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Articles 8431 - 8460 of 11833
Full-Text Articles in Physical Sciences and Mathematics
Implantable Polymer/Metal Thin Film Structures For The Localized Treatment Of Cancer By Joule Heating, Nima Rahbar, Kwabena Kan-Dapaah, Christian Theriault, Wole Soboyejo
Implantable Polymer/Metal Thin Film Structures For The Localized Treatment Of Cancer By Joule Heating, Nima Rahbar, Kwabena Kan-Dapaah, Christian Theriault, Wole Soboyejo
Nima Rahbar
This paper presents an implantable polymer/metal alloy thin film structure for localized post-operative treatment of breast cancer. A combination of experiments and models is used to study the temperature changes due to Joule heating by patterned metallic thin films embedded in poly-dimethylsiloxane. The heat conduction within the device and the surrounding normal/cancerous breast tissue is modeled with three-dimensional finite element method (FEM). The FEM simulations are used to explore the potential effects of device geometry and Joule heating on the temperature distribution and lesion (thermal dose). The FEM model is validated using a gel model that mimics biological media. The …
Multistrain Infections In Metapopulations, Sydney Garmer, Rachel Lynn, Dan Rossi, Alex Capaldi
Multistrain Infections In Metapopulations, Sydney Garmer, Rachel Lynn, Dan Rossi, Alex Capaldi
Alex Capaldi
Case Studies In Evaluating Time Series Prediction Models Using The Relative Mean Absolute Error, Nicholas G. Reich, Justin Lessler, Krzysztof Sakrejda, Stephen A. Lauer, Sopon Iamsirithaworn, Derek A T Cummings
Case Studies In Evaluating Time Series Prediction Models Using The Relative Mean Absolute Error, Nicholas G. Reich, Justin Lessler, Krzysztof Sakrejda, Stephen A. Lauer, Sopon Iamsirithaworn, Derek A T Cummings
Nicholas G Reich
Statistical prediction models inform decision-making processes in many real-world settings. Prior to using predictions in practice, one must rigorously test and validate candidate models to ensure that the proposed predictions have sufficient accuracy to be used in practice. In this paper, we present a framework for evaluating time series predictions that emphasizes computational simplicity and an intuitive interpretation using the relative mean absolute error metric. For a single time series, this metric enables comparisons of candidate model predictions against naive reference models, a method that can provide useful and standardized performance benchmarks. Additionally, in applications with multiple time series, this …
Use Of Geographical Information Systems To Identify Counties In Georgia With High Risk For Childhood Lead Poisoning, R. Christopher Rustin, Christy Kuriatnyk, Byron Lobsinger, Simone Charles
Use Of Geographical Information Systems To Identify Counties In Georgia With High Risk For Childhood Lead Poisoning, R. Christopher Rustin, Christy Kuriatnyk, Byron Lobsinger, Simone Charles
R. Christopher Rustin
Spin-Exchange Optical Pumping At High Xenon Densities And Laser Fluxes: Principles And Practice, Boyd M. Goodson, Nicholas Whiting, Hayley Newton, Jason G. Skinner, Kaili Ranta, Panayiotis Nikolaou, Michael J. Barlow, Eduard Y. Chekmenev
Spin-Exchange Optical Pumping At High Xenon Densities And Laser Fluxes: Principles And Practice, Boyd M. Goodson, Nicholas Whiting, Hayley Newton, Jason G. Skinner, Kaili Ranta, Panayiotis Nikolaou, Michael J. Barlow, Eduard Y. Chekmenev
Nicholas Whiting
Hyperpolarization Methods For Mrs, Boyd M. Goodson, Nicholas Whiting, Aaron M. Coffey, Panayiotis Nikolaou, Fan Shi, Brogan M. Gust, Maxwell E. Gemeinhardt, Roman Shchepin, Jason G. Skinner, Jonathan R. Birchall, Michael J. Barlow, Eduard Y. Chekmenev
Hyperpolarization Methods For Mrs, Boyd M. Goodson, Nicholas Whiting, Aaron M. Coffey, Panayiotis Nikolaou, Fan Shi, Brogan M. Gust, Maxwell E. Gemeinhardt, Roman Shchepin, Jason G. Skinner, Jonathan R. Birchall, Michael J. Barlow, Eduard Y. Chekmenev
Nicholas Whiting
Quantile Rank Maps: A New Tool For Understanding Individual Brain Development, Huaihou Chen, Clare Kelly, F. Xavier Castellanos, Ye He, Xi-Nian Zuo, Philip T. Reiss
Quantile Rank Maps: A New Tool For Understanding Individual Brain Development, Huaihou Chen, Clare Kelly, F. Xavier Castellanos, Ye He, Xi-Nian Zuo, Philip T. Reiss
Philip T. Reiss
We propose a novel method for neurodevelopmental brain mapping that displays how an individual’s values for a quantity of interest compare with age-specific norms. By estimating smoothly age-varying distributions at a set of brain regions of interest, we derive age-dependent region-wise quantile ranks for a given individual, which can be presented in the form of a brain map. Such quantile rank maps could potentially be used for clinical screening. Bootstrap-based confidence intervals are proposed for the quantile rank estimates. We also propose a recalibrated Kolmogorov-Smirnov test for detecting group differences in the age-varying distribution. This test is shown to be …
