Zhu Wen. / "May 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 217-249). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

TLR3 est un récepteur endosomal qui détecte les doubles brins d’ARN produits par HSV-1 lors de sa réplication. La majorité des patients déclarés portants des mutations dans le gène TLR3 ont souffert de l’encéphalite herpétique (EH) sans autre phénotype clinique majeur. Nous avons décrit trois patients présentant des mutations dans le gène TLR3. Ici, nous reportons trois nouvelles formes de défaut AD de TLR3: G743D+R811I et L360P, qui chez deux patients confèrent un défaut AD de TLR3 par dominance négative et haplo-insuffisance; et R867Q, qui confère à un patient un défaut partial AR de TLR3. Les fibroblastes des patients présentent une diminution des réponses médiées par TLR3 et sont plus susceptibles à l’infection par le HSV-1. Le défaut de TLR3 est donc présent chez six (5%) patients sur les 120 EH patients étudiés. De plus, de façon surprenante, nous avons identifé deux mutations dans le gène TLR3 chez deux patients présentant des pneumonies sévères dues au virus de l’influenza A (IAV). Deux patients sont hétérozygotes pour les mutations P554S et P680L dans le gène TLR3. Il a été reporté que P554S est délétère et exerte un effet dominant-négatif chez les patients d’EH. P680L est aussi délétère et cause un défaut AD de TLR3 par haplo-insuffisance. Les fibroblastes hétérozygotes pour la mutation P680L ainsi que les cellules épitheliales pulmonaires dérivées de iPSCs présentent une susceptibilité accrue à IAV. Ces résultats suggèrent que le défaut de TLR3 ne cause pas seulement l’EH mais aussi des pneumonies IAV sévères via une diminution des réponses immunitaires dépendantes de TLR3 et médiées par IFN intrinsèques au système nerveux central et aux poumons. / TLR3 is an endosomal receptor for dsRNA, an intermediate of viral replication. Most of the reported human TLR3 deficiency related to life-threatening HSV-1 encephalitis (HSE), in otherwise healthy children. To date, we have described 3 patients with TLR3 deficiency and 7 patients with TLR3 pathway gene deficiency. We herein report the three novel forms of TLR3 deficiency: G743D+R811I and L360P in two patients underlie AD TLR3 deficiency due to dominant negative (DN) and haploinsufficiency, respectively, and R867Q in one patient leads to a partial AR TLR3 deficiency. The patients’ fibroblasts display impaired TLR3 responses and enhanced HSV-1 susceptibility. TLR3 deficiency is therefore a relatively common in childhood HSE, as it is found in six (5%) of the 120 patients studied. In addition, we surprisingly found two TLR3 mutations in two patients with influenza A virus (IAV) pneumonitis. The pathogenesis of isolated severe influenza is largely unknown, until we recently reported a child with AR IRF7 deficiency. Two patients are each heterozygous for P554S and P680L in TLR3. P554S is previously found to be deleterious and DN in HSE patients. P680L is also deleterious and causes AD TLR3 deficiency by haploinsufficiency. We show that P680L heterozygous fibroblasts fail to produce IFN-β and -λ upon poly(I:C) and IAV infection. Furthermore, both P680L heterozygous and AR TLR3-deficient fibroblasts and iPSCs-derived lung epithelium display enhanced susceptibility to IAV, like IRF7-deficient cells. These findings suggest that TLR3 deficiency underlies not only HSE but also severe influenza due to impaired TLR3-dependent, IFN-mediated, CNS or lung-intrinsic antiviral immunity.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-08-10T13:09:08Z No. of bitstreams: 2 Dissertação - Adriana Batista da Silva - 2016.pdf: 3286914 bytes, checksum: 7be43fd6757af8224a3358e36202f297 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-08-10T13:12:09Z (GMT) No. of bitstreams: 2 Dissertação - Adriana Batista da Silva - 2016.pdf: 3286914 bytes, checksum: 7be43fd6757af8224a3358e36202f297 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-08-10T13:12:09Z (GMT). No. of bitstreams: 2 Dissertação - Adriana Batista da Silva - 2016.pdf: 3286914 bytes, checksum: 7be43fd6757af8224a3358e36202f297 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-04-29 / Financiadora de Estudos e Projetos- Finep / Linear Programming is an operational search tool applied to problem solving aimed at the optimization of a study system. This study aims to show some applications of linear programming and how it can be used as a motivating teaching skills of Mathematics in High school. We will cover two methods of linear programming problems resolution, Graphics resolution method and the algebraic solution way, which is the Simple Method. We so decided to solve under the assistance of these two methods quoted, optimization problems with two or three variables, since the problems with multiple variables do not match the curriculum of mathematics for high school. We suggest the use of two free applications for mobile phones, to solve optimization problems with several variables, in order to contribute in a di erent approach, seeking to boost in students, interest in the study of mathematics. / A Programação Linear é uma ferramenta da Pesquisa Operacional aplicada à solução de problemas que objetivam a otimização de um sistema de estudo. O presente trabalho busca mostrar algumas aplicações da Programação Linear e como ela pode ser utilizada como elemento motivador no ensino da Matemática no Ensino Médio. Abordaremos dois métodos de resolução de problemas de Programação Linear, o método de Resolução Grá ca e a forma algébrica de solução que é o Método Simplex. Vamos solucionar com auxílio desses dois métodos citados, problemas de otimização com duas e três variáveis, já que problemas com várias variáveis não se adequam a matriz curricular de Matemática para o Ensino Médio. Sugerimos a utilização de dois aplicativos gratuitos para celulares, que solucionam problemas de otimização com várias variáveis como forma de contribuir com uma abordagem diferente, visando despertar no aluno, o interesse pelo estudo da Matemática.

