Salmonella typhimurium infection in nonobese diabetic mice generates immunomodulatory dendritic cells able to prevent type 1 diabetes

Infection, commencing across a wide age range, with a live, attenuated strain of Salmonella typhimurium, will halt the development of type 1 diabetes in the NOD mouse. The protective mechanism appears to involve the regulation of autoreactive T cells in a manner associated with long lasting changes in the innate immune compartment of these mice. We show in this study that autoreactive T cell priming and trafficking are altered in mice that have been infected previously by S. typhimurium. These changes are associated with sustained alterations in patterns of chemokine expression. We find that small numbers of dendritic cells from mice that have been previously infected with, but cleared all trace of a S. typhimurium infection are able to prevent the development of diabetes in the highly synchronized and aggressive cyclophosphamide-induced model. The effects we observe on autoreactive T cell trafficking are recapitulated by the immunomodulatory dendritic cell transfers in the cyclophosphamide model.     

Nuclear magnetic resonance structure-based epitope mapping and modulation of dust mite group 13 allergen as a hypoallergen

IgE-mediated allergic response involves cross-linking of IgE bound on mast cells by specific surface epitopes of allergens. Structural studies on IgE epitopes of allergens are essential in understanding the characteristics of an allergen and for development of specific allergen immunotherapy. We have determined the structure of a group 13 dust mite allergen from Dermatophagoides farinae, Der f 13, using nuclear magnetic resonance. Sequence comparison of Der f 13 with homologous human fatty acid-binding proteins revealed unique surface charged residues on Der f 13 that may be involved in IgE binding and allergenicity. Site-directed mutagenesis and IgE binding assays have confirmed four surface charged residues on opposite sides of the protein that are involved in IgE binding. A triple mutant of Der f 13 (E41A_K63A_K91A) has been generated and found to have significantly reduced IgE binding and histamine release in skin prick tests on patients allergenic to group 13 dust mite allergens. The triple mutant is also able to induce PBMC proliferation in allergic patients with indices similar to those of wild-type Der f 13 and shift the secretion of cytokines from a Th2 to a Th1 pattern. Mouse IgG serum raised using the triple mutant is capable to block the binding of IgE from allergic patients to wild-type Der f 13, indicating potential for the triple mutant as a hypoallergen for specific immunotherapy. Findings in this study imply the importance of surface charged residues on IgE binding and allergenicity of an allergen, as was also demonstrated in other major allergens studied.     

Human CD4+CD25+ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas/Fas ligand-dependent mechanism

Although it is known that septic shock induces immunosuppression, the mechanism for this phenomenon is not well understood. Monocytes play a central role in septic shock pathophysiology, which is also characterized by an increased proportion of natural regulatory T (Treg) cells. We therefore investigated whether Treg could be involved in the decreased monocyte expression of CD14 and HLA-DR observed during septic shock. We demonstrated that human Treg inhibit LPS-induced retention of monocyte CD14. Because loss of CD14 is a hallmark of monocyte apoptosis, this suggests that Treg inhibit monocyte survival. This effect was largely mediated through the release of a soluble mediator that was not identical with either IL-10 or IL-4. The Fas/FasL pathway participated in the effect as it was blocked by anti-FasL Abs and reproduced by Fas agonist and recombinant soluble FasL. Furthermore, expression of FasL was much higher on Treg than on their CD25(-) counterparts. Collectively, these results indicate that Treg act on monocytes by inhibiting their LPS-induced survival through a proapoptotic mechanism involving the Fas/FasL pathway. This may be an important mechanism for septic shock-induced immunosuppression and may offer new perspectives for the treatment of this deadly disease.     

