Toward an atomistic understanding of the immune synapse:large-scale molecular dynamics simulation of a membrane-embedded TCR-pMHC-CD4 complex

T-cell activation requires interaction of T-cell receptors (TCR) with peptide epitopes bound by major histocompatibility complex (MHC) proteins. This interaction occurs at a special cell-cell junction known as the immune or immunological synapse. Fluorescence microscopy has shown that the interplay among one agonist peptide-MHC (pMHC), one TCR and one CD4 provides the minimum complexity needed to trigger transient calcium signalling. We describe a computational approach to the study of the immune synapse. Using molecular dynamics simulation, we report here on a study of the smallest viable model, a TCR-pMHC-CD4 complex in a membrane environment. The computed structural and thermodynamic properties are in fair agreement with experiment. A number of biomolecules participate in the formation of the immunological synapse. Multi-scale molecular dynamics simulations may be the best opportunity we have to reach a full understanding of this remarkable supra-macromolecular event at a cell-cell junction.

Life cycle of Deccan trap magma chambers: A crystal scale elemental and strontium isotopic investigation

The Deccan Trap basalts are the remnants of a massive series of lava flows that erupted at the K/T boundary and covered 1-2 million km2 of west-central India. This eruptive event is of global interest because of its possible link to the major mass extinction event, and there is much debate about the duration of this massive volcanic event. In contrast to isotopic or paleomagnetic dating methods, I explore an alternative approach to determine the lifecycle of the magma chambers that supplied the lavas, and extend the concept to obtain a tighter constraint on Deccan’s duration. My method relies on extracting time information from elemental and isotopic diffusion across zone boundaries in individual crystals. I determined elemental and Sr-isotopic variations across abnormally large (2-5 cm) plagioclase crystals from the Thalghat and Kashele “Giant Plagioclase Basalts” from the lowermost Jawhar and Igatpuri Formations respectively in the thickest Western Ghats section near Mumbai. I also obtained bulk rock major, trace and rare earth element chemistry of each lava flow from the two formations. Thalghat flows contain only 12% zoned crystals, with 87 Sr/86Sr ratios of 0.7096 in the core and 0.7106 in the rim, separated by a sharp boundary. In contrast, all Kashele crystals have a wider range of 87Sr/86Sr values, with multiple zones. Geochemical modeling of the data suggests that the two types of crystals grew in distinct magmatic environments. Modeling intracrystalline diffusive equilibration between the core and rim of Thalghat crystals led me to obtain a crystal growth rate of 2.03x10-10 cm/s and a residence time of 780 years for the crystals in the magma chamber(s). Employing some assumptions based on field and geochronologic evidence, I extrapolated this residence time to the entire Western Ghats and obtained an estimate of 25,000–35,000 years for the duration of Western Ghats volcanism. This gave an eruptive rate of 30–40 km3/yr, which is much higher than any presently erupting volcano. This result will remain speculative until a similarly detailed analytical-modeling study is performed for the rest of the Western Ghats formations.

Spatial scale and abundance patterns of large fish communities in freshwater marshes of the Florida Everglades

Anthropogenic habitat alterations and water-management practices have imposed an artificial spatial scale onto the once contiguous freshwater marshes of the Florida Everglades. To gain insight into how these changes may affect biotic communities, we examined whether variation in the abundance and community structure of large fishes (SL . 8 cm) in Everglades marshes varied more at regional or intraregional scales, and whether this variation was related to hydroperiod, water depth, floating mat volume, and vegetation density. From October 1997 to October 2002, we used an airboat electrofisher to sample large fishes at sites within three regions of the Everglades. Each of these regions is subject to unique watermanagement schedules. Dry-down events (water depth , 10 cm) occurred at several sites during spring in 1999, 2000, 2001, and 2002. The 2001 dry-down event was the most severe and widespread. Abundance of several fishes decreased significantly through time, and the number of days post-dry-down covaried significantly with abundance for several species. Processes operating at the regional scale appear to play important roles in regulating large fishes. The most pronounced patterns in abundance and community structure occurred at the regional scale, and the effect size for region was greater than the effect size for sites nested within region for abundance of all species combined, all predators combined, and each of the seven most abundant species. Non-metric multi-dimensional scaling revealed distinct groupings of sites corresponding to the three regions. We also found significant variation in community structure through time that correlated with the number of days post-dry-down. Our results suggest that hydroperiod and water management at the regional scale influence large fish communities of Everglades marshes.

