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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.
371

Hydrodynamics of plane liquid jets aimed at applications in paper manufacturing

Söderberg, Daniel January 1999 (has links)
Process industries are in general depending, in one way or the other, on fluid mechanics.Specifically, paper manufacturing, which probably is the dominant processindustry in Sweden, is depending on the flow of cellulose fibres suspended in water.As a part of the process the suspension, consisting of fibres in water, is spread out onor between two moving permeable weaves, i.e. wires. The speed of this is usually 10–30 m/s and the suspension is spread out by a plane jet issuing from a headbox nozzle.It has been show that the conditions in the headbox and jet have a large influence onthe quality of the final paper sheet. Primarily, streaks in the paper sheet are believedto be the result of streamwise streaks in the headbox jet.The thesis is aimed at the flow phenomena which occur in the headbox jet. Theinvestigations have been made with numerical calculations, stability theory and modelexperiments using water, as well as experiments with a real paper machine headboxand fibre suspension. In the thesis an introduction to the hydrodynamics of planeliquid jets is presented together with a description of the paper forming process andthe fluid mechanics of headbox flow.The basic flow and stability of a two-dimensional plane liquid jet has been investigatedby numerical calculations, stability theory and experiments. The calculationsof the laminar basic flow is successfully compared to pitot-tube measurements of thestreamwise velocity profile. By visualisations of the flow it is found that wave disturbanceson the jet has a severe effect on the flow. These waves can be predicted bylinear stability theory, which shows the presence of five convectively unstable modes.These can be divided into three types and by comparison with the experiments thetype of the visible waves is determined. These waves seem to initiate a break-up ofthe jet, which leads to strong streamwise streaks inside the jet.By flow visualisation of headbox flow of an experimental paper machine, togetherwith analysis of the resulting paper structure using the wavelet method the correspondencebetween flow disturbances and paper quality was investigated. It was shownthat the wave instability, which is present on the low Reynolds number water jet, alsocan be found in the real the headbox jet. It is shown that these waves play an importantrole in the dynamics of the headbox jet and also have an influence on the final papersheet. / QC 20100825
372

The Great Indian Growth Puzzle: What Caused a Spike in 2003?

Bindal, Aditya 01 January 2011 (has links)
This paper will employ unit root tests for finding structural breaks endogenously among India’s key macroeconomic aggregate series, as well as their components and subcomponents. The same analysis will be repeated, wherever data are available, for states. The results from these unit root tests will then be used in regression models for national and state level data to understand the causes behind structural breaks. We find that breakpoints cluster around 1982 and 2003 for most series at the national and state level. The services component appears to be a promising candidate for explaining the 2003 structural break in some of the series.
373

A double strand DNA break model of photon and electron relative biological effectiveness

Bellamy, Michael Bruce 03 April 2013 (has links)
The ICRP recommends a radiation weighting factor of one for all low-LET radiation. However, many experimental studies find inconsistencies between low-LET RBE and the ICRP's current radiation weighting factor. Generally, there is evidence that dependence exists between radiation energy and radiation RBE where lower energy radiations tend to have a greater biological effect than higher energy radiation. Specifically, the radiations of tritium and carbon K-shell x-rays have been studied in numerous experiments and the biological effects of both of these radiations are consistently greater than that of Co-60. In this work, the relationship between radiation energy and radiation effect has been investigated with the use of a newly developed double strand break (DSB) yield estimation algorithm. This algorithm makes use of a detailed solenoidal 30 nm DNA chromatin model to describe the radiation-sensitive biological target. In addition to the DNA model, NOREC, an event by event Monte Carlo code, was used in this algorithm to characterize the electron track. As an alternative to the conventional approach of computationally simulating DNA damage by spatial overlay of an electron track on DNA, this algorithm instead focuses on quantifying the distance between ionizations in an electron track and next determining the likelihood that any given ionization pair forms a DSB. The first step of the algorithm involves electron characterization while the second step relies on DNA molecule characterization. By assuming a DSB biological endpoint and determining the DSB yield as a function of electron energy, energy dependent RBE values were estimated for monoenergetic electrons from 10 eV to 1 MeV. Photon RBE values, x-ray RBE values and radionuclide RBE values were also calculated and reported in this work in addition to electron RBE values. Photon RBE values were estimated based upon the electron RBE calculation. Photon RBE values were reported from 1 eV to 10 MeV. In turn, x-ray RBE values were calculated based upon photon values for several tube voltage and filter combinations. Finally, RBE values for over 1000 radionuclides were estimated and reported.
374

