Por meio de ensaios em reatores estáticos (em equipamento de jarteste) foram estudados os efeitos da ruptura e da refloculação na sedimentação dos flocos, para diferentes velocidades de sedimentação. A água de estudo foi preparada com substâncias húmicas aquáticas (SHA) extraídas de água coletada do rio Itapanhaú - Bertioga/SP, resultando cor verdadeira de 100 uH, e coagulada com sulfato de alumínio e cloreto férrico. Para os dois coagulantes, foram realizadas as etapas de coagulação, mistura rápida, floculação, ruptura (G=50, 100 e 150/s) e refloculação (G=10 e 20/s). Na sedimentação sem a ocorrência de ruptura o cloreto férrico teve um desempenho superior ao sulfato de alumínio, principalmente nas velocidades de sedimentação mais altas. Isso se deve ao fato da floculação da água coagulada com o cloreto férrico ter gerado flocos de tamanho muito superior aos flocos gerados com o sulfato de alumínio. A ruptura, em poucos segundos, prejudicou a remoção dos flocos por sedimentação. Quanto maior o gradiente de velocidade na ruptura, maiores foram os valores da cor aparente remanescente, mesmo após a refloculação. A refloculação, mesmo nos primeiros minutos, diminuiu a cor aparente remanescente se comparada a logo após a ruptura. O menor gradiente de velocidade durante a refloculação testado (10/s) apresentou menores valores da cor aparente remanescente. Tanto na água coagulada com o sulfato de alumínio quanto na coagulada com o cloreto férrico a refloculação se comportou de modo semelhante, havendo recuperação na eficiência de remoção de cor sem, porém, atingir os resultados obtidos antes da ruptura. / By using the jar test equipment, the effects of breakage and reflocullation on the efficiency of floc sedimentation were studied, using different settling velocities. Water of study was prepared with aquatic humic substances (AHS) extracted from the Itapanhaú river (Bertioga, SP, Brazil), resulting a true color of 100 uH. Coagulation was performed by using aluminum sulfate and ferric chloride. For both coagulants, coagulation, flocculation, breakage (G=50, 100 and 150/s) and reflocculation (G=10 and 20/s) tests were carried out. In the sedimentation without the floc breakage occurrence the ferric chloride had a superior performance to aluminum sulphate, mainly in higher settling velocities. This occurred because of flocculation of the ferric chloride coagulated water have generated higher size flocs than that generated with aluminum sulphate. The breakage of flocs, in few seconds, hindered the settling removal. The higher the average shear rate in the break-up, the higher result the residual turbidity even after the reflocculation. The reflocculation, even in the first minutes, decreased the apparent color if compared to the results just after the break-up and sedimentation. The lower average share rate used during the reflocculation (10/s) resulted lower values of the remaining apparent color. During the flocculation, the aluminum sulphate coagulated water as well as in the ferric chloride coagulated water held in similar way, recovering the efficiency of removal of color without, however, reach the results gotten before the breakage.

Sedan 2012 har UEFA implementerat ett nytt regelverk vid namn Financial Fair Play, där klubblag måste följa denna reglering för att kunna delta i UEFA:s två största turneringar (Champions League och UEFA Europa League). Den större vikten av regleringen har lagts på en regel vid namn break-even rule som innebär att de relevanta kostnaderna inte får överstiga de relevanta intäkterna. Syftet med denna reglering är att förbättra den ekonomiska ställningen inom Europeisk fotboll, samt förbättra konkurrensbalansen i de olika ligorna.    Studiens syfte är att undersöka vilken ekonomisk effekt regleringen haft på fotbollsklubbar i den engelska högstaligan. Vidare är syftet att granska hur klubbarna förhållt sig till Financial fair play och hur klubbarna klarat implementeringen, detta för att se om klubbarna har stärkt deras position i hierarkin och hur konkurrensbalansen i ligan har påverkats. En analys av ekonomiska rapporter har genomförts för de klubblag som deltagit i den Engelska Premier League säsongerna 2005/2006-2014/2015. Den totala populationen för studien blev 36 lag. En totalundersökning har gjorts där studien använt sig av beräkningar som Herfindahl-Hirschman Index, C5 Ratio och Pearsons korrelationskoefficient. Studien har utgått ifrån regleringsteorin public interest theory, den nyinstitutionella teorin med fokus på den tvingande isomorfismen samt contest theory model för att kunna ge svar på studiens frågeställning. Det kan konstateras att lagen i Premier League förbättrat deras ekonomiska ställning efter att regleringen sattes i kraft. Break-even kravet har tvingat lag att ta mer hänsyn till ekonomin, detta kan ha i kombination med andra faktorer resulterat i en bättre ekonomisk utveckling. Vidare kan det konstateras att konkurrensbalansen har förbättrats överlag mellan lagen men samtidigt har den försämrats mellan topp fem och resterande, det vill säga konkurrensbalansen mellan lagen under topp fem har förbättrats. Det går dock inte att fastställa om den ekonomiska utvecklingen samt konkurrensbalansen förändring beror just på FFP.

