With the increase in the complexity of computer systems, existing security measures are not enough to prevent attacks. Intrusion detection systems have become an integral part of computer security to detect attempted intrusions. Intrusion detection systems need to be fast in order to detect intrusions in real time. Furthermore, intrusion detection systems need to be robust against the attacks which are disguised to evade them. We improve the runtime complexity and space requirements of a host-based anomaly detection system that uses q-gram matching. q-gram matching is often used for approximate substring matching problems in a wide range of application areas, including intrusion detection. During the text pre-processing phase, we store all the q-grams present in the text in a tree. We use a tree redundancy pruning algorithm to reduce the size of the tree without losing any information. We also use suffix links for fast linear-time q-gram search during query matching. We compare our work with the Rabin-Karp based hash-table technique, commonly used for multiple q-gram matching. To analyze the robustness of network anomaly detection systems, we develop a new class of polymorphic attacks called polymorphic blending attacks, that can effectively evade payload-based network anomaly IDSs by carefully matching the statistics of the mutated attack instances to the normal profile. Using PAYL anomaly detection system for our case study, we show that these attacks are practically feasible. We develop a formal framework which is used to analyze polymorphic blending attacks for several network anomaly detection systems. We show that generating an optimal polymorphic blending attack is NP-hard for these anomaly detection systems. However, we can generate polymorphic blending attacks using the proposed approximation algorithms. The framework can also be used to improve the robustness of an intrusion detector. We suggest some possible countermeasures one can take to improve the robustness of an intrusion detection system against polymorphic blending attacks.

To fortify their cytoplasmic membrane and protect it from osmotic rupture, most bacteria surround themselves with a peptidoglycan (PG) exoskeleton. The PG synthases that build this structure are called penicillin-binding proteins (PBPs). Since they are the targets of penicillin and related antibiotics, the structures and in vitro biochemical functions of the PBPs have been extensively studied. However, the in vivo functions of the PBPs and the factors they work with to build the PG meshwork remain poorly understood. PBPs work in the context of multicomponent complexes organized by cytoskeletal elements. A major outstanding question has been whether or not these complexes contain factors required for PBP function. I addressed this using Escherichia coli as a model system by taking advantage of the synthetic lethal phenotype resulting from simultaneous inactivation of the major PG synthases: PBP1a and PBP1b. Using a screen for mutants synthetically lethal with the inactivation of PBP1b, I identified LpoA as a factor required for PBP1a function. A colleague in the lab performed the analogous screen for mutants synthetically lethal with the inactivation of PBP1a and identified LpoB as a factor required for PBP1b function. We showed that the Lpo factors are outer membrane lipoproteins that form specific trans-envelope complexes with their cognate PBPs in the inner membrane and that LpoB can stimulate the activity of PBP1b in vitro. Our results reveal unexpected complexity in the control of PBP activity and indicate that they likely receive regulatory input from the outer membrane in addition to cytoskeletal elements in the cytoplasm. To investigate the role of LpoB in morphogenesis further, I took a genetic approach that has identified PBP1b* variants capable of functioning in vivo in the absence of LpoB. Preliminary characterization of these variants indicates that LpoB has cellular functions in addition to PBP1b activation and that LpoB may be important for coordinating the two different catalytic activities of PBP1b. Future study of these mutants is likely to uncover important insights into PBP function and their control by the Lpo factors. These insights may open new avenues for the development of novel therapeutics that target the PBPs.