Förändring av pappersegenskaper vid lagring under dragspänning

Larsson, Johan, Sonemalm, Annica January 2006 (has links)
Sammanfattning I en pappersrulle är de yttre lagren utsatta för dragspänning. Om det finns variationer i rullens diameter i form av valkar finns det risk för att papperet förlängs irreversibelt i dessa positioner och orsaka slappa stråk. Den deformation som uppstår vid långvarig belastning av papper kallas krypning. Uppgiften i detta arbete var, att på lab., simulera valkar genom att utsätta pappersremsor för konstant dragspänning av olika storlekar. En av frågeställningarna var om egenskapsförändringar kan påvisas när papper utsätts för konstant inspänningskraft under en längre tid. De parametrar som undersökts var töjning, kryphastighet och relaxation, även mätningar på papperets mekaniska egenskaper dragstyrka, brottöjning och dragstyvhet har utförts i detta arbete. De papperskvalitéer som undersöktes var 71g/m2 MG-papper, 80g/m2 optisk liner och 135g/m2 liner. Inspänningskraften som papperet utsattes för motsvarade 10 %, 30 % och 50 % av dragstyrkan hos varje kvalité. Provremsor belastades under ett, fyra och sju dygn, för att sedan relaxeras. Resultaten visar att dragstyrkan och dragstyvheten inte påverkas av att papperet varit utsatt för en inspänningskraft. Däremot blev brottöjningen mindre ju större den irreversibla förlängningen hos papperet var. Samtliga papperskvalitéer relaxerar tillbaka till ursprungslängd efter fyra dygn när belastningen var 10 %. Om belastningen däremot var 30 % och 50 % uppstod en irreversibel förlängning redan efter ett dygn. Vid belastning under sju dygn uppstod permanent förlängning hos samtliga kvalitéer och belastningar utom MG-papper 10 % som relaxerade till ursprungslängd. MG-papper är därmed den papperskvalité som står emot krypning bäst och är på så sätt minst känslig för valkar i pappersrullen. En högre belastning ger en högre kryphastighet och större irreversibel förlängning. För att undvika uppkomsten av slappa stråk bör därför banspänningen som används vid upprullningen av papperet inte vara större än 10 % av dragstyrkan hos papperskvalitén. Hur länge papperet är belastat påverkar också den slutliga irreversibla förlängningen. Det innebär att lagring ökar risken för att slappa stråk kommer att uppstå i efterbearbetningen. / Abstract In a paper roll the outer layers are under tensile stress. If there are variations in the roll diameter there is a risk that the thicker parts of the roll will make the paper elongate more in these regions, because they will be under a higher tensile stress. This may cause baggy webs. The deformation that occurs during a long time under tensile stress is called creep. Experiments have been performed with strips of paper that have been exposed to a constant load and constant climate (50 % RH, 23°C). The properties that have been examined are creep strain, creep rate and relaxation after creep. Studies of tensile strength, tensile stiffness and strain at break have also been made. The paper qualities that have been examined were 71g/m2 MG-paper, 80g/m2 liner and 135g/m2 liner. The paper qualities in this study are exposed to loads that correspond to 10 %, 30 % and 50 % of their tensile strength. The paper strips were under load during 24h, four and seven days. The results in these studies show that tensile strength and tensile stiffness remains the same after the paper has been exposed to a constant load. The strain at break, on the other hand, decreases with increasing irreversible elongation of the paper strips. All paper qualities recover to the initial length after four days under a load of 10 % of the tensile strength. If the load corresponds to 30 % or 50 % of the tensile strength a permanent elongation arose as early as after 24h. After seven days, only the MG-paper recovered to the initial length if the load corresponded to 10 % of the tensile strength. This means that MG-paper is more resistant to creep then the liner qualities. Consequently, MG-paper is the paper quality that is least sensitive to ridges. A higher load gives a higher creep rate and larger irreversible elongation of the paper. To avoid baggy webs to arise, the load should not exceed 10 % of the paper’s tensile strength when winding the paper roll. The time under which the paper is under load also influence the final irreversible elongation. Therefore, to avoid baggy webs the paper roll shouldn’t be stored for too long.
375

Är det dags att byta färg? : Vad tjänar varumärken på att bryta mot etablerade färgnormer?