Cross-Validation And Hypothesis Testing In Neuroimaging: An Irenic Comment On The Exchange Between Friston And Lindquist Et Al., Philip T. Reiss
Cross-Validation And Hypothesis Testing In Neuroimaging: An Irenic Comment On The Exchange Between Friston And Lindquist Et Al., Philip T. Reiss
Philip T. Reiss
The “ten ironic rules for statistical reviewers” presented by Friston (2012) prompted a rebuttal by Lindquist et al. (2013), which was followed by a rejoinder by Friston (2013). A key issue left unresolved in this discussion is the use of cross-validation to test the significance of predictive analyses. This note discusses the role that cross-validation-based and related hypothesis tests have come to play in modern data analyses, in neuroimaging and other fields. It is shown that such tests need not be suboptimal and can fill otherwise-unmet inferential needs.
Epidemiology Of Latency And Relapse In Plasmodium Vivax Malaria, Andrew A. Lover
Epidemiology Of Latency And Relapse In Plasmodium Vivax Malaria, Andrew A. Lover
Andrew Lover
Considerations For Comprehensive Analyses Of Sporozoite-Based Controlled Human Malaria Infection Studies, Andrew A. Lover
Considerations For Comprehensive Analyses Of Sporozoite-Based Controlled Human Malaria Infection Studies, Andrew A. Lover
Andrew Lover
Short Report: Study Variability In Recent Human Challenge Experiments With Plasmodium Falciparum Sporozoites (Pfspz Challenge), Andrew A. Lover
Short Report: Study Variability In Recent Human Challenge Experiments With Plasmodium Falciparum Sporozoites (Pfspz Challenge), Andrew A. Lover
Andrew Lover
Improvement Of Ifng Elispot Performance Following Overnight Resting Of Frozen Pbmc Samples Confirmed Through Rigorous Statistical Analysis, Radleigh Santos, Alcinette Bunying, Nazila Sabri, John Yu, Anthony Gringeri, James Bender, Sylvia Janetzki, Clemencia Pinilla, Valeria A. Judkowski
Improvement Of Ifng Elispot Performance Following Overnight Resting Of Frozen Pbmc Samples Confirmed Through Rigorous Statistical Analysis, Radleigh Santos, Alcinette Bunying, Nazila Sabri, John Yu, Anthony Gringeri, James Bender, Sylvia Janetzki, Clemencia Pinilla, Valeria A. Judkowski
Mathematics Faculty Articles
Immune monitoring of functional responses is a fundamental parameter to establish correlates of protection in clinical trials evaluating vaccines and therapies to boost antigen-specific responses. The IFNg ELISPOT assay is a well-standardized and validated method for the determination of functional IFNg-producing T-cells in peripheral blood mononuclear cells (PBMC); however, its performance greatly depends on the quality and integrity of the cryopreserved PBMC. Here, we investigate the effect of overnight (ON) resting of the PBMC on the detection of CD8-restricted peptide-specific responses by IFNg ELISPOT. The study used PBMC from healthy donors to evaluate the CD8 T-cell response to five pooled …
Ontogenetic Scaling Patterns And Functional Anatomy Of The Pelvic Limb Musculature In Emus (Dromaius Novaehollandiae), Luis P. Lamas, Russell P. Main, John R. Hutchinson
Ontogenetic Scaling Patterns And Functional Anatomy Of The Pelvic Limb Musculature In Emus (Dromaius Novaehollandiae), Luis P. Lamas, Russell P. Main, John R. Hutchinson
Department of Basic Medical Sciences Faculty Publications
Emus (Dromaius novaehollandiae) are exclusively terrestrial, bipedal and cursorial ratites with some similar biomechanical characteristics to humans. Their growth rates are impressive, as their body mass increases eighty-fold from hatching to adulthood whilst maintaining the same mode of locomotion throughout life. These ontogenetic characteristics stimulate biomechanical questions about the strategies that allow emus to cope with their rapid growth and locomotion, which can be partly addressed via scaling (allometric) analysis of morphology. In this study we have collected pelvic limb anatomical data (muscle architecture, tendon length, tendon mass and bone lengths) and calculated muscle physiological cross sectional area …
Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan
Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan
Troy Seidle, PhD
Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …
An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle
An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle
Troy Seidle, PhD
Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines …
The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung
The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung
Troy Seidle, PhD
Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.