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease with primary sites of pathology in the large sensory neurons of the dorsal root ganglia (DRG) and dentate nucleus of the cerebellum. FRDA is also often accompanied by severe cardiomyopathy and diabetes mellitus. FRDA is caused by loss of frataxin (FXN) expression, which is due to GAA repeat expansion in intron 1 of the FXN gene. Frataxin is a mitochondrial protein important in iron-sulphur cluster (ISC) biogenesis and in the electron transport chain (ETC). As a consequence of impaired mitochondrial energy metabolism, FRDA cells show increased levels of and sensitivity to oxidative stress, which is known to be associated with genome instability. In this study, we investigated DNA damage/repair in relation to FXN expression via immunostaining of γ-H2AX, a nuclear protein that is recruited to DNA double strand breaks (DSBs). We found FRDA patient and YG8sR FRDA mouse model fibroblasts to have inherently elevated DNA DSBs (1.8 and 0.9 foci/nucleus) compared to normal fibroblasts (0.6 and 0.2 foci/nucleus, in each case P < 0.001). By delivering the FXN gene to these cells with a lentivirus vector (LV) at a copy number of ~1/cell, FXN mRNA levels reached 48 fold (patient cells) and 42 fold (YG8sR cells) and protein levels reached 20 fold (patient cells) and 3.5 fold (YG8sR cells) that of untreated fibroblasts, without observable cytotoxicity. This resulted in a reduction in DNA DSB foci to 0.7 and 0.43 (in each case P < 0.001) in human and YG8sR fibroblasts, respectively and an increase in cell survival to that found for normal fibroblasts. We next irradiated the FRDA fibroblasts (2Gy) and measured their DSB repair profiles. Both human and mouse FRDA fibroblasts were unable to repair damaged DNA. However, repair returned to near normal levels following LV FXN gene transfer. Our data suggest frataxin may be important for genome stability and cell survival by ensuring ISC for DNA damage repair enzymes or may be required directly for DNA DSB repair.

Microbubbles, currently employed in diagnostic ultrasound as a contrast agent, have a potential new application as vehicles for targeted drug delivery, which could revolutionise medicine by eliminating side-effects. A new device is developed which outperforms all existing devices in terms of minimum microbubble size:channel diameter ratio. A numerical model is established to describe the flow behaviour and it is determined that the flow regime and resulting microbubble size are dependent on the ratio of inner- to outer Weber number.

