Dissertations / Theses on the topic 'Nibrin'

Das Nijmegen-Breakage-Syndrom (NBS) ist ein autosomal-rezessiv vererbtes Chromosomenbruchsyndrom, dem in > 90% der Patienten eine 5bp-Deletion im Nbs1-Gen zugrundeliegt. Klinisches Hauptmerkmal ist ein stark erhöhtes Krebsrisiko, insbesondere für B-Zell-Lymphome. Bereits bekannt ist die Funktion des entsprechenden Genprodukts, Nibrin, bei den für die Krebsprävention wichtigen Mechanismen der DNA-Reparatur und der Zellzykluskontrolle. Daneben spielt die Apoptose eine essentielle Rolle bei der Krebsentstehung. Zu untersuchen ob Nibrin auch hier Funktionen übernimmt war Gegenstand dieser Arbeit. Eine Störung der Apoptose könnte dabei mitverantwortlich für das hohe Krebsrisiko der NBS-Patienten sein. Kern der Arbeit war die Untersuchung von NBS-B-Lymphozyten hinsichtlich ihrer Fähigkeit, nach einer DNA-Schädigung die Apoptose zu induzieren. Hierzu wurde in den entsprechenden Zellen mittels Bleomycin der Apoptoseprozess ausgelöst und die prozentualen Apoptoseraten durchflusszytometrisch bestimmt. Die Mehrheit der NBS-Zelllinien zeigte eine Störung in der Apoptoseinduktion im Sinne signifikant verminderter Apoptoseraten. Dies weist auf eine Funktion des Nibrins bei der Induktion der Apoptose hin. Andere NBS-Zelllinien zeigten normale Apoptoseindices. Dies könnte auf dem individuellen genetischen Hintergrund der Zellen beruhen, der auch für die erhebliche klinische Variabilität des Krankheitsbildes verantwortlich ist. Eine Korrelation der Apoptoseraten mit der Krebsinzidenz zeigte, dass alle Patienten mit reduzierten Apoptoseraten bereits Lymphome entwickelt hatten, während Patienten mit normalen Apoptoseindices bisher keine Lymphome aufwiesen. Möglicherweise gibt es also generell zwei Gruppen von NBS-Patienten - Patienten mit höherem und mit niedrigerem Entartungsrisiko, wobei eine verminderte Apoptoseinduktion als Risikofaktor für Krebs angesehen werden könnte.
The human genetic disorder, Nijmegen-Breakage-Syndrome (NBS), is characterised by an in increased risk for cancer, particularly B-cell-lymphoma. The Nbs1-gene codes for a protein, Nibrin, involved in the processing/repair of DNA double strand breaks and in cell cycle checkpoints - mechanisms relevant for cancer-prevention. As a third mechanism, apoptosis is important in preventing cancer. To evaluate whether Nibrin plays a role in this process was the aim of this study. Failure of apoptosis-induction could be another factor responsible for the high cancer risk in NBS. For this purpose we examined a set of NBS-B-cell-lines for their capacitiy to enter into apoptosis after a DNA-damaging treatment with Bleomycin. The majority of NBS-cell-lines showed a deficiency in apoptosis-induction. This may indicate a function of Nibrin in mechanisms of apoptosis-regulation. Some NBS-cell-lines showed a proficient apoptotic response, though. The reason may be found in the variable genetic background of the cell lines, also responsible for the high clinical variability of the disease. Correlation of apoptosis rates with cancer incidence showed that all patients deficient in apoptosis had already developed B-cell-lymphoma, whereas patients with normal rates had not developed lymphoma so far. Possibly there are two groups of NBS-patients- patients with higher and with lower risk of malignancy, with reduced apoptotic rates being a risk-factor for the development of cancer in NBS.