Romberg, Minna, Johansson Måsén, Petra January 2012 (has links)
Problem: Färg har en stor associativ inverkan hos individer och är därför en viktig faktor vid varumärkesbyggande. Inom olika produktkategorier finns starkt etablerade färgnormer som följs men nu ser vi en utveckling på den svenska marknaden där etablerade färgnormer börjar ifrågasättas. Vi frågar oss vilka fördelar denna normbrottsstrategi har och hur den inverkar på konsumenter. Kanske har färgteorierna spelat ut sin roll och att det är dags för varumärken att bryta mönstret för att nå framgång. Vår frågeställning är således: Hur associerar svenska konsumenter färg till olika känslor, produktkategorier och varumärken? Vad tjänar varumärken på att bryta mot etablerade färgnormer? Syfte: Vi vill studera det glapp som finns mellan rådande färgteorier och det normbrott vi upptäckt på den svenska marknaden. Vi vill skapa en tydligare förståelse för konsumentens färgassociationer samt deras inställning till normbrottet för att undersöka vad varumärken kan tjäna på att avvika från färgnormen. Teori: Vårt teoretiska ramverk består av färgteorier, kommunikationsprocessen samt köpbeslutprocessen. Metod: Mailintervjuer med yrkesverksamma sker i syfte att sätta färg i ett produktperspektiv och vi analyserar meningsinnehållet i denna information för att se hur väl tillämpade färgteorierna är i deras arbetsprocess. Huvudstudien är riktad till potentiella konsumenter bosatta i Sverige och har skett genom ett webbaserat frågeformulär som sker genom ett bekvämlighetsurval. Deduktivt undersöker vi hur respondenterna förhåller sig till teorier om färg.  Del 1 i formuläret består av sluta svarsalternativ och testar vilken av elementarfärgerna respondenten kopplar till en given känsla enligt teorin. Del 2 består av bildfrågor som testar konsumentens förhållande till normbrottet ur ett produktperspektiv. Resultat: I mailintervjuerna med de yrkesverksamma åskådliggjordes en stor medvetenhet om färgteorier och färgens kommunikativa inverkan, färgvalet utgår från de emotionella reaktioner som färg väcker. Del 1 av undersökningen visade ett svagt associativt samband mellan färg och känsla enligt färgteorierna. Färgerna vit och gul hade högst respektive lägst associativt resultat. Det visades inga större skillnader mellan hur kvinnor och män svarat. Resultatet i del 2 visade en särskild benägenhet hos respondenter att välja en normbrytande färgsättning bland elektronikprodukterna. Slutsatser: Det visade sig att få respondenter är villiga att bryta mot färgnormer, vilket talar för tidigare forskning som säger att färgvalen ofta baseras utifrån vad de ska avbilda. Kvinnor och män tenderade att svara på samma sätt i båda delarna av frågeformuläret, vilket får tidigare diskussioner kring färgsättning och kön att kännas förlegad. Däremot valde en äldre åldersgrupp den röda TV:n. Arbete har betydelse då respondenter med heltidsarbete i större utsträckning valde att bryta mot normer. / Issue: Colour has great associative impact on individuals therefore colour plays an important role in brand building. We see a development on the Swedish marketplace where strongly established colour norms that are ruled in diverse product categories start to be called into question. We ask ourselves what benefits a break of norm has and how it affects consumers. Perhaps the theories of colour should be stepped away from and now it is time for brands to break the pattern for success. Our question is therefore: How do Swedish consumers associate colour to different emotions, product categories and brands? What can brands benefit from going against the established colour norms? Purpose: This study examines the existing gap between the current colour theories and the break of norm we have discovered on the Swedish market. We want to create a clearer picture of consumers associations of colour and their attitude to the break of norm in purpose to investigate what brands can benefit from deviating from the color norms. Theoretical framework: Our theoretical framework consists of colour theories, the communication process and the purchase decision process. Methodology: The mail interviews with professionals are done in order to bring suit in a product perspective, we analyze the meaning content of this information to see how well the applied colour theories are in their work process. The main study is aimed at potential consumers residing in Sweden and has been implemented with a web-based questionnaire that takes place through a convenience sample. Deductive, we examine how the respondents relate to theories of colour. Part 1 of the form consists of close-out response options, and test which of the elementary colours the respondent connects to a given emotion of the theory. Part 2 consists of picture questions that test the consumer's relationship to the break of norm from a product perspective. Results: The mail interviews with professionals showed a great awareness of colour theory and the communicative impact of colour. The color choice is based on the emotional responses that colour evokes. Part 1 of the survey showed a slight associative relationship between colour and emotion of the colour theory. The colour white showed the highest associative result and yellow showed the lowest. There were no major differences between how men and women responded. The results in Part 2 showed a particular tendency of respondents to choose a norm breaking colouration among electronic products. Conclusion: It turned out that few respondents were willing to break the colour norms, which points to previous research that says that the colour choices often are based on what they will portray. Women and men tended to respond similarly in both parts of the questionnaire, which make earlier discussions about colour and gender seem antiquated. However, an older age group tended to chose the norm breaking red TV. Employment is important, as respondents with full-time work increasingly chose to violate the norms.
376

