Digital Commons Network^™

Empirical Bayes Analysis Of Sequencing-Based Transcriptional Profiling Without Replicates, Zhijin Wu, Bethany D. Jenkins, Tatiana A. Rynearson, Sonya T. Dyhrman, Mak A. Saito, Melissa Mercier, Leann P. Whitney

Cell and Molecular Biology Faculty Publications

Background:

Recent technological advancements have made high throughput sequencing an increasingly popular approach for transcriptome analysis. Advantages of sequencing-based transcriptional profiling over microarrays have been reported, including lower technical variability. However, advances in technology do not remove biological variation between replicates and this variation is often neglected in many analyses.

Results:

We propose an empirical Bayes method, titled Analysis of Sequence Counts (ASC), to detect differential expression based on sequencing technology. ASC borrows information across sequences to establish prior distribution of sample variation, so that biological variation can be accounted for even when replicates are not available. Compared to current …

Freshman Record : The University Of Rhode Island, The Interfraternity/Panhellenic Councils

Freshman Record

No abstract provided.

Renaissance 2010, University Of Rhode Island

URI Yearbooks

This is a digitized, downloadable version of the University of Rhode Island yearbook.

Predator Effects In Predator-Free Space: The Remote Effects Of Predators On Prey, John L. Orrock, Lawerence M. Dill, Andrew Sih, Johnathan H. Grabowski, Scott D. Peacor, Barbara L. Peckarsky, Evan L. Preisser, James R. Vonesh, Earl E. Werner

Biological Sciences Faculty Publications

Predators can have remote effects on prey populations that are connected by migration (i.e. prey metapopulations) because predator-mediated changes in prey behavior and abundance effectively transmit the impact of predators into predator-free prey populations. Behavioral changes in prey that might give rise to remote effects are altered rates of migration or activity in the presence of predation risk (called non-consumptive effects, fear- or μ-driven effects, and risk effects). Changes in prey abundance that may result in remote effects arise from changes in prey density due to direct predation (i.e. consumptive effects, also called N-driven effects and predation effects). Remote effects …

Rational Quantitative Structure–Activity Relationship (Rqsar) Screen For Pxr And Car Isoform-Specific Nuclear Receptor Ligands, Ann M. Dring, Linnea E. Anderson, Saima Qamar, Matthew A. Stoner

Biomedical and Pharmaceutical Sciences Faculty Publications

Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related orphan nuclear receptor proteins that share several ligands and target overlapping sets of genes involved in homeostasis and all phases of drug metabolism. CAR and PXR are involved in the development of certain diseases, including diabetes, metabolic syndrome and obesity. Ligand screens for these receptors so far have typically focused on steroid hormone analogs with pharmacophore-based approaches, only to find relatively few new hits. Multiple CAR isoforms have been detected in human liver, with the most abundant being the constitutively active reference, CAR1, and the ligand-dependent isoform CAR3. …

KV4.2 Channels Tagged In The S1-S2 Loop For Alpha-Bungarotoxin Binding Provide A New Tool For Studies Of Channel Expression And Localization, Leonard Moise, Jing Liu, Evgeny Pryazhnikov, Leonard Khiroug, Andreas Jeromin, Edward Hawrot

Cell and Molecular Biology Faculty Publications

We report the first successful insertion of an engineered, high-affinity alpha-bungarotoxin (Bgtx) binding site into a voltage-gated ion channel, K_V4.2, using a short, intra-protein embedded sequence (GGWRYYESSLEPYPDGG), derived from a previously described mimotope peptide, HAP. A major benefit to this approach is the ability to live-image the distribution and fate of functional channels on the plasma membrane surface. The Bgtx binding sequence was introduced into the putative extracellular loop between the S1 and S2 transmembrane domains of K_V4.2. Following co-expression with KChIP3 in tsA201 cells, S1-S2 HAP-tagged channels express at levels comparable to wild-type K_{V …}

Synthesis, Antiviral And Contraceptive Activities Of Nucleoside–Sodium Cellulose Sulfate Acetate And Succinate Conjugates, Hitesh K. Agarwal, Anil Kumar, Gustavo F. Doncel, Keykavous Parang