Des composites matrice base nickel (nibsi), renforces par des particules de carbure de vanadium (vc) ont ete prepares par frittage. L'etude metallurgique et structurale a ete menee par microscopie optique (mo), microscopie electronique en balayage et en transmission avec analyse locale (meb-eds+wds, met-eds). Ces examens ont montre l'existence d'un reseau riche en bore englobant les particules des carbures, une forte diffusion du vanadium dans la structure nickel cfc et la bonne adhesion dans l'interface particule vc-matrice, bien que siege d'une deformation plastique. Les essais tribologiques ont ete effectues en utilisant des montages pion-anneau et pion-disque, suivis par des analyses morphologiques et chimiques des surfaces usees. En fonction du materiau du deuxieme corps, dans le couple tribologique des differents mecanismes d'usure se sont developpes. Ainsi, le contact avec l'alumine-zircone frittee favorise l'adhesion entre les deux surfaces. Par contre, l'acier, employe comme deuxieme corps, induit un mecanisme d'usure a plusieurs etapes: compression du reseau riche en b - extrusion de la matrice riche en ni - fracture du reseau riche en b - fluage du volume de materiau, la derniere etape s'accompagnant des chutes transitoires du coefficient de frottement, traitees comme evenements statistiques. Ce comportement est commun pour tous les materiaux etudies et une relation logarithmique a ete etablie entre l'intensite d'usure et le nombre cumule des evenements. L'etat de contraintes residuelles introduites par le frottement a ete etudie par diffraction de rayon x. La methode classique (dite de sinus carre psi) ne permettant pas l'interpretation des mesures, une methode originale a ete utilisee. Il s'agit de comparer la deformation superficielle produite par le test d'usure a celle produite par un essai statique de flexion bi-axiale

The aerial roots of Heteropsis flexuosa (Kunth) Bunting, a hemi-epiphyte, are harvested by indigenous communities in Guyana for a developing wicker furniture market. Nibbi roots have potential as a sustainably harvested product, but there is little data to guide management. I examined nibbi biology, harvest response, product yield and use at several forest sites. H. flexuosa is a relatively abundant plant and 35% of trees (≥ 10 cm dbh) in plots were hosts. Stems exhibited mean growth rates of 1-3 cm per month. Aerial roots grew a mean 156 cm per month and some reached maturity within 6 months. With present methods, harvest does not decimate populations because 97% of colonized trees possess few harvestable roots. But, only 28% of cut roots re-generated in experiments. For indigenous harvesters at Manawarin village, nibbi harvesting is a primary source of cash income and is important in daily subsistence.

The killing of parents and stepparents by biological and stepchildren is a rare event. Incidents involving multiple parricide victims and/or multiple parricide offenders are an even rarer occurrence. The majority of studies on parricide involve a single victim and single offender. Using the National Incident-Based Reporting System (NIBRS), this study identified 603 single-victim, single-offender incidents, 22 single-victim, multiple-offender incidents, 60 single-offender double parricide incidents, 17 multiple-offender double parricide incidents, and 15 familicide incidents over the 20 year period 1990 to 2010. Univariate and bivariate analyses examined parricidal incidents involving single or multiple offenders and single or multiple victims with the aim of investigating juvenile and adult involvement in double parricide and familicide. Frequencies reported include victim, offender, and incident characteristics for all types of parricide incidents. Consistent with prior research on single-victim, single-offender parricide, the results indicated that the typical parricide offender was a white male approximately 30 years of age. A firearm predominated as the weapon of choice for all parricide incidents; however, when a biological mother was one of the victims, the offender(s) used more diverse methods. When multiple offenders were involved in double parricides, however, the offenders tended to be younger and were more likely to include a female accomplice. Only one case of familicide involved a female offender, and none of the familicide incidents involved multiple offenders. Study limitations and implications for prevention are also discussed.

