language lexical representations were primed (subtitled Mandarin) than from foreign-language speech alone, regardless of whether they had received one or three days of talker identity training. These results suggest that the facilitatory effect of lexical access on talker identification depends on the availability of familiar phonological forms.

abstract: Research on priming has shown that a stimulus can cause people to behave according to the stereotype held about the stimulus. Two experiments were conducted in which the effects of elderly priming were tested by use of a driving simulator. In both experiments, participants drove through a simulated world guided by either an elderly or a younger female voice. The voices told the participants where to make each of six turns. Both experiments yielded slower driving speeds in the elderly voice condition. The effect was universal regardless of implicit and explicit attitudes towards elderly people. / Dissertation/Thesis / M.S. Applied Psychology 2012