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Smellie, Melissa. "Molecular and cellular pharmacology of rationally designed PBD dimers." Thesis, University of Portsmouth, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261402.
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Burger, A. M., Paul M. Loadman, D. E. Thurston, R. Schultz, H. H. Fiebig, and Michael C. Bibby. "Preclinical pharmacology of the pyrrolobenzodiazepine (PBD) monomer DRH-417 (NSC 709119)." Italian Society of Chemotherapy and the Italian Federation of Human and Animal Mycopathology, 2007. http://hdl.handle.net/10454/4571.
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noThe pyrrolobenzodiazepine monomer DRH-417 is a member of the anthramycin group of anti-tumor antibiotics that bind covalently to the N2 of guanine within the minor groove of DNA. DRH-417 emerged from the EORTC-Drug Discovery Committee and NCI 60 cell line in vitro screening programs as a potent antiproliferative agent with differential sensitivity towards certain cancer types such as melanoma, breast and renal cell carcinoma (mean IC(50) = 3 nM). DRH-417 was therefore tested for in vivo activity. The maximum tolerated dose (MTD) was established as 0.5 mg/kg given i.p. Marked anti-tumor activity was seen in two human renal cell cancers, one breast cancer and a murine colon tumor model (p<0.01). A selective HPLC (LC/MS) analytical method was developed and plasma pharmacokinetics determined. At a dose of 0.5 mg kg(-1), the plasma AUC was 540 nM h (197.1 ng h ml(-1)) and the peak plasma concentration (171 nM [62.4 ng ml(-1)]) occurred at 30 min., reaching doses levels well above those needed for in vitro antiproliferative activity. Genomic profiling of in vivo sensitive tumors revealed that the latter have an activated insulin-like growth factor signaling pathway.
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Chrisospathis, Aristomenis 1969. "A new approach in blade shape adjustment in PBD-14 design mode." Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/8606.
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Thesis (S.M. and Nav.E.)--Massachusetts Institute of Technology, Dept. of Ocean Engineering, 2001.Includes bibliographical references (leaves 68-70).
The purpose of this study is to develop a more efficient and robust algorithm for adjusting the blade shape as a part of a coupled lifting-surface design/analysis code for marine propulsors developed at MIT, known as PBD-14. The algorithm for adjusting the blade shape in the current version of PBD-14 works satisfactorily in most cases. However, with more complex schemes such as ducted propulsors and/or higher load distributions, the process has to be carefully monitored by the user and the blade surface can develop corrugations in the spanwise direction. A different approach investigated in this study is based on an idea of aligning the blade shape by tracing streamlines. In order to satisfy the kinematic boundary condition, the final blade shape has to exactly match the streamlines of the flow field in which the propeller blade operates. The algorithm that is developed traces streamlines by calculating the total velocity on a grid of points and then exactly fits the blade on this grid of points. Initial tests of this algorithm have demonstrated its robustness by producing accurate blade shapes both in uniform and in more complicated flow fields. Finally, propeller fabrication is investigated, and tolerance issues as well as propeller inspection methods, traditional and modem, are examined. A cost analysis is performed that investigates the economic impact of manufacturing an example propeller according to a certain tolerance system.
by Aristomenis Chrisospathis.
S.M.and Nav.E.
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Hipps, Henry. "Developing a continuous emulsion PBD-Graft-SAN polymerization process: factors for morphology control." Thesis, Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/10973.
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Gamom, Ngounou Ewo Roland Christian. "Déploiement d'applications parallèles sur une architecture distribuée matériellement reconfigurable." Thesis, Cergy-Pontoise, 2015. http://www.theses.fr/2015CERG0773/document.
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Parmi les cibles architecturales susceptibles d'être utilisées pour réaliser un système de traitement sur puce (SoC), les architectures reconfigurables dynamiquement (ARD) offrent un potentiel de flexibilité et de dynamicité intéressant. Cependant ce potentiel est encore difficile à exploiter pour réaliser des applications massivement parallèles sur puce. Dans nos travaux nous avons recensé et analysé les solutions actuellement proposées pour utiliser les ARD et nous avons constaté leurs limites parmi lesquelles : l'utilisation d'une technologie particulière ou d'architecture propriétaire, l'absence de prise en compte des applications parallèles, le passage à l'échelle difficile, l'absence de langage adopté par la communauté pour l'utilisation de la flexibilité des ARD, ...Pour déployer une application sur une ARD il est nécessaire de considérer l'hétérogénéité et la dynamicité de l'architecture matérielle d'une part et la parallélisation des traitements d'autre part. L'hétérogénéité permet d'avoir une architecture de traitement adaptée aux besoins fonctionnels de l'application. La dynamicité permet de prendre en compte la dépendance des applications au contexte et de la nature des données. Finalement, une application est naturellement parallèle.Dans nos travaux nous proposons une solution pour le déploiement sur une ARD d'une application parallèle en utilisant les flots de conception standard des SoC. Cette solution est appelée MATIP (MPI Application Task Integreation Platform) et utilise des primitives du standard MPI version 2 pour effectuer les communications et reconfigurer l'architecture de traitement. MATIP est une solution de déploiement au niveau de la conception basée plate-forme (PBD).La plateforme MATIP est modélisée en trois couches : interconnexion, communication et application. Nous avons conçu chaque couche pour que l'ensemble satisfasse les besoins en hétérogénéité et dynamicité des applications parallèles . Pour cela MATIP utilise une architecture à mémoire distribuée et exploite le paradigme de programmation parallèle par passage de message qui favorise le passage à l'échelle de la plateforme.MATIP facilite le déploiement d'une application parallèle sur puce à travers un template en langage Vhdl d'intégration de tâches. L'utilisation des primitives de communication se fait en invoquant des procédures Vhdl.MATIP libère le concepteur de tous les détails liés à l'interconnexion, la communication entre les tâches et à la gestion de la reconfiguration dynamique de la cible matérielle. Un démonstrateur de MATIP a été réalisée sur des FPGA Xilinx à travers la mise en oe{}uvre d'une application constituée de deux tâches statiques et deux tâches dynamiques. MATIP offre une bande passante de 2,4 Gb/s et une la latence pour le transfert d'un octet de 3,43 µs ce qui comparée à d'autres plateformes MPI (TMD-MPI, SOC-MPI, MPI HAL) met MATIP à l'état de l'artAmong the architectural targets that could be buid a system on chip (SoC), dynamically reconfigurable architectures (DRA) offer interesting potential for flexibility and dynamicity . However this potential is still difficult to use in massively parallel on chip applications. In our work we identified and analyzed the solutions currently proposed to use DRA and found their limitations including: the use of a particular technology or proprietary architecture, the lack of parallel applications consideration, the difficult scalability, the lack of a common language adopted by the community to use the flexibility of DRA ...In our work we propose a solution for deployment on an DRA of a parallel application using standard SoC design flows. This solution is called MATIP ( textit {MPI Application Platform Task Integreation}) and uses primitives of MPI standard Version 2 to make communications and to reconfigure the MP-RSoC architecture . MATIP is a Platform-Based Design (PBD) level solution.The MATIP platform is modeled in three layers: interconnection, communication and application. Each layer is designed to satisfies the requirements of heterogeneity and dynamicity of parallel applications. For this, MATIP uses a distributed memory architecture and utilizes the message passing parallel programming paradigm to enhance scalability of the platform.MATIP frees the designer of all the details related to interconnection, communication between tasks and management of dynamic reconfiguration of the hardware target. A demonstrator of MATIP was performed on Xilinx FPGA through the implementation of an application consisting of two static and two dynamic hardware tasks. MATIP offers a bandwidth of 2.4 Gb / s and latency of 3.43 microseconds for the transfer of a byte. Compared to other MPI platforms (TMD-MPI, SOC-MPI MPI HAL), MATIP is in the state of the art
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Kaliszczak, Maciej. "Rational design of pyrrolobenzodiazepine derivatives." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4923.
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Pyrrolobenzodiazepine (PBD) derivatives interact with the minor-groove of DNA to form mono-adducts (monomers) or cross-links (dimers). They show remarkable activity in vitro and in vivo in a wide range of tumour types and one dimer, SJG-136 is currently in clinical development. Preclinical studies have shown that SJG-136 is a P-gp substrate limiting its anti-tumour activity. The work presented in this thesis identifies key physicochemical properties influencing both the interaction of PBDs with ABC transporters P-gp, MRP1 and BCRP and their growth inhibitory potency. A testable hypothesis for further optimisation of PBDs is proposed. The biological activity of 4 dimers and 12 monomers was assessed using several in vitro models presenting differential expression of ABC transporters. Biological endpoints were the growth inhibitory effect determined using a sulforhodamine B assay and γ-H2AX foci formation. In addition PBD transport was evaluated using a Caco-2 transwell assay. P-gp substrate specificity was restricted to dimers. The MW, the number of (N+O) atoms (>8), a polar surface area (>75 Ǻ2) and hydrogen bonding energy (>10) could discriminate substrates among the PBDs. P-gp polymorphism was also evaluated. The mutation in position 2677 (G/T) was associated with reduced sensitivity to the PBDs. When combined mutations in position 3435/2677 were linked, the transporter abrogated this apparent gain of function. The impact of MRP1 was identified for all dimers and 1/12 monomers. In addition, the cooperative role of glutathione in the resistance mediated by MRP1 to the PBDs was revealed. The presence of a carbonyl moiety at the extremity was shown to discriminate the 7 substrate for MRP1 among the monomers. A structure-activity-relationship study showed that negatively charged (N+O) atoms and a greater number of aromatic rings confer greater dependency to BCRP. BCRP polymorphism was also evaluated. The T482 mutant was associated with an increase in drug transport. The cytotoxicity of the PBDs correlated to the interaction of the DNA as measured by ΔTm. Compounds, being non surface active, with a greater polar surface area and number of aromatic rings and a lower solvent accessible surface area were associated with a greater cytotoxicity. Van-der-waals energy and the electrostatic forces were identified in silico as predictable features involved in the DNA binding. New PBDs were designed and were predicted to be associated with a greater affinity for DNA and with minimal interaction with ABC transporters.
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Hai, Bin. "Development and Implementation of New In Situ Techniques for the Study of Interfacial Phenomena." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1259695728.
