Physical Sciences and Mathematics Commons^™

Finding Recurrent Regions Of Copy Number Variation: A Review, Oscar M. Rueda, Ramon Diaz-Uriarte

Ramon Diaz-Uriarte

Copy number alterations (CNA) in genomic DNA are linked to a variety of human diseases. Although many methods have been developed to analyze data from a single subject, disease-critical genes are more likely to be found in regions that are common or recurrent among diseased subjects. Unfortunately, finding recurrent CNA regions remains a challenge. We review existing methods for the identification of recurrent CNA regions. Methods differ in their working definition of ``recurrent region'', the type of input data, the statistical and computational methods used to identify recurrence, and the biological considerations they incorporate (which play a role in the …

Regressing Scalar Outcomes On Image Predictors Via Functional Principal Component Regression, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Survival Unchanged Five Months After Implementing The 2005 Aha Cpr And Ecc Guidelines For Out-Of-Hospital Cardiac Arrest., Blair L. Bigham, Kent M. Koprowicz, John Stouffer, Tom P. Aufderheide, Stuart Donn, Judy Powell, Dan Davis, Sarah Nafziger, Brian Suffoletto, Ahamed Idris, Mike Helbock, Laurie J. Morrison

Kent M Koprowicz

Introduction: To improve survival from out of hospital cardiac arrest (OHCA), the American Heart Association released guidelines in 2005. We examined the effect of these guidelines on survival in the Resuscitation Outcomes Consortium (ROC) Epistry – Cardiac Arrest. We hypothesized that survival would increase after guideline implementation. Methods: 174 EMS agencies from 8 of the 10 ROC sites were surveyed to determine 2005 AHA guideline implementation, or crossover, date. Two sites with 2005 compatible treatment algorithms prior to guideline release were not included. Patients with OHCA secondary to a non cardiac cause, EMS witnessed events, patients <18 years>old, and patients with …

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …

Composite Endpoint Analysis For Assessing Surrogacy With Censored Data, Debashis Ghosh

Debashis Ghosh

Background: There is great interest in the development of surrogate endpoints using new technologies in medical research. The promise of such endpoints is that they would allow for faster completion of clinical trials and would be potentially cost-effective.

Purpose: In determining surrogacy, it is important to distinguish the roles of surrogate from the true endpoint. The latter should be thought of as the gold standard. We discuss a framework in which the utility of a surrogate endpoint is based on whether or not as part of a composite endpoint, it yields treatment effects that associate with that on the true …

Simultaneous Confidence Bands For The Coefficient Function In Functional Regression, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Inferring Group Differences In Brain Connectivity From Functional Magnetic Resonance Images, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Surface Charge Effects Involved In The Control Of Stability Of Sols Comprising Uniform Cholesterol Particles, Vuk Uskoković

Pharmacy Faculty Articles and Research

The reported is a method for the preparation of stable dispersions of narrowly dispersed cholesterol crystals, which may provide an excellent model for the aggregation studies thereof. The effects of experimental parameters that include concentration, pH, ionic strength, temperature, and aging on the resulting morphologies are acknowledged. Regardless of the cause of destabilization, the multilayered aggregates of cholesterol particles are formed by “face-to-face” stacking of the original platelets, as promoted by higher surface charge density on particle sides comparing to their faces. In accordance with the crucial involvement of surface charge effects in stabilization of cholesterol dispersions produced hereby, aggregation …

Reliability Of Functional Connectivity Networks: How Can We Assess It?, Philip T. Reiss

Philip T. Reiss

No abstract provided.

On Correcting The Overestimation Of The Permutation Based False Discovery Rate Estimator., Shuo Jiao, Shunpu Zhang

Shuo Jiao

Motivation: Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR), which is defined as the expected percentage of the number of false positive genes among the claimed significant genes. As a consequence, the accuracy of the FDR estimators will

be important for correctly controlling FDR. Xie et al. found that the standard permutation method of estimating FDR is biased and proposed to delete the predicted differentially expressed (DE) genes in the estimation of FDR for one-sample comparison. However, we notice that the formula of the FDR used …

Radiotherapy Optimal Design: An Academic Radiotherapy Treatment Design System, R Acosta, W Brick, A Hanna, Allen Holder, D Lara, G Mcquillen, D Nevin, P Uhlig, B Salter

Mathematical Sciences Technical Reports (MSTR)

Optimally designing radiotherapy and radiosurgery treatments to increase the likelihood of a successful recovery from cancer is an important application of operations research. Researchers have been hindered by the lack of academic software that supports head-to-head comparisons of different techniques, and this article addresses the inherent difficulties of designing and implementing an academic treatment planning system. In particular, this article details the algorithms and the software design of Radiotherapy optimAl Design (RAD).