In the process of biodiesel production, glycerol is produced as a byproduct in bulk amounts. The amount of glycerol supplied is larger than its demand thus stockpiling and acting as waste. As a solution, glycerol which is a highly functionalized molecule must be converted to value-added products. Several catalytic routes were thoroughly investigated including, hydrogenolysis, dehydration, pyrolysis, transesterification, etherification, carboxylation and electro-oxidation. All of these routes produce products of high economic interests. However, electro-oxidation seems to be the most promising as it runs under milder conditions and the selectivity may be easily tuned by varying the applied potential and the catalyst type. In addition, the electrical energy required may be provided by renewable energy sources. Some of the value-added products that may be produced by electrooxidation listed from highest economic value to lowest are glyceraldehyde, dihydroxyacetone, lactate, glycerate, tartronate (C₃ products) > mesooxalate, glycolate, oxalate (C₂ products) > and formate (C₁ products). Noble metals (Pt, Pd and Au) are considered to be the best for alcohol electrooxidation reactions as they present high electrocatalytic activity and selectivity. To date, research is focused on enhancing the activity and selectivity of noble metals by changing the nanoparticles morphology and adding adatoms/promoters/supports. On the other hand, these metals are non-abundant and expensive which limits their actual use in the industry. For this reason, non-noble metals (Ni and Co) have gained interest as potential alternatives. Particularly, nickel has proved to have significant activity, high durability and anti-poisoning capability for GEOR. A few studies presented enhancement in catalytic performance by varying the nanoparticles structure and adjusting the surface with a bimetallic promoter. However, there is still so much space for further research to enhance the catalytic performance and selectivity of Ni-based materials. In this thesis, carbon supported bimetallic NiₓBi₁₀₀₋ₓ [x= 100, 95, 90, 80, and 50 at.%] and Ni₉₅Bi₅/C mixed with small amounts of metal oxides (CeO₂, SnO₂ and Sb₂O₃:SnO₂) were studied for GEOR application. All catalysts were synthesized by facile sodium borohydride reduction method which can be easily scaled up. Transmission electron microscopy (TEM) and electron dispersive x-ray spectroscopy (EDS) techniques were implemented to gather physical characterizations of the as-synthesized bimetallic NiBi/C catalyst. Different electrochemical tests such as; cyclic voltammetry, linear sweep voltammetry and chronoamperometry were conducted using a conventional three electrode electrochemical cell and a potentiostat to get insight on the electrochemical performance of all catalysts. Finally, quantitative product analysis was generated by running continuous glycerol electrolysis experiments in a 25 cm2 cell accompanied by HPLC analysis. The nanoparticles size of Ni₉₅Bi₅/C was ≥6nm as determined by TEM images. Results indicated that tuning the nanoparticles size has an impact on both activity and selectivity of bimetallic carbon supported NiBi catalyst. For instance, the NiBi/C (≥6nm NP size) synthesized herein had 40% higher selectivity to C₃ products compared to NiBi/C (≤3nm NP size) reported in literature. Additionally, the selectivity of Ni-based catalysts to C₃ products were largely enhanced by developing bimetallic carbon supported NiBi catalysts of different Ni:Bi atomic ratios and adding metal oxides (CeO₂, SnO₂ and Sb₂O₃.SnO₂) to NiBi/C catalysts. Results indicate that addition of metal oxides greatly enhanced selectivity to C₃ products in the following order; Ni₉₅Bi₅/C-ATO (100%)> Ni/C-ATO (99.17%)> Ni₉₅Bi₅/C-ceria (98.05%)> Ni/C-ceria (78.29%)> Ni₉₅Bi₅/C (41.43%)> Ni/C (34.57%). However, the activity of Ni₉₅Bi₅/C-X [X=CeO₂, SnO₂, and Sb₂O₃:SnO₂] was lower than that of Ni₉₅Bi₅/C and Ni/C which was explained by the strong metal support interactions between metal oxides and nickel.

Orientador: Lincoln de Assis Moura
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação
Made available in DSpace on 2018-07-22T23:19:57Z (GMT). No. of bitstreams: 1 Costa_MarlyGuimaraesFernandes_D.pdf: 12863637 bytes, checksum: a4c6503a71867851c435a6221aff7f2f (MD5) Previous issue date: 1996
Resumo: Publicações recentes têm mostrado a potencialidade da cintilografia mamária com MIEI - Tc99m no diagnóstico diferencial de câncer de mama de massas palpáveis. Nesta tese apresentamos um método automático de detecção e classificação de lesões (malignas ou benignas), através desse exame. O método de detecção da lesão faz uso do filtro de novidade de Kohonen e a classificação automática é obtida a partir da análise do perfil médio da lesão extraída. Um conjunto de 20 imagens cintilográficas de mamas normais é segmentado e padronizado anatomicamente de tal forma que as imagens se ajustem às dimensões, forma e orientação de uma mama padrão. Posteriormente são ortogonalizadas de modo a constituirem uma base de vetores ortogonais. Um conjunto de 34 imagens de mamas padronizadas foi apresentado ao filtro de novidade. O método descreve essas imagens como uma combinação linear dos vetores da base. Assumindo que as imagens da base sejam representativas de mamas normais, não há diferenças significativas entre uma imagem de teste normal e sua correspondente descrição como combinação linear das imagens da base. As lesões de mama (massas benignas ou malignas), são identificados como um componente ortogonal ao subespaço gerado pelos vetores da base de mamas normais (novidades). As lesões identificadas são então analisadas e classificadas como benignas ou malignas. Curvas de ROC (receiver-operating characteristic) de decisão de desempenho são obtidas para dois conjuntos de imagens da base. Os valores de sensibilidade e especificidade obtidos com o método proposto foram respectivamente 94,12% e 88,24%
Abstract: Recent reports have shown 99mTc- MIBI uptake in malignant and benign breast lesions. These reports emphasize that mammography remains the procedure of choice in screening asymptomatic women for breast cancer. However, in patients with symptoms, the use of 99mTc- MIBI scintimammography offers a simple non-invasive method for the detection of breast cancer which presents improved sensitivity and specificity that are compatible with mammograms. This thesis describes an automatic method for detecting breast lesions in such exams. The proposed method detects lesions and classifiesthem as benign or malignant. The detection method makes use of Kohonen's novelty filter and classification is achieved by the analysis of an identified lesion mean profile. Lateral prone images of 20 normal subjects were segmented and anatomically standardized, with respect to location and magnification. All image vectors were orthogonalized to create an orthogonal vector basis. A set of 34 standardized images were then tested by the novelty filter. The filter describes images as a linear combination of images in the orthogonal vector basis. Assuming that the image basis is representative of normal patterns, then it can be expected that there should be no major differences between a normal test image and its corresponding linear combination image. The breast lesion was identified as the orthogonal component to the basis vectors formed by normal breast images. Lesions were analysed and classified as benign or malignant (eaneer). ROC curves were created from two orthogonal image bases, the first with 20 images and the second with 30 images. There was no significant difference in performance. The proposed method was able to detect all lesions present in the scintimammogram and to correctly classify 16 out of 17 malignant lesions and 15 out of 17 benign lesions. The sensitivity of the method was 94,12% and specifieity was 88,24%
Doutorado
Doutor em Engenharia Elétrica