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Hawkins, Rachel Marina. "Design, synthesis and biological evaluation of novel PBD-heterocycle and conjugates as potential transcription factor binding inhibitors." Thesis, University College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498774.
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Lobo, Junior Marco Aurélio. "Design para a competitividade no Brasil: o caso do Projeto Design Export." reponame:Repositório Institucional da UnB, 2017. http://repositorio.unb.br/handle/10482/23983.
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Dissertação (mestrado)—Universidade de Brasília, Instituto de Artes, Programa de Pós-Graduação em Design, 2017.Submitted by Raquel Almeida (raquel.df13@gmail.com) on 2017-07-10T20:58:23Z No. of bitstreams: 1 2017_MarcoAurélioLoboJunior.pdf: 2897522 bytes, checksum: a5317ddbbd7608a6c09f80a610a74df4 (MD5)
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O objetivo deste trabalho foi analisar o design para a competitividade internacional de produtos brasileiros, tendo como estudo de caso o Projeto Design Export, da Agência Brasileira de Promoção das Exportações e Investimentos (Apex-Brasil). Desde o início do século XXI percebe-se que o preço competitivo e a alta qualidade do produto não são mais as garantias para manter e conquistar mercados. Destaca-se as contribuições do design para enfrentar esses novos desafios no desenvolvimento de elementos e características que identificam e diferenciam os produtos e serviços das empresas em relação aos seus competidores, tanto no mercado nacional quanto no internacional. Para isso, foi necessário pesquisar: a história recente da competitividade internacional brasileira; o Programa Brasileiro do Design (PBD) e seus resultados e consequências no setor industrial; os principais programas de apoio ao design para o aumento da competitividade, em outros países; e o papel da Apex-Brasil, na inserção do design para o aumento das exportações brasileiras, por meio dos resultados do Projeto Design Export. O trabalho em parceria dos atores envolvidos – designers, empresários, associações setoriais e gestores – esteve diretamente relacionado ao sucesso do processo de gestão do projeto, que proporcionou melhores condições de competição para as empresas exportadoras, pois demonstrou e revelou a importância da utilização do design no processo de desenvolvimento de novos produtos, novas embalagens, novas marcas e novos serviços. Foram 610 empresas brasileiras sensibilizadas para o design, com 144 empresas visitadas e 114 empresas diagnosticadas quanto ao uso do design. Foram contratados 50 escritórios de design, que desenvolveram 108 projetos, em 60 cidades de 7 estados brasileiros. A experiência direta contribuiu para criar uma cultura de inovação entre as empresas brasileiras envolvidas, o que poderá resultar no aumento da excelência da produção industrial brasileira com vistas à exportação e no fomento ao mercado profissional de design e áreas afins.
The aim of the present study is to analyze the role of design in the international competitiveness of Brazilian products, through a case study from the Design Export Project from the Brazilian Trade and Investment Promotion Agency (Apex-Brasil). In the beginning of the 21st century, competitive prices and higher quality of a product were not guarantees of conquering and keeping international markets. Thus, the contributions of design in the development of elements and characteristics must be noted, as they serve to identify and distinguish the companies’ products and services from their competitors. In this context, the first step was the research of four mains issues: the recent story of the Brazilian international competitiveness; the Brazilian Design Program, its results and consequences in the industrial sector; the most important design support programs to improve competitiveness abroad; and the role of the Brazilian Trade and Investment Promotion Agency in the insertion of design in the development of Brazilian exports through the Design Export Project. The partnership between designers, entrepreneurs, trade associations and project managers was directly related with the success of the Project administration, which supplied better competitive conditions to the involved export companies. In such way, the project showed and revealed the importance of using design in the development process of new products, packages, brands and services. Out of 610 companies that were made aware of the importance of design, 144 companies were visited and 144 companies were alerted to the importance of the proper use of design. 50 design agencies were hired, developing 108 projects in 60 cities of 7 Brazilian states. Such direct experience contributed to the creation of a culture of innovation within the companies involved. This culture will possibly result in an increase of the excellence of Brazilian industrial export production, and in the stimulation of the market of design and its related areas.
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Thompson, Thaddeus. "Rheological Study of Linear and Nonlinear Viscoelastic Behavior for Silica-Reinforced Polybutadiene and Polystyrene." University of Akron / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=akron1134566032.
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GONZALEZ, GONZALEZ JUVENAL 629192, and GONZALEZ JUVENAL GONZALEZ. "Detección de éter etílico en mezcla con etanol empleando compuestos poliméricos a base de polivinilpirrolidona (pvp), polibutadieno (pbd) y negro de carbono." Tesis de maestría, Universidad Autónoma del Estado de México, 2016. http://hdl.handle.net/20.500.11799/66101.
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GONZALEZ, GONZALEZ JUVENAL 629192, and GONZALEZ JUVENAL GONZALEZ. "Detección de éter etílico en mezcla con etanol empleando compuestos poliméricos a base de Polivinilpirrolidona (PVP), Polibutadieno (PBD) y Negro de Carbono." Tesis de maestría, UAEM, 2016. http://hdl.handle.net/20.500.11799/66120.
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Stenlund, Anna, Sanna Sjöström, and Cecilia Wännberg. "PRIVACY BY DESIGN likheter och skillnader mellan leverantörer och betällare : En studie med fokus på inställning, kunskap och utmaningar." Thesis, Umeå universitet, Institutionen för informatik, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-148135.
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The EU General Data Protection Regulation (GDPR) replaces the Data Protection Directive 95/46/EC in May 25, 2018. This will generate major changes for organizations that process personal data. Privacy by Design is a requirement in GDPR and a concept that implies that IT systems are designed in such way that personal privacy is protected. By taking early consideration of Privacy by Design in procurement of IT, public organizations can ensure that integrity requirements are met and that privacy is protected. This study aims at studying differences between clients from public sector and IT providers in their knowledge and attitude to the concept Privacy by Design in relation to GDPR. The study is a qualitative study that includes four interviews, two interviews with respondents from public organizations, and two with respondents from IT provider organizations. The interviews were based on an interview guide with a summary of Datainspektionens (2012) checklist for built-in data protection and data protection by default. The result shows that neither the clients nor IT providers in general know much about the concept of Privacy by Design, but they are aware of its principles. All respondents have a positive attitude to the principles of Privacy by Design and believe that the knowledge in their respective operation is generally low and must be raised. Some interesting differences have been shown in this study. One of them is that the IT providers lean towards the client regarding issues in data minimization because the client wear the responsibility, and public organizations tend to collect more personal data than necessary. This contradicts data minimization, which is a core principle of Privacy by Design.
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Saell, Franziska. "Female and male audiences' perception on a plant-based (Vegan) diet after having viewed the documentary film What the Health : How perception on a plant-based diet (Vegan) changes after having watched the documentary film What the Health." Thesis, Högskolan för lärande och kommunikation, Jönköping University, HLK, Medie- och kommunikationsvetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-48296.
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Veganism (or following a PBD) is scientifically proven to be one of the possible answers to the environmental, ethical and health issues our society is currently facing. The documentary film What the Health advocates this claim and presents the tremendous impacts, meat and dairy production and consumption, have on our environment, our personal health and for the people living on our planet. The documentary’s attempt of persuading people to adopt a PBD remained unanswered and was the chosen case-study for this research on audience reception and media effects. The purpose of this research is to provide new empirical data on how the documentary film What the Health changes females’ and males’ perception of a PBD. Using a qualitative method of in-depth interviews, this study aimed to understand how the documentary film What the Health changes females’ and males’ perception of a PBD in times of the 21st century Vegan social movement. Using theoretical insights from the following theories: Framing theory, schema theory, social representation theory, social cognition theory and the concept of hegemonic masculinity, this study aimed to assess whether the documentary film What the Health contributed to perception changes among its audience. And whether gender differences were prominent.The findings of this study indicated perception changes of a PBD among its audience. Preconceptions of Veganism as a social trend or for ethical justifications were changed to understanding people’s individual motivations for attaining such a diet. Overall, no significant gender differences were detected. The social determinant of perceived restrictions within a social context were the most dominant factors of not transitioning to a PBD. Meat is undoubtedly an inherent and substantial part of people’s lives and restricting oneself from it is not perceived to be the answer to environmental, personal health and ethical issues. However, the audience was observed to admire Vegans for their discipline and strength.This study indicated that the documentary film What the Health might have an effect on its audience in the long term, which is proposed as future research respectively.
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Errami, Jalal. "Modelling DNA Hairpins." Lyon, École normale supérieure (sciences), 2007. http://www.theses.fr/2007ENSL0403.
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Les « DNA beacons » sont des molécules composées de simple brins d'ADN dont les deux bouts contiennent des bases complémentaires et auxquels on attache un fluorophore et un quencher. Ainsi, ces deux extrémités peuvent s'assembler pour former un bout de double hélice d'ADN que nous appelons « stem », la partie centrale du brin forme alors une sorte de boucle. On appelle cette structure la configuration en « épingle à cheveux ». Un aspect important de cette structure est qu'elle représente des systèmes simples permettant une étude détaillée de l'assemblage/désassemblage de la double hélice d'ADN. Nous avons développé deux modèles différents pour étudier la thermodynamique et la cinétique de ces systèmes. Le premier est un modèle sur réseau inspiré des modèles utilisés pour l'étude des repliements des protéines. Le deuxième est un modèle qui inclut les ingrédients physiques du premier modèle mais sans la contrainte apportée par le réseau. Il combine la théorie des polymères et le modèle de Peyrard-Bishop et Dauxois (PBD) pour la double hélice. Avec cette nouvelle approche, nous sommes capable de comparer quantitativement nos résultats théoriques avec les résultats expérimentauxDNA beacons are made of short single strands of DNA with terminal regions consisting of complementary base sequences. As a result, the two end-regions can self-assemble in a short DNA double helix, called the stem, while the remaining central part of the strand makes a loop. In this closed configuration, the single strand has the shape of a hairpin. Such hairpin conformations are important in determining the secondary structure of long single strands of DNA or RNA. In this thesis, we have developed two different models in order to study the thermodynamics and the kinetics of such systems. The first one is a planar square lattice model inspired by the lattice models which have been used to study protein folding. The second one includes the physical ingredients of the lattice model but without the constraint of the lattice. It combines polymer theory and the Peyrard-Bishop and Dauxois (PBD) model of DNA melting. With this approach we can compare our results quantitatively with the experimental ones
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Maxwell, Megan Amanda, and n/a. "PEX1 Mutations in Australasian Patients with Disorders of Peroxisome Biogenesis." Griffith University. School of Biomolecular and Biomedical Science, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040219.100649.