Biochemical Characterization Of Saccharomyces cerevisiae Mre11/Rad50/Xrs2 Using Telomeric DNA : A Role For The Endonucleolytic Activity Of Mre11 In Telomere Length Maintenance And Its Regulation By Rad50

Ghosal, Gargi 04 1900 (has links)
Meiotic recombination is a prerequisite for exchange of genetic information in all Sexually reproducing organisms. This process is initiated by the formation of double stranded breaks (DSBs) in DNA followed by homology directed repair. The process is subjected to surveillance mechanisms that control DSB formation and allow for repair of DSBs by halting cell cycle progression. Interestingly, though generation of DSBs is an Essential event in meiosis they are nevertheless regarded as the most lethal forms of DNA damage. If left unrepaired a single DSB can lead to gene deletion, duplication, translocations and missegregation of large chromosome fragments leading to cell death. In Saccharomyces cerevisiae, genetic screens for mutants defective in meiotic recombination led to the identification of a group of genes called the RAD52 epistasis group which includes RAD50, RAD51, RAD52, RAD54, RAD55, RAD57, RAD59, MRE11 and XRS2. A subset of these genes, namely MRE11, RAD50 and XRS2, have been shown by genetic studies to be essential for several nuclear events including sensing DSBs, double strand break repair (DSBR) by homologous recombination (HR) and non homologous end joining (NHEJ), telomere length maintenance, cell cycle activation in response to DSBs, mitotic and meiotic recombination. In vitro, Mre11 displays Mn2+-dependent endonuclease activity on ssDNA, 3'-5' Exonuclease on single- and double-stranded DNA, strand annealing and weak hairpin Opening activities. Mutational analyses have revealed two functional domains in Mre11- Then terminal nuclease domain involved in telomere length maintenance and DSB Processing and the C terminal DNA binding domain involved in DSB formation during Meiosis. Rad50, a 153 kDa protein shares homology with the SMC (Structural Maintenance of Chromosome) family of proteins which are involved in chromosome Condensation and cohesion. It consists of a bipartite N- and C terminal Walker A and Walker B motifs separated by a heptad repeat sequence which folds into an antiparallel Coiled-coil structure. The heptad repeats are separated by a metal binding globular region the Zn hook. Rad50 is an ATP-dependent DNA-binding protein. hRad50 regulates the exonuclease activity of hMre11. Unlike Mre11 and Rad50, which are evolutionarily conserved, Xrs2 is found only in S. cerevisiae and Nbs1 in mammals. Xrs2 appears to be sequence non-specific DNA- binding protein. Xrs2 in yeast or Nbs1 is its counterpart in mammals target Mre11 and Rad50 to the sites of DNA damage and mediate S-phase cell cycle checkpoint activation. Mutations in either one of the MRX subunits results in defects in repair of DSBs, activation of cell cycle checkpoint and shortened telomeres leading to genomic instability. Hypomorphic mutations in MRE11 and NBS1 lead to genetic disorders- A-TLD (ataxia-telangiectasia-like disorder) and NBS (Nijmegen breakage syndrome) respectively, that are phenotypic ally related to AT (ataxia-telangiectasia) caused by mutations in ATM. Patients with AT, A-TLD or NBS syndromes are hypersensitive to radiomimetic agents and are predisposed to cancer. Several lines of evidence suggest that S. cerevisiae strains bearing mre11Δ, rad50Δ or xrs2Δ display shortening of telomeres. Telomeres are the nucleoprotein ends of all linear eukaryotic chromosomes that are important in maintaining the integrity of the genome.Telomeres are comprised of repetitive G rich sequence most of which is double stranded but the extreme 3' end protrudes to form 3' single stranded overhang called the G tail. elopers are essential in preventing end-end fusion of chromosome, are important for chromosome replication, segregation and genome stability. Genetic studies have implicated the MRX complex in both telomerase-dependent and independent telomere length maintenance. Studies have indicated a direct role for S. cerevisiae MRE11 in the proper establishment of telomere end-structure. However, the molecular mechanism of MRX at telomeres is poorly understood. To understand the role(s) of MRX complex at telomeres, it is important to elucidate the biochemical activities of MRX complex as well as its individual subunits on the telomere DNA structures. Since, Mre11 complex is known to function in several processes related to DNA metabolism it becomes imperative to study the function of Mre11 complex on DNA substrates in the context of a given nuclear process. The 3' single trended telomeric sequence is capable of acquiring folded conformation(s) as a mechanism of end protection which is mediated by several telomere-specific and nonspecific ending proteins. In mammals, the 3' ssDNA has been demonstrated to fold into tloop configuration mediated by some of the