<p>Nitric oxide (NO) is an endogenous gaseous signaling molecule produced by three NO synthase isoforms (NOS1, 2, 3) and important in host defense. The induction of NOS2 during bacterial sepsis is critical for pathogen clearance but its sustained activation has long been associated with increased mortality secondary to multiple organ dysfunction syndrome (MODS). High levels of NO produced by NOS2 incite intrinsic cellular dysfunction, in part by damaging macromolecules through nitration and/or nitrosylation. These include mitochondrial DNA (mtDNA) and enzymes of key mitochondrial pathways required for maintenance of normal O2 utilization and energy homeostasis. However, animal studies and clinical trials inhibiting NOS2 have demonstrated pronounced organ dysfunction and increased mortality in response to live bacterial infections, confirming that NOS2 confers pro-survival benefits. Of particular interest here, the constitutive NOS1 and NOS3 have been linked to the up-regulation of nuclear genes involved in mitochondrial biogenesis but no comparable role has been described for NOS2. <italic> Therefore, I hypothesized that NOS2 is indispensible for host protection but must be tightly regulated to ensure NO levels are high enough to activate mitochondrial and other pro-survival genes, but below the threshold for cellular damage.</italic></p><p>This hypothesis was explored with two major Aims. The <italic>first Aim</italic> was to define the role of NOS2 in the activation of mitochondrial biogenesis in the heart of <italic>E. coli</italic>-treated mice. The <italic>second</italic> was to investigate the ability of NOS2 to be transcriptionally regulated by an enzyme previously shown to induce mitochondrial biogenesis, heme oxygenase-1 (HO-1). This hypothesis was tested using an <italic>in vivo</italic> model of sublethal heat-killed <italic>E. coli</italic> (<italic>HkEC</italic>) peritonitis in C57B/L6 (Wt), NOS2-/-, and TLR4-/- mice. Additionally, <italic>in vitro</italic> systems of mouse AML-12 or Hepa 1-6 cells pretreated with HO-1 activators or <italic>Hmox1</italic> shRNA prior to inflammatory challenge with lipopolysaccharide (LPS) +/- tumor necrosis factor-&alpha; (TNF-&alpha;). For the first Aim, Wt, NOS2-/-, and TLR4-/- mice were treated with (<italic>HkEC</italic> and cardiac tissue analyzed for mitochondrial function, expression of nuclear and mitochondrial proteins needed for mitochondrial biogenesis, and histological expression of NOS2 and TLR4 relative to changes in mitochondrial mass. For the second Aim, Wt mice were pretreated with hemin or carbon monoxide (CO) to activate HO-1 prior to <italic>HkEC</italic>-peritonitis. Liver tissue in these animals was evaluated at four hours for HO-1 induction, <italic>Nos2</italic> mRNA expression, cytokine profiles, and nuclear factor (NF)-&kappa;B activation. Liver cell lines were pretreated with hemin, CO-releasing molecule (CORM), or bilirubin one hour before LPS exposure and the <italic>Nos2</italic> transcriptional response evaluated at two and 24 hours. The MTT assay was used to confirm that <italic>in vitro</italic> treatments were not lethal. </p><p>These studies demonstrated that <italic>HkEC</italic> induced mtDNA damage in the heart that was repaired in Wt mice but not in NOS2-deficient mice. In KO mice, sustained mtDNA damage was associated with the reduced expression of nuclear (NRF-1, PGC-1&alpha;) and mitochondrial (Tfam, Pol-&gamma;) proteins needed for mitochondrial biogenesis. The findings thus supported that NOS2 is required for mitochondrial biogenesis in the heart during Gram-negative challenge. Evaluation of the relationship between HO-1 and NOS2 in murine liver was more complex; HO-1 activation in <italic>HkEC</italic>-treated Wt mice attenuated 4-hour <italic>Nos2</italic> gene transcription. In liver cell lines, hemin, CORM, and bilirubin were unable to suppress <italic>Nos2</italic> expression at the time of maximal induction (2 hours). <italic>Nos2</italic> was, however, suppressed by 24 hours, suggesting that the regulatory impact of HO-1 induction was not engaged early enough to reduce <italic>Nos2</italic> transcription at 2 hours. It is concluded that NOS2 induction in bacterial sepsis optimizes the expression of the mitochondrial biogenesis transcriptional program, which subsequently can also be regulated by HO-1/CO in murine liver. This provides a potential new mechanism by which immune suppression and mitochondrial repair can occur in tandem during the acute inflammatory response.</p> / Dissertation