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The peroxisome is a subcellular organelle that carries out a diverse range of metabolic functions, including the b-oxidation of very long chain fatty acids, the breakdown of peroxide and the a-oxidation of fatty acids. Disruption of peroxisome metabolic functions leads to severe disease in humans. These diseases can be broadly grouped into two categories: those in which a single enzyme is defective, and those known as the peroxisome biogenesis disorders (PBDs), which result from a generalised failure to import peroxisomal matrix proteins (and consequently result in disruption of multiple metabolic pathways). The PBDs result from mutations in PEX genes, which encode protein products called peroxins, required for the normal biogenesis of the peroxisome. PEX1 encodes an AAA ATPase that is essential for peroxisome biogenesis, and mutations in PEX1 are the most common cause of PBDs worldwide. This study focused on the identification of mutations in PEX1 in an Australasian cohort of PBD patients, and the impact of these mutations on PEX1 function. As a result of the studies presented in this thesis, twelve mutations in PEX1 were identified in the Australasian cohort of patients. The identified mutations can be broadly grouped into three categories: missense mutations, mutations directly introducing a premature termination codon (PTC) and mutations that interrupt the reading frame of PEX1. The missense mutations that were identified were R798G, G843D, I989T and R998Q; all of these mutations affect amino acid residues located in the AAA domains of the PEX1 protein. Two mutations that directly introduce PTCs into the PEX1 transcript (R790X and R998X), and four frameshift mutations (A302fs, I370fs, I700fs and S797fs) were identified. There was also one mutation found in an intronic region (IVS22-19A>G) that is presumed to affect splicing of the PEX1 mRNA. Three of these mutations, G843D, I700fs and G973fs, were found at high frequency in this patient cohort. At the commencement of these studies, it was hypothesised that missense mutations would result in attenuation of PEX1 function, but mutations that introduced PTCs, either directly or indirectly, would have a deleterious effect on PEX1 function. Mutations introducing PTCs are thought to cause mRNA to be degraded by the nonsense-mediated decay of mRNA (NMD) pathway, and thus result in a decrease in PEX1 protein levels. The studies on the cellular impact of the identified PEX1 mutations were consistent with these hypotheses. Missense mutations were found to reduce peroxisomal protein import and PEX1 protein levels, but a residual level of function remained. PTC-generating mutations were found to have a major impact on PEX1 function, with PEX1 mRNA and protein levels being drastically reduced, and peroxisomal protein import capability abolished. Patients with two missense mutations showed the least impact on PEX1 function, patients with two PTC-generating mutations had a severe defect in PEX1 function, and patients carrying a combination of a missense mutation and a PTC-generating mutation showed levels of PEX1 function that were intermediate between these extremes. Thus, a correlation between PEX1 genotype and phenotype was defined for the Australasian cohort of patients investigated in these studies. For a number of patients, mutations in the coding sequence of one PEX1 allele could not be identified. Analysis of the 5' UTR of this gene was therefore pursued for potential novel mutations. The initial analyses demonstrated that the 5' end of PEX1 extended further than previously reported. Two co-segregating polymorphisms were also identified, termed 137 T>C and 53C>G. The -137T>C polymorphism resided in an upstream, in-frame ATG (termed ATG1), and the possibility that the additional sequence represented PEX1 coding sequence was examined. While both ATGs were found to be functional by virtue of in vitro and in vivo expression investigations, Western blot analysis of the PEX1 protein in patient and control cell extracts indicated that physiological translation of PEX1 was from the second ATG only. Using a luciferase reporter approach, the additional sequence was found to exhibit promoter activity. When examined alone the -137T>C polymorphism exerted a detrimental effect on PEX1 promoter activity, reducing activity to half that of wild-type levels, and the -53C>G polymorphism increased PEX1 promoter activity by 25%. When co-expressed (mimicking the physiological condition) these polymorphisms compensated for each other to bring PEX1 promoter activity to near wild-type levels. The PEX1 mutations identified in this study have been utilised by collaborators at the National Referral Laboratory for Lysosomal, Peroxisomal and Related Genetic Disorders (based at the Women's and Children's Hospital, Adelaide), in prenatal diagnosis of the PBDs. In addition, the identification of three common mutations in Australasian PBD patients has led to the implementation of screening for these mutations in newly referred patients, often enabling a precise diagnosis of a PBD to be made. Finally, the strong correlation between genotype and phenotype for the patient cohort investigated as part of these studies has generated a basis for the assessment of newly identified mutations in PEX1.
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Maxwell, Megan Amanda. "PEX1 Mutations in Australasian Patients with Disorders of Peroxisome Biogenesis." Thesis, Griffith University, 2004. http://hdl.handle.net/10072/366184.
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The peroxisome is a subcellular organelle that carries out a diverse range of metabolic functions, including the b-oxidation of very long chain fatty acids, the breakdown of peroxide and the a-oxidation of fatty acids. Disruption of peroxisome metabolic functions leads to severe disease in humans. These diseases can be broadly grouped into two categories: those in which a single enzyme is defective, and those known as the peroxisome biogenesis disorders (PBDs), which result from a generalised failure to import peroxisomal matrix proteins (and consequently result in disruption of multiple metabolic pathways). The PBDs result from mutations in PEX genes, which encode protein products called peroxins, required for the normal biogenesis of the peroxisome. PEX1 encodes an AAA ATPase that is essential for peroxisome biogenesis, and mutations in PEX1 are the most common cause of PBDs worldwide. This study focused on the identification of mutations in PEX1 in an Australasian cohort of PBD patients, and the impact of these mutations on PEX1 function. As a result of the studies presented in this thesis, twelve mutations in PEX1 were identified in the Australasian cohort of patients. The identified mutations can be broadly grouped into three categories: missense mutations, mutations directly introducing a premature termination codon (PTC) and mutations that interrupt the reading frame of PEX1. The missense mutations that were identified were R798G, G843D, I989T and R998Q; all of these mutations affect amino acid residues located in the AAA domains of the PEX1 protein. Two mutations that directly introduce PTCs into the PEX1 transcript (R790X and R998X), and four frameshift mutations (A302fs, I370fs, I700fs and S797fs) were identified. There was also one mutation found in an intronic region (IVS22-19A>G) that is presumed to affect splicing of the PEX1 mRNA. Three of these mutations, G843D, I700fs and G973fs, were found at high frequency in this patient cohort. At the commencement of these studies, it was hypothesised that missense mutations would result in attenuation of PEX1 function, but mutations that introduced PTCs, either directly or indirectly, would have a deleterious effect on PEX1 function. Mutations introducing PTCs are thought to cause mRNA to be degraded by the nonsense-mediated decay of mRNA (NMD) pathway, and thus result in a decrease in PEX1 protein levels. The studies on the cellular impact of the identified PEX1 mutations were consistent with these hypotheses. Missense mutations were found to reduce peroxisomal protein import and PEX1 protein levels, but a residual level of function remained. PTC-generating mutations were found to have a major impact on PEX1 function, with PEX1 mRNA and protein levels being drastically reduced, and peroxisomal protein import capability abolished. Patients with two missense mutations showed the least impact on PEX1 function, patients with two PTC-generating mutations had a severe defect in PEX1 function, and patients carrying a combination of a missense mutation and a PTC-generating mutation showed levels of PEX1 function that were intermediate between these extremes. Thus, a correlation between PEX1 genotype and phenotype was defined for the Australasian cohort of patients investigated in these studies. For a number of patients, mutations in the coding sequence of one PEX1 allele could not be identified. Analysis of the 5' UTR of this gene was therefore pursued for potential novel mutations. The initial analyses demonstrated that the 5' end of PEX1 extended further than previously reported. Two co-segregating polymorphisms were also identified, termed –137 T>C and –53C>G. The -137T>C polymorphism resided in an upstream, in-frame ATG (termed ATG1), and the possibility that the additional sequence represented PEX1 coding sequence was examined. While both ATGs were found to be functional by virtue of in vitro and in vivo expression investigations, Western blot analysis of the PEX1 protein in patient and control cell extracts indicated that physiological translation of PEX1 was from the second ATG only. Using a luciferase reporter approach, the additional sequence was found to exhibit promoter activity. When examined alone the -137T>C polymorphism exerted a detrimental effect on PEX1 promoter activity, reducing activity to half that of wild-type levels, and the -53C>G polymorphism increased PEX1 promoter activity by 25%. When co-expressed (mimicking the physiological condition) these polymorphisms compensated for each other to bring PEX1 promoter activity to near wild-type levels. The PEX1 mutations identified in this study have been utilised by collaborators at the National Referral Laboratory for Lysosomal, Peroxisomal and Related Genetic Disorders (based at the Women's and Children's Hospital, Adelaide), in prenatal diagnosis of the PBDs. In addition, the identification of three common mutations in Australasian PBD patients has led to the implementation of screening for these mutations in newly referred patients, often enabling a precise diagnosis of a PBD to be made. Finally, the strong correlation between genotype and phenotype for the patient cohort investigated as part of these studies has generated a basis for the assessment of newly identified mutations in PEX1.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
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Jarrett, John M. "Synthesis and In-Vitro Cell Viability/Cytotoxicity Studies of Novel Pyrrolobenzodiazepine Derivatives." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/honors/361.
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Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no more than three to four synthetic steps, beginning with commercially obtainable L-proline and isatoic anhydride. The MTT assay, which is a colorimetric assay that uses 3-(4,5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) to assess cell metabolic activity, was initially implimented to test the in vitro cytotoxicity of the compounds using multiple cell lines, namely: SKBR-3, MCF-7, SKMEL-2, CaCo 2, HCT 116, and Mia Paca. Nearly all of the compounds decreased the cell viability of MCF-7 by roughly 20%. Additionally, the anti-proliferative activity of the PBD products were further evaluated by the NCI-60 Human Tumor Cell Lines Screen, which is a part of the National Cancer Institute’s Development Therapeutics Program - Drug Synthesis and Chemistry Branch.
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Söderström, Gunilla. "On the combustion and photolytic degradation products of some brominated flame retardants." Doctoral thesis, Umeå University, Chemistry, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-107.
