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Item A Characterization of Different Spark Regimes for Ignition Delay Comparison with Conventional Spark Plugs(Office of the Vice Chancellor for Research, 2016-04-08) Wozniak, Zachary M.; Burton, Jesse C.; Hedrick, Cameron J.; Deng, Qiuyu; Robinson, Daniel W.The introduction of plasma into combustion and ignition processes has continuously proved to be advantageous when compared to the conventional spark ignition in a wide range of categories. From the capability to ignite leaner mixtures and improve fuel economy to an effective reduction of hazardous emissions and ignition delay, the benefits of integrating non-equilibrium plasma can be utilized for numerous applications including hot jet ignition. Detailed design specifications for the electrode configuration, circuit schematic, and combustion rig are developed and presented. Using a CCD camera and high performance oscilloscope, this paper aims to identify, characterize, and compare the different effects of frequency and pulse width of a driver circuit on the plasma sparks quantitatively in terms of the current, voltage, and energy attributes. Four different plasma regimes are investigated with frequencies ranging from 5.44 Hz to 95.46 kHz and pulse energies ranging from 168 μJ to 14.42 J. The maximum voltage and current characteristics of the plasmas indicate a glow discharge referencing previous experiments. Future work is laid out for a comparison of the ignition progression between a non-thermal plasma system and a traditional spark with using Schlieren imaging.Item A Comparison of Simple Analytical Methods for Determination of Fluoride in Microlitre-Volume Plasma Samples(Karger, 2019-04) Zohoori, F. Vida; Maguire, Anne; Martinez-Mier, E. Angeles; Buzalaf, Marília Afonso Rabelo; Sanderson, Roy; Eckert, George J.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryThe aim was to compare potential methods for fluoride analysis in microlitre-volume plasma samples containing nano-gram amounts of fluoride. Methods: A group of 4 laboratories analysed a set of standardised biological samples as well as plasma to determine fluoride concentration using 3 methods. In Phase-1, fluoride analysis was carried out using the established hexamethyldisiloxane (HMDS)-diffusion method (1 mL-aliquot/analysis) to obtain preliminary measurement of agreement between the laboratories. In Phase-2, the laboratories analysed the same samples using a micro-diffusion method and known-addition technique with 200 µL-aliquot/analysis. Coefficients of Variation (CVs) and intra-class correlation coefficients (ICCs) were estimated using analysis of variance to evaluate the amount of variation within- and between-laboratories. Based on the results of the Phase-2 analysis, 20 human plasma samples were analysed and compared using the HMDS-diffusion method and known-addition technique in Phase-3. Results: Comparison of Phase-1 results showed no statistically significant difference among the laboratories for the overall data set. The mean between- and within-laboratory CVs and ICCs were < 0.13 and ≥0.99, respectively, indicating very low variability and excellent reliability. In Phase-2, the overall results for between-laboratory variability showed a poor CV (1.16) and ICC (0.44) for the micro-diffusion method, whereas with the known-addition technique the corresponding values were 0.49 and 0.83. Phase-3 results showed no statistically significant difference in fluoride concentrations of the plasma samples measured with HMDS-diffusion method and known- addition technique, with a mean (SE) difference of 0.002 (0.003) µg/mL. In conclusion, the known-addition technique could be a suitable alternative for the measurement of fluoride in plasma with microlitre-volume samples.Item Development, validation, and comparison of four methods to simultaneously quantify L-arginine, citrulline, and ornithine in human plasma using hydrophilic interaction liquid chromatography and electrospray tandem mass spectrometry(Elsevier, 2015-11) Lai, Xianyin; Kline, Jeffrey A.; Wang, Mu; Department of Biochemistry and Molecular Biology, IU School of MedicineTo understand the role of l-arginine depletion in impaired nitric oxide synthesis in disease, it is important to simultaneously quantify arginine, citrulline, and ornithine in the plasma. Because the three amino acids are endogenous analytes, true blank matrix for them is not available. It is necessary and valuable to compare the performance of different approaches due to lack of regulatory clarity for validation. A two-step sample preparation method using methanol as protein precipitation reagent was developed in this study is used for sample preparation. Because true blank matrix for endogenous analytes is not available, water as blank matrix, 1% BSA in PBS as blank matrix, surrogate analyte, and background subtraction were designed to establish successful quantification methods. Four methods to simultaneously quantify arginine, citrulline, and ornithine in human plasma using hydrophilic interaction liquid chromatography and electrospray tandem mass spectrometry were developed, validated, and compared. The developed two-step sample preparation method using methanol as protein precipitation reagent in this study needs less time and provides higher recovery comparing with other approaches. Three of the four methods, water as blank matrix, 1% BSA in PBS as blank matrix, and surrogate analyte, have been successful in fulfilling all the criteria, while background subtraction has failed. Results of the measured concentrations in 97 human plasma samples using the three methods show that the difference between any two methods or among the three methods presents 100% of samples with less than 20% for all the three amino acids and majority of them are under 10%. The developed two-step sample preparation method using methanol as protein precipitation reagent is simple and convenient. Three of the four methods are fully validated and the validation is successful. The BSA functioned effectively as a blank matrix for these three amino acids, considering cost, data quality, matrix similarity, and practicality.Item Hypothesis: Potential Utility of Serum and Urine Uromodulin Measurement in Kidney Transplant Recipients?