The enzyme 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase catalyses the aldol condensation of the five-carbon sugar phosphate, arabinose 5-phosphate (A5P), and phosphoenol pyruvate (PEP) to give the eight-carbon phosphorylated sugar, KDO8P. It is the second committed step in the synthesis of KDO, a necessary component of the cell wall of Gram-negative bacteria. This thesis describes the design, synthesis and evaluation of a number of inhibitors of KDO8P synthase that utilise the functionality of one or both substrates. The KDO8P synthase family can be divided based on the requirement of a divalent metal ion. Chapter 2 describes the growth, purification and characterisation of an example from both the metal-independent KDO8P synthases (Neisseria meningitidis, Nme) and metal-dependent KDO8P synthases (Acidithiobacillus ferrooxidans, Afe) in order to utilise these enzymes for the inhibition studies described in this thesis. In Chapter 3, a number of small molecule PEP analogues were selected as mimics of KDO8P synthase reaction intermediates and tested as inhibitors of KDO8P synthase from N. meningitidis and A. ferrooxidans. Glyphosate, (E)-vinyl phosphonate and the fluorinated analogue of (E)-vinyl phosphonate were selected as mimics of the high-energy oxocarbenium intermediate through which the KDO8P synthase reaction is thought to occur. The two enantiomers of phospholactate were selected in order to investigate the chirality of the tetrahedral intermediate and determine the importance of this chirality for inhibition of KDO8P synthase. All five inhibitors were found to be moderate to poor inhibitors of both the KDO8P synthase from N. meningitidis and A. ferrooxidans. Chapter 4 describes the design and synthesis of inhibitors that incorporated structural features of the second substrate, A5P, in order to improve inhibition from that observed for the PEP analogues investigated in Chapter 3. A bisphosphate inhibitor was designed that incorporated a terminal phosphate moiety, representative of the phosphate of A5P. A large increase in inhibition was found, compared to the phospholactates from which it was derived. A structure-activity-relationship study was undertaken on this compound by design of compounds that lacked one of the two phosphate moieties of the bisphosphate inhibitor, in order to determine their relative importance. The inhibition results indicate that the primary terminal phosphate, thought to bind in the A5P phosphate binding site, is more important for inhibition of KDO8P synthase than the secondary phosphate. In Chapter 5 these investigations into the inhibition of KDO8P synthase are discussed in detail, and interpreted using the aid of computational studies. In addition several approaches are described for the completion and advancement of the studies presented here in this thesis.

In praktischen Aufgabenstellungen können zur Modellierung zufälliger Einflüsse, welche sich durch schwache Abhängigkeiten auszeichnen, schwach korrelierte zufällige Funktionen genutzt werden. Die nähere Untersuchung von Funktionalen schwach korrelierter zufälliger Funktionen ist durch die Gestalt der Lösungen von praktischen Fragestellungen motiviert. Die stochastischen Charakteristiken dieser Lösungen lassen sich im Allgemeinen nicht exakt bestimmen, so dass auf Approximationsverfahren zurückgegriffen werden muss. Diese stehen im Mittelpunkt der Dissertation. Zu Beginn werden Entwicklungen von Momenten und Kumulanten der betrachteten linearen Integralfunktionale schwach korrelierter Prozesse nach der Korrelationslänge des Prozesses hergeleitet und eine Vermutung über die exakte Darstellung der Kumulanten formuliert. Für Integralfunktionale von schwach korrelierten Simulationsprozessen, welche aus der Interpolation von Moving-Average-Prozessen entstehen, werden die definierten Charakteristiken hergeleitet. Außerdem steht die Approximation der unbekannten Dichtefunktion im Fokus der Arbeit. Es werden verschiedene Zugänge genutzt. Eine alternative Herleitung zur bereits in der Literatur untersuchten Gram-Charlier-Entwicklung wird in Form der Edgeworth-Entwicklung angegeben. Des Weiteren werden die Sattelpunkt-Approximation und die Maximum-Entropie-Methode untersucht und anhand von Simulationsergebnissen für Integralfunktionale von Simulationsprozessen miteinander verglichen. / In engineering applications stochastic influences which are characterized by weak dependencies can be modelled, among others, by weakly correlated random functions. The solutions of such problems shape up as integral functionals of weakly correlated random functions which motivates more detailed investigations. In general the exact calculation of stochastic characteristics of such integral functionals is impossible so that we have to be content with approximation methods this thesis focuses on. At the beginning expansions of moments and cumulants of linear integral functionals of weakly correlated random processes with respect to the correlation length are considered and an explicit formula of cumulants is conjectured. For integral functionals of weakly correlated random simulation processes, defined as interpolations of moving average processes, the required expansion coefficients are derived. Furthermore the approximation of the unknown probability density is requested. In the thesis there are different approaches used. First we state an alternative way to achieve the already known Gram Charlier approximation by means of Edgeworth expansion. Then we study two further methods, namely the saddlepoint approximation and the maximum entropy method and compare them on the basis of simulation results for integral functionals of simulation processes.