Biomedical and Pharmaceutical Sciences Faculty Publications

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2′,3′-dideoxy-3′-thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfate-acetate (CSA) (e.g., AZT–CSA and FLT–CSA) were found to be more potent than CS and other conjugates (e.g., AZT–succinate–CS, and FLT–succinate–CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type …

Dexamethasone Transcriptionally Increases The Expression Of The Pregnane X Receptor And Synergistically Enhances Pyrethroid Esfenvalerate In The Induction Of Cytochrome P450 3a23, Deshi Shi, Dongfang Yang, Bingfang Yan

Biomedical and Pharmaceutical Sciences Faculty Publications

The pregnane X receptor (PXR) is recognized as a key regulator for the induction of a large number of genes in drug metabolism and transport. The transactivation of PXR is enhanced by the glucocorticoid dexamethasone and the enhancement is linked to the induction of PXR in humans and rats. The present study was undertaken to determine the mechanism for the induction and ascertain the synergistic effect on the expression of CYP3A23, a rat PXR target. In primary hepatocytes, significant induction of PXR was detected as early as 2 h after the treatment and the maximal induction occurred at 1 μM …

Plasma Pharmacokinetics And Tissue Disposition Of Novel Dextran–Methylprednisolone Conjugates With Peptide Linkers In Rats, Suman Penugonda, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Biomedical and Pharmaceutical Sciences Faculty Publications

The plasma and tissue disposition of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP‐1) or five (DMP‐5) amino acids as linkers were studied in rats. Single 5‐mg/kg doses (MP equivalent) of each prodrug or MP were administered intravenously, and blood and tissue samples were collected. Prodrug and drug concentrations were quantitated using HPLC, and noncompartmental pharmacokinetic parameters were estimated. Whereas conjugation of MP with dextran in both prodrugs substantially decreased the clearance of the drug by ∼200‐fold, the accumulations of the drug in the liver, spleen, and kidneys were significantly increased by conjugation. However, the extent of accumulation …

Pregnane X Receptor Is Required For Interleukin-6-Mediated Down-Regulation Of Cytochrome P450 3a4 In Human Hepatocytes, Jian Yang, Chunshu Hao, Dongfang Yang, Deshi Shi, Xiulong Song, Xiaofei Luan, Gang Hu, Bingfang Yan

Biomedical and Pharmaceutical Sciences Faculty Publications

Cytochrome P450 3A4 (CYP3A4) is the most abundant cytochrome P450 enzyme in human liver and metabolizes more than 60% of prescribed drugs in human body. Patients with liver conditions such as cirrhosis show increased secretion of cytokines (e.g., interleukin-6) and decreased capacity of oxidation of many drugs. In this study, we provided molecular evidence that cytokine secretion directly contributed to the decreased capacity of oxidative biotransformation in human liver. After human hepatocytes were treated with IL-6, the expression of CYP3A4 decreased at both mRNA and protein levels, so did the CYP3A4 enzymatic activity. Meanwhile, the repression of CYP3A4 by IL-6 …

Using Molecular-Assisted Alpha Taxonomy To Better Understand Red Algal Biodiversity In Bermuda, Elisabeth N. Cianciola, Thea R. Popolizio, Craig W. Schneider, Christopher E. Lane

Biological Sciences Faculty Publications

Molecular-assisted alpha taxonomy has recently become an effective practice in reassessing biodiversity and floristics for a variety of different organisms. This paper presents a series of examples that have been drawn from biodiversity work being carried out on the marine red algae of Bermuda. Molecular sequencing of DNA from Bermuda samples has already begun to greatly alter the makeup of the flora as it was known just decades ago, and will help set a new database for future comparison as climate change affects species composition in the islands.

Research & Innovation For 2009-2010, University Of Rhode Island

Publications (Research and Economic Development)

The 2009-2010 issue of Research & Innovation, a periodical focused on research at the University of Rhode Island.

