Numerous factors that affect herpes simplex virus 1 (HSV1)-mediated pathogenesis have been identified. Such factors directly impact the replication of HSV1 as well as modulate host immune responses following HSV1 infection. In this work, I characterize how HSV1 replication is impacted by expression of the protein encoded by C21orf91, or “Cold Sore Susceptibility Gene” (CSSG1), that has been linked to HSV1 reactivation in humans. I investigated expression of CSSG1 mRNA expression in various tissues and found that CSSG1 mRNA was present in several tissues of importance in HSV1 disease, including brain, trigeminal ganglia (TG), cornea and spleen. Western blot analysis demonstrated that CSSG1 protein is expressed in human cells. Subcellular fractionation analysis reveals that CSSG1 is predominantly found in the cell nucleus, where it colocalizes with chromatin and with Tip60, a chromatin-binding histone modifying protein that has been shown to be essential for the replication of herpesviruses. I also discovered that CSSG1 is present in the cytosol of cells where it forms large cytosolic aggregates in presence of TRAF6, a downstream adapter that plays an important role in innate immune receptor signaling. To determine if CSSG1 directly impacts viral replication, I generated CSSG1 knockdown human cell lines. I found that HSV1 replication was reduced in CSSG1 knockdown cells compared to control cells, whereas replication of the unrelated virus, vesicular stomatitis virus (VSV), was not affected by knockdown of CSSG1. I demonstrate that CSSG1 was necessary for efficient expression of HSV1 viral proteins during infection. Western blot analysis and measurement of expression of HSV1 proteins expressed at various stages of viral replication illustrates that CSSG1 was required for HSV1 replication at very early stage of infection. I also noted that CSSG1 expression impacted the DNA damage response in HSV1 infected cells. Levels of H2AX phosphorylation, a marker of the DNA damage response, were increased in HSV1-infected CSSG1 knockdown cells compared to control cells. DNA damage responses are thought to promote HSV1 reactivation from latency and HSV1 gene expression, indicating a potential mechanism for role of CSSG1 in HSV1 replication through modulating the DNA damage response. Overall, my work demonstrates that CSSG1 affects HSV1 replication and provides insight on how CSSG1 polymorphisms in humans could affect HSV1 reactivation and replication to promote cold sores. These discoveries may also lead to a better understanding of pathogenesis of other herpesviruses in humans.

BACKGROUND:Aging is typically accompanied by memory decline and changes in hippocampal function. Among these changes is a decline in the activity of the dentate gyrus (DG) during behavior. Lasting memory, however, is thought to also require recapitulation of recent memory traces during subsequent rest - a phenomenon, termed memory trace reactivation, which is compromised in hippocampal CA1 with progressive age. This process has yet to be assessed in the aged DG, despite its prominent role in age-related memory impairment. Using zif268 transcription to measure granule cell recruitment, DG activity in adult and aged animals was assessed both during spatial exploration and as animals remained at rest in the home cage in order to detect potential memory-related replay.RESULTS:Consistent with the observation of memory trace reactivation in DG, the probability that an individual granule cell transcribes zif268 during rest in the animal's home cage is increased by recent experience in a novel environment. Surprisingly, a comparable increase was observed in the probability of granule cells in the aged DG expressing zif268 during rest. Moreover, no significant age-related difference was observed in the number of granule cells expressing zif268 during rest. Thus, the number and pattern of granule cell expression of zif268 during rest is preserved in aged animals, despite a significant decline in exploration-related zif268 expression.CONCLUSIONS:These data lead to the hypothesis that the input the aged DG receives from backprojections from CA3 (the region widely hypothesized to mediate reactivation) remains functionally intact despite loss of innervation from the perforant path.