A key aspect of the implementation of new testing strategies is the determination …
A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann
A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann
Troy Seidle, PhD
The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …
The Ecological Genomic Basis Of Salinity Adaptation In Tunisian Medicago Truncatula, Maren L. Friesen, Eric J.B. Von Wettberg, Mounawer Badri, Ken S. Moriuchi, Fathi Barhoumi, Peter L. Chang, Sonia Cuellar-Ortiz, Matilde A. Cordeiro, Wendy T. Vu, Soumaya Arraouadi, Naceur Djébali, Kais Zribi, Yazid Badri, Stephanie S. Porter, Mohammed Elarbi Aouani, Douglas R. Cook, Sharon Y. Strauss, Sergey V. Nuzhdin
The Ecological Genomic Basis Of Salinity Adaptation In Tunisian Medicago Truncatula, Maren L. Friesen, Eric J.B. Von Wettberg, Mounawer Badri, Ken S. Moriuchi, Fathi Barhoumi, Peter L. Chang, Sonia Cuellar-Ortiz, Matilde A. Cordeiro, Wendy T. Vu, Soumaya Arraouadi, Naceur Djébali, Kais Zribi, Yazid Badri, Stephanie S. Porter, Mohammed Elarbi Aouani, Douglas R. Cook, Sharon Y. Strauss, Sergey V. Nuzhdin
College of Agriculture and Life Sciences Faculty Publications
Background: As our world becomes warmer, agriculture is increasingly impacted by rising soil salinity and understanding plant adaptation to salt stress can help enable effective crop breeding. Salt tolerance is a complex plant phenotype and we know little about the pathways utilized by naturally tolerant plants. Legumes are important species in agricultural and natural ecosystems, since they engage in symbiotic nitrogen-fixation, but are especially vulnerable to salinity stress. Results: Our studies of the model legume Medicago truncatula in field and greenhouse settings demonstrate that Tunisian populations are locally adapted to saline soils at the metapopulation level and that saline origin …
The Fine-Scale Habitat Use Of Risso’S Dolphins Off Bardsey Island, Cardigan Bay (Uk), Marijke N. De Boer, Sonja Eisfeld, Mark P. Simmonds
The Fine-Scale Habitat Use Of Risso’S Dolphins Off Bardsey Island, Cardigan Bay (Uk), Marijke N. De Boer, Sonja Eisfeld, Mark P. Simmonds
Mark P. Simmonds, OBE
The main objectives of this study were (1) to estimate the population size of Risso’s dolphins off Bardsey Island using mark-recapture techniques (De Boer et al., 2013); and (2) to study habitat-use in relation to fine-scale oceanographic features. This work provides preliminary information on the habitat-use of Risso’s dolphins and will benefit future studies, along with the development of effective conservation measures for this species throughout the region.