Writing Research Proposal: Literature Review And Database Search, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

Preparation Of Halogenated Derivatives Of Thiazolo[5,4-D]Thiazole Via Direct Electrophilic Aromatic Substitution, Vladimir Benin, Alan T. Yeates, Douglas Dudis

Chemistry Faculty Publications

Chlorination and bromination reactions of thiazolo[5,4-d]thiazole led to the generation of its mono- and dihalogenated derivatives. These are the first instances of successful direct electrophilic aromatic substitution in the thiazolo[5,4-d]thiazole ring system. X-ray analysis demonstrates that both 2-bromothiazolo[5,4-d]-thiazole and 2,5-dibromothiazolo[5,4-d]thiazole are planar structures, with strongly manifested π-stacking in the solid state. Theoretical analysis of the pyridine-catalyzed halogenation (MP2/6-31+G(d) and B3LYP/6-31+G(d)calculations) reveals that introduction of one halogen actually leads to a slightly enhanced reactivity towards further halogenation. Several halogenation mechanisms have been investigated: 1) The direct C-halogenation with N-halopyridine as electrophile; …

Targeted Drug Delivery Systems For Cancer Therapy, Antonio Clementi, Christine O'Connor, Mary Mcnamara, A. Mazzaglia, M. C. Aversa, A. Giuffrida

Conference Papers

The role of cyclodextrin’s (CD) in drug delivery has advanced in recent years and this may be attributed to its biocompatibility and well established synthesis. Chemical modification of CDs has shown to extend the physicochemical properties and the host capacity for a variety of drugs. β-CD has been widely used in the early stages of pharmaceutical applications because of its ready availability and its cavity size suitability for a wide range of drugs. Chemical modification of β-CD has proven to enhance aqueous solubilisation, microbiological stability and reduced toxicity in previous studies.1 Folate Receptors are over-expressed in several human cancers including …

Microproteomics: Analysis Of Protein Diversity In Small Samples, Howard B. Gutstein, Jeffrey S. Morris, Suresh P. Annangudi, Jonathan V. Sweedler

Jeffrey S. Morris

Proteomics, the large-scale study of protein expression in organisms, offers the potential to evaluate global changes in protein expression and their post-translational modifications that take place in response to normal or pathological stimuli. One challenge has been the requirement for substantial amounts of tissue in order to perform comprehensive proteomic characterization. In heterogeneous tissues, such as brain, this has limited the application of proteomic methodologies. Efforts to adapt standard methods of tissue sampling, protein extraction, arraying, and identification are reviewed, with an emphasis on those appropriate to smaller samples ranging in size from several microliters down to single cells. The …

Comment On Global Dynamics Of Biological Systems, Radhakrishnan Nagarajan

Radhakrishnan Nagarajan

No abstract provided.

C–N Bond Rotation And E–Z Isomerism In Some N-Benzyl-N-Methylcarbamoyl Chlorides: A Dft Study, Michael Horwath, Vladimir Benin

Chemistry Faculty Publications

The current report presents the first theoretical study of the restricted CN bond rotation in carbamoyl chlorides. Several N-benzyl-N-methylcarbamoyl chlorides were investigated, with varying pattern of substitution in the aromatic ring. Optimizations and frequency calculations were conducted employing DFT at the B3LYP/6-31+G(d) level of theory. Each of the studied structures exhibits a pair of rotamers (s-Z and s-E), generated upon rotation around the C(O)N bond. The s-E isomer is the global minimum in every case, but the preference for it is usually less than 1 kcal/mol. Two possible transition state structures were identified …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

The T-Mixture Model Approach For Detecting Differentially Expressed Genes In Microarrays, Shuo Jiao, Shunpu Zhang

Shuo Jiao

The finite mixture model approach has attracted much attention in analyzing microarray data due to its robustness to the excessive variability which is common in the microarray data. Pan (2003) proposed to use the normal mixture model method (MMM) to estimate the distribution of a test statistic and its null distribution. However, considering the fact that the test statistic is often of t-type, our studies find that the rejection region from MMM is often significantly larger than the correct rejection region, resulting an inflated type I error. This motivates us to propose the t-mixture model (TMM) approach. In this paper, …

A Call For A Statewide Bioinformatics Institute, John R. Rose

Journal of the South Carolina Academy of Science

No abstract provided.