Middle and Upper Ordovician strata in the southernmost Appalachians document initial collision along the southeastern margin of Laurentia during the Blountian orogeny, an early phase of the Taconic orogeny. Coeval drowning and exposure of different parts of the former platform and variations in stratal architecture have been attributed to tectonic and depositional loading along the collisional margin. Stratigraphic correlations, using a bentonite-graptoliteconodont time framework, a palinspastic map, and a map of subsurface basement structures, suggest that basement-fault reactivation, flexural subsidence, and eustasy variously controlled uplift, subsidence, and deposition at different sites within the peripheral foreland basin. This dissertation documents how pre-existing structures in the continental margin and interior affected subsidence, deposition, diagenesis, and composition of foreland strata, and deformation in tectonic loads. Stratigraphic correlations document an early episode of basementfault inversion in the distal foreland, and heterogeneous subsidence and provenance patterns in the middle and proximal foreland. Abrupt variations in depth of erosion of passive-margin strata and in thickness of distal foreland deposits coincide with the boundaries of the intraplate Birmingham graben. Inversion of the former graben increased the magnitude of erosion on inverted upthrown blocks; increased tectonic subsidence in adjacent blocks; supplied chert and quartz detritus to shallow-marine carbonate depocenters; and facilitated influx of meteoric water to aquifers in shallow-marine limestones. Tectonic subsidence of middle and proximal foreland deposits reflects local irregularities in the foreland subsidence and different rates of migration of the flexural wave along strike. Differential subsidence between embayments and promontories may have caused reactivation of transverse basement faults. Relief produced by reactivation of transverse basement faults and flexural normal reactivation of basement faults may provide sources for local conglomerates interbedded with deep-water shales. Differences in orogenicbelt deformation are reflected in provenance analyses that suggest exposure of dominantly feldspar-bearing basement rocks in the orogenic belt adjacent to the promontory and exposure of basement rocks and sedimentary cover in the orogenic belt adjacent to the embayment. Results of this study reveal the importance of considering the effects of pre-existing structures in the interpretation of along- and across-strike variations of foreland strata. Therefore, geodynamic modeling of the Blountian foreland basin needs to consider along-strike variations in the geometry of tectonic loads and reactivation of different basement structures.

To safely store carbon dioxide in enhanced oil recovery/ CO2 sequestration projects it is important to ensure the integrity of the caprock during and after production and injection. A change in fluid pressure and temperature within a porous reservoir will generally induce stress changes within the reservoir and the rocks that surround it. Amongst the potential hazards resulting from these induced stress changes is the reactivation of existing faults or fractures and inducing new fractures, which may breach the hydraulic integrity of the caprock that bounds the reservoir.<p> The theories of inclusions and inhomogeneities have been used in this research to derive semi-analytical and closed-form solutions for induced stress change during pore pressure change within a reservoir and in the surrounding rock, under plane strain and axisymmetric conditions. Methods have been developed to assess fault reactivation and induced fracturing during injection or production within a reservoir. The failure stress change concept for a Coulomb failure criterion has been used to study the likelihood of fault reactivation and induced fracturing within the reservoir. Formulations have been adopted to calculate the critical pressure change for fault reactivation and induced fracturing within the reservoir and in the surrounding rock during injection and production. Sensitivity analysis has been performed to study the effects of different parameters such as initial in-situ stress, reservoir geometry, reservoir depth, reservoir tilt or dip , material property contrast between the reservoir and surrounding rock, fault geometry, fault strength, and intact rock strength. General patterns of induced stress change, in-situ stress evolution, fault reactivation, and induced fracturing have been identified.<p> The developed methodologies have been applied to six different case studies: fault reactivation analysis in the entire field for a synthetic case study; induced fracturing analysis in the entire field in a synthetic case study; fault reactivation and induced stress change analysis within the Ekofisk oil reservoir in North Sea; fault reactivation analysis in the Lacq gas reservoir in France; the Weyburn-Midale EOR/CO2 Storage project in southeast Saskatchewan; and acid gas injection in Zama oil field, Alberta. The results of these case studies show good consistency with field observation, and physical and numerical models.<p> The generality, simplicity, and straightforwardness of the developed methodologies, along with their flexibility to model different plausible scenarios and their ease of implementation for systematic sensitivity analyses makes them suitable for decision-making and uncertainty management, specifically in early stages of reservoir development or site assessment for geological sequestration of carbon dioxide.