3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase is the enzyme responsible for catalyzing the first reaction in the biosynthesis of KDO. KDO is an essential component in the cell wall of Gram-negative bacteria and plants. This compound is not present in mammals; therefore the enzymes responsible for its biosynthesis are potential targets for the development of new antibiotic agents. KDO8P synthase catalyzes the condensation reaction between phosphoenol pyruvate (PEP) and D-arabinose 5-phosphate (A5P) to form KDO8P. Two types of KDO8P synthase have been identified; a metal-dependent type and a non metal-dependent type. KDO8P synthase from the organism Chlorobium tepidum (Cte) has been partially purified and partially characterized. In line with predictions based on sequence alone, the activity of this enzyme is dependent on the presence of a divalent metal ion and is sensitive to the presence of the metal chelating agent EDTA. Cte KDO8P synthase was found to have the highest activity in the presence of Mn2+ or Cd2+. KDO8P synthase from the organism Acidithiobacillus ferrooxidans (Afe) has also been cloned, purified and biochemically characterized. Afe KDO8P synthase was also found to be a metallo enzyme and the catalytic activity is highest in the presence of Mn2+ or Co2+. Afe KDO8P synthase was found to exist as a tetramer in solution and is most active within the pH range of 6.8 to 7.5 and within a temperature range of 35 ºC to 40 ºC. Sequence analysis suggests that this enzyme has characteristics conserved throughout the metallo and the non-metallo KDO8P synthases and is closely related to the metal-dependent 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) synthases. The role of several active-site residues of Afe KDO8P synthase has been investigated. A C21N mutant of Afe KDO8P synthase was found to retain 0.5% of wildtype activity and did not require a divalent metal ion for catalytic activity. This suggests that the metallo and non-metallo KDO8P synthases have similar catalytic mechanisms.

Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2003. / Vita. Bibliography: 162-207.

Made available in DSpace on 2014-12-17T15:48:09Z (GMT). No. of bitstreams: 1 VivianeMR_DISSERT.pdf: 1295596 bytes, checksum: 1bb5688145cd1ce7005121d9de48c246 (MD5) Previous issue date: 2013-12-13 / The work proposed by Cleverton Hentz (2010) presented an approach to define tests from the formal description of a program s input. Since some programs, such as compilers, may have their inputs formalized through grammars, it is common to use context-free grammars to specify the set of its valid entries. In the original work the author developed a tool that automatically generates tests for compilers. In the present work we identify types of problems in various areas where grammars are used to describe them , for example, to specify software configurations, which are potential situations to use LGen. In addition, we conducted case studies with grammars of different domains and from these studies it was possible to evaluate the behavior and performance of LGen during the generation of sentences, evaluating aspects such as execution time, number of generated sentences and satisfaction of coverage criteria available in LGen / O trabalho proposto por Cleverton Hentz (2010) apresentou uma abordagem para defini??o de testes a partir da descri??o formal das entradas do programa. Considerando que alguns programas podem ter suas entradas formalizadas atrav?s de gram?ticas, como ? o caso dos compiladores, ? comum o uso de gram?ticas livres de contexto para especificar o conjunto de entradas v?lidas. No trabalho original foi desenvolvida LGen, uma ferramenta que consiste na gera??o autom?tica de testes para compiladores. No presente trabalho identificamos tipos de problemas recorrentes em diferentes ?reas, onde gram?ticas s?o usadas para descrev?-los, como por exemplo, para especificar configura??es de software, e que s?o situa??es potenciais para o uso de LGen. Al?m disso, realizamos estudos de caso com gram?ticas de dom?nios diferentes e a partir destes estudos foi poss?vel avaliar o comportamento e o desempenho de LGen durante o processo de gera??o das senten?as, avaliando aspectos como tempo de execu??o, quantidade de senten?as geradas e satisfa??o de crit?rios de cobertura dispon?veis em LGen