Acute myeloid leukaemia is a heterogeneous disease characterized by uncontrolled proliferation of neoplastic haematopoietic precursor cells, which leads to the disruption of normal haematopoiesis and bone marrow failure. Impaired haematopoiesis is often associated with balanced chromosomal translocations that involve the nucleoporin Nup98 fused to around 30 different partner genes, such as the homeobox genes HOXA9 and PMX1. Nup98-associated AML is characterized by poor prognosis and poor treatment outcome for the patients. The aim of the study was to elucidate the mechanisms underlying chemotherapy-resistance. Previous experiments showed that the expression of Nup98 fusion proteins leads to changes in nuclear organization. Based on these observations, we hypothesize that the expression of Nup98 fusion proteins affect DNA double-strand break (DSB) repair. Our work shows that the expression of Nup98-HoxA9 and Nup98-HHEX in U2OS cells does not induce any DSBs. Further, we examined the repair phenotype of exogenously induced DSBs. Experiments carried out using etoposide (ETO) or neocarzinostatin (NCS) revealed that Nup98 fusion proteins affect non-homologous end joining (NHEJ). The second major DSB repair pathway, homologous recombination (HR), remains unaffected by Nup98 fusion proteins. The repair phenotype showed that at most timepoints analyzed, cells expressing Nup98 fusion proteins present less DSBs that control cells. We further performed single cell gel electrophoresis assays, also called COMET assay. This assay determines the amount of broken DNA at the single cell level. COMET assays showed that cells expressing Nup98-HoxA9 get equally damaged as control cells. Taken together, these results show that Nup98-HoxA9 induces faster DNA repair by affecting NHEJ. Additional experiments, pointed toward a role of p53 in the effect of Nup98 fusion proteins on DSB repair. Monitoring the repair phenotype in a wild-type and p53 depletion background, revealed that the effect of Nup98-HoxA9 on NHEJ is partially p53 dependent. A further search for the potentially implicated factor in the accelerated NHEJ remained inconclusive so far. In conclusion, Nup98-HoxA9 induces accelerated NHEJ in a partially p53-dependent manner. / Option Biologie moléculaire du Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Diploma thesis discusses and summarizes the problematic how ovality effects durability of bended tubes. The work presents an approach to the solution, the experiments concerning change of ovality, changes in the thickness of the distorted cross-section. Final results represent connection between ovality and durability.

The major goal of this dissertation is to enhance software security by provably correct enforcement of in-depth policies. In-depth security policies allude to heterogeneous specification of security strategies that are required to be followed before and after sensitive operations. Prospective security is the enforcement of security, or detection of security violations before the execution of sensitive operations, e.g., in authorization, authentication and information flow. Retrospective security refers to security checks after the execution of sensitive operations, which is accomplished through accountability and deterrence. Retrospective security frameworks are built upon auditing in order to provide sufficient evidence to hold users accountable for their actions and potentially support other remediation actions. Correctness and efficiency of audit logs play significant roles in reaching the accountability goals that are required by retrospective, and consequently, in-depth security policies. This dissertation addresses correct audit logging in a formal framework. Leveraging retrospective controls beside the existing prospective measures enhances security in numerous applications. This dissertation focuses on two major application spaces for in-depth enforcement. The first is to enhance prospective security through surveillance and accountability. For example, authorization mechanisms could be improved by guaranteed retrospective checks in environments where there is a high cost of access denial, e.g., healthcare systems. The second application space is the amelioration of potentially flawed prospective measures through retrospective checks. For instance, erroneous implementations of input sanitization methods expose vulnerabilities in taint analysis tools that enforce direct flow of data integrity policies. In this regard, we propose an in-depth enforcement framework to mitigate such problems. We also propose a general semantic notion of explicit flow of information integrity in a high-level language with sanitization. This dissertation studies the ways by which prospective and retrospective security could be enforced uniformly in a provably correct manner to handle security challenges in legacy systems. Provable correctness of our results relies on the formal Programming Languages-based approach that we have taken in order to provide software security assurance. Moreover, this dissertation includes the implementation of such in-depth enforcement mechanisms for a medical records web application.

