The Scientist, Fall 2013

https://scholarworks.sjsu.edu/scientist/1006/thumbnail.jp

Positional identification and functional analysis of genes regulating autoimmune arthritis

The major histocompatibility complex (MHC) is the most gene-dense and polymorphic region in the human genome with strong associations to many autoimmune disorders, including rheumatoid arthritis (RA). However, even the genetic association between MHC and RA was known more than 40 years ago, we still have not fully explained the functional roles of the MHC genes and identified the underlying specific polymorphisms. This thesis describes some of our research aimed for a better understanding of this topic, which can largely be divided into three parts as follows. First, we made use of a panel of MHC class II (MHC-II) congenic strains to evaluate the functional roles of MHC-II polymorphisms in arthritis. By performing an extensive genetic and functional analysis, we showed that MHC-II RT1-B (the rat orthologs of HLA-DQ) determines the onset and severity of experimental arthritis, possibly due to the amino acid variations in the P1 pocket of RT1-B. In addition, we showed that natural allelic variants in Tap2, another gene in the MHC-II region, regulates the thymic selection of CD8+ T cells. Second, in order to investigate whether other MHC genes also contribute to arthritis susceptibility, we assessed arthritis development in congenic strains mapped to other parts of the MHC region. We identified a second arthritis-regulatory QTL in the MHC class III region, that regulates not only the onset and severity, but also chronicity of arthritis. We subsequently mapped this effect to a conserved, 33-kb large haplotype Ltab-Ncr3 comprising five polymorphic genes. Interestingly, unlike other positionally-identified arthritis genes in rats, Ltab-Ncr3 regulates only adjuvant arthritis models but not autoimmunity triggered by specific tissue antigens, such as type II collagen. Furthermore, we found that gene expression and alternative splicing of the Ltab-Ncr3 genes correlate remarkably with arthritis severity and some of the gene expression differences were reproduced in a cohort of RA patients and healthy controls. Third, the MHC-II gene expression is regulated by class II transactivator (CIITA or C2TA), and in humans, genetic variation in CIITA has been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Using a congenic mouse strain with an allelic variant in the type I promoter of C2ta, we demonstrate that whereas genetic polymorphisms in C2ta promoter result in differential MHC-II expression and antigen presentation, these do not necessarily have a strong impact on autoimmune diseases such as arthritis. In summary, these studies demonstrate how the congenic approach remains powerful to conclusively identify and characterise genes regulating a complex disease like arthriti

November 1999

Gary Hines \u2774 on the Concert Hall stage, Janet Wallace Fine Arts Center in August 1999. Story on page 32.https://digitalcommons.macalester.edu/mactodaycovers/1053/thumbnail.jp

Organizational knowledge transfer through creation, mobilization and diffusion: A case analysis of InTouch within Schlumberger

There is a paucity of theory for the effective management of knowledge transfer within large organisations. Practitioners continue to rely upon ‘experimental’ approaches to address the problem. This research attempts to reduce the gap between theory and application, thereby improving conceptual clarity for the transfer of knowledge. The paper, through an in-depth case analysis conducted within Schlumberger, studies the adoption of an intranet-based knowledge management (KM) system (called InTouch) to support, strategically align and transfer knowledge resources. The investigation was undertaken through the adoption of a robust methodological approach (abductive strategy) incorporating the role of technology as an enabler of knowledge management application. Consequently, the study addressed the important question of translating theoretical benefits of KM into practical reality. The research formulates a set of theoretical propositions which are seen as key to the development of an effective knowledge based infrastructure. The findings identify 30 generic attributes that are essential to the creation, mobilisation and diffusion of organisational knowledge. The research makes a significant contribution to identifying a theoretical and empirically based agenda for successful intranet-based KM which will be of benefit to both the academic and practitioner communities. The paper also highlights and proposes important areas for further research

Management by Trajectory Trade Study of Roles and Responsibilities Between Participants and Automation Report

This report describes a trade study of roles and responsibilities associated with the Management by Trajectory (MBT) concept. The MBT concept describes roles, responsibilities, and information and automation requirements for providing air traffic controllers and managers the ability to quickly generate, evaluate and implement changes to an aircraft's trajectory. In addition, the MBT concept describes mechanisms for imposing constraints on flight operator preferred trajectories only to the extent necessary to maintain safe and efficient traffic flows, and the concept provides a method for the exchange of trajectory information between ground automation systems and the aircraft that allows for trajectory synchronization and trajectory negotiation. The participant roles considered in this trade study include: airline dispatcher, flight crew, radar controller, traffic manager, and Air Traffic Control System Command Center (ATCSCC) traffic management specialists. The proposed allocation of roles and responsibilities was based on analysis of several use cases that were developed for this purpose as well as for walking through concept elements. The resulting allocation of roles and responsibilities reflects both increased automation capability to support many aviation functions, as well as increased flexibility to assign responsibilities to different participants - in many cases afforded by the increased automation capabilities. Note that the selection of participants to consider for allocation of each function is necessarily rooted in the current environment, in that MBT is envisioned as an evolution of the National Airspace System (NAS), and not a revolution. A key feature of the MBT allocations is a vision for the traffic management specialist to take on a greater role. This is facilitated by the vision that separation management functions, in addition to traffic management functions, will be carried out as trajectory management functions. This creates an opportunity for flexibility, allowing the traffic management specialist to carry out tasks that today can only be carried out by the controller currently in contact with the aircraft. This additional tasking for the traffic management specialist comes with requirements for workload management. An increased role for the Data-side (D-side) controller relative to the Radar-side (R-side) controller is a potential approach to mitigating workload for the traffic management specialist, as the D-side controller would have similar ability to perform separation management functions in what today might be considered the "trajectory management" timeframe. This analysis did not distinguish between the D-side and R-side controllers since in many cases the R-side controller works unassisted

Going back to the future: a modernized personalized system of instruction (MPSI) for cegep physics

Titre de l'écran-titre (visionné le 5 sept. 2013)Également disponible en version papier.Bibliogr. : p. 55-5