Ph-(Low)-Insertion-Peptide (Phlip) Translocation Of Membrane Impermeable Phalloidin Toxin Inhibits Cancer Cell Proliferation, Ming An, Dayanjali Wijesinghe, Oleg A. Andreev, Yana K. Reshetnyak, Donald M. Engelman

Physics Faculty Publications

We find that pH-(low)-insertion-peptide (pHLIP)-facilitated translocation of phalloidin, a cell-impermeable polar toxin, inhibits the proliferation of cancer cells in a pH-dependent fashion. The monomeric pHLIP inserts its C terminus across a membrane under slightly acidic conditions (pH 6–6.5), forming a transmembrane helix. The delivery construct carries phalloidin linked to its inserting C terminus via a disulfide bond that is cleaved inside cells, releasing the toxin. To facilitate delivery of the polar agent, a lipophilic rhodamine moiety is also attached to the inserting end of pHLIP. After a 3 h incubation at pH 6.1–6.2 with 2–4 μM concentrations of the …

Ph-Sensitive Membrane Peptides (Phlips) As A Novel Class Of Delivery Agents, Oleg A. Andreev, Donald M. Engelman, Yana K. Reshetnyak

Physics Faculty Publications

Here we review a novel class of delivery vehicles based on pH-sensitive, moderately polar membrane peptides, which we call pH (Low) Insertion Peptides (pHLIPs), that target cells located in the acidic environment found in many diseased tissues, including tumours. Acidity targeting by pHLIPs is achieved as a result of helix formation and transmembrane insertion. In contrast to the earlier technologies based on cell-penetrating peptides, pHLIPs act as monomeric membrane-inserting peptides that translocate one terminus across a membrane into the cytoplasm, while the other terminus remains in the extracellular space, locating the peptide in the membrane lipid bilayer. Therefore pHLIP has …

Partitioning Of Perfluorooctanoate Into Phosphatidylcholine Bilayers Is Chain Length-Independent, Wei Xie, Geoffrey D. Bothun, Hans-Joachim Lehmler

Chemical, Biomolecular, and Materials Engineering Faculty Publications

The chain length dependence of the interaction of PFOA, a persistent environmental contaminant, with dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) was investigated using steady-state fluorescence anisotropy spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). PFOA caused a linear depression of the main phase transition temperature T_m while increasing the width of the phase transition of all three phosphatidylcholines. Although PFOA's effect on T_m and the transition width decreased in the order DMPC > DPPC > DSPC, its relative effect on the phase behavior was largely independent of the phosphatidylcholine. PFOA caused swelling of DMPC but not DPPC …

Shorebird Migration Ecology At Monomoy National Wildlife Refuge, Stephanie Lianne Koch

Open Access Dissertations

Many species of shorebirds (Charadrii) are long-distance migrants that rely on disturbance-free stopover sites with abundant food. Adequate protection of stopover sites requires knowledge of migration chronology, effects of anthropogenic disturbances, and factors affecting habitat selection. We studied shorebird migration ecology at Monomoy National Wildlife Refuge (Refuge), Cape Cod, Massachusetts, one of the most important shorebird stopover sites in eastern North America. Our findings can be implemented by land managers in the future to maintain the integrity of this stopover site. In the first manuscript, we studied seasonal variation in shorebird abundance during migration and determined peak periods of human …

Functional, Metabolic And Ultrastructural Alterations As A Result Of Cardiac Hypertrophy, Michael Eugene Dunn

Open Access Dissertations

Effects of gene manipulation on mouse heart function generally require aortic banding or other additional molecular modification in order to achieve full expressions of cardiac responses. The neurohormonal independent characterization of myocardial functional and metabolic changes concurrent with skeletal muscle pathology resulting from aortic banding in the mouse have not been investigated. The objective of this study was to characterize the effects of thoracic aortic banding alone on mouse left ventricular function, skeletal muscle pathological changes and glycolytic flux three and six weeks post-banding. Working hearts were perfused (KH solution containing 3% albumin and 0.4 mM palmitate) at identical volume …

Uri Undergraduate And Graduate Course Catalog 2010-2011, University Of Rhode Island

URI Course Catalogs Archive

This is a digitized, downloadable version of the University of Rhode Island course catalog.

