A Physical Calibrator for Partial Discharge Meters

This article offers an alternative method of calibrating partial discharge meters for research and teaching purposes. Most current modern calibrators are implemented as precise voltage pulse sources with a coupling capacitor. However, our calibrator is based on the physical principles of dielectric materials distributed in a plane or space. Calibrator design is unique and there is an attempt to get closer to the behavior of the measured real objects. The calibration impulses are created by energy from a high voltage power supply at the specific or nominal value of the applied voltage. At the same time, it is possible to simulate the value and quantity of the discharges and their position in the object relative to the input electrodes. The calibrator creates conditions as a real measured object with adjustable parameters. This paper describes a design of this type of calibrator, its implementation, numerical simulation of discharge values and laboratory measurements with functional verification using the Tettex 9520 calibrator and galvanic measured system DDX 7000/8003 and DDX 9121b. All measurements are carried out using the CVVOZEPowerLab Research Infrastructure equipment

Measurements, Models, Systems and Design

531 s.

Modeling of calibration circuit for partial discharge measurement

Most of the high voltage equipment suffers from failure due to internal faults. The type of fault caused due to insulation failure as a consequence of local electrical stress concentration in the insulation, whether gas, solid or liquid is very widely prevalent. This is called as partial discharge. So, partial discharge detection is highly important for an early detection of insulation failure. In this study, the simulation of partial discharge has been carried out with consideration of a cylindrical void inside an epoxy resin. The PD characteristic is studied by applying different high voltages across the insulation, which is necessary for designing of a calibration circuit. A calibration circuit has been modeled in SIMULINK for generation of PD pulses of known charge magnitude. The calibrator was connected across the test object and the pulses were detected via detector. A physical model of calibrator was made and output calibrating pulses were observed at Digital Storage Oscilloscope

POPULATION PHARMACOKINETIC MODELING AND GENETIC ASSOCIATION ANALYSIS IN INFANTS WITH NEONATAL ABSTINENCE SYNDROME RECEIVING MORPHINE OR CLONIDINE

Neonatal abstinence syndrome, or NAS, is a postnatal opioid withdrawal syndrome occurring in 55% to 94% of neonates as a result of in utero exposure to opioids. It has emerged as a significant public health issue, as its incidence more than quadrupled in the past decade. There is significant variability in disease severity and treatment outcomes in neonates with NAS due to patient-specific factors and treatment- or site-specific factors. To understand what contributes to variability in length of hospital stay and other outcomes in neonates with NAS, we assessed population pharmacokinetics (PK) of clonidine and morphine, and we investigated potential associations between pre-specified single nucleotide polymorphisms (SNPs) and PK or disease severity/outcome measures. Samples collected from neonates enrolled in the No-POPPY trial (NCT03396588) up to early 2020 were used for analysis. PK samples from treated subjects on oral morphine or oral clonidine were analyzed for morphine, morphine-3-glucuronide, morphine-6-glucuronide and clonidine concentrations by LC-MS/MS. DNA was isolated from lysed whole blood or buccal swabs from treated and non-treated subjects and analyzed by TaqMan SNP genotyping assays using real-time PCR. Genetic association analysis was performed on COMT 472G\u3eA and OPRM1 118A\u3eG in all trial subjects, and on GNB3 825C\u3eT and ADRA2A -1291G\u3eC in clonidine-treated subjects. NONMEM (ver 7.3) was used to build population PK models and identify covariates associated with PK variability, including SNPs potentially associated with PK of morphine/clonidine (OCT1*2-*5, ABCC3 -211C\u3eT, and CYP2D6 metabolizer class). In the genetic association analysis, in contrast to a previous report, the relationship between COMT 472G\u3eA or OPRM1 118A\u3eG and hospital length of stay or other outcome measures was inconclusive. Clonidine-treated patients with TT genotype in GNB3 825C\u3eT had an average length of stay that was 3.7 days shorter than those with CC/CT genotypes (p=0.045), which did not meet experiment-wise significance. Significant associations between several clinical factors and one or more measures of NAS severity were identified, including breastfeeding and maternal use of benzodiazepines and gabapentin during pregnancy. In the population PK analysis, one-compartment models, with allometric scaling incorporated a priori, were used for clonidine and morphine. Age was a significant covariate in both models, and a sigmoidal maturation model incorporating postnatal age on clearance provided a good fit to clonidine concentration data. The clonidine PK model was successfully used to simulate alternative initial dosing regimens that were more likely to achieve earlier symptom stabilization. Genetic factors evaluated in the population PK analysis did not significantly affect the disposition of clonidine or morphine. Within the scope of this project, clinical factors appeared to be more important factors affecting disposition of treatment agents and NAS severity/treatment outcomes than the genetic factors evaluated. As the next step, efforts will be made to extend current analysis as the clinical trial continues to enroll subjects

Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs

In the development of anti-cancer drugs, it is essential to study the pharmacological profiles of the drugs. Among the analytical tools utilized in the pharmacological studies, LC-MS/MS has gained increased popularity due to its unequivocal sensitivity and specificity, as well as the ability of handling a wide variety of compounds with relatively simple sample preparation procedures. In this work, a brief review on the method rational, instrumentations, analytical method validation, and work flow of the method development was included. The processes of LC-MS/MS method development for the pharmacological studies of three anti-cancer drugs (i.e., methoxyamine, fludarabine, and 6-benzylthioinosine) were illustrated. To be more specific, a tetra-enzyme cocktail utilized for DNA adducts release was introduced. LC-MS/MS methods for the analysis of methoxyamine modified DNA abasic sites and fludarabine incorporated in DNA were developed toward the DNA adducts released from DNA with the enzyme cocktail. The methods were applied to the drug effect and drug mechanism studies. Another two LC-MS/MS method was developed for the quantification of 2-fluoroadenine released from the fludarabine incorporated DNA and free 6-benzylthioinosine drug molecule in mouse and human plasma. The first method helped to provide direct evidence to a newly proposed drug resistance mechanism toward fludarabine through DNA base excision repair while the second method realized the pharmacokinetic studies of the drug. The results in this work not only demonstrated the capability of LC-MS/MS in solving sophisticated pharmacological puzzles, but will provide useful information guiding the preclinical studies and clinical therapy development of the anti-cancer drugs listed abov

Development of an UFLC/MS/MS method for the comparative analysis of oxytocin and artesunate-amodiaquine for validation of field detection systems

Spurious, falsely-labeled, falsified or counterfeit (SFFC) pharmaceuticals are a health concern that claims hundreds of thousands of lives annually1, a violation of intellectual property rights which cost legitimate companies billions2, and a low-risk high yield revenue stream for organized crime2. While ports of entry and border control points are the primary access control points for SFFC3,4, advances in field portable detection and equipment offers an increasingly effective method for the assessment of pharmaceuticals at regional centers and points of distribution. This is particularly important for less developed countries (LDC) who do not maintain satellite or regional testing facilities. As part of a proposed protocol to assess field portable detection equipment, an ultrafast liquid chromatography, tandem mass spectrometry (UFLC-MS/MS) method for the quantification of liquid formulation Oxytocin was developed. The six minute method was found to have a within run %bias of +/-16%, a linear dynamic range of 150-1000 nanograms/milliliter (ng/ml), and an accuracy within acceptability criteria for all tested concentrations. The effectiveness of three identified transition ions, 723.1, 86.2 and 70.1 Daltons, for the analysis of oxytocin by mass spectrometry was assessed across several figures of merit to include signal to noise ratio, %CV, calibration sensitivity, and analytical sensitivity. The 723.1 ion fragment was recommended for quantification, while the 70.1 dalton ion was recommended as a qualifier ion, although 86.2 also performed within acceptability criteria. A method for the UFLC-MS/MS assessment of degradation products for oxytocin was proposed for specificity testing. Degradation of oxytocin by exposure to highly acidic, basic, and thermal conditions for one hour was attempted. Formation of degraded products was not observed. Additionally, existing High Performance Liquid Chromatography (HPLC) methods for the simultaneous assessment of Artesunate and Amodiaquine HCl were modified to assess compatibility with UFLC. No method assessed produced sufficient quality signal to continue with method development