components of sheltrin protein complex, wherein the ssDNA invades the duplex DNA resulting in the formation of a displacement loop (D loop). Evidence for the formation of t-loop has been shown in vitro with human telomeres. However, the formation of t-loops has not been demonstrated in S. cerevisiae. Nevertheless, there is growing body of evidence which suggests the formation of alternative DNA structures such as G4 DNA at the yeast telomeres. G quadruplexes (G quartets or G4 DNA) are thermodynamically stable structures formed by Hoogsteen base pairing between guanine residues. In a G quartet the four guanine residues are paired, where each guanine residue is an electron acceptor and a donor and stabilized by a metal cation. The presence of G rich motifs at the promoter regions, rDNA, telomeres and recombination hot spots indicate that G4 DNA has important functions in vivo. Although the existence of G4 DNA has been the subject of much debate, the identification of several proteins that promote (Rap1, Hop1, Topo I, TEBPβ), modify and resolve (POT1, TERT, KEM1, GQN1, BLM, WRN, Rte1) G4 DNA, together with the direct visualization of G4 DNA using G4 DNA specific antibodies and RNA interference have provided compelling for the existence of G4 DNA in vivo. To elucidate the function of MRX complex or its individual subunits at telomeres, the biochemical activities of purified MRX complex and its individual subunits on G4 DNA, D loop, duplex DNA and G rich ssDNA has been analyzed in this study. G4 DNA was assembled from S. cerevisiae telomeric sequence. G4 DNA was isolated and its identity was ascertained by chemical probing and circular dichroism. S. cerevisiae MRE11 and XRS2 was cloned and expressed in E. coli BL21 (DE3)plysS. S. cerevisiae RAD50 in pPM231 vector in S. cerevisiae BJ5464 strain was a gift from Dr. Patrick Sung (Yale University). Mre11, Rad50 and Xrs2 were overexpressed and purified to >98% homogeneity. The identity of the proteins was ascertained by Western bloting using polyclonal antibodies. Using purified proteins heterotrimeric MRX and heterodimeric MR and MX protein complexes were formed in the absence of ATP, DNA or Mn2+. The ability of M/R/X to bind to telomeric DNA substrates was studied by electrophoretic mobility shift assays. Mre11, Rad50, Xrs2 and MRX displayed higher binding affinity for G4 DNA over D loop, ss- or dsDNA. MRX bound G4 DNA more efficiently compared to its individual subunits as 10-fold lower concentration of MRX was able to shift the DNA into the protein-DNA complex. The protein-G4 DNA complexes were stable as >0.8 M NaCl as required to dissociate 50% of protein-G4 DNA complexes. Efficient competition by poly(dG), which is known to fold into G4 DNA, suggested that the protein-G4 DNA complex was specific. Competition experiments with tetra-[N-methyl- pyridyl]-porphyrin suggested that M/R/X recognizes distinct determinants and makes specific interactions with G4 DNA. G4 DNA is highly polymorphic and can exist as intramolecular or intermolecular (parallel and antiparallel) structures. High affinity binding of Mre11 to G4 DNA (parallel) over G2' DNA (antiparallel), ss- and dsDNA suggests the existence of parallel G4 DNA structures at the telomeres and that G4 DNA may be the natural substrate for MRX complex in vivo. Telomeres are elongated by telomerase that requires access to the 3' G-tail for its activity. Formation of G4 DNA structures renders the 3' G-tail inaccessible to telomerase thereby inhibiting telomere elongation. To elucidate the functional relevance of high affinity of M/R/X for G4 DNA, the ability of the complex to generate the appropriate DNA structure for telomere elongation has been analyzed. In this study, I considered the possibility that MRX could act as: (a) a helicase that opens up the G4 DNA structures making it accessible to telomerase or (b) as a nuclease that cleaves the G4 DNA generating substrates for telomerase. Helicase assay with Mre11, Xrs2, MX and MRX on G4 DNA and duplex DNA showed no detectable DNA unwinding activity. Interestingly, nuclease assays with Mre11 on G4 DNA showed that Mre11 cleaved G4 DNA in Mn2+-dependent manner and the cleavage was mapped to the G residues at the stacks of G quartets. Mre11 cleaved telomeric duplex DNA in the center of TGTG repeat sequence, G rich ssDNA at 5' G residue in an array of 3 G residues and D loop structure preferentially at the 5' ends at TG residues. Significantly, the endonuclease activity of Mre11 was abrogated by Rad50. Xrs2 had no effect on the endonuclease activity of Mre11. Structural studies on Rad50 and Mre11 showed that binding of ATP by Rad50 positions the Rad50 catalytic domain in close proximity to the nuclease active site of Mre11. In yeast, disruption of ATP binding Walker motifs results in a null phenotype, suggesting that ATP is required for Rad50 functions in vivo. hRad50 is known to regulate the exonuclease activity of hMre11 in the