<p>Traffic planning in a modern congested society is an important and time consuming procedure. Finding fast algorithms for solving traffic problems is therefore of great interest for traffic planners allover the world. </p><p>This thesis concerns solving the fixed demand traffic assignment problem (TAP) on a number of different transportation test networks. TAP is solved using the Frank-Wolfe algorithm and the shortest path problems that arise as subproblems to the Frank-Wolfe algorithm are solved using the network simplex algorithm. We evaluate how a number of existing pricing strategies to the network simplex algorithm performs with TAP. We also construct a new efficient pricing strategy, the Bucket Pricing Strategy, inspired by the heap implementation of Dijkstra's method for shortest path problems. This pricing strategy is, together with the actual use of the network simplex algorithm, the main result of the thesis and the pricing strategy is designed to take advantage of the special structure of TAP. In addition to performing tests on the conventional Frank-Wolfe algorithm, we also test how the different pricing strategies perform on Frank-Wolfe algorithms using conjugate and bi-conjugate search directions. </p><p>These test results show that the updating shortest path calculations obtained by using the network simplex outperforms the non-updating Frank-Wolfe algorithms. Comparisons with Bar-Gera's OBA show that our implementation, especially together with the bucket pricing strategy, also outperforms this algorithm for relative gaps down to 10E-6.</p>

Traffic planning in a modern congested society is an important and time consuming procedure. Finding fast algorithms for solving traffic problems is therefore of great interest for traffic planners allover the world. This thesis concerns solving the fixed demand traffic assignment problem (TAP) on a number of different transportation test networks. TAP is solved using the Frank-Wolfe algorithm and the shortest path problems that arise as subproblems to the Frank-Wolfe algorithm are solved using the network simplex algorithm. We evaluate how a number of existing pricing strategies to the network simplex algorithm performs with TAP. We also construct a new efficient pricing strategy, the Bucket Pricing Strategy, inspired by the heap implementation of Dijkstra's method for shortest path problems. This pricing strategy is, together with the actual use of the network simplex algorithm, the main result of the thesis and the pricing strategy is designed to take advantage of the special structure of TAP. In addition to performing tests on the conventional Frank-Wolfe algorithm, we also test how the different pricing strategies perform on Frank-Wolfe algorithms using conjugate and bi-conjugate search directions. These test results show that the updating shortest path calculations obtained by using the network simplex outperforms the non-updating Frank-Wolfe algorithms. Comparisons with Bar-Gera's OBA show that our implementation, especially together with the bucket pricing strategy, also outperforms this algorithm for relative gaps down to 10E-6.