Theft of construction equipment, materials, and tools from construction sites results in approximately one billion dollars in direct annual losses to the U.S. construction industry per year. A better understanding of theft characteristics is vital to reducing this figure. This study analyzes over 15,000 incidents from the National Incident-Based Reporting System (NIBRS) to understand characteristics such as theft prevalence, average monetary losses, and recovery rates. The study finds that contractors lost an average of about $6,000 per incident. Trucks are the most expensive theft targets, with an average loss of about $42,000 per incident, and also the most likely item to be recovered (55% of the time). However, recovery rate across all targets was less than 7%. The results of this study provide the most accurate and extensive statistics to date on construction theft characteristics. The study also identifies best practices to reduce thefts such as the use of survellience systems. Further, the use of advanced marking and tracking systems to safeguard expensive equipment and vehicles and aid their recoveries are discussed. The findings are expected to aid contractors and law enforcement agencies in formulating methods for reducing thefts of construction items and improving the likelihood of their recoveries.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering; and, (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; in conjunction with the Leaders for Global Operations Program at MIT, 2010.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 82-84).
Given that research is based on innovation, it has been believed that its activities can only be optimized with equipment upgrade, increment in personnel scientific knowledge, development of new analytical software and/or changing the areas of study. After realizing the limited results achieved with these approaches, lab representatives started to notice the opportunity of introducing process optimization tools, such as Lean and Six Sigma, which showed success in manufacturing environments,. This project analyzes the interrelation between process and results, providing a clear explanation of cause and effect conditions, and a concise list of areas for improvement. Specifically, the document defines a measurement system using process maps and key performance indicators (KPIs). With this, the document describes the current state through historic trends, provides a complete data and root cause analysis for current state description, and provides a process capability study for the available indicators. Implementation of the steps mentioned above show how focus in lab turnaround times have been deviating attention from more impactful improvements, which can greatly affect overall drug discovery duration. Also, the analysis identifies that constant technology changes caused constant adaptation of process procedures, which generated non-value added activities. These non-value added activities today occupy about 50% of a lab associate's time. Lastly, historic data evaluation shows that root cause statistical analysis is limited by the presence of a combination of special and common cause variations. Some of the project recommendations include: incorporation of chemist's knowledge about compound potency, integration of equipment and software information, change in booking system, incorporation of assay and plate criteria, definition of standard procedures for specific activities, and integration of assay development and data submission tools. Overall, these changes can lead to a 50% reduction in the profiling times greater than 60 days, decrease of 62% and 60% in Compound Manager (CM) and Compound Profiler (CP) non-value added times respectively, 30% decrease in CM and CP total duration per assay plate, and increase in profiling time stability and predictability. Despite the fact that timing and scale of available resources will impact the realized benefits, the proposed framework gives EPP the opportunity to assess the improvements by their effect and alignment with goals.
by Tatiana Yglesias.
M.B.A.
S.M.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Michal Rataj Supervisor: Doc. PharmDr. Martin Beránek Ph.D. Title of diploma thesis: Genetic polymorphism in the NBS1 gene for diagnosis and treatment of patients with cervical carcinoma The aim of this diploma thesis is to find optimal methods for screening of mutation 657del5 and estimate frequency of heterozygotes and homozygotes for the mutation 657del5 in population of the Czech republic. In the first section of the theoretical part is comprehensively pointed out the effect of factors affecting the integrity of genetic information and the formation of mutations in DNA. On the contrary, the second section devotes to the ability of cells to respond to this damage. In detail, the thesis devotes to the NBS1 gene and its product nibrin. In the complex MRE11/Rad50/NBN nibrin is an important member of the mechanisms of repair of double strand breaks NHEJ (non-homologous end joining) and HR (homologous recombination). The thesis is focused on nibrin and its functions, but also to mutations that prevent these functions and causes genetic disease Nijmegen breakage syndrome. Nibrin is translated from the sequence of the NBS1 gene. Gene NBS1 appears in population with several various...