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Many modern products, especially electronic goods, are protected by brominated flame retardants (BFR). Some of the most common flame retardants are polybrominated diphenylethers (PBDE), tetrabromobisphenol-A (TBBP-A) and hexabromocyclododecane (HBCD). These compounds have been found in environmental samples and shown to have physiological effects on experimental animals. This thesis considers end-of-life aspects of brominated flame retardants. When spread in the environment, these compounds may be degraded into other forms. For example, if sludge contaminated with PBDE is used as an agricultural fertilizer, the PBDE could be degraded by sunlight to species of PBDE with lower degree of bromination and, to some extent, also form polybrominated dibenzofurans (PBDF). In addition, PBDF and polybrominated dibenzo-p-dioxins (PBDD) are formed during combustion of brominated flame retardants. When waste products with brominated flame retardants are co-combusted with household waste or other chlorinated fuel, polybrominated- chlorinated dibenzo-p-dioxins (PBCDD) and polybrominated- chlorinated dibenzofurans (PBCDF)will be formed. The bromin/chlorine composition of dioxins and furans is dependent on the bromine/chlorine ratio in the fuel, but the types of brominated flame retardants that are being combusted is less important. In the studies reported here, bromine levels higher than "normal" for household waste has been used. The results show that there is a pronounced increase in total dioxin levels in fluegas when when bromine is present, implying that waste containing brominated flame retardants should only be incinerated at combustion plants with effecient air pollution control devices.
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Mingle, David. "Synthesis, Characterization and Biological Evaluation of Novel (S,E)-11-[2-(Arylmethylene) Hydrazono] Pyrrolo [2,1-c] [1,4] Benzodiazepine Derivatives." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etd/3596.
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Pyrrolo [2,1-c] [1,4] benzodiazepine (PBD) is a class of natural products obtained from various actinomycetes which have both anti-tumor and antibiotic activities and can bind to specific sequences of DNA. PBD-dilactam was initially produced using isatoic anhydride and (L)-proline which was then converted to the PBD-thiolactam using Lawesson's reagent. Reaction of thiolactam with hydrazine in ethanol afforded PBD-11-hydrazinyl. Condensation of 11-hydrazinyl PBD with aldehydes possessing various substitutions was performed to obtain (S,E)-11-[2-(arylmethylene) hydrazono] pyrrolo [2,1-c] [1,4] benzodiazepine derivatives. 1HNMR, 13C-NMR, DEPT, IR, GC-MS and X-ray crystallography were used for the characterization. Inhibition activity of the products were carried out using TEM-1, AmpC and P99 β-lactamases. A minimal inhibition growth of 25% was observed for one of the selected PBDs on cancer cell line. A promising result was observed on preliminary cannabinoid binding activity test on one of the compounds.
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Wilkinson, Gary P. "Pharmacological characterisation of selected pyrrolobenzodiazepines as anti-cancer agents. Pharmacokinetic and pharmacodynamic characterisation of the pyrrolobenzodiazepine dimer SJG-136 and the monomers D709119, MMY-SJG and SJG-303." Thesis, University of Bradford, 2004. http://hdl.handle.net/10454/12542.
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This study aimed to investigate the pharmacology of selected pyrrolobenzodiazepine (PBD) compounds shown to have cytotoxic activity with predicted DNA sequence selectivity. Research focused upon the PBD dimer, SJG-136, selected for clinical trials, and the novel PBD monomer compounds D709119, MMY-SJG and SJG-303.
SJG-136, a novel sequence-selective DNA minor groove cross-linking agent, was shown to have potent tumour cell type selective cytotoxicity in in vitro assays. Pharmacokinetic studies in mice via both the i.p. and i.v. route (dosed at the maximum tolerated dose (MTD)) showed that SJG-136 reaches concentrations in plasma well in excess of the in vitro IC50 values for 1 h exposure, and was detected in tumour and brain samples also above the in vitro IC50 values. Furthermore, SJG-136 showed linear pharmacokinetics over a 3-fold drug dose range. Metabolism studies showed SJG-136 is readily metabolised in vitro by hepatic microsomes, predominantly to a monodemethylated metabolite; this metabolite could be detected in vivo. Analytical method development work was also conducted for the imminent Phase I clinical trial of SJG-136 resulting in a sensitive and selective bio-analytical detection protocol. Comet analysis showed that SJG-136 dosed at the MTD and ⅓MTD causes significant interstrand DNA cross-linking in lymphocytes in vivo. In vitro studies demonstrated that SJG-136 localises within the cell nucleus, and acts to disrupt cell division via a G2/M block in the cell cycle at realistic concentrations and exposure times that are achievable in vivo.
In vivo pharmacokinetic studies of D709119 showed the compound is easily detectable in mouse plasma following i.p. dosing at the MTD, but could not be detected in either tumour or brain samples. In vitro cytotoxicity studies revealed D709119 to have potent activity across a selection of tumour cell lines.
SJG-136, D709119, MMY-SJG, SJG-303 and DC-81 demonstrated a non-enzyme-catalysed reactivity with the biologically relevant thiol, reduced glutathione (GSH). Studies demonstrated that reactivity of the PBD compounds toward GSH was dependent on GSH concentrations. At levels of GSH found in plasma, the PBD compounds showed considerably lower reactivity with GSH than at intracellular GSH levels.
SJG-136 and D709119 also showed favourable pharmacokinetic profiles in mice, and warrant further study for anti-tumour activity in vivo and progression to use in patients.
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Follet-Houttemane, Claudine. "Les Phases oxyfluorées du système BiO-Pbo-PbF stabilité-propriétés électriques, caractéristiques structurales /." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb376051434.
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Magnusson, Wilhelm. "The EU General Data Protection Regulations and their consequences on computer system design." Thesis, KTH, Skolan för datavetenskap och kommunikation (CSC), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-213025.
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As of writing this thesis, the EU’s new data protection laws (GDPR) will start to apply within one year. The new regulations are poorly understood by many and rumours of varying accuracy are circling the IT industry. This thesis takes a look at the parts of the GDPR concerning system design and architecture, clarifying what they mean and their consequences for system design. The new regulations are compared to the old data protection laws (Directive 95/46/EC), showing how companies must alter their computer systems in order to adapt. Using evaluations of the old data protection laws predictions are made for how the GDPR will affect the IT industry going forward. One of the more important questions are what tools are available for companies when adapting to privacy protection regulations and threats. This thesis aims to identify the most common processes for this kind of system modification and compare their effectiveness in relation to the GDPR.Vid framställningen av denna avhandling är det mindre än ett år innan EUs nya dataskyddsförordning (GDPR) träder i kraft. Många har bristande förståelse av de nya förordningarna och rykten av varierande korrekthet cirkulerar inom IT industrin. Denna avhandling utför en kritisk undersökning utav de delar inom GDPR som berör system design och arkitektur och beskriver dess innebörd för system design. De nya lagarna jämförs med de föregående dataskyddslagarna (Direktiv 95/46/EC) för att påvisa de modifikationer som kommer krävas för att anpassa datorsystem till de nya förordningarna. Genom att undersöka de äldre dataskyddslagarnas effekt på industrin görs även förutsägelser kring hur GDPR kommer påverka IT industrin inom den närmaste framtiden. Än av de intressantare frågorna är vilka metoder som finns tillgängliga för att underlätta systemanpassningar relaterade till dataskyddsförordningar. Denna avhandling syftar att identifiera de mest etablerade av dessa typer av processer och jämföra deras lämplighet i förhållande till GDPR.
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Wilkinson, Gary Paul. "Pharmacological characterisation of selected pyrrolobenzodiazepines as anti-cancer agents : pharmacokinetic and pharmacodynamic characterisation of the pyrrolobenzodiazepine dimer SJG-136 and the monomers D709119, MMY-SJG and SJG-303." Thesis, University of Bradford, 2004. http://hdl.handle.net/10454/12542.
Full textAbstract:
This study aimed to investigate the pharmacology of selected pyrrolobenzodiazepine (PBD) compounds shown to have cytotoxic activity with predicted DNA sequence selectivity. Research focused upon the PBD dimer, SJG-136, selected for clinical trials, and the novel PBD monomer compounds D709119, MMY-SJG and SJG-303. SJG-136, a novel sequence-selective DNA minor groove cross-linking agent, was shown to have potent tumour cell type selective cytotoxicity in in vitro assays. Pharmacokinetic studies in mice via both the i.p. and i.v. route (dosed at the maximum tolerated dose (MTD)) showed that SJG-136 reaches concentrations in plasma well in excess of the in vitro IC50 values for 1 h exposure, and was detected in tumour and brain samples also above the in vitro IC50 values. Furthermore, SJG-136 showed linear pharmacokinetics over a 3-fold drug dose range. Metabolism studies showed SJG-136 is readily metabolised in vitro by hepatic microsomes, predominantly to a monodemethylated metabolite; this metabolite could be detected in vivo. Analytical method development work was also conducted for the imminent Phase I clinical trial of SJG-136 resulting in a sensitive and selective bio-analytical detection protocol. Comet analysis showed that SJG-136 dosed at the MTD and ⅓MTD causes significant interstrand DNA cross-linking in lymphocytes in vivo. In vitro studies demonstrated that SJG-136 localises within the cell nucleus, and acts to disrupt cell division via a G2/M block in the cell cycle at realistic concentrations and exposure times that are achievable in vivo. In vivo pharmacokinetic studies of D709119 showed the compound is easily detectable in mouse plasma following i.p. dosing at the MTD, but could not be detected in either tumour or brain samples. In vitro cytotoxicity studies revealed D709119 to have potent activity across a selection of tumour cell lines. SJG-136, D709119, MMY-SJG, SJG-303 and DC-81 demonstrated a non-enzyme-catalysed reactivity with the biologically relevant thiol, reduced glutathione (GSH). Studies demonstrated that reactivity of the PBD compounds toward GSH was dependent on GSH concentrations. At levels of GSH found in plasma, the PBD compounds showed considerably lower reactivity with GSH than at intracellular GSH levels. SJG-136 and D709119 also showed favourable pharmacokinetic profiles in mice, and warrant further study for anti-tumour activity in vivo and progression to use in patients.
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Ellis, Cameron B. "Tribopairs in Wellbore Drilling: A Study of PCD Tilting Pad Bearings in an Electric Submersible Pump." BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/7233.