A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms

Pseudomonas aeruginosa produces extracellular DNA which functions as a cell-to-cell interconnecting matrix component in biofilms. Comparison of extracellular DNA and chromosomal DNA by the use of polymerase chain reaction and Southern analysis suggested that the extracellular DNA is similar to whole-genome DNA. Evidence that the extracellular DNA in P. aeruginosa biofilms and cultures is generated via lysis of a subpopulation of the bacteria was obtained through experiments where extracellular beta-galactosidase released from lacZ-containing P. aeruginosa strains was assessed. Experiments with the wild type and lasIrhlI, pqsA, pqsL and fliMpilA mutants indicated that the extracellular DNA is generated via a mechanism which is dependent on acyl homoserine lactone and Pseudomonas quinolone signalling, as well as on flagella and type IV pili. Microscopic investigation of flow chamber-grown wild-type P. aeruginosa biofilms stained with different DNA stains suggested that the extracellular DNA is located primarily in the stalks of mushroom-shaped multicellular structures, with a high concentration especially in the outer part of the stalks forming a border between the stalk-forming bacteria and the cap-forming bacteria. Biofilms formed by lasIrhlI, pqsA and fliMpilA mutants contained less extracellular DNA than biofilms formed by the wild type, and the mutant biofilms were more susceptible to treatment with sodium dodecyl sulphate than the wild-type biofilm.     

A flexible multi-dimensional QoS performance measure framework for distributed heterogeneous systems