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-11-22T19:37:02Z No. of bitstreams: 1 MariaAparecidaDaSilvaAndrade_TESE.pdf: 1006466 bytes, checksum: 427477fb09de3e3d616d6bea87cc97a6 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-11-22T23:17:33Z (GMT) No. of bitstreams: 1 MariaAparecidaDaSilvaAndrade_TESE.pdf: 1006466 bytes, checksum: 427477fb09de3e3d616d6bea87cc97a6 (MD5) / Made available in DSpace on 2017-11-22T23:17:33Z (GMT). No. of bitstreams: 1 MariaAparecidaDaSilvaAndrade_TESE.pdf: 1006466 bytes, checksum: 427477fb09de3e3d616d6bea87cc97a6 (MD5) Previous issue date: 2017-08-29 / Esta tese examina constru??es gramaticais com o verbo ir no portugu?s brasileiro contempor?neo. A hip?tese ? que esse verbo, acompanhado de outros elementos lingu?sticos (como ver, que, l? e ainda) mais outra ora??o, forma constru??es gramaticais, nos termos de Goldberg (1995, 2003). Assim, interessa investigar fun??es sem?ntico-cognitivas e discursivo-pragm?ticas dessas constru??es, examinando-se: 1) os elementos constitutivos da constru??o em seus aspectos morfossint?ticos e sem?nticos; 2) contextos de uso dessas constru??es e suas instancia??es; 3) processos cognitivos envolvidos para a diferencia??o categorial e sem?ntica; e 4) motiva??es discursivo-pragm?ticas implicadas nos usos dessas constru??es. A pesquisa fundamenta-se teoricamente nos pressupostos da Lingu?stica Funcional Centrada no Uso articulada ao modelo te?rico da Gram?tica de Constru??es. A metodologia ? de base qualitativo-interpretativista, na qual se analisam exemplares encontrados em alguns padr?es discursivos constantes em jornais e revistas, provenientes do Buscador Google, produzidos em situa??es reais de comunica??o. Os resultados apontam que as constru??es gramaticais com ir podem ser consideradas, em certa medida, parcialmente especificadas, de produtividade limitada e gradientes quanto ? composicionalidade. Ademais, indicam que essas constru??es resultam de extens?es de sentido (meton?micas e metaf?ricas), estando fortemente vinculadas ? (inter)subjetividade. / This thesis examines grammatical constructions with the verb to go in Brazilian Portuguese. The hypothesis is that this verb, accompanied by other linguistic elements (like ver, que, l? and ainda) plus another sentence, forms grammatical constructions, as proposed in Goldberg (1995). Thus, it is important to investigate the semantic-cognitive and discursive-pragmatic functions of these constructions, examining: 1) the constitutive elements of the construction in its morphosyntactic and semantic aspects; 2) the contexts of use of these constructions and their instantiations; 3) cognitive processes involved for the categorical and semantic differentiation; and 4) discursive-pragmatic motivations implicated in the uses of these constructions. The research is theoretically based on the assumptions of Usage-Based Linguistics associated with the theoretical model of the Construction Grammar. The methodology is composed of a qualitative-interpretative basis, in which exemplars found in some discursive patterns in newspapers and magazines produced in real communication situations are analyzed, coming from the Google search engine. The results indicate that the constructions with ir can be considered, to some extent, partially filled, with limited types and gradient in compositionality. Moreover, they point out that these constructions emerged based on semantic extensions (metonymy and metaphorical) and that they are strongly linked to (inter)subjectivity.