Chromosome preparations from 102 ICR albino mice were examined using a modified trypsin Giemsa staining technique. The mice were from four lines selected for maximum rate of post-weaning gain (28 generations), one line selected for minimum rate of post-weaning gain (25 generations), and two unselected control lines. Mitotic metaphase chromosome preparations were obtained from bone marrow cells of adult male and female mice. Two similar treatments were utilized in obtaining the chromosome preparations. The first treatment consisted of: 50 minute colchicine pretreatment, 30 minute hypotionic pretreatment, four-glacial acetic acid-methnanol fixation periods, 15 second trypsin period and 15 minute Giemsa staining period. The second treatment varied from the first, basically, in the length of hypotonic pretreatment, and length and number of fixation periods. A mean number of 40 telocentric chromosomes with very similar banding patterns was observed in all lines. Relative chromosome lengths for each chromosome were obtained. The lengths for the various lines, control, high and low, were compared by means of a pooled "t" test. Non-significant a₂ levels were obtained for the pairwise comparisons of the lines. Significant a₂ levels were obtained for the effects of the two treatments, trypsin and no trypsin. Karyotypes for each line were made with no chromosomal abnormalities detected in any of the lines. The selection regime followed has produced significant genetic change in several characteristics of these mice. However, these changes have apparently not been accompanied by observable alterations at the chromosomal level. / Master of Science

No description available.