When users’ tasks in a distributed heterogeneous computing environment (e.g., cluster of heterogeneous computers) are allocated resources, the total demand placed on some system resources by the tasks, for a given interval of time, may exceed the availability of those resources. In such a case, some tasks may receive degraded service or be dropped from the system. One part of a measure to quantify the success of a resource management system (RMS) in such a distributed environment is the collective value of the tasks completed during an interval of time, as perceived by the user, application, or policy maker. The Flexible Integrated System Capability (FISC) measure presented here is a measure for quantifying this collective value. The FISC measure is a flexible multi-dimensional measure such that any task attribute can be inserted and may include priorities, versions of a task or data, deadlines, situational mode, security, application- and domain-specific QoS, and task dependencies. For an environment where it is important to investigate how well data communication requests are satisfied, the data communication request satisfied can be the basis of the FISC measure instead of tasks completed. The motivation behind the FISC measure is to determine the performance of resource management schemes if tasks have multiple attributes that needs to be satisfied. The goal of this measure is to compare the results of different resource management heuristics that are trying to achieve the same performance objective but with different approaches. This research was supported by the DARPA/ITO Quorum Program, by the DARPA/ISO BADD Program and the Office of Naval Research under ONR grant number N00014-97-1-0804, by the DARPA/ITO AICE program under contract numbers DABT63-99-C-0010 and DABT63-99-C-0012, and by the Colorado State University George T. Abell Endowment. Intel and Microsoft donated some of the equipment used in this research. Jong-Kook Kim is pursuing a Ph.D. degree from the School of Electrical and Computer Engineering at Purdue University (expected in August 2004). Jong-Kook received his M.S. degree in electrical and computer engineering from Purdue University in May 2000. He received his B.S. degree in electronic engineering from Korea University, Seoul, Korea in 1998. He has presented his work at several international conferences and has been a reviewer for numerous conferences and journals. His research interests include heterogeneous distributed computing, computer architecture, performance measure, resource management, evolutionary heuristics, and power-aware computing. He is a student member of the IEEE, IEEE Computer Society, and ACM. Debra Hensgen is a member of the Research and Evaluation Team at OpenTV in Mountain View, California. OpenTV produces middleware for set-top boxes in support of interactive television. She received her Ph.D. in the area of Distributed Operating Systems from the University of Kentucky. Prior to moving to private industry, as an Associate Professor in the systems area, she worked with students and colleagues to design and develop tools and systems for resource management, network re-routing algorithms and systems that preserve quality of service guarantees, and visualization tools for performance debugging of parallel and distributed systems. She has published numerous papers concerning her contributions to the Concurra toolkit for automatically generating safe, efficient concurrent code, the Graze parallel processing performance debugger, the SAAM path information base, and the SmartNet and MSHN Resource Management Systems. Taylor Kidd is currently a Software Architect for Vidiom Systems in Portland Oregon. His current work involves the writing of multi-company industrial specifications and the architecting of software systems for the digital cable television industry. He has been involved in the establishment of international specifications for digital interactive television in both Europe and in the US. Prior to his current position, Dr. Kidd has been a researcher for the US Navy as well as an Associate Professor at the Naval Postgraduate School. Dr Kidd received his Ph.D. in Electrical Engineering in 1991 from the University of California, San Diego. H. J. Siegel was appointed the George T. Abell Endowed Chair Distinguished Professor of Electrical and Computer Engineering at Colorado State University (CSU) in August 2001, where he is also a Professor of Computer Science. In December 2002, he became the first Director of the CSU Information Science and Technology Center (ISTeC). ISTeC is a university-wide organization for promoting, facilitating, and enhancing CSU’s research, education, and outreach activities pertaining to the design and innovative application of computer, communication, and information systems. From 1976 to 2001, he was a professor at Purdue University. He received two BS degrees from MIT, and the MA, MSE, and PhD degrees from Princeton University. His research interests include parallel and distributed computing, heterogeneous computing, robust computing systems, parallel algorithms, parallel machine interconnection networks, and reconfigurable parallel computer systems. He has co-authored over 300 published papers on parallel and distributed computing and communication, is an IEEE Fellow, is an ACM Fellow, was a Coeditor-in-Chief of the Journal of Parallel and Distributed Computing, and was on the Editorial Boards of both the IEEE Transactions on Parallel and Distributed Systems and the IEEE Transactions on Computers. He was Program Chair/Co-Chair of three major international conferences, General Chair/Co-Chair of four international conferences, and Chair/Co-Chair of five workshops. He has been an international keynote speaker and tutorial lecturer, and has consulted for industry and government. David St. John is Chief Information Officer for WeatherFlow, Inc., a weather services company specializing in coastal weather observations and forecasts. He received a master’s degree in Engineering from the University of California, Irvine. He spent several years as the head of staff on the Management System for Heterogeneous Networks project in the Computer Science Department of the Naval Postgraduate School. His current relationship with cluster computing is as a user of the Regional Atmospheric Modeling System (RAMS), a numerical weather model developed at Colorado State University. WeatherFlow runs RAMS operationally on a Linux-based cluster. Cynthia Irvine is a Professor of Computer Science at the Naval Postgraduate School in Monterey, California. She received her Ph.D. from Case Western Reserve University and her B.A. in Physics from Rice University. She joined the faculty of the Naval Postgraduate School in 1994. Previously she worked in industry on the development of high assurance secure systems. In 2001, Dr. Irvine received the Naval Information Assurance Award. Dr. Irvine is the Director of the Center for Information Systems Security Studies and Research at the Naval Postgraduate School. She has served on special panels for NSF, DARPA, and OSD. In the area of computer security education Dr. Irvine has most recently served as the general chair of the Third World Conference on Information Security Education and the Fifth Workshop on Education in Computer Security. She co-chaired the NSF workshop on Cyber-security Workforce Needs Assessment and Educational Innovation and was a participant in the Computing Research Association/NSF sponsored Grand Challenges in Information Assurance meeting. She is a member of the editorial board of the Journal of Information Warfare and has served as a reviewer and/or program committee member of a variety of security related conferences. She has written over 100 papers and articles and has supervised the work of over 80 students. Professor Irvine is a member of the ACM, the AAS, a life member of the ASP, and a Senior Member of the IEEE. Timothy E. Levin is a Research Associate Professor at the Naval Postgraduate School. He has spent over 18 years working in the design, development, evaluation, and verification of secure computer systems, including operating systems, databases and networks. His current research interests include high assurance system design and analysis, development of models and methods for the dynamic selection of QoS security attributes, and the application of formal methods to the development of secure computer systems. Viktor K. Prasanna received his BS in Electronics Engineering from the Bangalore University and his MS from the School of Automation, Indian Institute of Science. He obtained his Ph.D. in Computer Science from the Pennsylvania State University in 1983. Currently, he is a Professor in the Department of Electrical Engineering as well as in the Department of Computer Science at the University of Southern California, Los Angeles. He is also an associate member of the Center for Applied Mathematical Sciences (CAMS) at USC. He served as the Division Director for the Computer Engineering Division during 1994–98. His research interests include parallel and distributed systems, embedded systems, configurable architectures and high performance computing. Dr. Prasanna has published extensively and consulted for industries in the above areas. He has served on the organizing committees of several international meetings in VLSI computations, parallel computation, and high performance computing. He is the Steering Co-chair of the International Parallel and Distributed Processing Symposium [merged IEEE International Parallel Processing Symposium (IPPS) and the Symposium on Parallel and Distributed Processing (SPDP)] and is the Steering Chair of the International Conference on High Performance Computing(HiPC). He serves on the editorial boards of the Journal of Parallel and Distributed Computing and the Proceedings of the IEEE. He is the Editor-in-Chief of the IEEE Transactions on Computers. He was the founding Chair of the IEEE Computer Society Technical Committee on Parallel Processing. He is a Fellow of the IEEE. Richard F. Freund is the originator of GridIQ’s network scheduling concepts that arose from mathematical and computing approaches he developed for the Department of Defense in the early 1980’s. Dr. Freund has over twenty-five years experience in computational mathematics, algorithm design, high performance computing, distributed computing, network planning, and heterogeneous scheduling. Since 1989, Dr. Freund has published over 45 journal articles in these fields. He has also been an editor of special editions of IEEE Computer and the Journal of Parallel and Distributed Computing. In addition, he is a founder of the Heterogeneous Computing Workshop, held annually in conjunction with the International Parallel Processing Symposium. Dr. Freund is the recipient of many awards, which includes the prestigious Department of Defense Meritorious Civilian Service Award in 1984 and the Lauritsen-Bennet Award from the Space and Naval Warfare Systems Command in San Diego, California.     