Cetaceans And Marine Debris: The Great Unknown, Mark Peter Simmonds
Cetaceans And Marine Debris: The Great Unknown, Mark Peter Simmonds
Mark P. Simmonds, OBE
Plastics and other marine debris have been found in the gastrointestinal tracts of cetaceans, including instances where large quantities of material have been found that are likely to cause impairment to digestive processes and other examples, where other morbidity and even death have resulted. In some instances, debris may have been ingested as a result of the stranding process and, in others, it may have been ingested when feeding. Those species that are suction or “ram” feeders may be most at risk. There is also evidence of entanglement of cetaceans in marine debris. However, it is usually difficult to distinguish …
Expert Testimony In Capital Sentencing: Juror Responses, John H. Montgomery, J. Richard Ciccone, Stephen P. Garvey, Theodore Eisenberg
Expert Testimony In Capital Sentencing: Juror Responses, John H. Montgomery, J. Richard Ciccone, Stephen P. Garvey, Theodore Eisenberg
Stephen P. Garvey
The U.S. Supreme Court, in Furman v. Georgia (1972), held that the death penalty is constitutional only when applied on an individualized basis. The resultant changes in the laws in death penalty states fostered the involvement of psychiatric and psychologic expert witnesses at the sentencing phase of the trial, to testify on two major issues: (1) the mitigating factor of a defendant’s abnormal mental state and (2) the aggravating factor of a defendant’s potential for future violence. This study was an exploration of the responses of capital jurors to psychiatric/psychologic expert testimony during capital sentencing. The Capital Jury Project is …
Mediation Analysis Of Gestational Age, Congenital Heart Defects, And Infant Birth-Weight, Adane F. Wogu, Christopher A. Loffredo, Ionut Bebu, George Luta
Mediation Analysis Of Gestational Age, Congenital Heart Defects, And Infant Birth-Weight, Adane F. Wogu, Christopher A. Loffredo, Ionut Bebu, George Luta
GW Biostatistics Center
Background
In this study we assessed the mediation role of the gestational age on the effect of the infant’s congenital heart defects (CHD) on birth-weight.
Methods
We used secondary data from the Baltimore-Washington Infant Study (1981–1989). Mediation analysis was employed to investigate whether gestational age acted as a mediator of the association between CHD and reduced birth-weight. We estimated the mediated effect, the mediation proportion, and their corresponding 95% confidence intervals (CI) using several methods.
Results
There were 3362 CHD cases and 3564 controls in the dataset with mean birth-weight of 3071 (SD = 729) and 3353 (SD = 603) …
A More Efficient Nonparametric Test Of Symmetry Based On Overlapping Coefficient, Hani M. Samawi, Robert L. Vogel
A More Efficient Nonparametric Test Of Symmetry Based On Overlapping Coefficient, Hani M. Samawi, Robert L. Vogel
Biostatistics Faculty Publications
In this paper we provide a more efficient nonparametric test of symmetry based on the empirical overlap coefficient using kernel density estimation applied to an extreme order statistics, namely extreme ranked set sampling. Our simulation investigation reveals that our proposed test of symmetry is at least as powerful as currently available tests of symmetry. Intensive simulation is conducted to examine the power of the proposed test. An illustration is provided using cardiac output and body weight of neonates in a neonatal intensive care unit.
Response Of Soil Nitrification To The Veterinary Pharmaceuticals Monensin, Ivermectin And Zinc Bacitracin, Magda A. Konopka
Response Of Soil Nitrification To The Veterinary Pharmaceuticals Monensin, Ivermectin And Zinc Bacitracin, Magda A. Konopka
Electronic Thesis and Dissertation Repository
Pharmaceutical residues can reach agricultural land through amendment with animal or human waste. Since 2010, a series of replicated plots received annual applications of ivermectin, monensin and zinc bacitracin, either singly or in a mixture, at 0.1 mg/kg and 10 mg/kg concentrations. I collected soil samples before and after the fourth annual application of pharmaceuticals and assayed them for functional changes and amoA gene abundance, a gene needed for ammonia oxidation. In 2013, I exposed the soils to 100 mg/kg in a laboratory experiment which resulted in acceleration of nitrification. Under 10 mg/kg treatments in the field the abundance of …
Simulation Based Evaluation Of Multiscale Small Area Health Models, Purbasha Dasgupta
Simulation Based Evaluation Of Multiscale Small Area Health Models, Purbasha Dasgupta
Theses and Dissertations
The effects of scale on the analysis of spatial data, often referred to as the modifiable areal unit problem in spatial studies, is one of the issues often encountered in small area health models. These spatial effects of scale are also seen in the areas of disease mapping where data are usually available in counts. Often there is a need to consider the different scales of aggregation that exist within count data, since inferences based on analyses can vary if we change the definition of the unit of analysis. This thesis provides a framework that describes the distribution of relative …