presence of ATP. Therefore, can ATP modulate the effect of S. cerevisiae (Sc) Rad50 on ScMre11? To address this question, I monitored the ATPase activity of Rad50 in the absence or presence of DNA. Rad50 hydrolyzed ATP in a DNA-independent manner; however, ATPase activity was enhanced in the presence of Mre11 and Xrs2. However, Rad50 exhibited a low turnover indicating that ATP could function as a switch molecule. Based on these observations, the effect of ATP on the nuclease activity was examined. The binding of ATP and its hydrolysis by Rad50 attenuated the inhibition exerted by Rad50 on the Mre11 endonuclease activity. Cleavage of G4 DNA, D loop, duplex DNA and ssDNA required ATP hydrolysis, since no cleavage product was observed when ADP or ATPγS was substituted for ATP. This observation was corroborated using a hairpin DNA substrate that mimics a intermediate in VDJ recombination, thereby confirming the generality of regulation of Rad50 on the endonuclease activity of Mre11. Does Rad50 regulate the exonuclease activity of Mre11 as well? To address this question, exonuclease activity of Mre11, MR and MRX on 3' labeled duplex DNA and G4 DNA was assayed. Rad50 had no measurable effect on the exonuclease activity of Mre11. Based on previous studies and my observations, I propose a model for the role of MRX in telomere length maintenance and its regulation by the ATP-binding pocket of Rad50. MRX binds telomeric DNA substrates in a non-productive complex, which is converted to a catalytically active complex upon binding of ATP by Rad50. ATP induces conformational changes, repositioning the complex such that the catalytic site of Mre11 now has access to the substrate. Following cleavage of DNA by Mre11, the release of ADP and inorganic phosphate, generate the cleaved product. The cleaved DNA is now accessible to telomerase or telomere binding proteins. In summary, the data presented in my PhD thesis demonstrates that Mre11 is a structure- and sequence-specific endonuclease. The natural substrate for telomerase is the 3' ssDNA. G quartets at telomeres not only protect the ends from degradation but also make the ends inaccessible for telomerase activity. Genetic studies have shown that cells proficient for telomerase activity but lacking any one of the components of the MRX complex display shortening in telomere length. The ability of Mre11 to cleave G4 DNA at the stacks of G quartets therefore, suggests a mechanism by which the 3' ssDNA is rendered accessible to telomerase or other telomere binding proteins. Yeast telomeres are characterized by the presence of subtelomeric Y' elements proximal to the terminal TG1- 3 repeat sequences. The Y' element has been shown to be amplified by telomerase in a fraction of mutants with short telomeres. The mechanism by which Y' DNA is amplified is unclear. The ability of Mre11 to cleave telomere duplex DNA at the center of TGTG repeats could contribute to the generation of appropriate substrate for elongation by telomerase, thereby contributing to Y' DNA amplification. Telomere length is maintained by homeostasis between processes that contribute to telomere elongation and those that cause attrition in telomeric ends. Overelongated telomeres are brought to wild type telomere size by a unique recombinational single step deletion process termed telomere rapid deletion (TRD). TRD involves invasion of the elongated 3' G tail into the proximal telomeric tract resulting in the formation of the D loop structure. Following branch migration the D-loop is nicked and resolved into a deleted telomere and a circular liner product. Cells deleted for MRE11, RAD50 or XRS2 are deficient in TRD process. It has been hypothesized that Mre11 could be a candidate for cleaving the D-loop structure. The endonuclease activity of Mre11 on D-loop structure, preferentially at the 5' ends at TG residues demonstrated in this study, show that Mre11 could function as the nuclease required to generate the deleted telomere in TRD. MRX complex is involved in several processes involving DNA metabolism. It is important that the activities of the complex are regulated in the in vivo context. Complex formation and the interaction of the individual subunits with nucleotide cofactors and metal ions constitute a mode of regulation. This study shows that Rad50 regulates the endonuclease, but not exonuclease activity of Mre11. The binding of ATP and its hydrolysis by Rad50 brings in the regulatory factor necessary to keep the uncontrolled nuclease activity of MRX in check, thus preventing any deleterious effects on telomere length. Telomere maintenance by telomerase is activated in 80% of cancer cells. Inhibition of telomerase by G quartets provides a new drug targets for potential anti-cancer drugs. It is, therefore, likely that understanding the biological consequences of G quadruplex interactions would provide a better insight in development of therapeutics for cancer.
377