Event mining for system and service management

Modern IT infrastructures are constructed by large scale computing systems and administered by IT service providers. Manually maintaining such large computing systems is costly and inefficient. Service providers often seek automatic or semi-automatic methodologies of detecting and resolving system issues to improve their service quality and efficiency. This dissertation investigates several data-driven approaches for assisting service providers in achieving this goal. The detailed problems studied by these approaches can be categorized into the three aspects in the service workflow: 1) preprocessing raw textual system logs to structural events; 2) refining monitoring configurations for eliminating false positives and false negatives; 3) improving the efficiency of system diagnosis on detected alerts. Solving these problems usually requires a huge amount of domain knowledge about the particular computing systems. The approaches investigated by this dissertation are developed based on event mining algorithms, which are able to automatically derive part of that knowledge from the historical system logs, events and tickets. ^ In particular, two textual clustering algorithms are developed for converting raw textual logs into system events. For refining the monitoring configuration, a rule based alert prediction algorithm is proposed for eliminating false alerts (false positives) without losing any real alert and a textual classification method is applied to identify the missing alerts (false negatives) from manual incident tickets. For system diagnosis, this dissertation presents an efficient algorithm for discovering the temporal dependencies between system events with corresponding time lags, which can help the administrators to determine the redundancies of deployed monitoring situations and dependencies of system components. To improve the efficiency of incident ticket resolving, several KNN-based algorithms that recommend relevant historical tickets with resolutions for incoming tickets are investigated. Finally, this dissertation offers a novel algorithm for searching similar textual event segments over large system logs that assists administrators to locate similar system behaviors in the logs. Extensive empirical evaluation on system logs, events and tickets from real IT infrastructures demonstrates the effectiveness and efficiency of the proposed approaches.^

FRAMEWORK SYNTHESIS FOR SYMBOLIC EXECUTION OF EVENT-DRIVEN FRAMEWORKS

Symbolic execution is a powerful program analysis technique, but it is very challenging to apply to programs built using event-driven frameworks, such as Android. The main reason is that the framework code itself is too complex to symbolically execute. The standard solution is to manually create a framework model that is simpler and more amenable to symbolic execution. However, developing and maintaining such a model by hand is difficult and error-prone. We claim that we can leverage program synthesis to introduce a high-degree of automation to the process of framework modeling. To support this thesis, we present three pieces of work. First, we introduced SymDroid, a symbolic executor for Android. While Android apps are written in Java, they are compiled to Dalvik bytecode format. Instead of analyzing an app’s Java source, which may not be available, or decompiling from Dalvik back to Java, which requires significant engineering effort and introduces yet another source of potential bugs in an analysis, SymDroid works directly on Dalvik bytecode. Second, we introduced Pasket, a new system that takes a first step toward automatically generating Java framework models to support symbolic execution. Pasket takes as input the framework API and tutorial programs that exercise the framework. From these artifacts and Pasket's internal knowledge of design patterns, Pasket synthesizes an executable framework model by instantiating design patterns, such that the behavior of a synthesized model on the tutorial programs matches that of the original framework. Lastly, in order to scale program synthesis to framework models, we devised adaptive concretization, a novel program synthesis algorithm that combines the best of the two major synthesis strategies: symbolic search, i.e., using SAT or SMT solvers, and explicit search, e.g., stochastic enumeration of possible solutions. Adaptive concretization parallelizes multiple sub-synthesis problems by partially concretizing highly influential unknowns in the original synthesis problem. Thanks to adaptive concretization, Pasket can generate a large-scale model, e.g., thousands lines of code. In addition, we have used an Android model synthesized by Pasket and found that the model is sufficient to allow SymDroid to execute a range of apps.

