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The Immunosignature of Canine Lymphoma: Characterization and Diagnostic Application

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Background: Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the

Background: Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the immunosignature as a diagnostic for spontaneous canine lymphoma at both at initial diagnosis and evaluating the disease free interval following treatment.

Methods: Sera from dogs with confirmed lymphoma (B cell n = 38, T cell n = 11) and clinically normal dogs (n = 39) were analyzed. Serum antibody responses were characterized by analyzing the binding pattern, or immunosignature, of serum antibodies on a non-natural sequence peptide microarray. Peptides were selected and tested for the ability to distinguish healthy dogs from those with lymphoma and to distinguish lymphoma subtypes based on immunophenotype. The immunosignature of dogs with lymphoma were evaluated for individual signatures. Changes in the immunosignatures were evaluated following treatment and eventual relapse.

Results: Despite being a clonal disease, both an individual immunosignature and a generalized lymphoma immunosignature were observed in each dog. The general lymphoma immunosignature identified in the initial set of dogs (n = 32) was able to predict disease status in an independent set of dogs (n = 42, 97% accuracy). A separate immunosignature was able to distinguish the lymphoma based on immunophenotype (n = 25, 88% accuracy). The individual immunosignature was capable of confirming remission three months following diagnosis. Immunosignature at diagnosis was able to predict which dogs with B cell lymphoma would relapse in less than 120 days (n = 33, 97% accuracy).

Conclusion: We conclude that the immunosignature can serve as a multilevel diagnostic for canine, and potentially human, lymphoma.

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2014-09-08

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Scalable High-Density Peptide Arrays for Comprehensive Health Monitoring

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There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed microarrays are not scalable. Here we demonstrate a platform based on fabricating microarrays (~10 M peptides per slide, 330,000 peptides per assay) on silicon wafers using equipment common to semiconductor manufacturing. The potential of these microarrays for comprehensive health monitoring is verified through the simultaneous detection and classification of six different infectious diseases and six different cancers. Besides diagnostics, these high-density peptide chips have numerous other applications both in health care and elsewhere.

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2014-09-03

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A Simple Platform for the Rapid Development of Antimicrobials

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Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as

Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as little as one week thousands of doses of an intervention for a new pathogen. We tested the feasibility of a system based on antimicrobial synbodies. The system involves creating an array of 100 peptides that have been selected for broad capability to bind and/or kill viruses and bacteria. The peptides are pre-screened for low cell toxicity prior to large scale synthesis. Any pathogen is then assayed on the chip to find peptides that bind or kill it. Peptides are combined in pairs as synbodies and further screened for activity and toxicity. The lead synbody can be quickly produced in large scale, with completion of the entire process in one week.

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2017-12-14

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Application of TMPP Labeling and Ammonia Gas Cleavage in MALDI-MS Analysis of Resin-bound Peptides

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One of the major challenges that were yet to be solved for solid phase peptide synthesis was the lack of an efficient peptide sequencing technique that was less hazardous, easier to perform , and was more cost-effective. Sequencing peptides were

One of the major challenges that were yet to be solved for solid phase peptide synthesis was the lack of an efficient peptide sequencing technique that was less hazardous, easier to perform , and was more cost-effective. Sequencing peptides were held important in the field of Chemistry and Biochemistry because it aided in drug discovery, finding ligands that bind to a specific target protein and finding alternative agents in transporting molecules to its desired location. Therefore, the overall purpose of this experiment was to develop a method of solid phase sequencing technique that was more environmental friendly, sequences at a faster rate, and was more cost-effective.

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2014-05

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Furniture longevity: how mass-produced heirloom furniture supports sustainable consumption

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In recent years, the length of time people use and keep belongings has decreased. With the acceptance of short-lived furniture and inexpensive replacements, the American mentality has shifted to thinking that discarding furniture is normal, often in the guise of

In recent years, the length of time people use and keep belongings has decreased. With the acceptance of short-lived furniture and inexpensive replacements, the American mentality has shifted to thinking that discarding furniture is normal, often in the guise of recycling. Americans are addicted to landfills. The high cost of landfill real estate and other considerable ecological impacts created by the manufacturing of furniture should persuade people to give their belongings a longer life, but in reality, furniture is often prematurely discarded. This grounded theory study takes a multi-method approach to analyze why some types of furniture are kept longer and to theorize about new ways to design and sell furniture that lasts well past its warranty. Case studies bring new insight into designer intention, manufacturer intent, the world of auction-worthy collectables and heirlooms, why there is a booming second-hand furniture market and the growing importance of informed interior designers and architects who specify or help clients choose interior furnishings. An environmental life cycle assessment compares how the length of furniture life affects environmental impacts. A product's life could continue for generations if properly maintained. Designers and manufacturers hoping to promote longevity can apply the conclusions of this report in bringing new pieces to the market that have a much longer life span. This study finds areas of opportunity that promote user attachment, anticipate future repurposing, and provide services. This thinking envisions a paradigm for furniture that can re-invent itself over multiple generations of users, and ultimately lead to a new wave of desirable heirloom furniture.