To safely store carbon dioxide in enhanced oil recovery/ CO2 sequestration projects it is important to ensure the integrity of the caprock during and after production and injection. A change in fluid pressure and temperature within a porous reservoir will generally induce stress changes within the reservoir and the rocks that surround it. Amongst the potential hazards resulting from these induced stress changes is the reactivation of existing faults or fractures and inducing new fractures, which may breach the hydraulic integrity of the caprock that bounds the reservoir.<p> The theories of inclusions and inhomogeneities have been used in this research to derive semi-analytical and closed-form solutions for induced stress change during pore pressure change within a reservoir and in the surrounding rock, under plane strain and axisymmetric conditions. Methods have been developed to assess fault reactivation and induced fracturing during injection or production within a reservoir. The failure stress change concept for a Coulomb failure criterion has been used to study the likelihood of fault reactivation and induced fracturing within the reservoir. Formulations have been adopted to calculate the critical pressure change for fault reactivation and induced fracturing within the reservoir and in the surrounding rock during injection and production. Sensitivity analysis has been performed to study the effects of different parameters such as initial in-situ stress, reservoir geometry, reservoir depth, reservoir tilt or dip , material property contrast between the reservoir and surrounding rock, fault geometry, fault strength, and intact rock strength. General patterns of induced stress change, in-situ stress evolution, fault reactivation, and induced fracturing have been identified.<p> The developed methodologies have been applied to six different case studies: fault reactivation analysis in the entire field for a synthetic case study; induced fracturing analysis in the entire field in a synthetic case study; fault reactivation and induced stress change analysis within the Ekofisk oil reservoir in North Sea; fault reactivation analysis in the Lacq gas reservoir in France; the Weyburn-Midale EOR/CO2 Storage project in southeast Saskatchewan; and acid gas injection in Zama oil field, Alberta. The results of these case studies show good consistency with field observation, and physical and numerical models.<p> The generality, simplicity, and straightforwardness of the developed methodologies, along with their flexibility to model different plausible scenarios and their ease of implementation for systematic sensitivity analyses makes them suitable for decision-making and uncertainty management, specifically in early stages of reservoir development or site assessment for geological sequestration of carbon dioxide.

<p>The ability to re-experience the past is a defining feature of episodic memory. Yet we know that even the most detailed memories are distinct from the initial experiences to which they refer. This relationship between the initial encoding and subsequent retrieval of information is central to our understanding of memory and its capacity to connect us to the past. Past research has shown that neural signatures present during perception are reactivated during later memory, but the correspondence between this reactivation and various aspects of memory function remains unclear. This dissertation attempts to connect behavioral measures of memory to the reinstatement and modification of neural information that takes place when memories are retrieved. In the first two studies reported, functional magnetic resonance imaging (fMRI) is used to assess event-specific cortical patterns from encoding that are reinstated during retrieval (encoding-retrieval similarity, ERS). Increases in this fine-grained of reinstatement are found in occipitotemporal cortex (OTC) during detailed memory for scenes (Study 1), and in the medial temporal lobes (MTL) for the recovery of relational information (Study 2). In addition to reflecting encoding-related content, retrieval is also found to strengthen previously encoded information via hippocampally-mediated mechanisms in Study 3. Together, these studies demonstrate the detailed nature of information that is recovered across varying degrees of memory and show how retrieval can also alter stored representations, emphasizing the interactive nature of memory processes.</p> / Dissertation

