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Chaudhuri A.,Stanford University | Ozawa M.,Lambda Research | Everly M.J.,Lambda Research | Ettenger R.,Mattel Childrens Hospital | And 24 more authors.
Journal of the American Society of Nephrology | Year: 2013

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in lowrisk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serumanti-HLA antibodies to donorHLA antigens (donorspecific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months.We detected de novo antibodies after transplant in 24%(23% of SF group and 25%of SB group),most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies toHLA andMICA antigens appear in approximately 25%of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study. Copyright © 2013 by the American Society of Nephrology.


PubMed | University of Michigan, Iowa State University, Lambda Research, Sam Houston State University and 13 more.
Type: Journal Article | Journal: Ecology and evolution | Year: 2016

Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging. One idea from the field of aging that has gained considerable traction in the area of life histories is that life-history trade-offs may be mediated by free radical production and oxidative stress. We outline here developments in this field and summarize a number of important unresolved issues that may guide future research efforts. The issues are as follows. First, different tissues and macromolecular targets of oxidative stress respond differently during reproduction. The functional significance of these changes, however, remains uncertain. Consequently there is a need for studies that link oxidative stress measurements to functional outcomes, such as survival. Second, measurements of oxidative stress are often highly invasive or terminal. Terminal studies of oxidative stress in wild animals, where detailed life-history information is available, cannot generally be performed without compromising the aims of the studies that generated the life-history data. There is a need therefore for novel non-invasive measurements of multi-tissue oxidative stress. Third, laboratory studies provide unrivaled opportunities for experimental manipulation but may fail to expose the physiology underpinning life-history effects, because of the benign laboratory environment. Fourth, the idea that oxidative stress might underlie life-history trade-offs does not make specific enough predictions that are amenable to testing. Moreover, there is a paucity of good alternative theoretical models on which contrasting predictions might be based. Fifth, there is an enormous diversity of life-history variation to test the idea that oxidative stress may be a key mediator. So far we have only scratched the surface. Broadening the scope may reveal new strategies linked to the processes of oxidative damage and repair. Finally, understanding the trade-offs in life histories and understanding the process of aging are related but not identical questions. Scientists inhabiting these two spheres of activity seldom collide, yet they have much to learn from each other.


Vermeulen N.,Vrije Universiteit Brussel | Wasylczyk P.,University of Warsaw | Tonchev S.,Jean Monnet University | Muys P.,Lambda Research | And 3 more authors.
Laser Physics Letters | Year: 2011

We report the first demonstration of resonant-grating-based laser wavelength tuning in the mid-infrared spectral domain and with Littrow mounting of the grating. We show for a mid-infrared Cr:ZnSe laser that this tuning technique is much more wavelength selective than prism-based tuning, while inducing very low cavity losses (around 2%), which are at least two times smaller than in the case of a standard metal grating. Furthermore, the resonant grating allows tuning the Cr:ZnSe laser over as much as 400 nm around a center wavelength of 2.38 μm. This shows the potential of employing Littrow-mounted resonant diffraction gratings for controlling and tuning the emission wavelength of lasers emitting in the mid-infrared spectral domain and other wavelength regions. © 2011 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA.


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 | Year: 2012

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.


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 | Year: 2014

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.


Freniere E.,Lambda Research | Gauvin M.A.,Lambda Research | Youngworth R.N.,Riyo LLC
Proceedings of SPIE - The International Society for Optical Engineering | Year: 2015

The field of non-imaging optics is currently a diverse and fertile ground for innovation and analysis. Modeling systems for illumination and stray light effects influences a wide variety of electrical, optical, mechanical, material science, and system design decisions. Applications are also diverse in non-imaging including not only modeling these effects in imaging systems, but also important technologies such as solar energy, illumination, and projection systems, to name just a few areas of interest. Although design and analysis for illumination and stray light problems are both done in nonsequential ray-tracing programs, many practitioners only operate in one arena. Furthermore, the tasks associated with each of these types of problems have both similarities and distinct features. The goal of this paper is to provide a wide audience, including experts and people new to the field, an overview of the differences and similarities in modeling these two different (yet alike) types of problem. © 2015 SPIE.


Gauvin M.A.,Lambda Research | Jacobsen D.,Lambda Research | Byrne D.J.,Product Development Solutions
Proceedings of SPIE - The International Society for Optical Engineering | Year: 2015

This paper examines the role of the optimization process in illumination design. We will discuss why the starting point of the optimization process is crucial to a better design and why it is also important that the user understands the basic design problem and implements the correct merit function. Both a brute force method and the Downhill Simplex method will be used to demonstrate optimization methods with focus on using interactive design tools to create better starting points to streamline the optimization process. © 2015 SPIE.

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