The Effects Of Concentric Ring Electrode Electrical Stimulation On Rat Skin, Walter Besio, V. Sharma, J. Spaulding

Electrical, Computer, and Biomedical Engineering Faculty Publications

Surface electrodes are commonly used electrodes clinically, in applications such as functional electrical stimulation for the restoration of motor functions, pain relief, transcutaneous electrical nerve stimulation, electrocardiographic monitoring, defibrillation, surface cardiac pacing, and advanced drug delivery systems. Common to these applications are occasional reports of pain, tissue damage, rash, or burns on the skin at the point where electrodes are placed. In this study, we quantitatively analyzed the effects of acute noninvasive electrical stimulation from concentric ring electrodes (CRE) to determine the maximum safe current limit. We developed a three-dimensional multi-layer model and calculated the temperature profile under the CRE …

Spatial Patterns Of The Humpback Whale (Megaptera Novaeangliae) And Its Summer Habitat In The North Atlantic Ocean, Kathleen J. Vigness-Raposa

Open Access Dissertations

The humpback whale (Megaptera novaeangliae) is found in all oceans of the world, migrating between low-latitude breeding grounds in the winter and high-latitude feeding grounds in the summer. In addition to these broad-scale spatial patterns, individuals in the North Atlantic Ocean exhibit fine-scale site fidelity, with median re-sighting distances of less than 40 km in consecutive years. Because they occur close to coasts and demonstrate a predictable distribution, humpback whales are particularly susceptible to disturbance from human activities. A clear understanding of the geographic pattern of summer sightings, along with the environmental features that characterize areas of concentrated distribution, could …

The Role Of Pedagogical Documentation In Developing Young Children's Thinking Processes, Leslie A. Sevey

Open Access Dissertations

This study examines the role of pedagogical documentation on young children's thinking processes. Pedagogical documentation is utilized as part of the Reggio Emilia Approach for several purposes, such as assessment, curriculum planning, and instructional accountability. This study was conducted in a kindergarten classroom that utilizes the Reggio Emilia Approach, at a laboratory school on a college campus. Acting in the role of participant observer I spent nine weeks observing and at times interacting with the students as they engaged in activities involving science kits. I specifically looked at the experiences of the children as they interacted with the pedagogical documentation, …

Characterizing The Advanced Glycation Endproducts Formation Of Proteins And Nucleotides By Methylglyoxal And Glyoxal, Praveen Kumar Pampati

Open Access Dissertations

Advanced glycation endproducts (AGEs) are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and nucleic acids. The initial product of this reaction is called a Schiff base, which rearranges itself into an Amadori or glycation product which can further rearrange to AGEs. The reaction is called Maillard reaction and is the basis for all protein glycation studies. AGEs accumulate in tissues and associate with the pathology of various diseases like Diabetes, Alzheimer's disease, renal failure, aging, etc. Methylglyoxal, 3-Deoxyglucosone and glyoxal (oxoaldehydes or α-dicarbonyls) have recently been proposed …

Trophoblasts And Endothelial Cells In Pregnancy-Associated Vascularization, Satyan Kalkunte

Open Access Dissertations

Dysregulated uteroplacental interaction and vascular remodeling are thought to be associated with the molecular events in preeclampsia. Due to the co-onset of maternal symptoms and placental pathology, we hypothesize that serum from preeclampsia patients could provide a "blueprint" of etiologic factors. To substantiate the hypothesis, a novel three dimensional dual cell culture in vitro model, a mimic of the vascular remodeling events during pregnancy, was established. In this model, unlike term trophoblasts, first trimester trophoblasts engage in a dynamic cross-talk and synchronize with the endothelial cells in a capillary network. Mechanistic studies indicate that poor expression of VEGF C and …

Spatial And Temporal Variation In Otolith Chemistry For Tautog (Tautoga Onitis) In Narragansett Bay And Rhode Island Coastal Ponds, Ivan Mateo, Edward G. Durbin, David A. Bengtson, Richard Kingsley, Peter K. Swart, Daisy Durant

Fisheries, Animal and Veterinary Sciences Faculty Publications

The elemental composition of otoliths may provide valuable information for establishing connectivity between fish nursery grounds and adult fish populations. Concentrations of Rb, Mg, Ca, Mn, Sr, Na, K, Sr, Pb, and Ba were determined by using solution-based inductively coupled plasma mass spectrometry in otoliths of young-of-the year tautog (Tautoga onitis) captured in nursery areas along the Rhode Island coast during two consecutive years. Stable oxygen (δ¹⁸O) and carbon (δ¹³C) isotopic ratios in young-of-the year otoliths were also analyzed with isotope ratio mass spectrometry. Chemical signatures differed significantly among the distinct nurseries within Narragansett …