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2011

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Schooling choice during structural transformation

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This dissertation consists of two essays. The first measures the degree to which schooling accounts for differences in industry value added per worker. Using a sample of 107 economies and seven industries, the paper considers the patterns in the education

This dissertation consists of two essays. The first measures the degree to which schooling accounts for differences in industry value added per worker. Using a sample of 107 economies and seven industries, the paper considers the patterns in the education levels of various industries and their relative value added per worker. Agriculture has notably less schooling and is less productive than other sectors, while a group of services including financial services, education and health care has higher rates of schooling and higher value added per worker. The essay finds that in the case of these specific industries education is important in explaining sector differences, and the role of education all other industries are less defined. The second essay provides theory to investigate the relationship between agriculture and schooling. During structural transformation, workers shift from the agriculture sector with relatively low schooling to other sectors which have more schooling. This essay explores to what extent changes in the costs of acquiring schooling drive structural transformation using a multi-sector growth model which includes a schooling choice. The model is disciplined using cross country data on sector of employment and schooling constructed from the IPUM International census collection. Counterfactual exercises are used to determine how much structural transformation is accounted for by changes in the cost of acquiring schooling. These changes account for small shares of structural transformation in all economies with a median near zero.

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2011

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Laboratory determination of hydraulic conductivity functions for unsaturated cracked fine grained soil

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In geotechnical engineering, measuring the unsaturated hydraulic conductivity of fine grained soils can be time consuming and tedious. The various applications that require knowledge of the unsaturated hydraulic conductivity function are great, and in geotechnical engineering, they range from

In geotechnical engineering, measuring the unsaturated hydraulic conductivity of fine grained soils can be time consuming and tedious. The various applications that require knowledge of the unsaturated hydraulic conductivity function are great, and in geotechnical engineering, they range from modeling seepage through landfill covers to determining infiltration of water under a building slab. The unsaturated hydraulic conductivity function can be measured using various direct and indirect techniques. The instantaneous profile method has been found to be the most promising unsteady state method for measuring the unsaturated hydraulic conductivity function for fine grained soils over a wide range of suction values. The instantaneous profile method can be modified by using different techniques to measure suction and water content and also through the way water is introduced or removed from the soil profile. In this study, the instantaneous profile method was modified by creating duplicate soil samples compacted into cylindrical tubes at two different water contents. The techniques used in the duplicate method to measure the water content and matric suction included volumetric moisture probes, manual water content measurements, and filter paper tests. The experimental testing conducted in this study provided insight into determining the unsaturated hydraulic conductivity using the instantaneous profile method for a sandy clay soil and recommendations are provided for further evaluation. Overall, this study has demonstrated that the presence of cracks has no significant impact on the hydraulic behavior of soil in high suction ranges. The results of this study do not examine the behavior of cracked soil unsaturated hydraulic conductivity at low suction and at moisture contents near saturation.

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Date Created
2011

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The emergence and scaling of division of labor in insect societies

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Division of labor, whereby different group members perform different functions, is a fundamental attribute of sociality. It appears across social systems, from simple cooperative groups to complex eusocial colonies. A core challenge in sociobiology is to explain how patterns of