CORMASS: A Compact and Efficient NIR Spectrograph for Studying Low-Mass Objects

CorMASS (Cornell Massachusetts Slit Spectrograph) is a compact, low-resolution (R=300), double-pass prism cross-dispersed near-infrared (NIR) spectrograph in operation on the Palomar Observatory 60-inch telescope. Its 2-dimensional spectral format provides simultaneous coverage from lambda ~ 0.75 microns to lambda ~ 2.5 microns (z'JHK bands). A remotely operated cold flip mirror permits its NICMOS3 detector to function as a K_s slit viewer to assist object placement into the 2 arcsec x 15 arcsec slit. CorMASS was primarily designed for the rapid spectral classification of low-mass stellar and sub-stellar objects identified by the Two-Micron All Sky Survey (2MASS). CorMASS' efficiency and resolution also make it a versatile instrument for the spectral observation and classification of many other types of bright objects (K<14) including quasars, novae, and emission line objects.Comment: To be published in Feb 2001 PASP, 19 pages, 12 Figures, High Resolution file can be retrieved from ftp://iras2.tn.cornell.edu/pub/wilson/papers/cormass.ps.g

Master of Science

thesisThis thesis presents the validation results on a modified heavy metal panel assay known as HYMET4 Blood Panel. It lays out the importance of metal testing in the clinical setting, and presents the underlying motivations that compelled the improvement of the current assay. We validated the measurement of arsenic, cadmium, lead, and mercury in whole blood using an Agilent Isocratic HPLC system and autosampler as the sample introduction system, herein referred to as Isocratic Pump Direct Injection (IPDI). The autosampler accommodates two 45 vial holders that increases sample throughputs. Sample preparation and introduction have been modified as well as data analysis parameters. Validation studies conducted were imprecision, sensitivity, accuracy, Analytical Measurement Range (AMR) or linearity, recovery, and carryover. EDTA, gold, DMSA, and DMPS have been used to study mercury stability in solution. The data from the validation studies of all four metals in the panel are analyzed. The results of the imprecision, sensitivity, accuracy, AMR, recovery, and carryover studies are as follows and are well promising. Of the four chelators used for the mercury stability study, DMPS gave the best results. The validation results suggest that the modifications made to the HYMET4 Blood Panel assay have substantially improved the assay. The successful validation of the modified assay also suggests that the improved assay will increase the laboratory throughput with the use of the two 45 vial holders. It will increase sensitivity of the results using the newer analytical system. It will also reduce current sample volume by one fifth, which leads to laboratory cost saving and patient specimen volume reduction. It has been proposed based on comparison data that the use of Cetac autosampler will give a more robust touch to the improvement process of the assay. Cetac autosampler is engineered uniquely for use in trace element testing as opposed to the IPDI system engineered for biochemical analysis

Quantitative and Qualitative Mass Spectrometric Analysis of Anticancer Agents, Drugs of Abuse and Enzyme-Inhibitor Complexes

Mass spectrometry is a valuable tool in the analysis of many types of compounds. From small molecules to large proteins, mass spectrometry can help to interrogate samples and give insights to the origins of disease as well as calculate an exact concentration. Bioanalytical method development is an integral component in the measurement of such compounds. To facilitate proper analytical investigation, the process of method development, analysis, and interpretation must be understood. This work describes the basis and procedure for bioanalytical method development and its detailed application to preclinical studies of the antineoplastic agent hexamethylene bisacetamide and measurement ofillicit drugs of abuse benzylpiperazine and trifluoromethylphenyl piperazine using liquid chromatography tandem mass spectrometry. Additionally, procedures for analyzing protein-drug interactions and their implication in antibiotic resistance are discusse

Quantitative and Qualitative Mass Spectrometric Analysis of Anticancer Agents, Drugs of Abuse and Enzyme-Inhibitor Complexes

Mass spectrometry is a valuable tool in the analysis of many types of compounds. From small molecules to large proteins, mass spectrometry can help to interrogate samples and give insights to the origins of disease as well as calculate an exact concentration. Bioanalytical method development is an integral component in the measurement of such compounds. To facilitate proper analytical investigation, the process of method development, analysis, and interpretation must be understood. This work describes the basis and procedure for bioanalytical method development and its detailed application to preclinical studies of the antineoplastic agent hexamethylene bisacetamide and measurement ofillicit drugs of abuse benzylpiperazine and trifluoromethylphenyl piperazine using liquid chromatography tandem mass spectrometry. Additionally, procedures for analyzing protein-drug interactions and their implication in antibiotic resistance are discusse