Droid: The Drosophila Interactions Database, A Comprehensive Resource For Annotated Gene And Protein Interactions, Jingkai Yu, Svetlana Pacifico, Guozhen Liu, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Charting the interactions among genes and among their protein products is essential for understanding biological systems. A flood of interaction data is emerging from high throughput technologies, computational approaches, and literature mining methods. Quick and efficient access to this data has become a critical issue for biologists. Several excellent multi-organism databases for gene and protein interactions are available, yet most of these have understandable difficulty maintaining comprehensive information for any one organism. No single database, for example, includes all available interactions, integrated gene expression data, and comprehensive and searchable gene information for the important model organism, Drosophila melanogaster. …

Direct Effect Models, Mark J. Van Der Laan, Maya L. Petersen

Maya Petersen

The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is not mediated by an intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Robins, Greenland and Pearl develop counterfactual definitions for two types of direct effects, natural and controlled, and discuss assumptions, beyond those of sequential randomization, required for the identifiability of natural direct effects. Building on their earlier work and that of others, this article …

Characterizing Pharmacy And Medical Claims For A Private Insurance Polypharmacy Population, Brian W. Bresnahan, Kent M. Koprowicz, Sanchita Roy Choudhury, Louis P. Garrison, Ed Wong

Kent M Koprowicz

Objectives: To describe and characterize a group of private insurance members taking multiple medications over a one-year period. Methods: Persons were selected for this polypharmacy analysis if they had at least five unique maintenance prescriptions in their pharmacy claims records for the period of January-March 2005, based on a customized list of chronic medications. The full set of pharmacy and medical claims for these members were evaluated for a twelve month period, October 2004 to September 2005. Standard descriptive statistics were calculated to characterize the population. Logistic regression models were used to assess the association of pharmacy claims and “safety …

Multiple Testing Procedures Under Confounding, Debashis Ghosh

Debashis Ghosh

While multiple testing procedures have been the focus of much statistical research, an important facet of the problem is how to deal with possible confounding. Procedures have been developed by authors in genetics and statistics. In this chapter, we relate these proposals. We propose two new multiple testing approaches within this framework. The first combines sensitivity analysis methods with false discovery rate estimation procedures. The second involves construction of shrinkage estimators that utilize the mixture model for multiple testing. The procedures are illustrated with applications to a gene expression profiling experiment in prostate cancer.

Joint Variable Selection And Classification With Immunohistochemical Data, Debashis Ghosh, Ratna Chakrabarti

Debashis Ghosh

To determine if candidate cancer biomarkers have utility in a clinical setting, validation using immunohistochemical methods is typically done. Most analyses of such data have not incorporated the multivariate nature of the staining profiles. In this article, we consider modelling such data using recently developed ideas from the machine learning community. In particular, we consider the joint goals of feature selection and classification. We develop esti- mation procedures for the analysis of immunohistochemical profiles using the least absolute selection and shrinkage operator. These lead to novel and flexible models and algorithms for the analysis of compositional data. The techniques are …

An Improved Model Averaging Scheme For Logistic Regression, Debashis Ghosh, Zheng Yuan

Debashis Ghosh

Recently, penalized regression methods have attracted much attention in the statistical literature. In this article, we argue that such methods can be improved for the purposes of prediction by utilizing model averaging ideas. We propose a new algorithm that combines penalized regression with model averaging for improved prediction. We also discuss the issue of model selection versus model averaging and propose a diagnostic based on the notion of generalized degrees of freedom. The proposed methods are studied using both simulated and real data.

Sc Inbre: A Catalyst For Biomedical Research Development In South Carolina, Lucia A. Pirisi-Creek M.D, Scott Little, Ph.D.

Journal of the South Carolina Academy of Science

No abstract provided.

In-Vivo Delivery Of Dna Vaccines Using Metallo-Lipid Nanoparticles, Clarissa Sara Gomez

Open Access Theses & Dissertations

There has been a rapidly growing area of research in the design and synthesis of molecules that self-organize in water to form functional nanosystems and due to the high interest in the area metal ligand complexes were tested as drug delivery systems with a Leishmania vaccine. Herein, we present the design, synthesis and functional activity of Cu(II) and Zn(II) complexes that self-assemble in water to form spherical nanoscale structures that exhibit an affinity to bind DNA and deliver it into eukaryotic cells with a high percent efficiency in-vitro. In order to assess the effectiveness of these nanoparticles to deliver DNA …

Inflammation: The Key To Health And Disease, Prakash Nagarkatti Ph. D, Donald J. Dipette M. D.

Journal of the South Carolina Academy of Science

No abstract provided.

Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for conjugation. We further …