Comparative in vitro study of bileaflet and tilting disk valve behavior in the pulmonary position

A study of mechanical heart valve behavior in the pulmonary position as a function of pulmonary vascular resistance is reported for the St. Jude Medical bileaflet (SJMB) valve and the MedicalCV Omnicarbon (OTD) tilting disk valve. Tests were conducted in a pulmonic mock circulatory system and impedance was varied in terms of system pulmonary vascular resistance (PVR). An impedance spectrum was found using instantaneous pulmonary artery pressure and flow rate curves. Both valves fully opened and closed at and above a nominal PVR of 3.0 mmHg/L/min. The SJMB valve was prone to leaflet bounce at closure, but otherwise completely closed, at settings above and below this nominal setting. At PVR values at and below 2.0 mmHg/L/min, the SJMB valve exhibited two types of leaflet aberrant behavior: single leaflet only closure while the other leaflet fluttered, and incomplete closure where both leaflets flutter but neither remain fully closed. The OTD valve fully opened and closed to a PVR value of 1.6 mmHg/L/min. At lower values, the valve did not close. Valves designed for the left heart can show aberrant behavior under normal conditions as pulmonary valves.     

Modelling calcium carbonate biomineralisation processes

The structure-directing influence of the organic dicarboxylates malonate, succinate, glutarate and adipate as templating species on the hydrothermal formation of CaCO(3) was investigated at different temperatures (60, 80, 90, 120, 150 and 190 degrees C) and with a range of molar ratios of [Ca(2+)]/[templating species] (20, 14.3, 10, 7.7, 5, 1, 0.5 and 0.33). In the presence of the dicarboxylates, one, two or three polymorphs of CaCO(3) - calcite, aragonite and vaterite - could be formed, depending on the reaction conditions. In addition changes in crystal morphology were observed for the CaCO(3) polymorphs depending on the concentration of the template. In contrast, synthesis under ambient conditions of temperature and pressure resulted only in calcite formation, although template-dependent morphological changes were again observed. Crystalline products were all characterized by powder X-ray patterns and SEM (Scanning Electron Microscopy) micrographs. The ambient reactions with the chelating, dinucleating carboxylato ligands H(3)heidi and H(5)hpdta produce more profound changes in calcite morphology. With H(3)heidi rounded calcite crystals with shapes similar to that of otoliths are formed and with H(5)hpdta the formation of microtrumpets of constructed from bundles of nanocrystals of calcite is observed. The possible mode of action of these ligands on calcite formation is discussed in the context of known coordination chemistry with other metal ions.