Submitted by JOSE EDUARDO SARTORI null (edu_sammy@yahoo.com.br) on 2018-03-08T23:03:10Z No. of bitstreams: 1 Tese_JES.pdf: 11494584 bytes, checksum: 689b2ca420e30f0b0e97f388ecc4d2d2 (MD5) / Approved for entry into archive by Adriana Aparecida Puerta null (dripuerta@rc.unesp.br) on 2018-03-09T17:23:59Z (GMT) No. of bitstreams: 1 sartori_je_dr_rcla.pdf: 10806564 bytes, checksum: 16932cd737c53cf35719973ca5cab2ef (MD5) / Made available in DSpace on 2018-03-09T17:23:59Z (GMT). No. of bitstreams: 1 sartori_je_dr_rcla.pdf: 10806564 bytes, checksum: 16932cd737c53cf35719973ca5cab2ef (MD5) Previous issue date: 2018-01-11 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Zona de Falha de Cássia corresponde a uma zona de falha transcorrente sinistral oblíqua orientada segundo a direção geral NNW-SSE. A estrutura se desenvolveu em decorrência de movimentações tardias do Cinturão de Cisalhamento Campo do Meio durante o Ciclo Orogênico Brasiliano. A Zona de Falha de Cássia está registrada através de uma faixa de rochas deformadas de largura variável entre 0,5 a 3,0 km, composta por rochas miloníticas, caracterizadas por deformação dúctil-rúptil em condições metamórficas de fácies xisto verde, zona da clorita. A descontinuidade foi reativada como uma zona de falha normal, com bloco baixo a sudoeste (reativação geométrica) durante o Neocretáceo, correlacionada com o Soerguimento do Alto Paranaíba. A reativação tectônica foi marcada por intensa brechação, cataclase e a formação de dois conjuntos de falhas normais com arranjo em blocos escalonados progressivamente rebaixados para oeste. As feições microestruturais e reações de alteração constatadas, juntamente com a ocorrência de pseudotaquilito permitiram inferir que estas rochas de falha foram desenvolvidas em profundidades inferiores a 11 km, com temperaturas menores que 300°C, provavelmente associadas a sismos. Uma segunda etapa de reativação está registrada através da formação de depósitos sedimentares argilosos e arenosos quaternários, respectivamente nas regiões de Cássia-Pratápolis e Desemboque. Tratam-se de depósitos correlativos de falha relacionados à movimentação da Zona de Falha de Cássia como uma zona de falha normal, com bloco baixo a sudoeste, configurando uma reativação cinemática. Localmente os sedimentos exibem feições de deformação rúptil como falhas, fraturas e zonas brechadas, indicando atividade neotectônica na região. Este rico acervo de produtos geológicos transforma a Zona de Falha de Cássia em modelo para estudos de reativação tectônica em ambiente intraplaca e evolução de longo termo. / The Cássia Fault Zone corresponds to an oblique sinistral transcurrent fault zone oriented in the general direction NNW-SSE. The structure developed as a result of late movements of the Campo do Meio Shear Belt during the Brasilian Orogenic Cycle. The Cássia Fault Zone is recorded through a range of deformed rocks varying in width ranging from 0.5 to 3.0 km, composed of milonitic rocks, characterized by ductile deformation in metamorphic conditions of green schist facies (chlorite zone). The discontinuity was reactivated as a normal fault zone, with a lower block to the southwest (geometric reactivation) during the Neocretaceous, correlated with the Soerguimento do Alto Paranaíba. The tectonic reactivation was marked by intense breccia, cataclase and the formation of two sets of normal faults with arrangement in stepped blocks progressively lowered to the west. The microstructural features and alteration reactions observed together with the occurrence of pseudotaquilite allowed us to infer that these fault rocks were developed at depths lower than 11 km, with temperatures lower than 300 ° C, probably associated with earthquakes. A second stage of reactivation is recorded through the formation of quaternary sedimentary deposits in the regions of Cássia-Pratápolis and Desemboque. These are correlative fault deposits related to the movement of the Cássia Fault Zone as a normal fault zone, with a lower block to the southwest, forming a kinematic reactivation. Locally, the sediments exhibit features of deformation such as faults, fractures and breccias, indicating neotectonic activity in the region. This rich collection of geological products transforms the Cássia Fault Zone into a model for studies of tectonic reactivation in intraplate environment and long term evolution. / CNPq: 165801/2014-0