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-08-26T23:00:34Z No. of bitstreams: 1 BeatrizDeLucenaMoreira_DISSERT.pdf: 880222 bytes, checksum: be8a2954e28c370a8f48778914a66dc4 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-08-30T20:28:08Z (GMT) No. of bitstreams: 1 BeatrizDeLucenaMoreira_DISSERT.pdf: 880222 bytes, checksum: be8a2954e28c370a8f48778914a66dc4 (MD5) / Made available in DSpace on 2016-08-30T20:28:08Z (GMT). No. of bitstreams: 1 BeatrizDeLucenaMoreira_DISSERT.pdf: 880222 bytes, checksum: be8a2954e28c370a8f48778914a66dc4 (MD5) Previous issue date: 2016-05-16 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Neste trabalho, focalizo a constru??o temporal [XTEMP + (EM) + QUE + O], em seus aspectos formais e funcionais. Objetivo analisar aspectos estruturais, sem?ntico-cognitivos e pragm?ticos envolvidos em seu uso. Em termos metodol?gicos, esta pesquisa envolve tanto o vi?s quantitativo - relacionado ? verifica??o da frequ?ncia de uso da constru??o em foco e sua descri??o - como o qualitativo, que diz respeito ao estabelecimento das motiva??es implicadas no uso dessa constru??o. O banco de dados utilizado para an?lise consiste de exemplares escritos do corpus m?nimo do Projeto Para a Hist?ria do Portugu?s Brasileiro (PHPB) e de textos escritos e falados do portugu?s contempor?neo, coletados no Corpus Discurso & Gram?tica. O trabalho fundamenta-se no aporte te?rico da Lingu?stica Funcional Centrada no Uso (LFCU), conforme caracterizada por Furtado da Cunhas, Bispo e Silva (2013). Ademais, agrego contribui??es da Gram?tica de Constru??es, conforme Croft (2001), Goldberg (2006) e Traugott e Trousdale (2013). Os resultados mostram, dentre outros aspectos, que a constru??o temporal investigada licencia dois padr?es subesquem?ticos (distintos pela presen?a ou n?o de preposi??o em antes de que), os quais apresentam especificidades sem?ntico-cognitivas e pragm?ticas, estando seu uso correlacionado ao g?nero textual e ? modalidade de l?ngua em que foram produzidos. Esses dois subesquemas convivem, pelo menos, desde o s?culo XIX, e parecem representar formas em competi??o, revelando um caso de mudan?a construcional. Tamb?m parece haver um processo de construcionaliza??o no interior da constru??o em estudo, envolvendo estruturas menores, no caso [XTEMP] e [EM QUE], que passam a constituir um novo pareamento forma-fun??o [XTEMP + QUE], o qual funciona como conector oracional. / In this work, I investigate the temporal construction [XTEMP + (EM) + QUE + O], by considering its formal and functional aspects. I aim to analyze structural, semantic-cognitive and pragmatic aspects in its use. In terms of methodology, this paper is quantitative - being related to the construction description and its frequency, as well as qualitative - being related to its use motivation. In terms of corpus, this research uses historical written data from Projeto Para a Hist?ria do Portugu?s Brasileiro (PHPB), and modern written and spoken texts from Corpus Discurso & Gram?tica. This work is based on Lingu?stica Funcional Centrada no Uso (LFCU) theory, according to Bispo, Silva e Furtado da Cunha (2013). Furthermore, there are also Grammar Construction contributions, according to Goldberg (2006) and Traugott and Trousdale (2013). The results show, among other things, that the temporal construction license two subschematic patterns (different between each other due to preposition em presence or absence), which have semantic-syntactic and discursive-pragmatic specificities Also, the use of subschematic structures is related to the gender and linguistic modality in which they were produced and to invited inference. These subschemas occur together at least since 19th century and seem to be in competition, revealing constructional change. Besides, it looks like there is a constructionalization process inside the temporal construction investigated, involving smaller structures (in this case, [XTEMP], [(EM) QUE] and [O]), which become two new form-meaning pairings.