Modelling human behaviour and event detection from videos

Automatic analysis of human behaviour in large collections of videos is gaining interest, even more so with the advent of file sharing sites such as YouTube. However, challenges still exist owing to several factors such as inter- and intra-class variations, cluttered backgrounds, occlusion, camera motion, scale, view and illumination changes. This research focuses on modelling human behaviour for action recognition in videos. The developed techniques are validated on large scale benchmark datasets and applied on real-world scenarios such as soccer videos. Three major contributions are made. The first contribution is in the area of proper choice of a feature representation for videos. This involved a study of state-of-the-art techniques for action recognition, feature extraction processing and dimensional reduction techniques so as to yield the best performance with optimal computational requirements. Secondly, temporal modelling of human behaviour is performed. This involved frequency analysis and temporal integration of local information in the video frames to yield a temporal feature vector. Current practices mostly average the frame information over an entire video and neglect the temporal order. Lastly, the proposed framework is applied and further adapted to real-world scenario such as soccer videos. A dataset consisting of video sequences depicting events of players falling is created from actual match data to this end and used to experimentally evaluate the proposed framework.

Vertical distribution of benthic invertebrate larvae during an upwelling event along a transect off the tropical Brazilian continental margin

Abundance and composition of marine benthic communities have been relatively well studied in the SE Brazilian coast, but little is known on patterns controlling the distribution of their planktonic larval stages. A survey of larval abundance in the continental margin, using a Multi-Plankton Sampler, was conducted in a cross-shelf transect off Cabo Frio (23 degrees S and 42 degrees W) during a costal upwelling event. Hydrographic conditions were monitored through discrete CDT casts. Chlorophyll-a in the top 100 m of the water column was determined and changes in surface chlorophyll-a was estimated using SeaWiFS images. Based on the larval abundances and the meso-scale hydrodynamics scenario, our results suggest two different processes affecting larval distributions. High larval densities were found nearshore due to the upwelling event associated with high chlorophyll a and strong along shore current. on the continental slope, high larval abundance was associated with a clockwise rotating meander, which may have entrapped larvae from a region located further north (Cabo de Sao Tome, 22 degrees S and 41 degrees W). In mid-shelf areas, our data suggests that vertical migration may likely occur as a response to avoid offshore transport by upwelling plumes and/or cyclonic meanders. The hydrodynamic scenario observed in the study area has two distinct yet extremely important consequences: larval retention on food-rich upwelling areas and the broadening of the tropical domain to southernmost subtropical areas. (C) 2009 Elsevier B.V. All rights reserved.

Life Cycle of Deccan Trap Magma Chambers: A Crystal Scale Elemental and Strontium Isotopic Investigation

The Deccan Trap basalts are the remnants of a massive series of lava flows that erupted at the K/T boundary and covered 1-2 million km2 of west-central India. This eruptive event is of global interest because of its possible link to the major mass extinction event, and there is much debate about the duration of this massive volcanic event. In contrast to isotopic or paleomagnetic dating methods, I explore an alternative approach to determine the lifecycle of the magma chambers that supplied the lavas, and extend the concept to obtain a tighter constraint on Deccan’s duration. My method relies on extracting time information from elemental and isotopic diffusion across zone boundary in an individual crystal. I determined elemental and Sr-isotopic variations across abnormally large (2-5 cm) plagioclase crystals from the Thalghat and Kashele “Giant Plagioclase Basalts” from the lowermost Jawhar and Igatpuri Formations respectively in the thickest Western Ghats section near Mumbai. I also obtained bulk rock major, trace and rare earth element chemistry of each lava flow from the two formations. Thalghat flows contain only 12% zoned crystals, with 87Sr/86Sr ratios of 0.7096 in the core and 0.7106 in the rim, separated by a sharp boundary. In contrast, all Kashele crystals have a wider range of 87Sr/86Sr values, with multiple zones. Geochemical modeling of the data suggests that the two types of crystals grew in distinct magmatic environments. Modeling intracrystalline diffusive equilibration between the core and rim of Thalghat crystals led me to obtain a crystal growth rate of 2.03x10-10 cm/s and a residence time of 780 years for the crystals in the magma chamber(s). Employing some assumptions based on field and geochronologic evidence, I extrapolated this residence time to the entire Western Ghats and obtained an estimate of 25,000 – 35,000 years for the duration of Western Ghats volcanism. This gave an eruptive rate of 30 – 40 km3/yr, which is much higher than any presently erupting volcano. This result will remain speculative until a similarly detailed analytical-modeling study is performed for the rest of the Western Ghats formations.