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A polycrystalline diamond was tested as a bearing material for a tilting pad thrust bearing to be used in an electric submersible pump, which elevates process fluids from the bottom of well bores. The goal of this study was to compare the PCD to a current best of technology, which is stainless steel with an engineering polymer.This study found that PCD can handle larger loads than current technology but is limited in size due to diamond sintering and manufacturing constraints. The maximum size is Ø75mm.
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Renner, Annelies. "Mise au point de tests "preuve de principe" pour l'étude des inhibiteurs de la Plk1 et caractérisation de la Plk1 en tant que cible dans le traitement des leucémies aigües myéloïdes." Toulouse 3, 2008. http://thesesups.ups-tlse.fr/430/.
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La Polo-like kinase1 (Plk1) est un régulateur mitotique majeur, surexprimé dans différents cancers et souvent associé à un mauvais pronostic. D'un point de vue expérimental, l'expression constitutive de la Plk1 dans des cellules NIH 3T3 entraîne leur transformation et leurs confère la capacité à former des tumeurs chez des souris athymiques. De plus, la déplétion de Plk1 dans des cellules cancéreuses induit souvent leur apoptose. Plk1 est donc une cible potentielle très étudiée dans le cadre des thérapies anti-cancéreuses. L'un des objectifs de ma thèse a été de générer des outils moléculaires et cellulaires afin de mettre au point des tests "preuve de principe" rendant compte de l'activité d'inhibiteurs de Plk1. La construction de ces outils avait également pour objectif de mieux appréhender le rôle de Plk1 dans les différentes étapes de la division cellulaire, et de rechercher de nouveaux substrats et partenaires de cette kinase. Des lignées cellulaires inductibles permettant l'expression de la Plk1 sauvage et de différents mutants (inactifs, suractivés) ont été construites. L'effet de l'induction de ces diverses formes de Plk1 sur la prolifération, la répartition des cellules dans le cycle et les substrats de la kinase a été étudié. Comme attendu, plus la protéine est active, plus l'effet sur ces paramètres est marqué. Divers inhibiteurs de Plk1 ont été testés sur ces modèles cellulaires avec, in fine, la mise au point de tests permettant d'évaluer rapidement et à haut débit l'efficacité de molécules inhibitrices. La technologie Luminex a été notamment mise à profit pour doser Plk1 et certains de ses substrats (phosphorylés ou non), représentatifs de l'activité de la kinase, à partir de lysats cellulaires. Cette approche permet d'évaluer l'effet d'inhibiteurs potentiels de Plk1 in cellulo par une série de dosages réalisés simultanément à partir d'extraits cellulaires. Les Leucémies Aiguës Myéloïdes (LAM) sont des hémopathies clonales liées à la transformation maligne d'une cellule souche hématopoïétique qui présente un blocage de maturation et une prolifération anarchique. Les mécanismes moléculaires impliqués dans la dérégulation du cycle cellulaire dans cette pathologie sont encore mal connus. L'un des objectifs de cette étude a été de caractériser le statut et le rôle de la Plk1 dans la physiopathologie des LAM, afin d'évaluer l'intérêt d'un traitement spécifique ciblant cette kinase dans cette pathologie. .Polo-like kinase 1, a major regulator of mitosis, is found overexpressed in many cancers and its overexpression correlates with a bad prognosis. Experimentally, the constitutive expression of Plk1 induces transformation of NIH3T3 cells and confer them the ability to initiate new tumours in athymic mice. In addition, Plk1 depletion in cancer cells induces apoptosis, suggesting that Plk1 may be a new pharmacological target in anticancer therapies. The first aim of my thesis was to generate molecular and cellular tools in order to characterize the activity of Plk1 inhibitors, evaluate the implication of Plk1 in different steps of cell division and to find new partners Plk1. We generated inducible cell lines allowing the expression of wild type and mutants' forms (inactivated, overactivated) of Plk1, and the analysis of their impact on growth, proliferation, cell cycle and also on known substrates of Plk1. As expected, the higher the activity of Plk1 is, the best its impact on these biological processes. We have tested on these inducible cell lines several inhibitors of Plk1, and developed an assay allowing a rapid and highly efficient evaluation of the effect of these inhibitors on the Plk1 pathway. The Luminex methodology was used on cell extracts in order to assess the activity of Plk1 on its downstream effectors. This methodology appears to be very efficient to analyse the effects of putative Plk1 inhibitors in cellulo. The second aim of my thesis was to analyse the status and role of Plk1 in a malignant hemopathy, Acute Myeloid Leukemia (AML). AML is a clonal hemopathy characterized by a block in differentiation and by an uncontrolled proliferation of immature leukemic cells. Molecular mechanisms involved in the dysregulation of cell cycle in AML are still poorly understood. We have characterized the expression and the role of Plk1 in AML cell lines and primary cells and analysed the consequences of a specific Plk1 inhibition in this pathology. .
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Löfstrand, Karin. "Trends and exposure of naturally produced brominated substances in Baltic biota - with focus on OH-PBDEs, MeO-PBDEs and PBDDs." Doctoral thesis, Stockholms universitet, Institutionen för material- och miljökemi (MMK), 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-54421.
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The semi-enclosed and brackish Baltic Sea has become heavily polluted by nutrients, anthropogenic organic and inorganic chemicals via human activities. Persistent organic pollutants (POPs) have been thoroughly investigated due to their linkage to toxic effects observed in Baltic biota. There has been far less focus on semi-persistent pollutants e.g. naturally produced oraganohalogen compounds (NOCs) and their disturbances in the environment. This thesis is aimed on assessment of levels and trends of naturally produced brominated compounds in Baltic biota; more specifically on hydroxylated polybrominated diphenyl ethers (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs) and polybrominated dibenzo-p-dioxins (PBDDs). These, NOCs, may originate from production in algae and cyanobacteria. OH-PBDEs and MeO-PBDEs may also be formed as metabolites of polybrominated diphenyl ethers (PBDEs), i.e. well-known commercial flame retardants. High levels of OH-PBDEs, MeO-PBDEs and PBDDs are shown within Baltic biota (cyanobacteria, algae, mussels, fish), often in much higher concentrations than PBDEs which are possible anthropogenic precursors of OH- and MeO-PBDEs. The levels of OH-PBDEs, MeO-PBDEs and PBDDs are higher in the Baltic Sea than on the west coast of Sweden. Temporal and seasonal variations show fluctuations in concentrations of OH-PBDEs, MeO-PBDEs and PBDDs, possibly related with macroalgal life-cycles. OH-PBDEs, MeO-PBDEs and PBDDs are present in several filamentous macroalgae species, but considering the levels quantified, the time of peak exposure and the species life-cycle the macroalgae, Pilayella, Ceramium and Cladophora are suggested as major natural producers of OH-PBDEs and PBDDs. The high levels of OH-PBDEs, MeO-PBDEs and PBDDs in the Baltic Sea may affect numerous organisms in the ecosystem. The toxic effects of OH-PBDEs and PBDDs are of particular concern. This thesis stress the importance of assessing and monitoring these substances, since the exposure to OH-PBDEs and PBDDs, during summer, may cause acute effects in Baltic fish and wildlife.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: In press. Paper 4: Manuscript.
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Andersson, Carl, and John Pettersson. "Behovet av ökad kontroll i stålbyggnadskonstruktioner." Thesis, Linnéuniversitetet, Institutionen för byggteknik (BY), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-85778.
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I arbetet undersöks behovet av ökad kontroll i stålbyggnadskonstruktioner med avseende på utförandefel. Riksdagen beslutade 1 juni 1994 att förändra Plan- och bygglagen (PBL) där förändringen trädde i kraft 1995 och bland annat innebar att hela ansvaret för en byggnads uppförande och kontroll lades på byggherren. Efter vintrarna 2009/10 och 2010/11 där flera tak rasade av snötyngden uppdagades en rad dimensionerings- och utförandefel. Under examensarbetet undersöktes vad som händer med säkerheten i byggnadskonstruktioner i stål som genomgår förändringar under dess livslängd och en jämförelse mot gällande regelverk genomfördes. En fältstudie och flera intervjuer genomfördes där fokus låg på utförandefel och hur förändringar av regelverk lett fram till dagens egenkontrollsystem som påverkat antalet utförandefel. Arbetets resultat visar att det kan finnas ett behov av att se över dagens kontrollsystem och att antalet allvarliga utförandefel i fallstudieobjektet ökat efter 1995.In the work the need of increased inspections of steel structures with respect to errors of execution was examined. On 1 June 1994, the Swedish parliament decided to change the Planning and Building Act (PBL) and the changes came into force in 1995, where the entire responsibility for the construction and control of a building was placed on the developer. After the winters of 2009/10 and 2010/11, when several roofs collapsed by the snow weight, a number of design and execution faults were discovered. During the thesis work it was investigated what happens to the safety of building structures in steel that undergo changes during its lifetime and a comparison with current regulations was made. A field study and several interviews were conducted where the focus was on execution errors and how changes in regulations led to today's self-control systems that affect the number of execution errors. The results of the work show that there may be a need to review the current control system and that the number of serious execution errors in the case study object increased after 1995.
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Gonzalez, Walter G. "Protein-Ligand Interactions and Allosteric Regulation of Activity in DREAM Protein." FIU Digital Commons, 2016. http://digitalcommons.fiu.edu/etd/2503.