京都大学 / 新制・課程博士 / 博士(薬学) / 甲第23845号 / 薬博第852号 / 新制||薬||242(附属図書館) / 京都大学大学院薬学研究科薬学専攻 / (主査)教授 髙倉 喜信, 教授 山下 富義, 教授 小野 正博 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Malaria infects over 200 million individuals and leads to the death of over 600 000 people annually. Currently artemisinin combination therapy treatments are effective in treating the disease, but resistance has started to emerge in Cambodia and it is suspected in parts of Vietnam. To maintain the drive to eradicate malaria globally, a great deal of research is aimed at identifying novel prevention strategies, vaccines and antimalarial compounds. Plasmodium falciparum, the most deadly of the malaria parasites, is entirely dependent on glycolysis for ATP. Several of the enzymes within this pathway have been proposed as drug targets and studied in isolation, but the pathway as a whole has not been considered. In this study we employ a bottom up approach for drug target identification in P. falciparum glycolysis. In this thesis we present the biochemical characterisation each of the glycolytic enzymes in P. falciparum trophozoites. The kinetic rate equations, which described the kinetic behaviour of the individual enzymes, were incorporated into a kinetic model. The unfitted model was validated in its ability to predict experimentally measured steady state metabolite concentrations and fluxes as well as the experimental inhibition of the glucose transporter. The validated model provided a tool for drug target identification in P. falciparum glycolysis. Metabolic control analysis and differential control analysis identified the glucose transporter, PfHT1, as a drug target based on its high control of glycolytic flux in the parasite, but low control of flux in the host erythrocyte. This differential control makes the transporter an attractive drug target, as even if both the erythrocyte and parasite glucose transporters are inhibited to the same degree, it is expected that the parasite glycolytic flux would be inhibited to a much greater degree. To demonstrate the differential control of the glucose transporter on the flux and provide further evidence that PfHT1 is an attractive drug target, we investigated the inhibition of the glucose transporter in isolated trophozoites by cytochalasin B. We also measured the inhibition of lactate production flux by cytochalasin B in both isolated P. falciparum trophozoites as well as in erythrocytes. Our findings demonstrated that differential control analysis can be used as a tool for drug target identification and that PfHT1 is an attractive drug target. In this study the fields of biochemistry and systems biology were merged to create a detailed kinetic model of asexual P. falciparum glycolysis and identify several drug targets in the pathway. The model prediction and experimental evidence of differential flux control of the glucose transporter in the host and parasite, has highlighted PfHT1 as a drug target and also demonstrates the strength of differential control analysis in identifying drug targets within a system. The kinetic model is a valuable tool for furthering our understanding of P. falciparum glycolysis and it provides a good foundation for expansion to identify drug targets in the entire central carbon metabolism of P. falciparum. / AFRIKAANSE OPSOMMING: Malaria infekteer meer as 200 miljoen mense en veroorsaak jaarliks tot 600 000 sterftes. Tans is die artemisinien-kombinasieterapie effektief in die bestryding van die siekte, maar weerstandbiedendheid van die parasiet teen die middel blyk reeds ’n merkbare effek in Kambodja en vermoedelik ook in dele van Viëtnam te hê. Om ’n wêreldwye bestryding van malaria moontlik te maak, is ’n groot deel van die huidige navorsing gemik op die identifisering van nuwe voorkomingsstrategieë, entstowwe en malariateenmiddels. Plasmodium falciparum, die dodelikste van die malaria-parasiete, is geheel en al afhanklik van glikolise vir ATP vorming. Verskeie van die ensieme in hierdie metaboliese pad is as teenmiddelteikens voorgestel, en in isolasie bestudeer, maar die pad as ’n geheel is nie bestudeer nie. In hierdie studie het ons ’n ’bottom-up’ benadering vir teenmiddel teikenidentifisering in P. falciparum glikolise gebruik. In hierdie tesis bied ons die biochemiese karakterisering van elk van die glikolitiese ensieme in P. falciparum trofozoïete aan. Die kinetiese vergelykings wat die kinetiese gedrag van die individuele ensieme beskryf, is geintegreer in ’n enkele kinetiese model. Die model waarop geen datapassing toegepas is nie, is gevalideer om eksperimenteel bepaalde bestendige-toestand metabolietkonsentrasies en fluksiewaardes, asook die eksperimentele inhibisie van die glukose transporter, te voorspel. Die gevalideerde model verskaf ’n bykomende hulpmiddel om teenmiddelteikens te identifiseer in P. falciparum glikolise. Metaboliese kontrole-analise en differensiële kontrole-analise het die glukose transporter, PfHT1, as ’n teenmiddelteiken geïdentifiseer, gebaseer op sy hoë kontrole van glikolitiese fluksie in die parasiet, tesame met ’n lae beheer van die glukose transporter op die fluksie in die gasheer eritrosiet. Dié differensiële kontrole maak die glukose transporter ’n aantreklike teenmiddelteiken, want selfs as beide die eritrosiet en die parasiet glukose transporters tot dieselfde mate geïnhibeer word, sal dit steeds ’n hoër glikolietiese fluksieinhibisie van die parasiet tot gevolg hê. Om die differensiële kontrole van die glukose transporter op die fluks te demonstreer en verdere bewyse te lewer dat PfHT1 ’n teenmiddelteiken kan wees, het ons die inhibisie van die glukosetransporter in geïsoleerde trofozoïete deur sitokalasien B ondersoek. Ons het ook die inhibisie van die laktaatproduksiefluksie deur sitokalasien B in beide geïsoleerde P. falciparum trofozoïete sowel as in eritrosiete ondersoek. Ons bevindings bewys dat differensiële kontroleanalise as ’n hulpmiddel vir teenmiddelteikenidentifikasie gebruik kan word en dat PfHT1 ’n aantreklike teenmiddelteiken is. In hierdie studie is die velde van biochemie en sisteembiologie gekombineer om ’n gedetaileerde kinetiese model van ongeslagtelike P. falciparum glikolise te konstueer en verskeie teenmiddelteikens in die metaboliese pad te identifiseer. Die modelvoorspelling sowel as eksperimentele bewyse van die differensiële flukskontrole van die glukose transporter in die gasheer en parasiet het PfHT1 uitgelig as ’n teenmiddelteiken en demonstreer ook die krag van differensiële kontrole analise in die identifisering van teenmiddelteikens binne ’n biologiese stelsel. Die kinetiese model is ’n waardevolle hulpmiddel vir die bevordering van ons begrip van P. falciparum glikolise en dit bied ’n goeie basis vir uitbreiding om teenmiddelteikens in die hele sentrale koolstofmetabolisme van P. falciparum te identifiseer.