The microstructures and performance of Ni-based alloys and Ni-WC (nickel-tungsten carbide) composite overlays deposited by plasma transferred arc welding have been studied. The Ni-alloy overlays had similar microstructures consisting of Ni dendrites, with interdendritic Ni-based eutectics, borides and carbides. Low hardness alloy overlays contained a smaller fraction of interdendritic phases relative to the high hardness alloys. The interdendritic regions make a significant contribution to the hardness since they are more than twice as hard as primary dendrites. The Ni-WC composites contained similar phases, however WC dissolution was observed leading to the formation of other carbides. Ni-alloys with low carbon and Cr content exhibited the lowest WC dissolution. The Ni-WC overlays produced using these dilute alloys generally performed better in ASTM G65 wear tests. This was likely due to the reduced dissolution which avoided formation of brittle secondary phases, maintaining a short mean free path between WC particles and allowing increased impact energy absorption.
Materials Engineering

In a world where software gradually plays a key role daily, a failure may bring unpleasant consequences for its users. An example of a serious failure was the case Apple iCloud security exploit in 2014 where several private photos of celebrities have been accessed without permission[icl14a][icl14b]. Apart from economic and commercial implications, these faults lead to loss of trust in software by users, thus leading to the consequent search for an alternative and even result in leaving the old software for a new alternative. To address these shortcomings, the software industry started to use software testing to make sure that the software contains the minimum possible failures before is deployment. Software tests are used to analyse the program, namely to search some bugs. This analysis can be done without program execution (static analysis) or during execution (dynamic analysis). Static analysis tools can be used to check for potential execution of the program that have not been prematurely aborted due to unexpected event at runtime, not ensuring that the program will display the correct result. We studied some static analysis tools, JSFlow, JSPrime and TAJS, which analyse JavaScript code. These tools have been modified so they can be integrated into the Nibiru framework. Nibiru is a modular framework that aims to help in the implementation of software testing. It uses a micro-services architecture, enabling the use of multiple programming languages in his modules and has the ability to enable the implementation of its modules on multiple machines. So far the Nibiru has three operating modules and its ready to start growing with the community, so they can contribute in the construction of new modules or make small adjustments on the existing testing software to integrate the Nibiru framework.
Num mundo onde cada vez mais o software tem um papel fundamental nas atividades do dia-a-dia, uma falha pode trazer consequências desagradáveis para os seus utilizadores. Como exemplo de uma falha grave, temos o caso Apple iCloud security exploit em 2014 [icl14a][icl14b], onde várias fotos de celebridades foram acedidas sem permissão. Para além de repercussões económicas e comerciais estas falhas levam à perca de confiança no software por parte dos utilizadores, levando assim à consequente procura de alternativas ao mesmo, podendo até resultar no abandono do software antigo. Para colmatar estas falhas, hoje em dia a indústria cada vez aposta mais nos testes de software para certificar-se que o software contém o mínimo de falhas possíveis antes de sair para o mercado. Os testes de software servem para analisar o programa, nomeadamente na obtenção de bugs. Esta análise pode ser feita sem execução do programa (análise estática) ou durante a sua execução (análise dinâmica). As ferramentas de análise estática são utilizadas para verificar se existem potenciais execuções do programa que possam falhar durante a sua execução devido a eventos inesperados, isto faz com que o programa apresente um resultado incorreto ou até mesmo bloqueie. Foram estudadas algumas ferramentas de análise estática, JSFlow, JSPrime e TAJS, que analisam código JavaScript. Estas ferramentas foram modificadas para serem integradas na framework Nibiru. O Nibiru é uma framework modular que tem como intuito ajudar na execução de testes de software. Esta utiliza uma arquitetura de micro-serviços, possibilitando o uso de múltiplas linguagens de programação nos seus módulos e tem a capacidade de possibilitar a execução dos seus módulos em várias máquinas. Até ao momento o Nibiru conta com três módulos operacionais, encontrando-se pronto para crescer com a comunidade informática, podendo esta contribuir na construção de novos módulos.