Structural Characterizations of the Dimeric Anti-HIV Antibody 2G12 and the HIV-2 Envelope Glycoprotein

More than thirty years after the discovery that Human Immunodeficiency Virus (HIV) was the causative agent of Acquired Immunodeficiency Syndrome (AIDS), the disease remains pandemic as long as no effective universal vaccine is found. Over 34 million individuals in the world are infected with the virus, and the vast majority of them have no access to the antiretroviral therapies that have largely reduced HIV to a chronic disease in the developed world. The first chapter of this thesis introduces the history of the virus. The key to the infectious mechanism of the virus lies in its envelope glycoprotein (Env), a trimeric spike on the viral surface that utilizes host T cell receptors for entry. Though HIV-1 Env is immunogenic, most infected patients do not mount an effective neutralizing antibody response against it. Broadly-neutralizing anti-Env antibodies (bNAbs) present in the serum of a minority of infected individuals are usually sufficient to prevent the progression to full blown AIDS. Thus, the molecular details of these bNAbs as well as the antibody-antigen interface are of prime interest for structural studies, as insight gained would contribute to the design of a more effective immunogen and potential vaccine candidate. The second chapter of this thesis describes the low-resolution crystal structure of one such antibody, 2G12 dimer, which targets a high mannose epitope on the surface of Env. Patients infected with HIV-2, a related virus with ~35% sequence identity in the Env region, can generally mount a robust antibody response sufficient for viral control for reasons still unknown. The final two chapters of this thesis focus on the first reported structural studies of HIV-2 Env, the molecular details of which may inform HIV-1 therapy and immunogen design.

The origin of the super-resolution via a nonlinear thin film

In laser applications, resolutions beyond the diffraction limit can be obtained with a thin film of strong optical nonlinear effect. The optical index of the silicon thin film is modified with the incident laser beam as a function of the local field intensity n(r) similar to E-2(r). For ultrathin films of thickness d << lambda the transmitted light through the film forms a profile of annular rings. Therefore, the device can be related to the realization of super-resolution with annular pupils. Theoretical analysis shows that the focused light spot appears significantly reduced in comparison with the diffraction limit that is determined by the laser wavelength and the numerical aperture of the converging lens. Analysis on the additional optical transfer function due to the thin film confirms that the resolving power is improved in the high spatial frequency region. (C) 2007 Published by Elsevier B.V.

Diasporization and family relations in Nella Larsens Quicksand and Jamaica Kincaids Lucy: the construction of female identity

O principal objetivo desta dissertação é investigar e analisar como os movimentos diaspóricos e as relações familiares exercem influência na construção das identidades das mulheres em Quicksand, de Nella Larsen, e Lucy, de Jamaica Kincaid. As questões a que pretendo responder são: Como as personagens principais, Helga Crane e Lucy, lidam com as diferentes culturas que encontram nas suas trajetórias ? ; Como essas diferentes culturas lidam com essas mesmas personagens?; e Como o encontro entre essas diferentes culturas e as relações familiares são descritos e influenciam na construção da identidade feminina nessas obras?. Minha hipótese é que encontraremos nas obras selecionadas duas jornadas, portadoras tanto de aspectos comuns quanto distintos, que começam com o desejo das personagens principais de escapar da opressão patriarcal. Isto é, Helga Crane e Lucy passam por um período de muitas descobertas sobre elas mesmas e as sociedades com que têm que lidar, o que determina dois produtos diferentes: a construção das identidades híbridas de Lucy, em meio a sua solidão, na obra de Kincaid, e a construção e o sufocamento das identidades de Helga pela religião, o patriarcado e as relações familiares, na obra de Larsen

Visualization by High Resolution Immunoelectron Microscopy of the Transient Receptor Potential Vanilloid-1 at Inhibitory Synapses of the Mouse Dentate Gyrus

We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1), a non-selective cation channel in the peripheral and central nervous system, is localized at postsynaptic sites of the excitatory perforant path synapses in the hippocampal dentate molecular layer (ML). In the present work, we have studied the distribution of TRPV1 at inhibitory synapses in the ML. With this aim, a preembedding immunogold method for high resolution electron microscopy was applied to mouse hippocampus. About 30% of the inhibitory synapses in the ML are TRPV1 immunopositive, which is mostly localized perisynaptically (similar to 60% of total immunoparticles) at postsynaptic dendritic membranes receiving symmetric synapses in the inner 1/3 of the layer. This TRPV1 pattern distribution is not observed in the ML of TRPV1 knock-out mice. These findings extend the knowledge of the subcellular localization of TRPV1 to inhibitory synapses of the dentate molecular layer where the channel, in addition to excitatory synapses, is present.

High-resolution natural recording systems: intercomparisons of the response to interannual climatic variability [abstract]

The goal of this work is to examine the properties of recording mechanisms which are common to continuously recording high-resolution natural systems in which climatic signals are imprinted and preserved as proxy records. These systems produce seasonal structures as an indirect response to climatic variability over the annual cycle. We compare the proxy records from four different high-resolution systems: the Quelccaya ice cap of the Peruvian Andes; composite tree ring growth from southern California and the southwestern United States; and the marine varve sedimentation systems in the Santa Barbara basin (off California, United States) and in the Gulf of California, Mexico. An important focus of this work is to indicate how the interannual climatic signal is recorded in a variety of different natural systems with vastly different recording mechanisms and widely separated in space. These high-resolution records are the products of natural processes which should be comparable, to some degree, to human-engineered systems developed to transmit and record physical quantities. We therefore present a simple analogy of a data recording system as a heuristic model to provide some unifying concepts with which we may better understand the formation of the records. This analogy assumes special significance when we consider that natural proxy records are the principal means to extend our knowledge of climatic variability into the past, beyond the limits of instrumentally recorded data.

Patterns of scale-dependency and the influence of map resolution on the seascape ecology of reef fish

Detection and perception of ecological relationships between biota and their surrounding habitats is sensitive to analysis scale and resolution of habitat data. We measured strength of univariate linear correlations between reef fish and seascape variables at multiple spatial scales (25 to 800 m). Correlation strength was used to identify the scale that best associates fish to their surrounding habitat. To evaluate the influence of map resolution, seascape variables were calculated based on 4 separate benthic maps produced using 2 levels of spatial and thematic resolution, respectively. Individual seascape variables explained only 25% of the variability in fish distributions. Length of reef edge was correlated with more aspects of the fish assemblage than other features. Area of seagrass and bare sand correlated with distribution of many fish, not just obligate users. No fish variables correlated with habitat diversity. Individual fish species achieved a wider range of correlations than mobility guilds or the entire fish assemblage. Scales of peak correlation were the same for juveniles and adults in a majority of comparisons. Highly mobile species exhibited broader scales of peak correlation than either resident or moderately mobile fish. Use of different input maps changed perception of the strength and even the scale of peak correlations for many comparisons involving hard bottom edge length and area of sand, whereas results were consistent regardless of map type for comparisons involving area of seagrass and habitat diversity.