Submitted by Maike Costa (maiksebas@gmail.com) on 2017-06-06T11:36:19Z No. of bitstreams: 1 arquivototal.pdf: 2587851 bytes, checksum: 3aefbde79e924d09dc5d5bd83813c6c1 (MD5) / Made available in DSpace on 2017-06-06T11:36:19Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2587851 bytes, checksum: 3aefbde79e924d09dc5d5bd83813c6c1 (MD5) Previous issue date: 2016-01-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The present work aims at the development and implementation of the adaptive generalized predictive controller (GPC) and the proportional integral proportional controller (PID) in a two-degree planar manipulator robot (2 GDL) composed of a rotational link and another prismatic. The rotational link has as structure an extensive branch of aluminum in profile U, having as actuator a motor-reducer of continuous current, and as sensing a potentiometer of ten turns, that acts like transducer of angular position. The prismatic link consists of a double acting pneumatic cylinder with a through rod fixed inside the rotational link, having as actuator a proportional electropneumatic valve of five paths and three positions and as sensing a potentiometric ruler that acts as a linear position transducer . The obtaining of the representative mathematical model of the robot will occur through the estimator of recursive least squares (MQR). We present experimental results of the estimated models and system responses under the action of the designed controllers. / O presente trabalho tem como objetivo o desenvolvimento e implementação do controlador preditivo generalizado (GPC) adaptativo e do controlador proporcional integral derivativo (PID) convencional, em um robô manipulador planar de dois graus de liberdade (2 GDL) composto por um elo rotacional e outro prismático. O elo rotacional possui como estrutura um ramo extenso de alumínio em perfil U, possuindo como atuador um motor-redutor de corrente contínua, e como sensoriamento um potenciômetro de dez voltas, que atua como transdutor de posição angular. O elo prismático é constituído por um cilindro pneumático de dupla ação com haste passante, fixado no interior do elo rotacional, possuindo como atuador uma válvula eletropneumática proporcional de cinco vias e três posições e como sensoriamento uma régua potenciométrica, que atua como transdutor de posição linear. A obtenção do modelo matemático representativo do robô se dará através do estimador dos mínimos quadrados recursivos (MQR). São apresentados resultados experimentais dos modelos estimados e respostas do sistema sob ação dos controladores projetados.

Ein Algorithmus zur Identifizierung von Elektronen mit dem BABAR Detektor wird entwickelt. Basierend auf Spuren, deren Teilchenidentität aus rein kinematischen Überlegungen gefolgert werden kann, wird für Impulse zwischen 0.5 und 2.5 GeV/c die Selektionseffizienz für Elektronen zu 90% bestimmt. Im gleichen Impulsbereich liegt die Wahrscheinlichkeit, Pionen als Elektronen zu identifizieren, zwischen 0.05% und 0.1%. Auf diesem Algorithmus basiert die Messung des inklusiven Elektronen Impulsspektrums aus B-Meson Zerfällen anhand der Daten, die mit dem BABAR Detector am asymmetrischen Speicherring PEP-II ("B-Factory") aufgezeichnet wurden. Das Volumen der analysierten Daten entspricht einer integrierten Luminosität von 4.13 1/fb auf der Y(4S) Resonanz und 0.97 1/fb bei einer um 40 MeV verringerten Schwerpunktsenergie. B - Anti-B Ereignisse werden anhand hochenergetischer Elektronen identifiziert. Elektronen von einem semileptonischen Zerfall des zweiten B-Mesons werden durch die relative Ladung und Impulsrichtung zum hochenergetischen Elektron vom Untergrund aus semileptonischen Charm Zerfällen isoliert. Das inklusive Verzweigungsverhältnis für den semileptonischen Zerfall des B-Mesons wird zu (10.85 +-0.22(stat.) +-0.34(sys))% gemessen. Zusammen mit der Lebenszeit von B-Mesonen lässt sich daraus |V_cb| bestimmen: |V_{cb}| = 0.0406 +-0.0009(exp) +-0.0019(theory). / An algorithm for identification of electrons with the BABAR detector is developed. Based on pure samples of electrons and hadrons obtained from data, we determine the electron identification efficiency to be above 90% for momenta above 0.5 GeV/c in the laboratory frame, while the pion fake rate lies between 0.05% and 0.1%. Based on this algorithm, a measurement of the inclusive lepton momentum spectrum in B meson decays is performed. We analyze 4.13 fb^-1 and 0.97 fb^-1 of data recorded at and slightly below the Upsilon(4S) resonance with the BABAR detector at the PEP-II a symmetric B-Factory. B-Bbar events are tagged by a high momentum electron. Using charge and angular correlations, leptons from a second semileptonic $B$ decay are separated from secondary charm semileptonic decays. The inclusive branching ratio is measured to be (10.85 +-0.22(stat.) +-0.34(sys))% . Combined with the B lifetime we determine |V_cb| = 0.0406 +-0.0009(exp) +-0.0019(theory).

