The LFA-1 integrin plays a pivotal role in sustained leukocyte adhesion to the endothelial surface, which is a precondition for leukocyte recruitment into inflammation sites. Strong correlative evidence implicates LFA-1 clustering as being essential for sustained adhesion, and it may also facilitate rebinding events with its ligand ICAM-1. We cannot challenge those hypotheses directly because it is infeasible to measure either process during leukocyte adhesion following rolling. The alternative approach undertaken was to challenge the hypothesized mechanisms by experimenting on validated, working counterparts: simulations in which diffusible, LFA1 objects on the surfaces of quasi-autonomous leukocytes interact with simulated, diffusible, ICAM1 objects on endothelial surfaces during simulated adhesion following rolling. We used object-oriented, agent-based methods to build and execute multi-level, multi-attribute analogues of leukocytes and endothelial surfaces. Validation was achieved across different experimental conditions, in vitro, ex vivo, and in vivo, at both the individual cell and population levels. Because those mechanisms exhibit all of the characteristics of biological mechanisms, they can stand as a concrete, working theory about detailed events occurring at the leukocyte-surface interface during leukocyte rolling and adhesion experiments. We challenged mechanistic hypotheses by conducting experiments in which the consequences of multiple mechanistic events were tracked. We quantified rebinding events between individual components under different conditions, and the role of LFA1 clustering in sustaining leukocyte-surface adhesion and in improving adhesion efficiency. Early during simulations ICAM1 rebinding (to LFA1) but not LFA1 rebinding (to ICAM1) was enhanced by clustering. Later, clustering caused both types of rebinding events to increase. We discovered that clustering was not necessary to achieve adhesion as long as LFA1 and ICAM1 object densities were above a critical level. Importantly, at low densities LFA1 clustering enabled improved efficiency: adhesion exhibited measurable, cell level positive cooperativity.

An exoskeleton haptic interface is developed for functional training in virtual environments. A composite control scheme enables a variety of tasks to be implemented, and a ¿Qt¿ graphics library is used to generate the virtual environment for the haptic interface at the hand and graphical user interfaces for input and telemetry. Inter-process communications convert telemetry from the exoskeleton into motion commands for objects in the virtual environment. A second haptic interface at the upper arm is used to control the elbow orbit self-motion of the arm during tasks. Preliminary results are reviewed for a wall-painting task in which the virtual wall stiffness and viscosity are generated using an admittance controller.

A haptic interface is generated for a powered arm curl machine for modulating resistance "on-the-fly" during strength training and rehabilitation. Force signals from a load cell are input to an impedance loop based on the desired resistance law, which then outputs position commands to a servomotor. The kinematics between the actuator drive and arm curl angle are derived, and the admittance control implementation used for realizing the resistance laws is described. Preliminary experimental results are presented for viscous and inertial control laws.

This paper describes a logical extension to Microsoft Business Framework (MBF) called Analytical View (AV). AV consists of three components: Model Service for design time, Business Intelligence Entity (BIE) for programming model, and IntellDrill for runtime navigation between OLTP and OLAP data sources. AV feature-set fulfills enterprise application requirements for Analysis and Decision Support, complementing the transactional feature-set currently provided by MBF. Model Service automatically transforms an "object oriented model (transactional view)" to a "multi-dimensional model (analytical view)" without the traditional Extraction/Transformation/Loading (ETL) overhead and complexity. It infers dimensionality from the object layer where richer metadata is stored, eliminating the "guesswork" that a traditional data warehousing process requires when going through physical database schema. BI Entities are classes code-generated by Model Service. As an intrinsic part of the framework, BI Entities enable a consistent object oriented way of programming model with strong types and rich semantics for OLAP, similar to what MBF object persistence technology does for OLTP data. More importantly, data contained in BI Entities have a higher degree of "application awareness," such as the integrated application level security and customizability. IntelliDrill links together all the information islands in MBF using metadata. Because of the automatic transformation from transactional view to analytical view enabled by Model Service, we have the ability to understand natively what kind of drill-ability an object would have, thus making information navigation in MBF fully discover-able with built-in ontology.