Division of labor, whereby different group members perform different functions, is a fundamental attribute of sociality. It appears across social systems, from simple cooperative groups to complex eusocial colonies. A core challenge in sociobiology is to explain how patterns of collective organization are generated. Theoretical models propose that division of labor self-organizes, or emerges, from interactions among group members and the environment; division of labor is also predicted to scale positively with group size. I empirically investigated the emergence and scaling of division of labor in evolutionarily incipient groups of sweat bees and in eusocial colonies of harvester ants. To test whether division of labor is an emergent property of group living during early social evolution, I created de novo communal groups of the normally solitary sweat bee Lasioglossum (Ctenonomia) NDA-1. A division of labor repeatedly arose between nest excavation and guarding tasks; results were consistent with hypothesized effects of spatial organization and intrinsic behavioral variability. Moreover, an experimental increase in group size spontaneously promoted higher task specialization and division of labor. Next, I examined the influence of colony size on division of labor in larger, more integrated colonies of the harvester ant Pogonomyrmex californicus. Division of labor scaled positively with colony size in two contexts: during early colony ontogeny, as colonies grew from tens to hundreds of workers, and among same-aged colonies that varied naturally in size. However, manipulation of colony size did not elicit a short-term response, suggesting that the scaling of division of labor in P. californicus colonies is a product of functional integration and underlying developmental processes, rather than a purely emergent epiphenomenon. This research provides novel insights into the organization of work in insect societies, and raises broader questions about the role of size in sociobiology.

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2011

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Global behavior of finite energy solutions to the focusing nonlinear Schrödinger Equation in d dimension

Description

Nonlinear dispersive equations model nonlinear waves in a wide range of physical and mathematics contexts. They reinforce or dissipate effects of linear dispersion and nonlinear interactions, and thus, may be of a focusing or defocusing nature. The nonlinear Schrödinger equation

Nonlinear dispersive equations model nonlinear waves in a wide range of physical and mathematics contexts. They reinforce or dissipate effects of linear dispersion and nonlinear interactions, and thus, may be of a focusing or defocusing nature. The nonlinear Schrödinger equation or NLS is an example of such equations. It appears as a model in hydrodynamics, nonlinear optics, quantum condensates, heat pulses in solids and various other nonlinear instability phenomena. In mathematics, one of the interests is to look at the wave interaction: waves propagation with different speeds and/or different directions produces either small perturbations comparable with linear behavior, or creates solitary waves, or even leads to singular solutions. This dissertation studies the global behavior of finite energy solutions to the $d$-dimensional focusing NLS equation, $i partial _t u+Delta u+ |u|^{p-1}u=0, $ with initial data $u_0in H^1,; x in Rn$; the nonlinearity power $p$ and the dimension $d$ are chosen so that the scaling index $s=frac{d}{2}-frac{2}{p-1}$ is between 0 and 1, thus, the NLS is mass-supercritical $(s>0)$ and energy-subcritical $(s<1).$ For solutions with $ME[u_0]<1$ ($ME[u_0]$ stands for an invariant and conserved quantity in terms of the mass and energy of $u_0$), a sharp threshold for scattering and blowup is given. Namely, if the renormalized gradient $g_u$ of a solution $u$ to NLS is initially less than 1, i.e., $g_u(0)<1,$ then the solution exists globally in time and scatters in $H^1$ (approaches some linear Schr"odinger evolution as $ttopminfty$); if the renormalized gradient $g_u(0)>1,$ then the solution exhibits a blowup behavior, that is, either a finite time blowup occurs, or there is a divergence of $H^1$ norm in infinite time. This work generalizes the results for the 3d cubic NLS obtained in a series of papers by Holmer-Roudenko and Duyckaerts-Holmer-Roudenko with the key ingredients, the concentration compactness and localized variance, developed in the context of the energy-critical NLS and Nonlinear Wave equations by Kenig and Merle. One of the difficulties is fractional powers of nonlinearities which are overcome by considering Besov-Strichartz estimates and various fractional differentiation rules.

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Date Created
2011

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Migration aspirations, religiosity, and sexual behavior among youth: a new look at suicidal Ideation in Central Mexico

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While the suicide rate in Mexico is relatively low when compared to countries throughout the world, it is increasing at an alarming pace. Unfortunately, the amount of suicide research focused on Mexican populations is relatively scarce. Using a sample of

While the suicide rate in Mexico is relatively low when compared to countries throughout the world, it is increasing at an alarming pace. Unfortunately, the amount of suicide research focused on Mexican populations is relatively scarce. Using a sample of high school students living in Guanajuato, Mexico, this study explored the relationship between recent suicidal ideation and three factors that previous research in other countries has connected to suicide: Migration aspirations, religiosity, and sexual behavior. Using multiple and logistic regression, the results indicated the following: 1) Recent suicidal ideation predicted increased migration aspirations, 2) higher levels of external religiosity predicted lower odds of recent suicidal ideation, and 3) stronger parent-child relationships predicted lower odds of recent suicidal ideation. The findings are discussed in light of the Bronfenbrenner's ecological systems theory, Bogenschneider's risk/protection model, and Stark's religious commitment theory.

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2011