Introducción: Diversos estudios transversales han demostrado el impacto negativo quela violencia de pareja tiene en la salud mental, en la salud física y en el funcionamientode los sistemas fisiológicos de las mujeres. Si bien, han sido pocos los estudioslongitudinales realizados para establecer la evolución de dicho impacto en la salud delas mujeres a lo largo del tiempo. Objetivos: En este estudio se pretendió, en primerlugar, determinar la evolución del estado de salud física y del funcionamiento delsistema inmune de las mujeres víctimas de violencia de pareja y, en segundo lugar,establecer los factores personales y sociales que contribuyen a la recuperación de lasalud o la perjudican. Métodos: Las mujeres (n=91) que participaron en un estudiotransversal previo (T-1) fueron evaluadas tres años después (T-2): mujeres víctimas deviolencia psicológica (n=23), mujeres víctimas de violencia física/psicológica (n=33) ymujeres control en cuya relación de pareja no existía violencia (n=35). Tanto en elestudio transversal (T-1) como en el estudio longitudinal (T-2) se llevaron a caboentrevistas estructuradas a través de las cuales se recogió información sobrecaracterísticas sociodemográficas, relaciones de pareja, características de la violencia depareja, historial de victimización, salud física, apoyo social y acontecimientos vitales. Elestado de salud física de las mujeres se midió a través de tres indicadores: incidencia desíntomas físicos, incidencia de enfermedades físicas y utilización de servicios de salud.Finalmente, en ambos momentos temporales se recogieron muestras de saliva paraevaluar el control del sistema inmune sobre el virus Herpes simple tipo 1 (HS-1) através de tres medidas: neutralización del virus HS-1, cantidad de inmunoglobulina A(IgA) específica contra el virus HS-1 (IgA HS-1) y cantidad total de IgA en la saliva(IgA total). Resultados: La incidencia de síntomas físicos disminuyó significativamentea lo largo del tiempo en ambos grupos de mujeres víctimas de violencia de pareja,psicológica y física/psicológica, si bien se observó una mayor disminución en lasmujeres víctimas de violencia física/psicológica. Los factores que contribuyeron a estarecuperación fueron el estado de salud física de las mujeres en T-1, el grado de apoyosocial percibido y el cese de la violencia física. Por el contrario, los factoresperjudiciales para su recuperación fueron el consumo de psicofármacos, la convivenciacon el agresor, las experiencias de victimización en la edad adulta durante T-2, lapercepción negativa de los acontecimientos vitales y el mantenimiento de la violenciapsicológica. Por otro lado, en las mujeres víctimas de violencia física/psicológica seprodujo una disminución a lo largo del tiempo en la cantidad total de enfermedadesagudas padecidas, así como en el número de veces que utilizaron los servicios deurgencia por motivos de violencia. En cuanto al funcionamiento del sistema inmune a lolargo del tiempo, las mujeres víctimas de violencia física/psicológica mostraron unaumento tanto en la capacidad para neutralizar el virus HS-1 como en los niveles de IgAHS-1. El cese de la violencia física fue el principal factor predictor de dicharecuperación. Conclusiones: Este estudio muestra que es posible la recuperación de lasalud física previamente deteriorada en mujeres que han sido víctimas de violencia depareja, psicológica o física/psicológica. Además, indica que es posible la recuperacióndel control inmune sobre el virus HS-1 en mujeres que han estado expuestas a violenciafísica/psicológica a pesar de su baja capacidad antiviral inicial. Son necesarios otrosestudios longitudinales para determinar los factores que mejor predicen la recuperaciónde la salud de las mujeres con la finalidad de diseñar programas de intervención máseficaces. / Introduction: Several cross-sectional studies have demonstrated the negative impactthat intimate partner violence (IPV) has on women's health. However, few longitudinalstudies have been carried out to establish the course of this impact over time.Objectives: This study pretended to determine the course of the physical health and theimmune system function on women victims of IPV and to establish the factors thatcontribute or impair to its recovery. Methods: Women (n=91) who took part in aprevious cross-sectional study (T-1) were evaluated three years later (T-2): victims ofpsychological IPV (n=23), victims of physical/psychological IPV (n=33) and controlwomen (n=35). Information about characteristics of IPV, physical health and lifestylevariables was obtained by structured interviews. Finally, saliva samples were collectedto assess the immune system control over Herpes simplex virus type 1 (HSV-1).Results: The incidence of physical symptoms decreased in time in both groups ofwomen, psychological and physical/psychological victims of IPV. Factors thatcontributed to this recovery were the women's health condition in T-1, the socialsupport and the physical IPV cessation. On the contrary, factors that impaired thisrecovery were the psychopharmacological treatment, the cohabitation with theaggressor, the experiences of victimization during T-2, the negative perception of lifeevents and the continuation of psychological IPV. Furthermore, the amount of acutediseases suffered by women and the visits to emergency rooms because of violencereasons decreased in time in physical/psychological IPV victims. With regard to thecourse of immune system over time, women who were victims ofphysical/psychological IPV had a significant improvement in both the capacity toneutralize HSV-1 and HSV-sIgA levels. Physical IPV cessation was the main predictorof this recovery. Conclusions: This study shows that physical health recovery ispossible in women that have been IPV victims. Furthermore, it shows that recovery ofimmune control over HSV-1 is possible in women who have been exposed tophysical/psychological IPV. Other longitudinal studies are needed to determine whichfactors best predict the restoration of health in order to design effective interventionprograms.