Strömungskarten und Modelle für transiente Zweiphasenströmungen

Zschau, Jochen, Zippe, Winfried, Zippe, Cornelius, Prasser, Horst-Michael, Lucas, Dirk, Rohde, Ulrich, Böttger, Arnd, Schütz, Peter, Krepper, Eckhard, Weiß, Frank-Peter, Baldauf, Dieter 31 March 2010 (has links) (PDF)
Experimente mit neuartigen Messverfahren lieferten Daten über die Struktur von transienten Flüssig-keits-Gas-Strömungen für die Entwicklung und Validierung von mikroskopischen, d.h. geometrieunabhängigen Konstitutivbeziehungen zur Beschreibung des Impulsaustauschs zwischen Flüssig-phase und Gasblasen sowie zur Quantifizierung der Häufigkeit von Blasenkoaleszenz und -zerfall. Hierzu wurde eine vertikale Testsektion der Zweiphasentestschleife MTLoop in Rossendorf genutzt, wobei erstmals Gittersensoren mit einer Auflösung von 2-3 mm bei einer Messfrequenz von bis zu 10 kHz angewandt wurden. Dabei wurde die Evolution von Gasgehalts-, Geschwindigkeits- und Bla-sengrößenverteilungen entlang des Strömungsweges und bei schnellen Übergangsprozessen aufge-nommen und so die für die Modellbildung erforderlichen Daten bereitgestellt. Für den Test der Mo-dellbeziehungen wurde ein vereinfachtes Verfahren zur Lösung der Strömungsgleichungen entlang des Strömungswegs erstellt. Es basiert auf der Betrachtung einer größeren Anzahl von Blasengrö-ßenklassen. Die erhaltenen numerische Lösungen haben erstmals gezeigt, dass der bei Erhöhung der Gasvolumenstromdichte stattfindende Übergang von einer Blasenströmung mit Randmaximum zu einem Profil mit Zentrumsmaximum und anschließend zu einer Pfropfenströmung ausgehend von einem einheitlichen Satz physikalisch begründeter und geometrieunabhängiger Konstitutivgleichun-gen modelliert werden kann. Die Modellbeziehungen haben sich in einem abgegrenzten Gebiet der Volumenstromdichten als generalisierungsfähig erwiesen und sind für den Einbau in CFD-Modelle geeignet. Weiterhin wurden Arbeiten zur Kondensation durchgeführt, die direkten Bezug zu den Kon-densationsmodellen haben, die in Thermohydraulik-Codes enthalten sind. Die Untersuchung liefert darüber hinaus experimentelle Daten für die Modellvalidierung hinsichtlich des Verhaltens und des Einflusses nichtkondensierbarer Gase. Hierfür wurden spezielle Sonden für die Bestimmung der Konzentration und für die Lokalisierung von Pfropfen nichtkondensierbarer Gase entwickelt und bei transienten Kondensationsversuchen in einem leicht geneigten Wärmeübertragerrohr eingesetzt.
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The effect of laser contrast and target thickness on laser-plasma interactions at the Texas Petawatt

Meadows, Alexander Ross 16 February 2015 (has links)