Abstract Mutations in BRCA1 and BRCA2 explain only about 20% of familial aggregation of breast cancer, suggesting involvement of additional susceptibility genes. In this study five DNA damage response genes, ATM, ATR, MRE11, NBS1 and RAD50, were considered as putative candidates to explain some of the remaining familial breast cancer risk, and were screened for germline mutations in families displaying genetic predisposition. Analysis of ATM indicated that clearly pathogenic mutations seem to be restricted to those reported in ataxia-telangiectasia (A-T). However, a cancer risk modifying effect was suggested for a combination of two ATM polymorphisms, 5557G>A and IVS38-8T>C, as this allele seemed to associate with bilateral breast cancer (OR 10.2, 95% CI 3.1–33.8, p = 0.001). The relevance of ATM mutations, originally identified in Finnish A-T patients, in breast cancer susceptibility was evaluated by a large case-control study. Two such alleles, 6903insA and 7570G>C, in addition to 8734A>G previously associated with breast cancer susceptibility, were observed. The overall mutation frequency in unselected cases (7/1124) was higher than in controls (1/1107), but a significantly elevated frequency was observed only in familial cases (6/541, p = 0.006, OR 12.4, 95% CI 1.5–103.3). These three mutations showed founder effects in their geographical occurrence, and had different functional consequences at protein level. In ATR no disease-related mutations were observed, suggesting that it is not a breast cancer susceptibility gene. The mutation screening of the Mre11 complex genes, MRE11, NBS1 and RAD50, revealed two novel potentially breast cancer associated alleles: NBS1 Leu150Phe and RAD50 687delT were observed in 2.0% (3/151) of the studied families. The subsequent study of newly diagnosed, unselected breast cancer cases indicated that RAD50 687delT is a relatively common low-penetrance susceptibility allele in Northern Finland (cases 8/317 vs. controls 6/1000, OR 4.3, 95% CI 1.5–12.5, p = 0.008). NBS1 Leu150Phe (2/317) together with a novel RAD50 IVS3-1G>A mutation (1/317) was also observed, both being absent from controls. Loss of the wild-type allele was not observed in the tumors of the studied mutation carriers, but they all showed an increase in chromosomal instability of peripheral T-lymphocytes. This suggests an effect for RAD50 and NBS1 haploinsufficiency on genomic integrity and susceptibility to cancer.

>Magister Scientiae - MSc / The objective of this project is to study the production of Li, Be and B isotopes emitted in the interaction of 12C with 12C at incident energies of 200 and 400 MeV.The energies of these produced fragments were measured with a detector telescope consisting of two silicon detectors at the incident energy of 200 MeV while a third silicon detector was added for the measurements at 400 MeV. / South Africa

During IgH class switch recombination (CSR) in mature B lymphocytes, activation-induced cytidine deaminase (AID) initiates DNA double strand breaks (DSBs) within switch (S) regions flanking different sets of the IgH locus (IgH) constant \((C_H)\) region exons. End-Joining of DSBs in the upstream donor S region (Sm) to DSBs in a downstream acceptor S region \((S_{acc})\) replaces the initial set of \(C_H\) exons, Cm, with a set of downstream \(C_H\) exons, leading to Ig class switching from IgM to another IgH class (e.g., IgG, IgE, or IgA). In addition to joining to DSBs within another S region, AID-induced DSBs within a given S region are often rejoined or joined to other DSBs in the same S region to form internal switch deletions (ISDs). ISDs were frequently observed in Sm but rarely in \(S_{acc}s\), suggesting that AID targeting to \(S_{acc}s\) requires prior recruitment to Sm. To test this hypothesis, we assessed CSR and ISDs in B cells lacking Sm and found that AID frequently targets downstream \(S_{acc}s\) independently of Sm. These studies also led us to propose an alternative pathway of "downstream" IgE class switching that involves joining of DSBs within the downstream \(S\gamma1\) and \(S\epsilon\) regions as a first step before joining of \(S\mu\) to the hybrid downstream S region. To further elucidate the CSR mechanism, we addressed the long-standing question of whether S region DSBs during CSR involves a direction-specific mechanism similar to joining of RAG1/2 endonuclease-generated DSBs during V(D)J recombination. We used an unbiased high throughput method to isolate junctions between I-SceI meganuclease-generated DSBs at a target site that replaces the IgH \(S\gamma1\) region and other genomic DSBs of endogenous origin. Remarkably, we found that the I-SceI-generated DSBs were joined to both upstream DSBs in \(S\mu\) and downstream DSBs in \(S\epsilon\) predominantly in orientations associated with joining during productive CSR. This process required the DSB response factor 53BP1 to maintain the orientation-dependence, but not the overall levels, of joining between these widely separated IgH breaks. We propose that CSR exploits a mechanism involving 53BP1 to enhance directional joining of DSBs within IgH in an orientation that leads to productive CSR.