Subjectivities And Counterpublics In 20th-Century Christian Leftist Texts, Robert Leblanc

Open Access Dissertations

Subjectivities and Counterpublics in 20th-Century Christian Leftist Texts responds to the following question: How have recent film and literary voices of the Christian left addressed counterpublics suited to their emergent and pressing needs? In exploring answers to this question, the project considers the role of radical artistic expressions in addressing a politically motivated public sphere. The three core chapters provide close readings of literary texts and films from the second half of the 20th Century that seek to tie themselves to markers of Christian tradition while still operating in a radicalizing way on reading and viewing audiences. In these three …

The Development Of Novel Mr Molecular Imaging Agents Towards The Visualization Of Dat, Gregory R. Naumiec

Open Access Dissertations

The facile and definitive diagnosis of disease is paramount in treating patients effectively. The ability to image the body, and more precisely the ability to image the specific site of the ailment, has become a cornerstone in medicine. Currently, most imaging technologies focus on macroscopic physical, physiological, or metabolic changes rather than identifying specific molecular events that are responsible for disease. Magnetic resonance imaging (MRI) is a non-radioactive and high spatial resolution diagnostic technique capable of both anatomical and molecular imaging. Paramagnetic complexes, such as gadolinium, can be used as MRI contrast agents because their unpaired electrons increase the relaxivity …

Utilizing Modular Upgrades To Maintain An Effective Inventory Of Complex Machines, Brian T. Mckeon

Open Access Dissertations

The value of many machines and consumer devices can be extended considerably by planned upgrades of components or parts, contributing to increased sustainability, effectiveness and lower ownership costs. When machines are composed of components that can be replaced independently, they can be considered as complex machines. The performance of such machines is computable as some function of the performance of the constituent components. This concept of operations, sometimes known as modular upgrades, can require the coordination of a large inventory of machines and components in different conditions, sometimes geographically distributed over large areas. This dissertation introduces the concept of an …

The Development And Validation Of The Survey Of Attitudes Toward Research Methods, Elizabeth S. Dimond

Open Access Dissertations

Students' attitudes toward research methods may affect their learning approaches and outcomes in such courses. The four studies in this dissertation developed and provided evidence for the validity of the Survey of Attitudes Toward Research Methods (SATRM), a measure with which students' attitudes toward research methods can be better understood. The first objective was to develop the measure, including adaptation of items from an existing measure, the Survey of Attitudes Toward Statistics (Schau, Stevens, Dauphinee, & Del Vecchio, 1995), to reflect research methods, and determining the factor structure and the questions best representing those factors. The SATRM was then administered …

Physiology And Behavior Of The Jumbo Squid Dosidicus Gigas, Lloyd A. Trueblood

Open Access Dissertations

Dosidicus gigas is a large, epipelagic squid known to vertically migrate, spending night on the surface, and descending during the day into the oxygen minimum layer (OML). This dissertation seeks to examine physiological and behavioral adaptations of D. gigas to the environment in which it dwells. Life in the open ocean is unique in that there is little physical refuge. In order to capture prey in this environment, many pelagic fishes engage at high relative swimming speeds attempting to strike before being detected. This requires high metabolic rates and increasing anaerobic potential with increasing body size to overcome drag. I …

Carrying Capacity Of Bivalve Aquaculture, Carrie Jean Byron

Open Access Dissertations

A framework was developed for determining carrying capacity through mass-balance ecosystem modeling and stakeholder involvement that can be used to guide management of bivalve aquaculture. A collaborative working group was formed where stakeholders worked closely with scientists to calculate carrying capacity which was then used to inform a long-term aquaculture plan for Narragansett Bay and Rhode Island's coastal lagoons where aquaculture has doubled in six years and user conflicts are high. Stakeholders informed the modeling process at four critical steps: conceptualization of models, evaluation of data sources for parameterization, mass-balancing of the model, and calculation of carrying capacity. Cultured oysters, …