Privacy-Preserving And Outsourced Multi-User K-Means Clustering, Bharath Samanthula, Fang-Yu Rao, Elisa Bertino, Xun Yi, Dangxi Liu
Privacy-Preserving And Outsourced Multi-User K-Means Clustering, Bharath Samanthula, Fang-Yu Rao, Elisa Bertino, Xun Yi, Dangxi Liu
Cyber Center Publications
Many techniques for privacy-preserving data mining (PPDM) have been investigated over the past decade. Often, the entities involved in the data mining process are end-users or organizations with limited computing and storage resources. As a result, such entities may want to refrain from participating in the PPDM process. To overcome this issue and to take many other benefits of cloud computing, outsourcing PPDM tasks to the cloud environment has recently gained special attention. We consider the scenario where n entities outsource their databases (in encrypted format) to the cloud and ask the cloud to perform the clustering task on their …
Colloidal And Biological Properties Of Triscationic Amphiphiles With One Or Two Tails, John N. Marafino
Colloidal And Biological Properties Of Triscationic Amphiphiles With One Or Two Tails, John N. Marafino
Masters Theses, 2010-2019
The decline in the development of novel antimicrobials, combined with the misusage and over prescription of antibiotics, has contributed to the increasing prevalence of antimicrobial-resistant infections. Thus development of effective novel disinfectants could reduce the transmission of pathogens and decrease the risk of infection by antibiotic resistant organisms. The antimicrobial activity of amphiphiles, compounds with hydrophobic and hydrophilic regions, was first reported in 1935, and has influenced the synthesis of amphiphiles with variations in structure. In this study, three series of amphiphiles were synthesized by two subsequent Menshutkin reactions. Each amphiphile contains one or two hydrocarbon tails ranging from 8 …
Poly(Ester Amide) And Poly(Ethyl Glyoxylate) Nanoparticles For Controlled Drug Release, Amira Mohamed Moustafa
Poly(Ester Amide) And Poly(Ethyl Glyoxylate) Nanoparticles For Controlled Drug Release, Amira Mohamed Moustafa
Electronic Thesis and Dissertation Repository
The objective of this research was to develop polymeric nanoparticles (NPs) having improved drug release properties for drug delivery. Poly(ester amide)s (PEAs) are promising biodegradable polymers. PEA NPs were prepared via emulsification-evaporation and salting-out methods and optimized through by varying different processing parameters. Polymer-model drug conjugates based on PEAs containing L-aspartic acid and rhodamine B were synthesized and used for NP preparation. Release behavior was studied and compared to a control system with physically encapsulated rhodamine B. It was shown that the release of rhodamine B from the covalent system did not show the burst effect and exhibited a slower …
Environmental Health Effects Of Multiple Exposures: Systemic Risks And The Detroit River International Crossing Study, Tor H. Oiamo
Environmental Health Effects Of Multiple Exposures: Systemic Risks And The Detroit River International Crossing Study, Tor H. Oiamo
Electronic Thesis and Dissertation Repository
This thesis examines cumulative exposures to traffic noise and outdoor air pollution on environmental and health related quality of life in Windsor, Ontario, and provides a critical analysis of the environmental assessment process for the Detroit River International Crossing (DRIC) Study. The research utilizes a systemic risk framework to understand environmental health and stress effects of cumulative exposures. The significance of this research is based on a relative absence of literature on the systemic health risks of cumulative exposures and the need to elucidate environmental annoyance as a health outcome for risk assessment. The objectives of the research were to …
Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky
Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky
Department of Chemistry: Dissertations, Theses, and Student Research
High density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) are lipoproteins previously shown to bind many basic and neutral hydrophobic drugs in serum. These interactions impact the distribution, delivery, metabolism, and excretion of drugs and are important in determining drug activity, pharmacokinetics, and toxicity in the human body. Information about drug-lipoprotein interactions and the strength of these interactions can be useful in determining the distribution of drugs following administration.
The research presented in this dissertation uses high performance affinity chromatography (HPAC) and packed columns to study binding of the drug propranolol to immobilized lipoproteins such …