Estimation of Convective Extreme Events over Germany based on Large Scale Parameters

Strong convective events can produce extreme precipitation, hail, lightning or gusts, potentially inducing severe socio-economic impacts. These events have a relatively small spatial extension and, in most cases, a short lifetime. In this study, a model is developed for estimating convective extreme events based on large scale conditions. It is shown that strong convective events can be characterized by a Weibull distribution of radar-based rainfall with a low shape and high scale parameter value. A radius of 90km around a station reporting a convective situation turned out to be suitable. A methodology is developed to estimate the Weibull parameters and thus the occurrence probability of convective events from large scale atmospheric instability and enhanced near-surface humidity, which are usually found on a larger scale than the convective event itself. Here, the probability for the occurrence of extreme convective events is estimated from the KO-index indicating the stability, and relative humidity at 1000hPa. Both variables are computed from ERA-Interim reanalysis. In a first version of the methodology, these two variables are applied to estimate the spatial rainfall distribution and to estimate the occurrence of a convective event. The developed method shows significant skill in estimating the occurrence of convective events as observed at synoptic stations, lightning measurements, and severe weather reports. In order to take frontal influences into account, a scheme for the detection of atmospheric fronts is implemented. While generally higher instability is found in the vicinity of fronts, the skill of this approach is largely unchanged. Additional improvements were achieved by a bias-correction and the use of ERA-Interim precipitation. The resulting estimation method is applied to the ERA-Interim period (1979-2014) to establish a ranking of estimated convective extreme events. Two strong estimated events that reveal a frontal influence are analysed in detail. As a second application, the method is applied to GCM-based decadal predictions in the period 1979-2014, which were initialized every year. It is shown that decadal predictive skill for convective event frequencies over Germany is found for the first 3-4 years after the initialization.

Interdisciplinarity and Design Conceptualisation: Contributions from a Small-Scale Design Experiment

Literature emphasises the sparse research focused in collaborative and open approaches in the design conceptualisation stage, also known as the Fuzzy Front-End (FFE). Presently, the most challenging discussion arising from this specific field of research lies in understanding on whether or not to structure the referred conceptual stage. Accordingly, the established hypothesis behind this study sustains that a structured approach in the FFE would benefit the interdisciplinary dialogue. Therefore, two objectives support this study: to understand the benefits of an interdisciplinary approach in the FFE, and to test one proposed model for this conceptual stage. By means of a small-scale design experiment, this paper pretends to give additional contributions to this area of research, in the context of new product development (NPD). The general research supporting this specific study aims to conceptualise in the area of newly and futuristic aircraft configurations. Hence, this same topic based the conceptualisation process in the conducted ideation sessions, which are conducted by five different teams of three elements each. The results of the different ideation sessions reinforce the contemporary paradigm of Open Innovation (OI), which is based in trust and communication to better collaborate. The postulated hypothesis for this study is partially validated as teams testing the proposed and structured model generally consider that its usage would benefit the integration of different disciplines. Besides, a general feeling that a structured approach integrates different perspectives and gives creativity a focus pervades. Nevertheless, the small-scale of the design experiment attributes some limitations to this study, despite giving new insights in how to better organise coming and more sustained studies. Interestingly, the importance of sketching as an interdisciplinary means of communication is underlined with the obtained results.

Medication Adherence And Quality Of Life Among The Elderly With Diabetic Retinopathy.

one hundred (n=100) elderly outpatients with diabetic retinopathy taking antihypertensives and/or oral antidiabetics/insulin were interviewed. Adherence was evaluated by the adherence proportion and its association with the care taken in administrating medications and by the Morisky Scale. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was used to evaluate HRQoL. most (58%) reported the use of 80% or more of the prescribed dose and care in utilizing the medication. The item stopping the drug when experiencing an adverse event, from the Morisky Scale, explained 12.8% and 13.5% of the variability of adherence proportion to antihypertensives and oral antidiabetics/insulin, respectively. there was better HRQoL in the Color Vision, Driving and Social Functioning domains of the NEI VFQ-25. Individuals with lower scores on the NEI VFQ-25 and higher scores on the Morisky Scale presented greater chance to be nonadherent to the pharmacological treatment of diabetes and hypertension.

Validação da Body Appreciation Scale (BAS), Life Satisfaction Index for the Third Age (LSITA) e do Aging Perception Questionnaire (APQ) para a língua portuguesa no Brasil : um estudo em idosos brasileiros

Universidade Estadual de Campinas . Faculdade de Educação Física