A two-year experimental campaign is described during which diamond-like carbon and plastic targets with thicknesses from 20 nanometers to 15 micrometers were irradiated by the Texas Petawatt Laser. Target composition and thickness were varied to modify the specifics of the laser-matter interaction. Plasma mirrors were selectively implemented to affect the contrast of the laser system and provide additional control of the physical processes under investigation. A number of particle diagnostics were implemented to measure the distribution of laser accelerated ions and electrons. In addition, optical diagnostics were fielded to measure the intensity profile of the laser and measure the density of the target pre-plasma. The results of these experiments suggest that the Texas Petawatt laser pulse has pre-pulse and pedestal features with intensities at least 10⁻⁸ of the main pulse. Micronscale targets were able to survive these features and maintain a relatively sharp density gradient until the arrival of the main laser pulse, allowing for ion acceleration. Electron spectra measured in this configuration show an average temperature of 10 MeV, with no v angular dependence out to at least 60 degrees. By contrast, interferometric plasma density measurements and a lack of any observable ion acceleration suggest that nanoscale targets were destroyed well before the main pulse. In this case, the peak of the laser pulse interacted with a cloud of plasma between 10⁻³ and 10⁻² of critical density. The contrast improvement offered by the implementation of plasma mirrors was seen to increase the maximum energy of laser accelerated protons from targets thicker than 1 micrometer. In addition, the plasma mirrors allowed nanoscale targets to survive pre-pulse and pedestal features and support the production of ion beams. Proton spectra show that ions were accelerated to greater maximum energies from nanoscale targets than from more traditional micron-scale targets. This effect can be attributed to a reduction in the target pre-plasma scale length upon the introduction of plasma mirrors. These results indicate that the manipulation of target properties and laser contrast can significantly affect the interaction between an ultrahigh intensity laser and a target. / text
379

Induktion und Reparatur von DNA-Doppelstrangbrüchen nach kombinierter Einwirkung von Cisplatin und Bestrahlung auf eukaryote Zellen / The induction and repair of DNA double-strand breaks after treating eukaryotic cells with a combination of cisplatin and radiation

Wanke, Friederike 09 August 2010 (has links)
No description available.
380

Etablierung eines Plasmid-basierten Testsystems zur funktionellen Messung der zellulären Doppelstrangbruch-Reparaturfähigkeit in hämatopoetischen Zellen / functional double-strand-break repair analysis in haematopoietic cells

Hermann, Julia 08 March 2011 (has links)
No description available.

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