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Cincinnati, OH, United States

Kaneku H.,University of California at Los Angeles | Kaneku H.,Terasaki Foundation Laboratory | O'Leary J.G.,Baylor University | Taniguchi M.,Lambda Research | And 3 more authors.
Liver Transplantation

In a previous study, we found that 92% of patients with chronic rejection had donor-specific human leukocyte antigen antibodies (DSAs), but surprisingly, 61% of comparator patients without rejection also had DSAs. We hypothesized that immunoglobulin G (IgG) subclasses were differentially distributed between the 2 groups. A modified single-antigen bead assay was used to detect the presence of individual IgG subclasses against human leukocyte antigen in 39 chronic rejection patients and 66 comparator patients. DSAs of the IgG1 subclass were most common and were found in 45% of all patients; they were followed by IgG3 DSAs (21%), IgG4 DSAs (14%), and IgG2 DSAs (13%). The percentage of patients with multiple IgG subclasses was significantly higher in the chronic rejection group versus the comparator group (50% versus 14%, P < 0.001). Patients with normal graft function in the presence of DSAs mostly had isolated IgG1, whereas patients with chronic rejection had a combination of IgG subclasses. Patients who developed DSAs of the IgG3 subclass showed an increased risk of graft loss (hazard ratio = 3.35, 95% confidence interval = 1.39-8.05) in comparison with patients with DSAs of other IgG subclasses or without DSAs. Although further study is needed, the determination of the IgG subclass in DSA-positive patients may help us to identify patients with a higher risk of chronic rejection and graft loss. © 2012 American Association for the Study of Liver Diseases. Source

Edrey Y.H.,Sam and Ann Barshop Institute for Longevity and Aging Studies and San Antonio | Salmon A.B.,Sam and Ann Barshop Institute for Longevity and Aging Studies and San Antonio | Salmon A.B.,Lambda Research | Salmon A.B.,University of Texas Health Science Center at San Antonio
Free Radical Biology and Medicine

Significant advances in maintaining health throughout life can be made through a clear understanding of the fundamental mechanisms that regulate aging. The Oxidative Stress Theory of Aging (OSTA) is probably the most well studied mechanistic theory of aging and suggests that the rate of aging is controlled by accumulation of oxidative damage. To directly test the OSTA, aging has been measured in several lines of mice with genetic alterations in the expression of enzymatic antioxidants. Under its strictest interpretation, these studies do not support the OSTA, as modulation of antioxidant expression does not generally affect mouse life span. However, the incidence of many age-related diseases and pathologies is altered in these models, suggesting that oxidative stress does significantly influence some aspects of the aging process. Further, oxidative stress may affect aging in disparate patterns among tissues or under various environmental conditions. In this review, we summarize the current literature regarding aging in antioxidant mutant mice and offer several interpretations of their support of the OSTA. Source

Agency: National Aeronautics and Space Administration | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2011

Powder metal (PM) superalloys used for critical compressor and turbine disk applications are prone to fatigue failures in stress concentration features such as holes and radii, as well as from corrosion pits and inclusions. Residual stress and cold work will have a dramatic impact on the fatigue performance. Shot peening is widely used on PM disks to provide a fatigue benefit however, the relaxation due to thermal and mechanical loads can reduce or even eliminate the compressive residual stresses and increase the risk of a catastrophic disk failure. Up to now the evolution of the residual stress and cold work under typical operating conditions in PM disk superalloys is not well understood.In Phase I proprietary x-ray diffraction (XRD) techniques will be used to simultaneously measure the change in residual stress and cold work for fatigue specimens tested in a manner to approximate in-service conditions. XRD residual stress and cold work results will be used to establish the feasibility of applying analytical or empirically based modeling techniques to predict the residual stress and cold work evolution. The modeling technique will first be demonstrated on fatigue samples and further developed and proven on actual disk hardware in Phase II. The anticipated beginning and ending technology readiness levels (TRLs) for Phase I are 2 and 5, respectively.

Agency: Department of Defense | Branch: Navy | Program: SBIR | Phase: Phase II | Award Amount: 740.24K | Year: 2002

"Improved damage tolerance is critical to achieving reduced engineownership costs and increasing safety and fleet readiness. InPhase I, low plasticity burnishing (LPB) was successfullydemonstrated to improve the damage tolerance of the F404 1ststage fan blade by an order of magnitude through the introductionof high magnitude through-thickness compressive residual stressin the FOD sensitive leading edge. The objective of this PhaseII research effort is to apply LPB to the F402 LPC-V1 trailingedge to immediately address an HCF safety related problem, andthen to address the engineering issues necessary to transitionLPB blade processing to the fleet. Reverse engineering methodswill be established to efficiently develop LPB processingparameters and CNC code for other components. Finite elementmethods will be used to optimize the LPB residual stress fieldsand to predict the fatigue performance benefit for other bladesand materials. The data necessary to predict fatigueperformance, including thermal and overload relaxation to supportlong-range life prediction, will be generated.LPB processing will find initial Phase III application in Navydepots to increase damage tolerance of fan and compressor bladesduring engine overhaul, reducing replacement, maintenance andinspection costs. The introduction of LPB as a manufacturingprocess by engine OEMs will follow to extend the performance,improve safety and reduce the cost of ownership of milit

Agency: Department of Defense | Branch: Air Force | Program: SBIR | Phase: Phase I | Award Amount: 99.97K | Year: 2002

"The 4th stage compressor IBR of the JSF F119 engine is fatigue limited. Surface enhancement, by the introduction of compressive residual stress, is a practical means of improving fatigue performance without changing material or design. Low PlasticityBurnishing (LPB) provides twice the HCF strength and four times the damage tolerance of shot peening in Ti-64 and IN718 laboratory specimens. LPB applied to the leading edge of the F404 Ti-64 1st stage fan blade has been shown to produce sufficientthrough-thickness compression for complete tolerance of 1.3 mm (0.050 in.) deep FOD. LPB offers rapid, affordable, surface enhancement using conventional CNC machine tools in a manufacturing environment.With the support of Pratt and Whitney, the feasibility of improving damage tolerance of the F119 4th stage compressor IBR blades with LPB processing will be investigated. LPB parameters and control software will be developed using existing tooling and4-axis CNC facility. The HCF life and damage tolerance achievable with LPB will be documented and compared to the current practice of shot peening. Phase II will thoroughly document HCF performance of LPB processed blades, and address the development of anautomated production facility for LPB processing full IBRs in manufacturing and repair. The immediate anticipated benefit of the proposed effort to the Air Force is elimination of the fatigue related performance limitations imposed on the F119

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