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Downstream regulatory antagonist modulator (DREAM) is a calcium sensing protein that co-assembles with KV4 potassium channels to regulate ion currents as well as with DNA in the nucleus, where it regulates gene expression. The interaction of DREAM with A-type KV4 channels and DNA has been shown to regulate neuronal signaling, pain sensing, and memory retention. The role of DREAM in modulation of pain, onset of Alzheimer’s disease, and cardiac pacemaking has set this protein as a novel therapeutic target. Moreover, previous results have shown a Ca2+ dependent interaction between DREAM and KV4/DNA involving surface contacts at the N-terminus of DREAM. However, the mechanisms by which Ca2+ binding at the C-terminus of DREAM induces structural changes at the C- and N-terminus remain unknown. Here, we present the use of biophysics and biochemistry techniques in order to map the interactions of DREAM and numerous small synthetic ligands as well as KV channels. We further demonstrate that a highly conserved network of aromatic residues spanning the C- and N-terminus domains control protein dynamics and the pathways of signal transduction on DREAM. Using molecular dynamics simulations, site directed mutagenesis, and fluorescence spectroscopy we provide strong evidence in support of a highly dynamic mechanism of signal transduction and regulation. A set of aromatic amino acids including Trp169, Phe171, Tyr174, Phe218, Phe235, Phe219, and Phe252 are identified to form a dynamic network involved in propagation of Ca2+ induced structural changes. These amino acids form a hydrophobic network connecting the N- and C-terminus domains of DREAM and are well conserved in other neuronal calcium sensors. In addition, we show evidence in support of a mechanism in which Ca2+ signals are propagated towards the N-terminus and ultimately lead to the rearrangement of the inactive EF-hand 1. The observed structural motions provide a novel mechanism involved in control of the calcium dependent KV4 and DNA binding. Altogether, we provide the first mechanism of intramolecular and intermolecular signal transduction in a Ca2+ binding protein of the neuronal calcium sensor family.
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Khan, Simeen. "Colloidal PbS and PbS/CdS Core/Shell Nanosheets." Bowling Green State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1447955111.
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Flayhan, Ali. "Reconnaissance phage-bactérie dans le système phage T5 - E. Coli : Caractérisation biochimique et structurale du complexe FhuA-pb5 et de la protéine caudale pb9." Paris 7, 2012. http://www.theses.fr/2012PA077164.
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Au cours de cette thèse, j'ai abordé la première étape de l'infection dans le système E. Coli -phage T5. Mes travaux se sont focalisés sur la caractérisation du complexe formé entre pb5, la protéine de liaison au récepteur (RBP) de T5 et son récepteur FhuA à la surface d'E. Coli. J'ai montré que le complexe est très stable et identifié le domaine «bouchon» de FhuA comme un nouveau site d'interaction de pb5. La formation du complexe n'induit pas de réarrangements des structures de pb5 et/ou de FhuA. Seuls des changements de conformation subtils lors de la formation du complexe, au niveau de structures secondaires, ont été décelés et attribués à pb5. Ces derniers seraient à l'origine de la transmission du signal au reste du phage. Des cristaux 3D (8 A) et 2D (3 A) ont été obtenus. Des études de diffusion de neutrons et de rayons X aux petits angles ont permis d'obtenir une enveloppe de pb5 seule ou dans le complexe, en accord avec la structure à basse résolution de pb5 et du complexe, obtenues par microscopie électronique. Ces modèles montrent que l'interface de liaison couvre toute la section extracellulaire de FhuA. Pb5 se lie à FhuA par l'une de ses extrémités de telle manière que son grand axe et l'axe du tonneau de FhuA soient alignés. Contrairement aux différentes RBP décrites, pb5 semble composée d'un domaine unique et est présente en une seule copie au bout distal de la fibre droite de T5. Par ailleurs, je me suis intéressé à la surexpression, purification, caractérisation et structure de pb9, une protéine localisée dans la partie conique de la queue de T5. Une première carte expérimentale est obtenue et la résolution de sa structure atomique est en coursThis thesis approached the first step of infection in the System E. Coli - phage T5. My research has focused on the characterization of the complex formed between pb5, the receptor binding protein (RBP) of T5 and its receptor FhuA, on the surface of E. Coli. I showed that the complex FhuA-pb5 is very stable and determined the "plug" domain of FhuA as a novel interaction site of pb5. Complex formation does not induce major rearrangements of pb5 and/or FhuA. Only subtle conformational changes during complex formation, at the secondary structures level, were identified and assigned to pb5. These changes would be at the origin of the signal transmission to the phage. 3D crystals (8 À) and 2D crystals (3 À) were obtained. Small-angle neutron and X-ray scattering studies yielded a model of pb5 isolated and within the complex. These models are in agreement with the low resolution structure of pb5 and the complex, obtained by electron microscopy, and show that the binding interface covers the entire extracellular section of FhuA. Pb5 binds to FhuA by one of its ends in a way that its major axis and the axis of the FhuA barrel are aligned. Unlike the various RBPs described so far, pb5 seems composed of a single domain and is present in one copy at the distal end of the T5's straight fiber. Furthermore, I worked on the overexpression, purification, characterization and the structure of pb9, a protein that was located in the conical part of the tail of T5. The first experimental electron density map is obtained and the resolution of its atomic structure is underway
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Price, Jamie H., Aimee Govett, Misty Davis, Robyn Ivester, Teresa Howard, and Lisa Messimer. "PBL Meets PBL: Project-Based Learning Meets Planet-Based Learning." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/6025.
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Project-based learning (PBL) is centred on a challenging, yet meaningful, driving question and culminates in a product that students create or do to showcase their learning to a public audience. Other essential elements of a true PBL experience include: sustained inquiry, authentic tasks, opportunities for students to make decisions about their culminating product, reflection, critique, and revision (Hallermann, Larmer, & Mergendoller, 2011). A well-designed PBL combines curriculum and instructional activities to cultivate 21st century skills in students to prepare them for future success in the workforce. Two teams of Year five teachers designed a week-long PBL unit for students organised around the characteristics of the planets, which integrated science, mathematics, and English. The teachers implemented the PBL with six classes of Year five students, documenting their thoughts on planning and implementation to reflect upon the experience.
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Sepúlveda, Valenzuela Gabriel Ignacio. "Evaluación de la diversidad genética de los genes PB2, PB1 y PA del complejo polimerasa del virus influenza tipo A de origen porcino en Chile." Tesis, Universidad de Chile, 2018. http://repositorio.uchile.cl/handle/2250/171772.
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Memoria para optar al Título Profesional de Médico VeterinarioEl virus influenza A (FLUAV) ha sido ampliamente estudiado debido a su gran importancia en salud pública y animal. Una de las razones de esto es su gran variabilidad genética otorgada en gran medida por el proceso de reassorment o reordenamiento genético. Este estudio consistió en la determinación de la diversidad genética de los genes que componen el complejo polimerasa del virus, es decir, los genes que codifican para la polimerasa básica 2 (PB2), la polimerasa básica 1 (PB1) y la polimerasa ácida (PA) de virus aislados de planteles porcinos de producción intensiva en Chile y evidenciar procesos de reordenamientos genéticos independientes de dichos genes. Para esto, se analizaron 2824 muestras desde 33 planteles porcinos mediante diagnóstico viral por RT-PCR en tiempo real, aislamiento viral, amplificación de segmentos virales por RT-PCR multisegmento y secuenciación por Illumina. Se obtuvieron un total de 89 secuencias genómicas de PB2 y 92 tanto de PB1 como de PA. Luego se realizó un análisis filogenético con estas secuencias nucleotídicas, más secuencias de referencia mediante el método Maximum likelihood. Todas las secuencias para los tres genes estudiados pertenecen al linaje pandémico del 2009. Se constató además la presencia de reordenamientos de estos genes en aproximadamente un 35% de los casos. Estos resultados permitieron conocer sobre la diversidad genética de los genes que componen el complejo polimerasa de FLUAV en Chile y pesquisar fenómenos de reordenamientos de estos. Además, permitieron evidenciar posibles quiebres de bioseguridad en parte de las producciones porcinas intensivas en Chile, debido a las relaciones filogenéticas encontradas entre virus de diferentes planteles. Futuros estudios son necesarios para confirmar y entender estos hallazgos
The influenza A virus (FLUAV) has been extensively studied for the importance in public and animal health. The virus presented high genetic diversity, due to in part, by the reassortment events. The aim of this study it was to determinate the genetic diversity of the segments 1 (PB2), 2 (PB1) and 3 (PA) of FLUAV isolated from swine in intensive production farms in Chile and too evidence reassortment events in these genes. For this, 2824 samples were collected from 33 pig farms. Real time RT-PCR, viral isolation, and full genome sequencing were performed. A total of 89 genomic sequences of PB2 and 92 genomic sequences for PB1 and PA were obtained. Using phylogeny, we determinate that all segment belonged into the pandemic 09 cluster. The results suggest reassortment events of these genes in approximately 35% of the cases. This is the first study about the genetic diversity of the PB2, PB1 and PA, internal genes and to evidence reassortment events of them in swine population. In addition, the phylogeny suggests direct or indirect transmission between farms. Further studies are needed to better understand the viral dynamic of polymerase genes
FONDECYT 11170877 y ANILLO ACT 1408
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Friedman, Sandra de Castro. "Arcabouço teórico para discussões sobre o panorama multifacetado da privacidade na era digital." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/12371.
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Ameaças como vazamento de dados, roubo de identidade, vigilância, criação de perfis e dossiês, bem como as políticas de privacidade mutantes das redes sociais estão frequentemente relacionadas com danos à reputação e perda da privacidade. Este estudo faz uma explanação geral da legislação no contexto internacional e um exame crítico em artigos, documentos e pesquisas de opinião, analisando as questões de privacidade da informação – e as definições de privacidade como um todo – investigando as diferentes facetas da privacidade e como a tecnologia nos desafia a realinhar nossas expectativas de privacidade. Trabalhamos com a hipótese de que o cuidado com a proteção à privacidade de dados pessoais tende a figurar entre as qualidades buscadas por usuários de aplicativos de software, e, portanto, deverá se constituir em elemento fundamental de vantagem competitiva no mercado de aplicativos. Nossa hipótese foi suportada pela descoberta de estratégias e uma miríade de soluções de software para a proteção da privacidade nas fases de coleta, armazenamento, processamento e disseminação de informações. A privacidade está em necessidade urgente de preservação e as estratégias regulatórias vigentes parecem não estar à altura da tarefa. As empresas, que levam em conta a privacidade como um valor inerente aos projetos e desenvolvimento de seus produtos e tecnologias, estimulam o espírito de inovação e destacam-se no mercado, construindo um relacionamento de confiança com seus clientes e usuários. Espera-se trazer conhecimento científico a estudantes e profissionais comprometidos com a ética, com os valores de liberdade e autonomia e interessados no tema privacidade da informação.
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Lind, Herta. "Meningsfullt lärande med PBL?" Thesis, Linköping University, Department of Educational Science (IUV), 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-888.