(Lippincott, Williams & Wilkins, 2017-10-06) Bostom, Andrew G.; Steubl, Dominik; Friedman, Allon N.; Medicine, School of MedicineSeventy years after its discovery, studies of the myriad properties, and potential disease associations of uromodulin are now burgeoning. Although normative ranges for serum/plasma uromodulin concentrations were established over 30 years ago, their external validation occurred only in very recent, larger studies. As tubular function indices, serum and urinary uromodulin may be more sensitive indicators of kidney graft dysfunction undetected by glomerular filtration markers, or proteinuria. Moreover, 2 sizable, just published longitudinal reports revealed that lower serum uromodulin levels were associated with cardiovascular disease (CVD) outcomes, total mortality, and infectious disease deaths, in patients with known or suspected coronary heart disease. Preliminary longitudinal studies have reported that reduced levels of plasma or serum uromodulin were linked to progression to end-stage renal disease in chronic kidney disease patients, and graft failure in kidney transplant recipients (KTRs). Conflicting data on the associations, or lack thereof, between lower urinary uromodulin concentrations and accelerated loss of renal function, or renal failure, in nontransplant chronic kidney disease patients, are perhaps due, in part, to analytical limitations in determining urine uromodulin. Potential longitudinal associations between serum and urinary uromodulin concentrations, and CVD outcomes, graft failure, and all-cause mortality, await validation in large, diverse cohorts of chronic KTRs. Taking advantage of an efficient case-cohort design scheme, we demonstrate how the completed FAVORIT clinical trial cohort might be ideally suited to evaluate these associations. Using available case-cohort sample data, statistical power simulations are provided to detect relative risk estimates of 1.50 for CVD (n = 309 events), 1.56 for graft failure (n = 223 events) or 1.50 for death from any cause (n = 320 events), comparing values below the median, to values equal to or above the median for serum uromodulin values. Edifying data such as these would advance our understanding of the hypothetical utility of uromodulin measurement in KTRs considerably.Item A large, consistent plasma proteomics data set from prospectively collected breast cancer patient and healthy volunteer samples(BMC, 2011-05-27) Riley, Catherine P; Zhang, Xiang; Nakshatri, Harikrishna; Schneider, Bryan; Regnier, Fred E; Adamec, Jiri; Buck, CharlesBackground Variability of plasma sample collection and of proteomics technology platforms has been detrimental to generation of large proteomic profile datasets from human biospecimens. Methods We carried out a clinical trial-like protocol to standardize collection of plasma from 204 healthy and 216 breast cancer patient volunteers. The breast cancer patients provided follow up samples at 3 month intervals. We generated proteomics profiles from these samples with a stable and reproducible platform for differential proteomics that employs a highly consistent nanofabricated ChipCube™ chromatography system for peptide detection and quantification with fast, single dimension mass spectrometry (LC-MS). Protein identification is achieved with subsequent LC-MS/MS analysis employing the same ChipCube™ chromatography system. Results With this consistent platform, over 800 LC-MS plasma proteomic profiles from prospectively collected samples of 420 individuals were obtained. Using a web-based data analysis pipeline for LC-MS profiling data, analyses of all peptide peaks from these plasma LC-MS profiles reveals an average coefficient of variability of less than 15%. Protein identification of peptide peaks of interest has been achieved with subsequent LC-MS/MS analyses and by referring to a spectral library created from about 150 discrete LC-MS/MS runs. Verification of peptide quantity and identity is demonstrated with several Multiple Reaction Monitoring analyses. These plasma proteomic profiles are publicly available through ProteomeCommons. Conclusion From a large prospective cohort of healthy and breast cancer patient volunteers and using a nano-fabricated chromatography system, a consistent LC-MS proteomics dataset has been generated that includes more than 800 discrete human plasma profiles. This large proteomics dataset provides an important resource in support of breast cancer biomarker discovery and validation efforts.Item Nanoplasmonic sensor for the detection of cardiac Troponin(Office of the Vice Chancellor for Research, 2015-04-17) Liyanage, Thakshila; Joshi, Gayatri K.; Sardar, RajeshThe Isoform of troponin I is uniquely produce in the adult human myocardium and it overexpress at myocardial injury. Accordingly, Iso troponin 1 level in plasma and other biological fluids can serve as diagnostic and prognostic disease biomarkers. Our study focus on the design of a label free ultrasensitive nanoplasmonic sensor by utilizing unique localized surface Plasmon resonance (LSPR) property of highly sensitive gold nanoprisms. Herein our study reveals that chemically synthesized nanoprisms with 42 nm average edge lengths can be used in nanoplasmonic sensor fabrication for the troponin detection. The limit of detection has been found to be sub-picomolar concentrations in PBS buffer and we will explore this sensing mechanism to detect Troponin I of myocardial infarction patient’s samples.Item Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease(IOS Press, 2017-06-23) Deters, Kacie D.; Risacher, Shannon L.; Kim, Sungeun; Nho, Kwangsik; West, John D.; Blennow, Kaj; Zetterberg, Henrik; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineBackground: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer’s disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study., Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis., Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ɛ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ+) if CSF Aβ42 was <192 pg/mL., Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ+ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus., Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ+ participants and not Aβ–participants.