Background: The Division of Global HIV/AIDS at the Centers for Disease Control and Prevention (CDC) is working on a public health evaluation (PHE) in the eastern districts of Botswana. This PHE aims to evaluate the effectiveness of Project AIM, a group-level intervention designed to reduce HIV risk behaviors in youth ages 11 to 14, when combined with the regular Botswana Skills for Life Curriculum, a standard HIV prevention education curriculum in Botswana schools. In order to evaluate Project AIM, a self-report survey and a biological testing for herpes simplex virus type 2 (HSV-2) will be conducted. Methodology: Based on studies done on the psychosocial impact of HSV-2 diagnosis on asymptomatic individuals in the USA, the literature recommends providing pre and post counseling and education to individuals testing for genital herpes to help cope and diminish the psychosocial impact of the diagnosis. In order to prepare Botswana’s clinics and schools participating in the PHE to provide the support for newly diagnosed adolescents with HSV-2, guidance materials were developed for health care practitioners and school guidance teachers. Materials were created using Information Mapping technique to analyze, organize, and present the information, and the Microsoft Office Flesch Kinkade Grade Level (FK) tool to assess the readability levels of the materials. Results: Guidance materials were prepared using the 7±2 theoretical limit of human short-term memory information mapping rule, and the FK grade levels of 6.0 to 8.0 recommended readability scores. Guidance materials included information regarding HSV-2 symptoms, treatment, and prevention. They also included information on the PHE study, youth friendly health services, counseling and education, clinic referrals and contact information. Conclusions: The development of guidance materials for schools and clinic participants of the CDC PHE in Botswana will provide health practitioners and school guidance teachers with accurate HSV-2 information to counsel and educate student participants in this research study. The guidance materials should help students cope with potential psychosocial disorders associated with pre and post diagnosis of HSV-2.

Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 139-154).

Herpesviruses have co-speciated with several vertebrate and invertebrate animals throughout the history of evolution. In the immunocompetent human host, primary infection is usually benign, whereafter the virus is brought into life-long latency. Viral reactivation can however cause severe disease in immunocompromised, and rarely also in immunocompetent, patients. The overall aim of this thesis was to study the immunologic effects of cytomegalovirus (CMV) and herpes simplex type 1 (HSV-1) infection in neurocognitive disorders. CMV is known to promote T-cell differentiation towards a more effector-oriented phenotype, similar to what is seen in the elderly. We have addressed the frequency of CMV-specific CD8+ T-cells in Alzheimer's disease (AD). Furthermore, we have investigated whether AD patients present with a different CMV-specific immune profile, overall CD8 phenotype or inflammatory cytokine response to anti-CD3/CD28 beads, CMV pp65 and amyloid beta. Subjects with AD presented with a lower proportion of CMV-specific CD8+ T-cells compared to non-demented (ND) controls, but no differences in overall CD8 differentiation were seen. Overall, AD subjects presented with a more pro-inflammatory peripheral blood mononuclear cell (PBMC) phenotype. When PBMCs were challenged with CD3/CD28-stimulation, CMV seropositive AD subjects presented with more IFN-γ release than both CMV seronegative AD subjects and CMV seropositive ND controls. For effective screening of humoral herpesvirus immunity, both in research and in clinical practice, efficient immunoassays are needed. We have addressed the methodology of multiplex herpesvirus immunoassays and related bioinformatics and investigated antibody levels in AD patients and ND controls. Subjects with AD presented with lower levels of human herpesvirus 6 (HHV-6) IgG. However, there was no difference in HHV-6 DNA levels in PBMCs between the groups. Herpes simplex encephalitis (HSE) is a devastating disease, where antiviral treatment has greatly decreased mortality but not eliminated the associated long-term neurocognitive morbidity. We have investigated the correlation between N-Methyl-D-Aspartate Receptor (NMDAR) autoimmunity and recovery of neurocognitive functions after HSE. Approximately one quarter of all HSE cases developed NMDAR autoantibodies within 3 months after onset of disease. Antibody development was associated with an impaired neurocognitive recovery during the two year follow-up and could become an important therapy guiding factor in the future.

The thesis consists of four research papers. The first three deal with the Choquet theory of function spaces. In Chapter 1, a theory on products and projective limits of function spaces is developed. It is shown that the product of simplicial spaces is a simplicial space. The stability of the space of maximal measures under continuous affine mappings is studied in Chapter 2. The third chapter employs results from the previous chapters to construct an example of a function space where the abstract Dirichlet problem is not solvable for any class of Baire-n functions with $n\in N$. It is shown that such an example cannot be constructed via the space of harmonic functions. In the final chapter, the recently introduced class of sequentially Right Banach spaces is being investigated. Connections to other isomorphic properties of Banach spaces are established and several characterizations are given.