Investigating a crime of rape relies heavily upon physical evidence, which provides the court with tangible objects that are not subject to memory loss. The recognition ofphysical evidence plays a critical role in the investigation process. The first step of crime scene investigation is to conduct observation to locate valuable physical evidence; a task that depends on the skills of the investigating officer. The more common types of physical evidence that could link a suspect to the crime were identified in this study. This dissertation endeavours to provide crime scene investigators with answers on how to conduct observation at a rape crime scene. This research is based on interviews and a literature study, and will furnish insight and information about the observation process at rape crime scenes. The findings of the research may generate guidelines for crime scene observation. Recommendations and conclusions are indicated in the final chapter. / Police Practice / M. Tech (Forensic Investigation)

Made available in DSpace on 2014-12-17T14:55:36Z (GMT). No. of bitstreams: 1 JoaoPSM.pdf: 2736653 bytes, checksum: 0b1bd7853a47877b24c5f2042e0a5d8e (MD5) Previous issue date: 2009-06-19 / Petr?leo Brasileiro SA - PETROBRAS / A new method to perform TCP/IP fingerprinting is proposed. TCP/IP fingerprinting is the process of identify a remote machine through a TCP/IP based computer network. This method has many applications related to network security. Both intrusion and defence procedures may use this process to achieve their objectives. There are many known methods that perform this process in favorable conditions. However, nowadays there are many adversities that reduce the identification performance. This work aims the creation of a new OS fingerprinting tool that bypass these actual problems. The proposed method is based on the use of attractors reconstruction and neural networks to characterize and classify pseudo-random numbers generators / ? proposto um novo m?todo para identifica??o remota de sistemas operacionais que operam em redes TCP/IP. Este m?todo possui diversas aplica??es relacionadas ? seguran?a em redes de computadores e ? normalmente adotado tanto em atividades de ataque quanto de defesa de sistemas. O m?todo proposto ? capaz de obter sucesso em situa??es onde diversas solu??es atuais falham, inclusive no tratamento com dispositivos possivelmente vulner?veis ao processo de identifica??o. O novo m?todo realiza a an?lise dos geradores de n?meros aleat?rios usados nas pilhas TCP/IP e, atrav?s do uso de redes neurais artificiais, cria mapas que representam o comportamento destes geradores. Tais mapas s?o usados para compara??o com mapas rotulados que representam sistemas j? conhecidos, concretizando o processo de identifica??o

Ein Algorithmus zur Identifizierung von Elektronen mit dem BABAR Detektor wird entwickelt. Basierend auf Spuren, deren Teilchenidentität aus rein kinematischen Überlegungen gefolgert werden kann, wird für Impulse zwischen 0.5 und 2.5 GeV/c die Selektionseffizienz für Elektronen zu 90% bestimmt. Im gleichen Impulsbereich liegt die Wahrscheinlichkeit, Pionen als Elektronen zu identifizieren, zwischen 0.05% und 0.1%. Auf diesem Algorithmus basiert die Messung des inklusiven Elektronen Impulsspektrums aus B-Meson Zerfällen anhand der Daten, die mit dem BABAR Detector am asymmetrischen Speicherring PEP-II ("B-Factory") aufgezeichnet wurden. Das Volumen der analysierten Daten entspricht einer integrierten Luminosität von 4.13 1/fb auf der Y(4S) Resonanz und 0.97 1/fb bei einer um 40 MeV verringerten Schwerpunktsenergie. B - Anti-B Ereignisse werden anhand hochenergetischer Elektronen identifiziert. Elektronen von einem semileptonischen Zerfall des zweiten B-Mesons werden durch die relative Ladung und Impulsrichtung zum hochenergetischen Elektron vom Untergrund aus semileptonischen Charm Zerfällen isoliert. Das inklusive Verzweigungsverhältnis für den semileptonischen Zerfall des B-Mesons wird zu (10.85 +-0.22(stat.) +-0.34(sys))% gemessen. Zusammen mit der Lebenszeit von B-Mesonen lässt sich daraus |V_cb| bestimmen: |V_{cb}| = 0.0406 +-0.0009(exp) +-0.0019(theory). / An algorithm for identification of electrons with the BABAR detector is developed. Based on pure samples of electrons and hadrons obtained from data, we determine the electron identification efficiency to be above 90% for momenta above 0.5 GeV/c in the laboratory frame, while the pion fake rate lies between 0.05% and 0.1%. Based on this algorithm, a measurement of the inclusive lepton momentum spectrum in B meson decays is performed. We analyze 4.13 fb^-1 and 0.97 fb^-1 of data recorded at and slightly below the Upsilon(4S) resonance with the BABAR detector at the PEP-II a symmetric B-Factory. B-Bbar events are tagged by a high momentum electron. Using charge and angular correlations, leptons from a second semileptonic $B$ decay are separated from secondary charm semileptonic decays. The inclusive branching ratio is measured to be (10.85 +-0.22(stat.) +-0.34(sys))% . Combined with the B lifetime we determine |V_cb| = 0.0406 +-0.0009(exp) +-0.0019(theory).