Orientador: Regina Buffon / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-18T08:53:24Z (GMT). No. of bitstreams: 1 Bannwart_SandraCecilia_M.pdf: 812230 bytes, checksum: b6487d1c0a090fc43a9884c0ab756e15 (MD5) Previous issue date: 2011 / Resumo: Analisou-se a solução catalítica de um catalisador industrial de hidroformilação de olefinas através de espectroscopia RMN de P, eletroforese capilar, cromatografia em camada delgada, cromatografia gasosa acoplada à espectrometria de massas e espectrometria de massas de alta resolução, a fim de tentar determinar a natureza das espécies de ródio presentes na solução e entender o que estaria causando a desativação do catalisador. Contudo, as únicas afirmações que podem ser feitas é que a solução contém trifenilfosfina livre (TPP) e seu óxido. Análises da solução do catalisador reciclado antes e após lavagem com trietanolamina (TEA), por espectrometria de massas de alta resolução, mostraram a diminuição do pico em 515 m/z após a lavagem do catalisador reciclado (de 52 % no catalisador reciclado antes da lavagem para 9% após a lavagem com TEA), sugerindo que a espécie associada a esse pico seria a responsável pela desativação. Entretanto, sua análise por MSMS permitiu a identificação apenas da TPP livre, confirmando a grande complexidade do sistema. Como segunda etapa deste trabalho, foram avaliados diferentes tratamentos realizados na solução catalítica (que contém um catalisador industrial de hidroformilação de olefinas (Rh/TPP), também denominado de catalisador reciclado) capazes de reativá-la. Dentre os tratamentos empregados, destaca-se a solução de TEA ¿ 10% (1 parte catalisador: 1 parte solução TEA - 10% (massa) em água (v/v)). Testes catalíticos na hidroformilação do 1-hexeno mostraram que, sem tratamento, o catalisador reciclado permitiu alcançar um TON de 20.773 em 4 h e que, após tratamento com esta solução, o aumento do TON foi significativo (29.995), equiparando-se ao número de Turnover do catalisador Padrão, que está livre de desativadores (TON = 29.057). Esses resultados permitem concluir que a desativação ocorre principalmente devido à presença de cloretos ou ácidos carboxílicos e que o processo desenvolvido é eficiente para a reativação do catalisador / Abstract: A solution of an industrial catalyst for the hydroformylation of olefins was analyzed by 31P NMR spectroscopy, capillary electrophoresis, thin layer chromatography, gas chromatography/mass spectrometry and high resolution mass spectrometry in order to investigate the nature of the rhodium species and try to understand the causes of catalyst deactivation. However, only free triphenylphosphine (TPP) and its oxide could be precisely detected. Analyses of the recycled catalyst before and after washing with triethanolamine (TEA), by high resolution mass spectrometry, showed a decrease of the peak in 515 m/z after washing (52% of the recycled catalyst before washing to 9% after washing with TEA), suggesting that this peak could be associated to the species responsible for catalyst deactivation. However, MSMS analysis of this peak showed only free TPP, confirming the complexity of the system under study. In the second phase of this study, different treatments of the catalytic solution (containing the industrial catalyst for hydroformylation of olefins (Rh / TPP), also called recycled catalyst), susceptible to reactivate it, were evaluated. Among the tested treatments, a solution of TEA - 10% (1 part catalyst / 1 part solution TEA-10% (mass) in water (v / v)) showed good results. Without this treatment, the recycled catalyst presented a TON = 20.773, in 4 h, in the hydroformylation of 1-hexene. After treatment, the observed TON was 29.995, similar to that obtained with a standard catalyst, free of deactivators (TON = 29.057). Therefore, we can conclude that deactivation takes place mainlly due to the presence of chlorides or carboxylic acids, and the developed procedure is effective for the reactivation of the catalyst / Mestrado / Quimica Inorganica / Mestre em Química

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Natália Kuzmiaková Supervisor: PharmDr. Marie Vopršalová, CSc . Consultant: mjr. PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: In vivo evaluation of the efficacy of the novel reactivator against tabun. This study tackles the problem of irreversible inhibition of acetylcholinesterase (AChE). This enzyme degrades neurotransmitter acetylcholine (ACh), wich ensures transmisson of nerve impulses in central nervous system and in periphery. Organophospates (OP) are substances that cause irreversible blocade of AChE and that susubsequently leads to accumulation of AChE in synapses and inducing of muscarinic and nicotinic effects for life threatening condition. Oximic nature reactivators shown to this day the gratest potencial in inhibiting OP bond with AChE. Because reactivation abilities of to date synthesided oxime are not sufficient, new reactivators are being researched. The doal of my work was to test the potencial to reactivate AChe one of them (precisely oxime K 870). The method i used was colorimetric Ellman method modified by Bajgar, where the activity of AChE after reactivation was measured by absorbance in brain, diaphragm and blood of modeled orgamisms. The...

Rats were trained on a four-way shuttle box with a compound light-tone conditioned stimulus (CS) until they emitted 7 avoidance responses in 10 trials (7/10) prior to bilateral ablation of the visual cortex or sham surgery. On Day 5 after surgery, rats were cued with either the compound light-tone CS, the light or tone portion of the CS only, or had no exposure to the CS. On Day 10 after surgery, all animals were tested for avoidance retention under the same conditions as preoperative training. The findings indicate that following a lesion, cueing with the light-tone compound CS facilitates performance as does light alone. Cueing to the tone alone has no effect. In sham animals, only cueing with the light-tone CS was effective in enhancing avoidance retention. Results are interpreted as early and modality-specific sensory cueing may facilitate the recovery process.