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Arbetet handlar om huruvida man kan få till ett meningsfullt lärande genom att använda sig av metoden PBL, problembaserat lärande, i grundskolan. Jag gör en kort presentation av lärande under 1900-talet för att därefter koncentrera mig på tre pedagoger, Marton, Säljö och Dewey. Utifrån dessa tre pedagogers syn på lärande undersöker jag PBL. Jag beskriver hur metoden PBL fungerar och hur den är uppbyggd. Mycket i PBL överensstämmer med vad Marton, Säljö och Dewey anser vara ett lärande som ger bra resultat. Som motvikt har jag tagitmed Inger Enkvist som står för en helt annan syn på hur skolan ska arbeta.
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Andersen, Alexander. "Regional fysisk planering - I vägvalet om att planera enligt PBL eller utanför PBL." Thesis, Blekinge Tekniska Högskola, Institutionen för fysisk planering, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-22107.
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Denna uppsats avser att undersöka hur olika institutioner på olika politiska och geografiska nivåer förhåller sig till och tillämpar lagändringen gällande den regionala fysiska planeringen som kom år 2019. Uppsatsen utgår från två frågeställningar: Hur tolkas lagändringen och hur ser argumentationen ut kring en regional fysisk planering enligt plan- och bygglagen (PBL) och utanför PBL samt vilka konsekvenser en lagstadgad regional fysisk planering enligt PBL kan få för kommunerna, kommunalförbunden och regionerna. För att studera detta har jag valt att använda mig av en fallstudie. Fallet som studeras är Västra Götalandsregionen (VGR) som är en region bestående av 49 kommuner och 4 kommunalförbund. I regionen pågår det under tiden för uppsatsskrivandet ett remissarbete, där VGR skickat ut en remiss till kommunerna, kommunalförbunden och de andra aktuella remissinstanserna för att få svar på om regionen skall ansöka om att bli ett regionplaneorgan eller inte. Förutom den frågan vill regionen också ha svar från remissinstanserna på hur de vill att den regionala fysiska planeringen skall utvecklas framöver, främst gällande hur samverkan skall ske och vilka frågor som är aktuella. Det valda fallet ses som ett unikt fall då regionen består av en mängd olika geografier och aktörer, det ses även som ett aktuellt fall då det finns en pågående diskussion inom ämnet. I uppsatsen tillämpas tre olika insamlingsmetoder av data; intervjuer, en enkätstudie och en dokumentstudie. Gällande respondenterna ingår 31 tjänstepersoner och politiker som är verksamma i olika delar av regionen och som är hemmahörande i organisationer på olika nivåer. De dokument som används i uppsatsen är sådana som offentliggjorts online av organisationer så som VGR, Finansdepartementet och Sveriges Kommuner och Regioner. En kvalitativ innehållsanalys har använts för att analysera den data som insamlats. Vilket utgår från det analytiska ramverket som är uppbyggt på Nuissl & Heinrichs governance-koncept och dess fyra analyskategorier som består av aktörer, relationer, institutionella ramverk och beslutsprocessen. I uppsatsen framkommer det att det finns en del argument både för en regional fysisk planering enligt PBL och för en fortsatt regional planering utanför PBL. Det argument som nämns flest gånger på båda sidor är att det leder till en förbättrad samordning. Just vad denna samordning skall baseras på verkar vara den centrala frågan. Ena sidan vill att den ska bygga på frivillighet och äga rum i soft spaces och den andra sidan vill ha en tydligare struktur och att frågan om den regionala fysiska planeringen skall finnas i ett hard space. Trots att det finns en mängd olika argument som tas upp för och emot en regional fysisk planering enligt PBL, är de flesta av respondenterna överens om att de vill se en förstärkt regional fysisk planering som behandlar fler frågor än vad den gör idag. Politikerna sägs dock vara mer negativa mot en regional fysisk planering enligt PBL än vad tjänstepersonerna är, vilket kan bero på en oro att förlora makten när frågor kan bli föremål för rescaling upp till regionen. Slutligen utrycker respondenterna att det finns en otydlighet kring vilka konsekvenser en regionplan hade kunnat leda till. Ett flertal respondenter utrycker även en oro över VGR:s resurser och mognad för att ta sig an ett regionplanemandat. Otydligheten och avsaknaden av ställningstagande om de vill bli ett regionplaneorgan eller inte har inte bidragit till mindre oro, utan snarare mer. En av slutsatserna är att de olika aktiva aktörerna inom flernivåstyrningen av planeringsprocessen bör ta fram former för samverkan och samarbete så snart som möjligt, då flera frågor som till exempel bostadsförsörjningen och klimatet är i akut behov av åtgärder på en högre regional skala än de kommunala- och mellankommunala åtgärderna som finns idag. För att detta ska kunna ske behöver samordningen mellan soft och hard spaces förbättras, då det finns betydliga risker för negativa konsekvenser om den regionala planeringen fortsätter att endast äga rum i soft space vilket i stort sett är situationen idag, eller endast i hard space som kan hända om regionen får ett lagkrav på sig enligt PBL. Frågan om hur en bättre samverkan kan uppnås mellan aktörerna bör vara överordnad frågan om det ska planeras enligt PBL eller inte, då det är en mer akut fråga som mer ligger till grund för hela planeringsprocessen.
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Cuba, B. Elmer. "Estimación del PBI potencial y de la brecha del PBI: Perú 1970-1995." Economía, 2012. http://repositorio.pucp.edu.pe/index/handle/123456789/117258.
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Harris, Joel Mark. "Static characteristics and rotordynamic coefficients of a four-pad tilting-pad journal bearing with ball-in-socket pivots in load-between-pad configuration." [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-3194.
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Lantto, Joni, and Henri Lehtonen. "Medborgarinflytande i detaljprocessen : En jämförelse mellan PBL 1987 samt PBL 2010 ur ett demokratiperspektiv." Thesis, Uppsala universitet, Institutionen för geovetenskaper, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-183582.
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In the year 2002 a commission wasappointed by the government and taskedto clear up possible flaws in the lawgoverning spatial planning (Plan ochbygglagen, PBL). The commission's reportlaid the foundations for a new law whichwas adopted by the Swedish parliament onthe 20th of June 2010 and is scheduledto come into effect on the 2nd of May2011.The purpose of this thesis has been toexamine the changes made in the new law,primarily from a civil-rights point ofview, focusing on the appeal process.This is a highly interesting subjectconsidering one reason behind the newlaw was to simplify and streamline theplanning process while keeping civilrights intact.Through a comprehensive literature studyand interviews with experts the currentplanning process was mapped out andrelevant changes in the new law wereexamined. After the study had beenconcluded we were able to distinguishseveral areas that underwent especiallyinteresting changes;The requirement of a plan program wasremoved and the exhibition process wasremoved and replaced by a writtenreview. Individuals were given thepossibility of requesting a plan notice.The different spatial plan documentswere merged into one single document andthe number of responsible authoritiesfor spatial plans is no longer limitedto one.The study has shown that the aspirationfor a more effective spatial planningprocess has mostly been conducted at theexpense of individual rights.The single biggest obstacle forachieving a democratic planning processis learning how the law works and howthe spatial planning process isimplemented, this is has been proven tobe a very hard and time consuming taskfor individuals to undertake.
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Persson, Filip. "Med PBL i geografiundervisningens centrum." Thesis, Malmö högskola, Fakulteten för lärande och samhälle (LS), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-36130.
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I det här arbetet behandlas PBL och hur det fungerar som arbetssätt i geografiundervisning på gymnasiet. Jag undersöker vilka positiva respektive negativa aspekter det finns med att använda PBL i verksamheten samt vad arbetssättet utifrån dess positiva sidor kan tillföra geografiundervisning på gymnasiet. För att besvara min frågeställning har jag genomfört två olika typer av semistrukturerade intervjuer. Den första var en samtalsintervju med en pedagog som har mångårig erfarenhet av PBL-baserad undervisning på gymnasiet. Den andra en fokusgruppintervju med fyra elever från en årskurs två-klass som arbetat med arbetssättet under sin tid på gymnasiet. Resultatet visar att personerna som deltog i intervjuerna upplever att det finns många fördelar med att använda PBL som arbetssätt. De anser att PBL underlättar för elever att se helhetsperspektiv och större sammanhang i undervisningen. De mer negativa aspekterna av PBL kopplas främst till att arbetssättet kräver stora lärarresurser. Resultatet visar även att PBL fungerar bra i relation till undervisning i geografi på gymnasiet. Ämnets bredd upplevs gå väl ihop med idén om ämnesintegrerad undervisning som PBL bygger på. Dessutom finns det tydliga kopplingar mellan den kunskapssyn som genomsyrar PBL och den som aktuella styrdokument menar ska utgöra grunden för geografiämnet i gymnasieskolan.
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Vlk, Bronislav. "Možnosti videokonferencí v PBX Asterisk." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219738.
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This thesis deals with the possibilities of video conferencing in Asterisk PBX and their use in practice. They also described the contingencies and how its configuration. Particular attention is paid to the protocols SIP, IAX and H.323, which are described in one of the chapters. The thesis was created by the Asterisk PBX, which demonstrates cooperation with videoconferencing clients. The thesis describes the configuration files so that the central set. Conclusion the work assesses the use of codecs for different clients.
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Hensley, John Eric. "Rotordynamic coefficients for a load-between-pad, flexible-pivot tilting pad bearing at high loads." Texas A&M University, 2006. http://hdl.handle.net/1969.1/4404.
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The dynamic and static performance of a flexure-pivot tilting pad bearing is presented at
a load between pad configuration for various load and speed combinations. A similar
work performed on the same bearing at lower loads ranging from 0-1 MPa (0-150 psi) by
Al-Ghasem was tested, whereas the current work investigates effects in the load range
between 1-2.2 MPa (150-320 psi). The bearing design parameters include: 4 pads with
pad arc angle 72ú and 50% pivot offset, pad axial length 0.0762 m (3 in), pad radial
clearance 0.254 mm (0.010 in), bearing radial clearance 190.5 õm (0.0075 in), preload
0.25, and shaft nominal diameter of 0.11684 m (4.600 in). An important distinction
between the two sets of tests is the difference in experimental bearing radial clearance,
which for this case measured 208 õm (0.00082 in), and for Al-GhasemâÂÂs was 165.1 õm
(0.0065 in). The rotordynamic coefficients are determined experimentally using a test rig
equipped with motion and load sensors. The rig is modeled using NewtonâÂÂs laws, which
is converted from the time to frequency domain using Fourier Transform to give complex
dynamic stiffnesses. From the resulting complex dynamic stiffnesses the associated real
and imaginary components are plotted as a function of excitation frequency and curve
fitted via linear regression to give the rotordynamic coefficients. The primary objectives
were to determine whether the real component of the complex dynamic stiffnesses could
be better modeled with or without the mass coefficient and to contrast the rotordynamic
coefficients with an analytical model. Only in the load range of 1 to 2.2 MPa were the
unloaded direct mass coefficients near or at 0, which would allow for a [K][C] model to
be used. The remaining real components are better represented with the mass term. The
analytical model generally overpredicted the stiffness, damping and mass coefficients,
especially for the direct components; the trends were generally consistent.
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Errami, Jalal. "Modélisation d'un simple brin d'ADN : Configuration en "épingle à cheveux"." Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2007. http://tel.archives-ouvertes.fr/tel-00156784.
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Les « DNA beacons » sont des molécules composées de simple brins d'ADN dont les deux bouts contiennent des bases complémentaires et auxquels on attache un fluorophore et un quencher. Ainsi, ces deux extrémités peuvent s'assembler pour former un bout de double hélice d'ADN que nous appelons « stem », la partie centrale du brin forme alors une sorte de boucle. On appelle cette structure la configuration en « épingle à cheveux ». Un aspect important de cette structure est qu'elle représente des systèmes simples permettant une étude détaillée de l'assemblage/désassemblage de la double hélice d'ADN. Nous avons développé deux modèles différents pour étudier la thermodynamique et la cinétique de ces systèmes. Le premier est un modèle sur réseau inspiré des modèles utilisés pour l'étude des repliements des protéines. Le deuxième est un modèle qui inclut les ingrédients physiques du premier modèle mais sans la contrainte apportée par le réseau. Il combine la théorie des polymères et le modèle de Peyrard-Bishop et Dauxois (PBD) pour la double hélice. Avec cette nouvelle approche, nous sommes capable de comparer quantitativement nos résultats théoriques avec les résultats expérimentaux.
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Ito, Edson Noriyuki. "Estudos microrreológicos da blenda PBT/SAN." Universidade Federal de São Carlos, 2006. https://repositorio.ufscar.br/handle/ufscar/647.
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This work was motivated by the need of a better understanding of the microrheological characteristics of polybutylene terephthalate, PBT, polymer blends, such as the matrix phase PBT and the styrene-acrylonitrile, SAN copolymer as dispersed phase. The main purpose of the microrheological studies carried out was to analyze the rheological behavior and the morphology, as well as their correlation, in the preparation of the PBT/SAN immiscible blend, with and without the use of an interfacial compatibilizer. The rheological behavior was analyzed by torque rheometry, rotational rheometry with parallelplates geometry, and capillary rheometry. The interfacial tensions were measured by the modified ellipsoidal drop retraction method, using an optical polarized light microscope coupled to a hot stage. Two complementary techniques were used in the morphological analyses: scanning electron microscopy (SEM) with tetrahydrofuran (THF) extraction of the dispersed phase, and transmission electron microscopy (TEM) with rutene tetroxide (RuO4) deposition in the dispersed phase. The interfacial tension between the PBT polymer and the SAN copolymer was found to increase as the molar mass of the PBT increased. The use of rotational rheometry with parallel plates at low shear rates allowed the increase in viscosity to be quantified as a function of the reaction of the polymeric macromolecules in the PBT/SAN blend compatibilized or not with the interfacial compatibilizer, the MMA-GMA-EA copolymer. Based on the morphological characterizations, an analysis was made of the fibril formation mechanisms, break up and coalescence of the particles of dispersed phase and their interactions with the addition of interfacial compatibilizers. The rotational rheometry at low shear rates proved to be extremely efficient in the analysis of blend compatibilization, which is usually analyzed by torque rheometry. It was checked that, at high shear rates, the viscosity ratio influenced the formation of more finely dispersed phases.
O motivo que levou à realização deste trabalho de doutorado consistiu na necessidade de um melhor entendimento das características microrreológicas de blendas poliméricas constituídas de poli(tereftalato de butileno), PBT, como fase matriz, e do copolímero estireno-acrilonitrila, SAN, como fase dispersa. Os estudos microrreológicos realizados tiveram como enfoque principal analisar o comportamento reológico e a morfologia, bem como suas correlações na preparação da blenda imiscível PBT/SAN, com e sem a utilização de um compatibilizante interfacial. Nas análises do comportamento reológico, foram utilizadas reometria de torque, reometria rotacional na geometria de placas paralelas e reometria capilar. As medidas de tensões interfaciais foram realizadas através do método de retração de gotas elipsoidais modificado, utilizando-se de um microscópio óptico com luz polarizada acoplado a um estágio a quente. Nas análises morfológicas, foram utilizadas duas técnicas complementares, através de microscopia eletrônica de varredura (MEV) com extração da fase dispersa com tetrahidrofurano (THF) e por microscopia eletrônica de transmissão (MET) com a deposição de tetróxido de rutênio (RuO4) sobre a fase dispersa. Utilizando-se do método de retração de gota modificado, verificou-se que a tensão interfacial entre o polímero PBT e o copolímero SAN aumenta com o aumento da massa molar do PBT. Utilizando-se da reometria de placas paralelas a baixas taxas de cisalhamento, foi possível quantificar o aumento de viscosidade em função da reação das macromoléculas poliméricas na blenda PBT/SAN, compatibilizada ou não com o agente de compatibilização interfacial (o terpolímero metacrilato de metilametacrilato de glicidila-acrilato de etila, MMA-GMA-EA). Por meio das caracterizações morfológicas, foi possível analisar os mecanismos de formação de fibrilas, cominuição e coalescência das partículas de fase dispersa e de suas interações com a adição de agentes de compatibilização interfacial. A técnica de reometria rotacional de placas paralelas em baixas taxas de cisalhamento mostrou-se extremamente eficiente na análise de compatibilização de blendas, que, na maioria das vezes, é feita através de reometria de torque. Verificou-se que, a altas taxas de cisalhamento, a razão de viscosidade influencia a formação de fases mais finamente dispersas em função da taxa de cisalhamento aplicada à blenda PBT/SAN.
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Sestak, Mark R. Carleton University Dissertation Computer Science. "Traffic flow monitoring in PBX networks." Ottawa, 1990.
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Benýšek, Jiří. "Vazba GSM modemu na PBX Asterisk." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2010. http://www.nusl.cz/ntk/nusl-218255.
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Short Message Service (shortly SMS) is the most widely used type of communication systems. The main advantages are that allow a fast exchange of messages between devices, a very good availability through GSM and a reasonable price. Nowadays the SMS service support has expanded to include other technologies such as a service of the information navigation and the remote connection. The master‘s thesis concentrates on the Short Message Service, deals with basic principles and statements using by this service. The topic of the thesis is software PBX Asterisk and its possibility of SMS implementation, especially verification of SMS processing goes through the PSTN. After the basic introduction the master‘s work deals with the installation and configuration of the server. The main focus is on an installation of the operating system with an additional pack including necessary libraries and modules for a correct working of the server. The following section is paying attention to the Asterisk server configuration, especially a hardware card installation which is necessary for a connection with analog telephones, done by Bluetooth connections, set up user’s profiles of the SIP protocol and create a dial plan. This is followed by a verification of SMS option of the implementation and communication with GSM modem which is used as a gate for an exchange SMS between PSTN and GSM network. The last chapter of this master‘s thesis comes with the aimed results.
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Orsák, David. "Zabezpečení Open source PBX proti útokům." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219480.
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This master's thesis deals with open source PBX security against security attacks. In the theoretical part is detailed description of problematic about attacks that could be used on VoIP systems with high focus on the Denial of Service attack. Furthermore are in theoretical part described methods of security of initialization protocol SIP. Individual chapter is devoted to intrusion detection and prevention of IDS and IPS systems, focusing on Snort and OSSEC. In the practical part of the work was created generator of attacks against various PBX systems, which was subsequently used for detailed testing. Special tests of PBX system are then used against DoS attacks, for which was created protection in form of active elements consisting of IDS Snort & OSSEC. These are capable to provide protection in real-time. The protection was tested on particular PBX systems and in matter of comparison were measured possibilities before and after of security implementation. The output of this work is attacks generator VoIPtester and creation of configuration rules for Snort and OSSEC.
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Hynek, Luboš. "Metody zajištění IP PBX proti útokům." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2013. http://www.nusl.cz/ntk/nusl-220328.
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This master project focuses on the possibilities of protecting the most common free software PBX Asterisk, FreeSWITCH and YATE. In practice, it was verified the behavior of PBX in the attacks and suggested protection against them on one of the most popular distributions of Linux server on CentOS. Tool was created to simulate several types of attacks targeting denial of service. Both protective options PBX themselves and operating system capabilities are used in this work. Comparison was also the possibility of protection of individual PBX with each other. It also includes a brief description of the protocol, topology attacks and recommendation for the operation of softswitches.
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Janeček, Václav. "Open source PBX Kamailo a OpenSIPs." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2014. http://www.nusl.cz/ntk/nusl-220656.
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Open source PBX Kamailio and OpenSIPS diploma thesis covers familiarization with appointed SIP exchanges and with their power comparing. A detailed installation instructions on the operating system Ubuntu is the aim of this work too. The work includes the historical development of telephone exchanges with a focus on the latest generation. The following is SIP protocol basic description and components that can be composed SIP exchanges. Another part is devoted to the development of exchanges Kamailio and OpenSIPS. The thesis contain the archutecture and configuration file description. The practical part of the thesis deals with high-capacity switches, and comparing it in terms of memory and computational demands. Selected measurements are compared with the Asterisk PBX.
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Bednář, Vít. "Implementace protokolu SIP v PBX Asterisk." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2017. http://www.nusl.cz/ntk/nusl-317016.
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The thesis compares native SIP stack with PJSIP stack in the open source telephone private branch exchange (PBX) Asterisk. First, there are described both SIP protocol and Asterisk application. Subsequently, the architecture, new function support and the stacks setting possibilities are explored. For different exchange scenarios several commented configuration files are presented. The stacks are tested using Spirent TestCenter C1 software thereafter. In conclusion, selected properties are assessed and new PJSIP stack benefits are summarized. In addition, the laboratory assignment is attached.